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BACKGROUND OF THE INVENTION
The present invention relates to a bed, particularly to a patient bed.
The beds known in the prior art, particularly patient or hospital beds, comprise an underlay, frame and legs which are generally provided with wheels. On top of the underlay there is located a mattress on which the patient rests.
There are patient groups such as chronically non-ambulant old people, who need hospital treatment but are fairly little moved within the nursing facilities. For these patient groups the conventional patient beds are problematic. Moving the patients away from the bed and back is cumbersome. In connection with basic nursing, the repeated lifting of non-ambulant patients is necessary.
Another problem is that generally at least two nurses are needed for carrying out basic nursing measures, because one nurse should not do the shifting or lifting of the patient alone. Particularly the care of chronic patients in conventional beds requires a lot of personnel. Continuous lifting and shifting of the patients cause spinal symptoms and defects to the nurses.
SUMMARY OF THE INVENTION
The object of the present invention is to eliminate the above mentioned drawbacks.
According to the invention, the bed comprises an underlay for the patient; a support frame, provided with at least one support member, which is arranged above the underlay; and suspension means such as straps, whereby the underlay is suspended from the support member.
Thus the essential element of the support frame of the bed of the invention is the support member, the number whereof is advantageously one or two. The support member is arranged in the patient room or other suitable space at a suitable height, such as 1.5 . . . 2.5 m, and is attached to the structures of the premises by means of other elements of the support frame, such as one or more wall or roof fastener and/or vertical support. The same support member can also be employed as the suspension support of several, for instance two, separate underlays.
In a preferred embodiment of the bed, the underlay is attached with suspension means to the support member, so that the support points are located at a distance from each other, and that at least one of the support points is located outside the line drawn via two or more support points.
This fastening by three or more points secures that the underlay is suspended in a stabile fashion to the support member of the support frame. Thus the underlay does not easily swing from side to side, and in case it does swing during the nursing measures, the winging motion is easily attenuated.
In a preferred embodiment of the bed, the support member is formed of an essentially horizontal elongate bar, the first end whereof is free, and in the lengthwise direction whereof the underlay is suspended.
The length of the support member is advantageously designed so that one underlay can be suitably suspended thereto, and that it is easily fastened to the structures of the premises.
In a preferred embodiment of the bed, the support frame comprises at least one essentially vertical support member, whereto the horizontal support member is connected.
By means of the vertical support member, the fastening of the support frame to the wall structures of the premises can be carried out for instance at the height of 0.5 . . . 1.0 m from the floor, and if necessary supported against the floor.
In a preferred embodiment of the bed, the support frame comprises a leg member, which is attached to the vertical support member and is arranged to extend to underneath the underlay.
Thus the horizontal support member, the vertical support member and the leg member together form, when seen from the side, a U-shaped structure, where the major part of the patient's weight against the horizontal support member is directed towards the floor via the leg member. This means that the fastening of the support frame to the structures of the premises can be realized with equipment with a fairly light structure.
In a preferred embodiment of the bed, the leg member is formed of an elongate bar, which is on the same vertical level as the horizontal support member. Such a structure makes the support frame remarkably lighter, at the same time maintaining a good solid strength and support capacity.
In a preferred embodiment of the bed, the support frame is detachably fastened to the structures of the premises.
In a preferred embodiment of the bed, the support frame is detachably fastened to the structures of the premises, and in similar fashion it can be fastened to a transport couch, particularly to the transport couch of the patient.
In a preferred embodiment of the bed, the structures of the premises are provided with a first socket member, and the transport couch is provided with a second socket member, and the bed is provided with fastening means which can be connected both to the first and the second socket member.
When the patient is being moved from one room to another on the transport couch, the support frame of the bed can be coupled to the transport couch and be transported along with the patient. Then the support frame of the bed can again be fastened to a suitable, specially reserved spot. The patient can be left lying on the couch to wait for treatment. Now the transport couch can again be used for moving other patients.
In a preferred embodiment of the bed, the support frame is attached at its vertical support member, essentially turnably on the horizontal level, to the fastening means.
In a preferred embodiment of the bed, the bed includes a hauling apparatus, whereby the underlay can be raised and lowered with respect to the floor level.
The steps of horizontal turning and vertical adjusting of the underlay can be used in various nursing measures carried out for the patient.
In a preferred embodiment of the bed, the bed includes a hauling apparatus which is connected to the essentially vertical support member provided in the support frame, by means of which hauling apparatus at least the horizontal support member and the underlay suspended therefrom can be raised or lowered.
In a preferred embodiment of the bed, the hauling apparatus comprises at least one fluid cylinder. Generally speaking the transmission equipment, particularly the hauling apparatus, can be formed of manually operated power means such as a bottle jack, or of electric, pneumatic or hydraulic power actuators and power transmission means connected thereto.
In a preferred embodiment of the bed, there is provided at least one crossbar in connection with the support member, the arms of the crossbar being at an angle with respect to the horizontal support member and connected to the underlay by means of straps or other such suspending means.
In a preferred embodiment of the bed, the crossbar is fastened to the horizontal support member by means of fastening members, so that the crossbar can be moved along the horizontal support member and locked at a desired point. Thus the crossbar can be adjusted to an advantageous spot so that the underlay and hence the patient are firmly and securely in the support of the support member.
Generally the number of these crossbars is one or two. They are installed in the support member at the patient's shoulders and, in case there are two, at the patient's knees, supposing that the patient rests on the underlay. The arms of the crossbars are either stationary, folding or adjustable with respect to the horizontal support member. They can also be constructed in a telescopic fashion of nested parts.
In a preferred embodiment of the bed, there is at least one additional member provided at the free end of the support member, whereby the support member can be lengthened. It can be fitted, for instance, mostly within the support member, and pulled out therefrom to form a continuation to the support member. Thus the support member can be lengthened when necessary.
In a preferred embodiment of the bed, the straps or other such suspension means are arranged on rollers. The rollers are provided in connection with the horizontal support member and/or crossbar, and they can be provided with for example mechanical or electric rotation means in order to facilitate the reeling of the straps. When the bed is not in use, the straps are in rest position wound on the rollers, from which rollers the straps are again easily pulled down and fastened to the underlay.
In a preferred embodiment of the bed, the rollers are charged with springs so that the straps are in the rest position, wound on the rollers, when the bed is not in use, from which rollers the straps can be pulled out and fastened to the underlay when the bed is being used. The employed spring-charged rollers can be any of the known types, such as the strap-and-roller types used in connection with car safety belts.
In a preferred embodiment of the bed, the underlay comprises a bottom part which is made of some flexible material, and support rails, which are fitted at least on the long sides of the underlay. Advantageously the support rails are fitted on all sides of the underlay and interconnected so that they form a frame for the underlay.
The support rails are advantageously fastened to the underlay in a detachable fashion. While using the bed of the present invention, the straps are easily fastened at four points to the support rails located on the long sides of the underlay, in the vicinity of the ends of the underlay. In practice such an underlay is a cot-like bed where the patient gets a comfortable rest.
In a preferred embodiment of the bed the underlay is formed of net.
In a preferred embodiment of the bed the underlay is made of some waterproof material.
In a preferred embodiment of the bed the bottom of the underlay is made of two layers: a first layer, which is made of some material well permeable to air and water, such as net or some resembling material; and of a second layer, which is made of some waterproof material such as plastic foil; and which second layer can be detachably fastened under the first layer.
Normally the patient lies on the first layer of the underlay. The second layer is used when the patient is washed, in which case it is produced and fastened under the first layer. The first layer is advantageously made of some water-repellent material, so that it does not absorb water in connection with the washing.
In a preferred embodiment of the bed, the second layer of the underlay is arranged to be rolled on a roller along the long side of the underlay, wherefrom it can be drawn to under the first layer.
In a preferred embodiment of the bed that layer of the underlay which is made of waterproof material is provided with an aperture whereto a discharge hose can be connected. This underlay can be used while washing the patient, in which case the washing water is conducted, via the hose, to a sewer or other receptable where water can be collected. When the washing of the patient is arranged thus, it can be carried out conveniently in bed.
In a preferred embodiment of the bed, the underlay is provided with an aperture for a bedpan. This aperture is advantageously provided with a hatch which is made of the same material as the underlay. This hatch is opened when necessary. Thus it is not necessary to lift the patient up from the underlay, but the bedpan is arranged underneath the underlay, at the aperture provided therein.
In a preferred embodiment of the bed, the underlay includes an insulating layer, which is detachably fastened underneath the underlay. By means of this insulating layer the patient keeps warm and does not get cold underneath. Generally there is not used a mattress and usually not even a sheet in between the patient and the underlay.
In a preferred embodiment of the bed, in connection with the support frame there are arranged means for measuring the weight of the patient. The weighing is carried out easily by means of the measuring sensor or device installed in connection with the bed.
An advantage of the invention is that the bed is simple and reduced in structure.
Another advantage of the invention is that the bed is particularly suited for non-ambulant chronic patients.
Yet another advantage of the invention is that the underlay connected to the bed can be modified in many different ways according to the needs.
Further, owing to the invention it is not necessary to lift the patient out of bed when he must be taken for instance to separate nursing premises, but the patient can be moved with suitable transport equipment while he is lying in his own bed.
Yet another advantage of the invention is that the patient on his underlay can be suspended, after being transported from one room to another, to the support of the support frame arranged in the new premises.
Yet another advantage of the invention is that in a preferred embodiment of the invention, the support frame can be moved, on a suitable shifting platform, as a while for instance from the dormitory to a nursing room.
Yet another advantage of the invention is that the height of the underlay from the floor can be adjusted.
Another further advantage of the invention is that the support member and at the same time the underlay can be turned on the horizontal level.
Furthermore, the maintenance, such as cleaning, of the premises becomes easier owing to the present invention.
Moreover, owing to the invention and particularly to the versatility of the underlay, the nursing measures such as washing the patient and adjusting the bedpan, become easier.
Moreover, owing to the invention the patient rests on an underlay which is easily air-conditioned.
Yet another advantage of the invention is that the underlay conforms flexibly to the movements of the patient, so that the formation of bedsores is prevented or at least reduced.
Further, owing to the invention less personnel is required for taking care of the patients.
Yet another advantage of the invention is that it remarkably facilitates the work of the nursing personnel, and increases their safety at work.
Moreover, owing to the invention the transport of the patients can be carried out irrespective of the conditions, for instance in narrow, crowded spaces.
Yet another advantage of the invention is that in connection with the bed of the present invention, there can be used many different types of underlays, which are designed for different uses.
Yet another advantage of the invention is that the structures of the bed, particularly the horizontal support member above it, can be utilized in the nursing or auxiliary measures for instance for suspending various devices such as rehabilitation and training devices. This is possible because the support member extending above the bed does not necessarily include any obstacles for the instalment of auxiliary devices.
Yet another advantage of the invention is that the bed can easily be provided with means for weighing the patient. Controlling the patient's weight is important particularly with certain patient groups, such as non-ambulant old people.
BRIEF DESCRIPTION OF THE DRAWINGS
In the following the invention and its advantages are explained in more detail with reference to the appended drawings, where
FIG. 1 illustrates a bed as seen from the side;
FIG. 2 illustrates another bed as seen from the side;
FIG. 3 illustrates the bed of FIG. 2 as seen from the top;
FIG. 4 illustrates a third bed as seen from the side;
FIG. 5 illustrates the bed of FIG. 4 as seen from the top;
FIG. 6 illustrates the crossbar connected to the horizontal support member of the bed;
FIG. 7 illustrates the joining of the support frame of the bed to the transport couch;
FIGS. 8A and 8B illustrate details from FIG. 7, seen along the sections F--F and G--G;
FIG. 9 illustrates an underlay seen from the top;
FIG. 10 illustrates the underlay of FIG. 9, seen from the side;
FIG. 11 illustrates another underlay seen from the top;
FIG. 12 illustrates a cross-section of the underlay of FIG. 11; and
FIG. 13 illustrates a cross-section of an underlay which is provided with heat insulation.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The bed of the present invention comprises the underlay 1, on top of which the patient is arranged to lie; a support frame 2, which comprises an essentially horizontal support member 2a, and an essentially vertical support member 2b, which horizontal support member 2a is arranged above the underlay; and suspension means 3, such as straps, whereby the underlay 1 is suspended from the horizontal support member 2a.
The support frame 2 is attached to the structures of the premises, for instance to the wall 5, as is illustrated in FIG. 1. In this case the support frame 2 is fastened to the wall with fastening means, such as studs 5, at the vertical support member 2b.
The support member 2a is formed of an at least roughly horizontal, elongate bar, the first end whereof is free and the second end whereof is connected to the vertical support member 2b, which also is formed of an elongate bar. The support members 2a and 2b can be interconnected in an arched or angular fashion.
In the embodiments of FIGS. 1, 2 and 3, the horizontal support member 2a of the support frame 2 is provided with a continuation 6. This is fitted at least partly inside the support member 2a, and can be pulled out to form a continuation for the support member 2a when the need arises to lengthen the support member 2a. Thus the distance of the suspending means 3 from each other can be lengthened, so that there can be used a long underlay 1, or shortened, so that a short underlay 1 is used, depending on the length of the patient.
In connection with the support member 2a there is provided a crossbar 4. The arms 4a, 4b of the crossbar 4 are placed at an angle, advantageously 90°, with respect to the support member 2a.
The suspension means 3, which in the following are generally called straps, can be formed of members of a given length, which members are flexible and bendable but maintain their length.
The underlay 1 is fastened, by means of the straps 3, to the support member 2a of the support frame 2, above the underlay 1, at least when the bed is being used. The support points C, D, E of the straps 3 in the support frame 2, i.e. in the support member 2a and the connected crossbar 4 and continuation 6, are located at intervals from each other. At least one for instance C, of the support points is located outside the line drawn via the other support points D, E. Thus the underlay 1 is supported against the support frame at three points C, D, E falling on the apices of a triangle, preferably an equilateral triangle. In that case the patient P lies in the bed in a stabile fashion, in the support of the support frame 2.
The said fastening points C, D are in FIG. 3 located at the ends of the arms 4a, 4b of the crossbar 4, wherefrom the arms 4a, 4b are connected, by means of the straps 3, to the sides of the underlay 1, on both sides of the top part of the patient's body. In FIG. 3 the third support point E is located at the end of the auxiliary member 6, where the straps 3 are fastened at their other end, and further connected to the sides of the underlay 1, on both sides of the patient's feet.
The free end of the support member 2a, or the continuation 6 connected thereto, can also be provided with another crossbar 7 which in structure corresponds to the crossbar 4. This second crossbar is illustrated with dotted lines in FIGS. 1, 2 and 3. Thus for instance the foot of the patient's bed can be lifted in similar fashion as the head.
It is, however, maintained that in most cases the attaching of the fastening members directly to the support member 2a (or continuation 6) is a fully satisfactory measure, and the patient can rest in a perfectly safe and stabile fashion in an underlay thus suspended.
In the embodiments of FIGS. 2 and 3, the bed comprises a hauling apparatus 8. It is connected to the vertical support member 2b. Thereby the vertical support member 2b can be raised and lowered, so that simultaneously the horizontal support member 2a and the underlay 3 suspended thereto rise or descend.
The hauling apparatus 8 can be realized with a gear rack and gear wheel combination, where the gear rack is arranged in connection with the support member 2b. The gear wheel can be rotated with a suitable power means such as a hand crank or an electric motor. Alternatively the hauling apparatus can also be realized with a fluid cylinder, whereto the fluid is fed by means of a hand pump or suitable actuator, such as a pump operated with an electric motor.
The hauling apparatus 8 is connected to the fastening means 9, such as a flange, whereby the support frame 2 of the bed is fastened to the wall S of the premises by means of studs 5 or other corresponding fastening means.
The support frame 2 of the bed is attached, at the vertical support member 2b and turnably around the axis B--B, to the hauling apparatus 8. The support frame 2, particularly the horizontal support member 2a, can thus be turned at a predetermined angle α from the basic position, which is perpendicular to the wall structure S, to either side thereof. The support frame 2 can be locked in a desired position.
In FIGS. 4 and 5, there is illustrated a third bed according to the invention. The support member 2a of the support frame 2 is adjusted at a small angle β (for instance 5°) with respect to the horizontal plane, and it is diagonally connected to the vertical support member 2b. The vertical support member 2a is fitted in a tubular member 10, which is attached to the wall S by means of fastening members 11.
The vertical support member 2b of the support frame 2 is fastened to the tubular member 10 by means of an annular support member such as a sliding bearing. The sliding bearing 12 rests above the top part of the tubular member 10 either freely or suitably attached thereto. The vertical support member 2b is provided with a bracket, such as a pin 13 or an annular flange. This bracket 13 is suitably fastened to the vertical support member 2b, and thereon the support frame 2 rests on top of the sliding bearing 12 and the tubular member 10.
The horizontal support member 2a of the support frame 2 is advantageously locked in place, so that it cannot be turned in the direction of the axis B--B of the vertical support member 2b. This can be realized with a mechanical locking member that locks the tubular member 10 and the support member 2b suitably together. When necessary, the locking member can be opened and the horizontal support member 2a together with the connected underlay 1 can be turned.
The support frame 2 of the bed comprises, in addition to the horizontal and vertical support members 2a, 2b, a leg support 2c. The leg support 2c is connected to the vertical support member 2b, and it is directed to underneath the underlay 1 on the same vertical level as the horizontal support member 2a. In the embodiments of FIGS. 4 and 5, the leg member 2c is attached to the end of the vertical support member 2b that reaches through the tubular member 10. Advantageously the leg member 2c is an elongate bar, the free end whereof, located underneath the underlay 1, is supported against the floor L.
At its free end the leg member 2c can be provided with one or several wheels, rollers or the like members. In the embodiments of FIGS. 4 and 5, the free end of the leg member 2c is supported with a cross-bar 14, which is provided with small wheels or rollers 15 at intervals from each other.
In connection with the roughly horizontal support member 2a of the support frame 2, there is provided a crossbar 16 in FIGS. 4, 5 and 6. The crossbar 16 is attached to the support member 2a by means of fastening members so that it can be moved along the support member 2a and locked in place at a desired point.
In this case the fastening members include an aperture 17 or a similar member of the crossbar 16, wherethrough the support member 2a is arranged to pass, a hole 18 in the crossbar and a number of apertures, such as holes 19, which are arranged at intervals from each other in connection with the horizontal support member 2a, and a pin 20 or similar locking member. The pin 20 is inserted in the holes 18, 19, in which case the crossbar is locked in place. The crossbar 16 is positioned, on a suitable spot in the horizontal support member 2a, so that the underlay 1 complete with the patient is safely suspended from the support frame 2.
The straps 3 are arranged, according to FIG. 6, on rollers 21. These rollers 21 are placed in the crossbar 16, in the vicinity of the fastening point of the support member 2a, parallel to the support member and at the same time to the lengthwise axis A--A of the underlay 1. At the ends 16a, 16b of the arms of the crossbar 16, there are installed folding wheels 22, wherethrough the straps 3 are arranged to pass, as is seen from FIG. 6.
In the vicinity of the free end of the support member 2a of the support frame 2, there is arranged a second set of rollers 23 on both sides of the support member 2a, so that the axes thereof are parallel to the lengthwise axis A--A of the support member. The second set of rollers 23 is provided with straps 3 in similar fashion as the first set 21.
The rollers 21, 23 are advantageously charged with springs so that the straps are in their rest position wound on the rollers 21, 23. From the rollers 21, 23 the straps can be pulled down from the crossbar 16 or from the support member 2a, and fastened to the underlay 1 by means of clasps 24 or other such fastening means.
The straps 3 arranged on the rollers 21, 23 are of defined lengths. The lengths of the straps are such that the underlay 1 complete with the patient P rests at a suitable height from the floor, for instance 60 . . . 70 cm. Alternatively the rollers 21, 23 can be provided with locking members in order to prevent winding or lengthening of the strap after the desired height of the underlay has been set.
The patient is placed in the bed of the present invention as follows. A transport couch is used as an aid in the process. The underlay 1 is arranged on top of the transport couch for the patient, whereafter the patient is lifted on top of the underlay 1 and the transport couch. The patient is transported on the couch to beside the bed of the invention, to underneath the horizontal support member 2a of the support frame 2. Thereafter the straps 3 are pulled down from the rollers 21, 23, and fastened at the sides of the underlay 1, in the vicinity of both ends thereof, on the left and right sides of the patient. Thereafter the transport couch is lowered, until the underlay 1 complete with the patient P rests freely from the straps 3 in the support of the support frame 2. Now the transport couch can be removed.
If the bed of the invention is provided with a hauling apparatus 8 as in FIG. 2 and 3, the height of the transport couch does not necessarily have to be adjustable. In that case the hauling apparatus 8 is utilized while shifting the patient onto the underlay, to be supported by the support member 21 by means of the straps 3.
The support frame 2 of the bed of the invention can be detachably fastened to the structures of the premises, for instance to the wall. On the other hand, the support frame can be detachably fastened to a suitable transport couch, for example the transport couch of the patient. One such arrangement is illustrated in FIGS. 7 and 8.
The support frame 2 is provided with fastening means 25 and the structures of the premises, for instance the wall S of the patient room, is provided with a first socket member 26 and the transport couch 28 with a second socket member 27. The first socket member 26 is formed of a plate-like housing 29 provided with a number of brackets such as pins 30, and the first set of locking members 31. These locking members include at least two lock bolts 31a or similar members, which are fastened so that they can be moved in a direction parallel to the surface of the housing 29.
The vertical support member 2b of the support frame 2 is provided with fastening means 25 including a fastening flange 32 with holes 33 for the pins 30 of the first socket member 26, and a first set of nests 34a for the lock bolts 31a or corresponding members of the locking members 31 of the first socket member. The fastening members 25 also include a second set of nests 34b for the second set of locking members 38. The fastening flange 32 also is provided with a second set of brackets, such as pins 35.
The second socket member 27 of the transport couch 28 is provided with a recess 36 for the vertical support member 2b of the support frame 2 and for the tubular member 10, with apertures 37 whereto the second set of pins 35 of the fastening members 25 can be fitted, and further a second set of locking members 38, which are advantageously similar as the first set of locking members 31. The lock bolts 38a of the second set of locking members 38 can be locked to the second set of nests 34b provided in connection with the fastening members 25.
The locking members 31, 38 and nests 34a, 34b provided in the fastening members 25 and socket members 26, 27 together form two sets of fast coupling means, whereby the support frame 2 can be easily attached to the wall structure and detached therefrom, and respectively the support frame 2 can be easily attached to the transport couch 28 and detached therefrom.
The coupling of the support frame 2 on one hand to the wall S of the premises, and on the other hand to the transport couch 28, takes place as follows. In FIG. 7 the support frame 2 is attached to the wall S. The holes 33 of the fastening flange 32 of the fastening members 25 are fitted to the first set of pins 30 of the firs socket member, and the bolts 31a of the locking members 31 of the socket member are inserted to the nests 34a of the fastening flange 32. When the support frame 2 is desired to be attached to the transport couch 28, it is moved so that first comes the end provided with the recess 36, to against the vertical support member 26 of the support frame 2 and the tubular member 10, so that the pins 35 provided in the fastening flange 32 match the apertures 37 of the transport couch 28. Thereafter the bolts 38a of the locking members 38 of the transport couch 28 are shifted and locked in the nests 34b of the fastening flange 32, so that the transport couch 28 is coupled to the fastening members 25. Thereafter the bolts 31a of the locking members 31 of the first socket member 26 are released and pulled out of the nests 34a of the fastening flange 32, so that the fastening flange 32 can be drawn, together with the transport couch 28, apart from the pins 30 of the socket member 26. Now the support frame 2 is attached to the end of the transport couch 28 with fastening members. In a corresponding fashion but opposite order, the support frame 2 together with fastening members 25 can be reattached either to the same socket member 26 or to a similar socket member 26 in other premises.
FIGS. 9 and 10 show a schematical illustration of an underlay 1. In width and length this underlay corresponds at least roughly to a normal bed. The underlay 1 comprises the bed bottom 40 and the frame 41. The bottom 40 is formed of some flexible, advantageously thin material, which, however, carries even a heavy patient well. The frame 41 is formed of support rails 42, which are fitted on all sides of the bottom 40. Along the sides of the bottom 40, there are formed tubular passages, where the support rails 42 are inserted and then connected to each other. In order to fasten the clasps 24 of the straps 3, there are provided apertures 43 on the sides of the bottom 40. Now the clasps 24 are easily inserted through the apertures 43 and fastened to the support rails 42.
The bottom 40 of the underlay 1 can be made of many different materials, such as cloth or net. FIG. 11 illustrates an underlay 1, the bottom 40 whereof is made of net. The bottom is most advantageously made of some such material that can be left under the patient when the patient is put on the transport couch and taken for instance to the examination rooms of the hospital. Thus the shift from the transport couch back to the suport of the support frame 2 naturally becomes easier, because the underlay 1 is continuously under the patient.
The bottom 40 can be made for example of some waterproof material such as plastic. The bottom 40 is provided with an aperture 44, which is most advantageously placed in the middle region of the underlay. To this aperture 44, there can be connected a hose 45 for instance by means of a suitable bayonet catch 46. The hose 45 can be conducted from the aperture 44 of the underlay further to a sewer or other vessel where water can be collected. This type of underlay 1 is suitable to be used as a shower basin, where the patient can be conveniently washed.
The bottom 40 of the underlay 1 can be made of two different parts, as is shown in FIG. 12. The first bottom part 40a is made of net or other such material, which is well permeable to air and water. The second part 40b is made of some waterproof material, such as plastic foil. The second part 40b is arranged on a roller 47 along the long side of the underlay 1, wherefrom it can be drawn to underneath the first part 40a. The second bottom part 40b can be attached, with suitable fastening means, to the frame 41 of the underlay 1. The second part 40b is used when the patient is washed for instance by means of a shower. When the second part 40b is not needed, it is rolled along the long side of the bed bottom 40. This second bottom part can naturally be provided with a corresponding aperture 44, whereto a hose can be fastened by means of a suitable catch, in similar fashion as was explained in connection with the underlay 1 of FIGS. 9 and 10.
It is advantageous to provide the bottom 40 of the underlay 1 with an aperture 48 for a bedpan (marked with dotted lines in FIGS. 9 and 10). This aperture is adjusted on the bottom, in an area where the patient's buttocks rest when he is lying on the underlay 1. This aperture 48 is used for collecting the excretion, i.e. urine and excrement, of the patient. Accordingly, a bedpan is adjusted underneath this aperture, so that the patient can relieve himself. This arrangement means a remarkable help in treating chronic patients in hospitals, because now the nurse doe snot have to lift the patient manually out of bed and then adjust the bedpan, which is uncomfortable for the patient.
The aperture 48 for the bedpan can be arranged by means of a hatch 49, as is illustrated in FIG. 11. The hatch 49 is a stretch of the bottom 40, which can be turned aside from underneath the patient when the bedpan is needed.
The underlay 1 can be provided underneath with heat insulation, as is shown in FIG. 13. In this case the underlay 1 comprises a heat insulation layer 50, which in all essential length and width measures corresponds to those of the underlay 1. It is detachably fastened under the underlay 1 for instance by means of straps 51 or other suitable fastening means. The straps 51 are attached for example by means of clasps to the support railings 42 located on the long sides of the underlay 1, and are brought under the insulation layer and fastened to the other support railing 42 on the opposite side. The heat insulation layer 50 can be formed of a suitable heat insulating material known as such, for instance of felt, polyurethane or the like.
In the bed of the present invention, particularly in connection with the support frame thereof, there can be provided means for measuring the patient's weight. For example in between the bearing 12 of the vertical support member and the tubular member 10 in FIG. 4, there can be installed a power sensor 52 which measures compressive force. By means of this, the total weight of the support frame 2, the connected equipment plus the patient P can be measured. The signal obtained from the power sensor 52 is processed with some suitable processor 53, such as microprocessor, and the patient's weight is indicated for example in a digital display 54.
In the above specification the invention has been mainly explained with reference to a few preferred embodiments, but it is pointed out that the invention can be modified in many ways within the scope of the inventional idea defined in the appended patent claims. | 1a
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BACKGROUND OF THE INVENTION
This invention relates to a leg therapy apparatus which has a frame structure composed of at least two support structures, each having a generally arc shaped inner surface, with the support structures being adjustably coupled together. Each support structure has rounded user engagement elements along the arced inner surface of the structure which may be used to engage the thigh and calf of the user, allowing the user to perform body therapy routines on these areas of the lower body. These therapy routines may be performed while the user is in any type of relaxed position by grasping the invention with their hands and moving the invention over the desired thigh or calf area of the lower body. The invention will automatically adjust itself to different thigh and calf contours, since these muscles are typically smaller at the lower ends. The ability of the apparatus to engage any area of the leg muscle with the engagement elements of the support structure, and also its ability to easily adjust itself for the various thickness and contours of the thigh and calf muscles, allows for an easy and comfortable message type therapy for those particular leg muscle groups which are sore or have been traumatized due to an accident or illness. The invention may also be used to assist in the removal of fat tissues and cellulite from any affected leg muscle area.
SUMMARY AND OBJECTS OF THE INVENTION
It is the object of this invention to provide a therapeutic apparatus which may provide the user an efficient and inexpensive means for messaging the leg muscle groups of the lower body. The main purpose of this application is to demonstrate an apparatus which performs the stated function, and to demonstrate the many options and configurations this apparatus may take on
Briefly stated, the apparatus that forms the basis of the present invention comprises a frame structure means, a coupling means, and a user engagement means. The frame structure means may be comprised of at least two main support members, each having an arc shaped inner surface onto which the user engagement means may mount. The main support members may include a hand engagement member so that the user may easily grasp the structure with their hands. The coupling means of the apparatus couples the two main support members together so that they may easily move in a controlled manner away and towards one other as the varying contours of the leg muscles are being engaged by the user engagement means. Movement may be in either along a generally arced path or along a generally linear path, depending upon the design of the apparatus. The apparatus may also utilize a resistance means which provides resistance to the members moving apart from one another, and which may also provide a force against the leg muscles by the user engagement means.
In order to operate the apparatus, the user will grasp the main support members with their hand, place their leg within the opening created by the main support members, and move the leg therapy apparatus along the thigh and/or calf area of the lower body, in either a. linear or circular pattern. As mentioned, the leg of the user will be placed within the apparatus, which has a ring type form when the two main support members are coupled together. As the apparatus moves along an area of the leg, such as the thigh muscles, the main support members will beging to separate, or move opposite one another, as the apparatus moves over the larger areas of the thigh muscles. This separation may be resisted by the hands of the user, or by the optional resistance means, or both. Also, as the apparatus moves back over the smaller areas of the thigh muscles, the main support members will move back towards one another, either by the user pushing the members back together or by the force exerted on the members by the optional resistance means which pulls them back together, or both. The resistance to separation, as provided by either the hands of the user or the optional resistance means, thus allows a force to be applied to the thigh area as the apparatus moves along its various contours.
Also, other configurations may be possible which allow the apparatus to increase it flexibility. The apparatus may be designed to utilize more than two main support members coupled together to increase the amount of leg muscles area being engaged at any given time. Also additional resistance components may be added to the apparatus to easily vary the amount of resistance to separation, and thus the amount of force provided by the apparatus against the leg muscle of the user. Also, having a user engagement means which is a completely separate component from the main support member may be preferred.
The overall basic design of the apparatus is such that the user engagement means may be a component which mounts upon the arced inner surface of the main support member and provides the main contact with the leg muscle of the user. The user engagement means may be a series of user engaging elements which are rounded. nodule-like elements which extend outward from the arced inner surface of the main support members. They may be spaced apart from each other so that maximum contact is provided upon the leg muscle. The user engaging elements may be a molded part of the main support member, individually attached components, or part of a user engagement means which is separately attached. The user engaging elements may also be a type of roller bearing elements which roll as they engage the leg muscle of the user. As mentioned previously, the force exerted on the leg muscles by the user engaging elements may be applied by the hands of the user, by an optional resistance component, or both. The user engaging elements will therefore apply a firm force against the leg muscles, and provide a deep therapeutic message. The arc design of the inner surface of the main support members allows numerous engaging elements to simultaneously be in contact with the leg muscles, allowing for a maximum therapeutic effect The arced inner surface of the main support member also allows the apparatus to be easily moved by the user along the leg muscles not only in a forward and backward linear motion, but also in a circular motion around the leg muscle, either individually or simultaneously, In addition to providing a type of therapeutic exercise of the thigh and calf muscles as described, the apparatus will also assist with the removal of fat tissues and cellulite from affected areas of the leg by breaking them down and allowing the body to naturally dissolve the fat tissue.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A is a front view of the leg therapy apparatus.
FIG. 1B is a side view of the leg therapy apparatus.
FIG. 1C is a top view of the leg therapy apparatus.
FIG. 2A is a front view of a main support member of the frame structure means and the user engagement means of the leg therapy apparatus.
FIG. 2B is a side view of a main support member of the frame structure means and the user engagement means of the leg therapy apparatus.
FIG. 2C is a top view of a main support member of the frame structure means of the leg therapy apparatus.
FIG. 3A is a front view of the coupling means of the leg therapy apparatus.
FIG. 3B is a side view of the coupling means of the leg therapy apparatus.
FIG. 3C is a top view of the coupling means of the leg therapy apparatus.
FIG. 3D is a side view of the leg therapy apparatus demonstrating how the coupling means joins together the main support members of the frame structure means.
FIGS. 4A and 4B are front views of the leg therapy apparatus demonstrating the automatic adjusting feature of the apparatus which occurs as the apparatus is moved along the various contours of the leg muscles, along with the optional resistance means.
FIG. 4C is a side view of the leg therapy apparatus demonstrating a cross sectional area of a user leg located within the apparatus, and demonstrating how the user engagement means of the apparatus engages the leg of the user while moving along its contour and also how the main support members reacts accordingly.
FIG. 4D is a side view of the muscle therapy apparatus demonstrating a cross sectional area of a user leg located within the apparatus, and demonstrating how the user engagement means of the apparatus engages the leg of the user while moving along its contour, and also how the main support members reacts accordingly, with a resistance means located at the top, and the main support members being shorter in length.
FIG. 5A is a front view of the leg therapy apparatus having roller bearings as user engagement elements of the user engagement means for making movement of the body therapy apparatus smoother.
FIG. 5B is a side view of the inner surface of the leg therapy apparatus demonstrating multiple row series of user engagement elements which may allow for greater contact with the leg muscle and thus a greater therapeutic message.
FIG. 6A is a front view of the leg therapy apparatus having user engagement means which are separate components pivotally mounted to the inner surface of the main support members.
FIG. 6B is a front view of the leg therapy apparatus having user engagement means which are separate components pivotally mounted to the inner surface of the main support members, and also demonstrating a cross sectional area a user leg located within the apparatus, and demonstrating how the user engagement means and main support members of the apparatus react as the user engagement means engages the leg of the user while moving along its contour.
FIG. 6C is a side view of the user engagement means of the muscle therapy apparatus which is pivotally mounted to the inner surface of the main support members.
FIG. 6D is a side view of the user engagement means of the muscle therapy apparatus, showing two user engagement means pivotally mounted to the inner surface of the main support members, with each mounted so that they may pivot independent of one another.
FIG. 7A is a front view of a second version of the leg therapy apparatus.
FIG. 7B is a side view of a second version of the leg therapy apparatus.
FIG. 7C is a top view of a second version of the leg therapy apparatus.
FIG. 8A is a front view of a main support member of the frame structure means, along with the user engagement means, both for the second version of the leg therapy apparatus.
FIG. 8B is a side view of the inner surface of a main support member of the frame structure means along with the user engagement means, both for the second version of the leg therapy apparatus.
FIG. 8C is a top view of a main support member of the frame structure means, both for the second version of the leg therapy apparatus.
FIG. 8D is a side view of the outer surface of a main support member of the frame structure means, for the second version of the leg therapy apparatus.
FIG. 9A is a front view of the coupling means for the second version of the leg therapy apparatus.
FIG. 9B is a side view of the coupling means for the second version of the leg therapy apparatus.
FIG. 9C is a top view of the coupling means for the second version of the leg therapy apparatus.
FIG. 9D is a side view of the coupling means for the second version of the leg therapy apparatus, demonstrating the various components of the coupling means.
FIGS. 10A and 10B are side views of the second version of the leg therapy apparatus demonstrating a cross sectional area of a user leg located within the apparatus, and demonstrating how the user engagement means of the apparatus engages the leg of the user while moving along its contour, and also how the main support members react accordingly.
FIGS. 10C and 10D are front views of the leg therapy apparatus demonstrating the automatic adjusting feature of the apparatus which occurs as the apparatus is moved along the various contours of the leg muscles, along with the optional resistance means.
FIGS. 11A and 11B are front views of the second version of the leg therapy apparatus having user engagement means which are separate components pivotally mounted to the inner surface of the main support members, and also demonstrating a cross sectional area of a user leg located within the apparatus, and demonstrating how the user engagement means and main support members of the apparatus react as the user engagement means engages the leg of the user while moving along its contour.
FIGS. 12A and 12B are front views of the second version of the leg therapy apparatus demonstrating the main support members of the apparatus having a larger inner radius of curvature.
FIGS. 13A,13B, and 13C are front views of a third version of the leg therapy apparatus demonstrating an apparatus with more than two main support members, and how the main support members react as the user engagement means is moved along the leg of the user.
FIGS. 14A and 14B are front views of the leg therapy apparatus with a main support member having a user engagement means which is both pivotally and linearly mounted as a separate component such that the user engagement means may pivot in an arced path and simultaneously move back and forth along a linear path.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Before explaining in detail the present invention, it is to be understood that the invention is not limited in its application to the details of construction or arrangement of parts illustrated in the accompanying drawings, since the invention is capable of other embodiments and of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description, and not limitation.
As best can be seen by references to the drawings, and in particular to FIGS. 1A-1C , the leg therapy apparatus that forms the basis of the present invention is designated generally by the reference numeral 1 , and includes a frame structure means 10 , coupling means 20 , and user engagement means 30 . The frame structure means 10 may be structured in such a manner that it has a circular form into which the leg of the user may be placed. The components of the frame structure means 10 and the coupling means 20 are mounted together in such a manner that the apparatus may automatically adjust to different leg muscles sizes and contours.
As may be seen in FIGS. 2A-2D , the frame structure means 10 may comprise at least two main support members 11 . user handle members 12 , and support coupling members 13 with coupling member openings 14 . The main support member 11 may be a relatively rigid structure having an outer surface and a curved inner surface. The curved inner surface supports user engagement means 30 . The user engagement means 30 may be a series of rounded nodule-like user engagement elements 31 which extend outward from the inner surface of the main support member 11 . They may be a molded part of the main support member 11 , or they may be individually attached in some typical manner such as a screw. User handle member 12 may be an open area extending through main support member 11 which allows the user to more easily grasp and hold the main support member 11 with their hand. As further shown, main support member 11 has support coupling members 13 mounted at one end, with the support coupling member 13 having a coupling member opening 14 . Coupling member opening 14 is an elongated shaft-like opening extending from one side of the main support member 11 to its opposite side.
In the figures, user engagement means 30 has user engaging elements 31 which are rigidly mounted to the inner surface of main support member 11 . As mentioned, they may be individually mounted elements or molded to the inner surface of the main support member. They could also be part of a separate curved user engagement means which rigidly mounts to the inner surface of main support member 11 through a mounting element such as a screw. The figures also show a handle member 12 which extends as a curved opening through the main support member 11 , but the user handle member 12 could also be just an indented space extending a small distance into the main support member 11 . The handle member 12 could also be a separate component mounted at some location on main support member 11 . It is also possible for the user to just grasp each main support member 11 with their respective hand so that the members themselves function as a type of handle member, provided the members are sized to easily grasp. Many variations of this apparatus are thus possible.
As may be seen in FIGS. 3A-3D , coupling means 20 comprises a generally elongated shaft member 21 with stop members 22 mounted on each end. Stop members 22 are used to prohibit the main support members 11 from separating completely from on another as they move. The stop members 22 may be a type of locking cap which slide onto shaft member 21 and lock in place. Shaft member 21 and stop members 22 may also be a type of bolt and screw assembly. FIG. 3D demonstrates how the coupling means 20 and frame structure means 10 mount together so that the main support members 11 may pivot about shaft member 21 .
FIGS. 4A and 4B demonstrate the basic configuration and operation of the apparatus. As shown, the support coupling members 13 of main support members 11 are coupled together by shaft members 21 and form a generally loop shaped structure. Shaft members 21 extend through the coupling member openings 14 of each support coupling members 13 . As mentioned, stop members 22 are mounted on each end of shaft member 21 to limit the amount of separation possible between the two main support members 11 . The apparatus may include an optional resistance component 40 , such as a resistance band.
As may be further seen, the user may operate the apparatus by grasping the apparatus with their hands using the user handle members 12 , while placing their leg within the open loop area created by the coupling of the two main support members 11 . Shown in the FIG. 4C is a typical cross section of a human leg. Using the handle members 12 , the user may grasp the apparatus and move it over the desired leg muscle, with the leg muscles being engaged by the user engaging members 31 of the user engagement means. As the apparatus moves along the respective leg muscle group, the user engaging members 31 will make contact with the respective muscles, providing a type of therapeutic message. As also shown, as the apparatus moves along the contour of the thigh or calf muscles, the main support structures 11 of the apparatus will pivot apart from one another as larger areas of the leg muscles are being engaged. They will pivot closer to one another as smaller portions of the leg muscles are being engaged. While moving the body therapy apparatus along the thigh or calf muscles of the leg, the user may also simultaneously rotate the apparatus in a circular pattern around the leg to provide an even better theraputic action. For a smaller area that may need a heavy message, the user may want to rotate the apparatus in a back and forth circular motion only over that area of the leg needing the heavier message. This ability to engage the leg muscle in a linear or circular motion, either individually or simultaneously, makes the apparatus extremely flexible. FIG. 4D is a side view of the muscle therapy apparatus demonstrating a resistance means located at the top, and the main support members being shorter in length. This should allow the apparatus to more easily be placed upon the leg.
As shown, the main support members 11 are guided as they pivot away and towards one another by shaft member 21 . Optional resistance component 40 may be mounted at either end of main support member 11 , and may be utilized to provide a resistance to the pivoting motion of main support members 11 , while also pushing the main support members 11 back towards one another. When the resistance component 40 utilizes a conventional resistant band different resistant band with different strengths may be used to provide different amount of resistance. These resistance bands 40 may be convention resistance bands found and used in various fitness equipment and may mount to main support members 11 through a typical securing means such as a pin or bolt 41 . Multiple resistance bands 40 may be utilized which mount to the main support members 11 at the top and bottom, and on both the front and back sides. When the resistance component 40 is not utilized, the resistance to separation and the pushing motion of the members back together may be accomplished manually by the hands of the user.
It is also possible to disassemble the leg apparatus so that the individual main support structures 11 are utilized separate from one another. The user may grasp a single main support member 11 , either one at a time or one in each hand, and perform a therapy routine on parts of the body other than the leg muscles. For example, if the user is suffering from a sore arm bleep muscle, the user may grasp one of the main support members 11 with one hand, and move the user engaging elements 31 along the bleep muscle, in either a linear motion, circular motion, or both. This routine may be performed also on other parts of the body, such as the stomach, hips, or buttocks. Using an individual main support member 11 may also be performed on the leg muscles, but would not provide as much therapeutic action as the members would when coupled together.
FIG. 5A demonstrates the leg therapy apparatus using conventional roller bearings 32 as user engaging elements 31 . Roller bearings 32 may be mounted within curved openings 33 , which are semi-spherical in shape and have a larger diameter than do the roller bearings 32 . This is to allow the roller bearings 32 to rotate within in any direction. The roller bearings 32 may be held in place by inner surface support 34 , which may have surface openings 35 which are smaller in diameter than the roller bearings 32 . The inner surface support 34 may be securely mounted to the arced inner surface of the main support member 11 through some common securing means, such as a screw, with the surface openings 35 of the inner surface support 34 being place over the roller bearings 32 . This allows roller bearings 32 to rotate, but keeps them from exiting out of curved openings 33 . In this instance, the user engagement means 30 is comprised of roller bearings 32 , curved openings 33 , inner surface support 34 , and surface openings 35 .
FIG. 5B demonstrates the leg therapy apparatus utilizing multiple rows of user engaging elements 31 mounted to main support member 11 , instead of only a single row. Multiple rows should allow for a better therapy message, since multiple user engaging elements 31 will move over the same area. It may also prove better to have each row staggered from the one next to it, so that more contact is made with the muscles. The figures show three rows of user engaging members 31 , but many versions of the apparatus may be created having four, five, six, or even more rows, depending on what works best for the individual user. It may be possible to connect two or more apparatuses together, so that the number of rows in contact with the user muscles may be selectively varied. As mentioned previously, the user engaging elements 31 may be a molded part of main support member 11 , may be individually attached to main support member, or may be part of a separately attached user engagement means. The best configuration, which is that shown, may prove to be a series of rows of roller bearings 32 mounted into curved openings 33 and held in place by inner surface support 34 having surface openings 35 .
FIGS. 6A and 6B demonstrate a leg therapy apparatus having the user engaging elements 31 incorporated into a user engagement means 30 which is a completely separate component from the main support member 11 . The user engaging members 31 may mount upon or may be part of an engagement support structure 36 , which may be pivotally mounted at its approximate center to the inner surface of main support member 11 . The engagement support structure 36 may be an arced structure having an outer and inner arced surface. As shown, the outer arc surface may be pivotally mounted at its proximate center to the arced inner surface of main support member 11 , while the user engaging members 31 may mount upon the inner arced surface of engagement support structure 36 . The engagement support structure 36 may also be constructed with curved openings so that user engaging members 31 may be roller bearings, as has been discussed previously. As also shown, an alternate configuration may have the resistance band 40 located near the coupling means 20 , instead of being located on the opposite end of the main support members. This configuration will allow the user to position the apparatus over the leg muscles, instead of the leg muscles having to be placed within. FIG. 6B shows a cross sectional area of a user leg placed with the apparatus, and demonstrates how the user engagement means 30 reacts when it engages the leg of the user.
FIGS. 6C and 6D show side views of one type of user engagement means 30 for the leg therapy apparatus. In this type, there is at least one row of user engaging members 31 mounted to the engagement support structure 36 . As may be seen, it is possible to have more than one in this ease, two engagement support structures 36 pivotally mounted to the inner surface of main support member 11 such that they pivot independent of one another. This could prove useful for not only engaging a larger area of the leg of the user, but also allow better adjustment to the varying contours of the leg of the user. Having more than one row of user engaging members 31 may also prove beneficial in use with the multiple engagement support structures 36 .
A second version of the leg therapy apparatus 1 may be seen in FIGS. 7A-7C . As with the original version, the leg therapy apparatus is designated generally by the reference numeral 1 , and includes a frame structure means 10 , coupling means 20 , and user engagement means 30 . The frame structure means 10 may be structured in such a manner that it has a circular form into which the leg of the user may be placed. The components of the frame structure means 10 and the coupling means 20 are mounted together in such a manner that the apparatus may automatically adjust to different leg muscles sizes.
As may be seen in FIGS. 8A-8D . the frame structure means 10 may again comprise at least two main support members 11 , user handle members 12 , and support coupling members 13 with coupling member openings 14 . The main support member 11 may be a relatively rigid structure having an outer surface and a curved inner surface. The curved inner surface supports user engagement means 30 . The user engagement means 30 may be rounded nodule-like user engagement elements 31 which extend outward from the inner surface of the main support member 11 . They may be a molded part of the main support member 11 , or they may be individually attached in some typical manner such as a screw. User handle member 12 may he an open area extending through main support member 11 which allows the user to more easily grasp and hold the main support member 11 with their hand. As further shown, main support member 11 has support coupling members 13 mounted at each end, with each support coupling member 13 having a coupling member opening 14 . Coupling member opening 14 is an elongated shaft-like opening extending from the inner portion of the main support member 11 to its outer portion.
As may be seen in FIGS. 9A-9D , coupling means 20 comprises a generally elongated shaft member 21 with stop members 22 mounted on each end. Coupling means 20 may also comprise optional resistance spring members 23 , which arc basically conventional coiled spring members located on each end of shaft member 21 , and are held in place by stop members 22 . Stop members 22 are used to prohibit the main support members 11 from separating completely from on another as they move, whether the optional resistance springs 23 are utilized or not The stop members 22 may be a type of locking cap which slide onto shaft member 21 and lock in place. Shaft member 21 and stop members 22 may also be a type of bolt and screw assembly.
As with the original version, the components of the frame structure means 10 , the coupling means 20 , and the user engagement means 30 , all function in similar manner and may also take on various configurations. The main difference in this version is that main support members 11 move away and toward one another along a linear path of motion, as opposed to an arced path of motion.
FIGS. 10A and 108 show a cross sectional area of a user leg placed within the apparatus. As may be seen when various parts of the leg which are different in size are engaged by the user engaging members 31 , the main support members will move accordingly. When a larger cross sectional area is engaged, the main support members 11 move away from one another. When a small cross sectional area is engaged, the main support members 11 move towards one another. Again, motion is along a linear path.
As shown in FIGS. 10C and 10D , optional resistance means 40 comprising optional resistant bands 41 may be also utilized with this version of the apparatus. As before, different resistant bands having different resistance strengths may be used to vary the amount of resistance. These resistance bands 40 may be convention resistance bands found and used in various fitness equipment and may mount to support coupling members 13 through a typical securing means such as a pin or bolt 42 . Multiple resistance bands 41 may also be utilized which mount to the support coupling members 13 at the top and bottom of each main support member, and on both the front and back sides. When the resistance component 40 is not utilized, the resistance to separation and the pushing motion of the members back together may be accomplished manually by the hands of the user.
FIGS. 11A and 11B demonstrate the second version of the leg therapy apparatus having the user engaging elements 31 incorporated into a user engagement means which is a completely separate component from the main support member 11 . The user engaging members 31 may mount upon or may be part of an engagement support structure 36 , which may be pivotally mounted at its approximate center to the inner surface of main support member 11 . The engagement support structure 36 may be an arced structure having an outer and inner arced surface. As shown, the outer arc surface may be pivotally mounted at its proximate center to the the arced inner surface of main support member 11 , while the user engaging members 31 may mount upon the inner arced surface of engagement support structure 36 . The engagement support structure 36 may also be constructed with curved openings so that user engaging members 31 may be roller bearings, as has been discussed previously. FIGS. 11A and 11B both demonstrates a cross sectional area of a user leg which has the apparatus placed within. FIGS. 11A and 11B show a cross sectional area of a user leg placed within the apparatus, and demonstrates how the user engagement means 30 reacts when it engages the leg of the user.
In any version, having the user engaging member 31 mounted on an engagement support structure 36 which is pivotally mounted as a separate component to the main support member 11 should provide a much more flexible body therapy apparatus. As also shown, the engagement support structure 36 may pivot both towards and away from the inner surface of main support member 11 , Shown in the figures is a cross section of the human leg. When the apparatus is moved along a portion of the leg of the user, the pivoting motion of the engagement support structure 36 allows the user engaging members 31 to remain in better contact with the leg muscle of the user. This concept will make the apparatus more complicated and thus more expensive, but should provide more flexible and a better therapy routine. This concept may be incorporated into any of the versions described previously. As also mentioned previously, a single main support member 11 having this pivoting engagement support structure 36 may be used to provide therapy to other parts of the body, such as the biceps of the arm, the hips, the stomach, and the buttocks.
FIGS. 12A and 12B demonstrate a different construction feature for the second version of the leg therapy apparatus 1 . In this version, the frame structure means 10 forms a more elliptical shape when coupled together by coupling means 20 , as opposed to the more circular shape shown previously. This elliptical shape may prove to provide better contact between user engagement means 30 and leg muscles which are larger in size than normal. This may prove true also for the original pivoting version, and also for the user engagement means when it is a separately attached component.
FIGS. 13A and 13B demonstrate another version of leg therapy apparatus 1 having a frame structure means 10 with more than two main support members coupled together. In this instance, frame structure means 10 has four main support members coupled together by four coupling means 20 . In this version, each of the main support members comprise a quarter-arc shape, with all four quarter-arc shaped main support member creating a closed circular shaped frame structure means 10 when coupled together. FIG. 13C demonstrates this version having a separately mounted user engagement means 30 .
FIGS. 14A and 14B demonstrate a leg therapy apparatus having an engagement support structure 36 which is both pivotally and linearly coupled to the main support member 11 . The engagement support structure 36 will not only pivot towards and away from the inner surface of the main support member 11 , but also move along a linear path towards and away from its inner surface. The main support member 11 thus serves as a type of guide bearing for guiding the engagement support structure 36 along a linear path of motion. In this ease the handle member 12 would more than likely need to be an indented space into the main support member 11 instead of a through space.
In this version, a spring member 23 may also be used to resist the movement of the engagement support structure 36 towards the inner surface of the main support member 11 . It will also push the engagement support structure back against the leg muscle of the user. Therefore a spring member or some type of resistance band will not necessarily be used by the coupling means and the support coupling members as previously shown. Instead of two or more main support members, the main structure means may now be constructed of only one arced or circular shaped main member, since the linear movement away and towards the leg muscle of the user is now done by the engagement support member, not the support coupling member and the coupling means. The main disadvantage with this version is that resistance may no longer be applied by the hands of the user. Multiple main support members may still be utilized, but may now be rigidly connected together using a bolt and nut. However, an apparatus may still be constructed which has two or more main support members connected together using a coupling means, and also utilize a pivoting and linear moving engagement support structure. Hence the combinations and variations of the body therapy apparatus derived from this capability are numerous.
Many variations of the leg therapy apparatus exist, along with the configurations described above. While it will be apparent that the preferred embodiment of the invention herein disclosed is well calculated to fulfill the objects above stated, it will be appreciated that the invention is susceptible to modification, variation, and change without departing from the proper scope or fair meaning of the subjoined claims. | 1a
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CROSS REFERENCE TO RELATED APPLICATION
This application is a Continuation-in-Part of U.S. Design application Ser. No. 29/278,067 entitled RESPIRATORY MASK, filed Mar. 19, 2007.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to face masks for use in delivering respiratory gasses to a patient under positive pressure including such masks for use in treating sleep apnea or for other conditions requiring non-invasive positive pressure ventilation.
2. Background
The most effective and frequent therapy for obstructive sleep apnea is application of continuous positive airway pressure (CPAP). For such therapy, a patient is fitted with a tight fitting mask connected through an airway to a blower which supplies air to the patient's nasal passages or the nasal passages and mouth at a slight positive pressure. The application of the slight positive pressure is immediately effective in reversing the airway obstructions associated with obstructive sleep apnea. Although the therapeutic results of nasal CPAP are often dramatic and immediate, it is only effective when used properly and on a regular basis. Failure to apply nasal CPAP for even a single night results in recurrence of hypersomnolence the next day resulting from sleep apnea.
Problems associated with wearing existing masks or positive airway pressure delivery systems during periods of attempted sleep are sufficient to deter many patients from continuing CPAP therapy. Some problems include excessive noise and irritation resulting from leaks around improperly fitting masks or general discomfort caused by the design of the mask or the CPAP delivery system. Leakage of air between the mask and the face often allows air to blow on the eyes which wakes the patient and/or substantially irritates the eyes.
Most respiratory masks have integrally formed seals in the form of flexible or pliable flanges, cushions, pillows or the like extending around their outer periphery to form a seal between the mask and the face of the wearer. See for example the masks shown and described in U.S. Pat. Nos. 5,265,595 and 6,192,886. The seals are designed to prevent air from leaking through the interface between the mask and the wearer's face. However, patient movement and variations in the contours of different wearers' faces make it difficult to maintain a complete seal with existing face masks.
There remains a need for a respiratory mask for supplying gas to a patient under pressure which incorporates a seal which readily conforms to varying contours of wearer's to prevent leaks.
SUMMARY OF THE INVENTION
In order to provide a respiratory mask with better sealing capabilities a sealing flange is connected to a mask body by a cushioning member which in a preferred embodiment is S-shaped. The S-shaped cushioning member resiliently compresses when the sealing flange is pressed against the face of a wearer to ensure an airtight seal between the sealing flange and the face of the wearer.
The mask body is generally cup shaped forming a mask chamber or cavity the outer periphery of which is generally circumscribed or defined by a peripheral edge that encircles the nose and mouth of a wearer when the mask body is positioned over the nose and mouth of the wearer. The S-shaped cushioning member includes a first arc which curves inward toward the mask chamber and a second arc which curves outward relative to the first arc and away from the mask chamber to form the s-shape of the S-shaped cushioning member. The S-shaped cushioning member generally functions as a spring, compressing to allow the sealing member to better conform to the face of the wearer but resiliently urging the sealing flange outward against the face of the wearer to prevent leaks.
The sealing flange preferably includes at least an inwardly extending sealing flange and may also include an outwardly extending sealing flange. Positive pressure air delivered into the mask chamber from an inlet in the front of the mask also acts on the inwardly extending sealing flange to urge the flange against the face of the wearer. Resilient ribs are formed in second arc of the S-shaped cushioning member and help resist compression of the second arc. Portions of the ribs also preferably engage the outer surface of the outwardly extending sealing flange to biasingly urge the outwardly extending sealing flange against the face of the wearer.
The mask body, S-shaped cushion, sealing flange assembly and ribs are preferably integrally formed from silicone or other like material that is flexible and resilient and which does not cause substantial skin irritation to the wearer. Rigid plastic supports are mounted on the outer surface of the mask body to provide rigidity to the respiratory mask and to resist excessive outward expansion of the mask body due to the internal pressure exerted on the mask body by the pressurized air directed therein. A first support extends across the portion of the mask extending across the bridge of a wearer's nose. A second support extends across the portion of the mask extending across the wearer's chin. The first and second supports also extend on opposite sides of the mask inlet.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a partially schematic, perspective view of a respiratory mask with an improved sealing assembly shown secured to the face of a wearer.
FIG. 2 is a rear view of the respiratory mask.
FIG. 3 is an exploded and fragmentary cross-sectional view of the respiratory mask taken along line 3 - 3 of FIG. 2 .
FIG. 4 is a fragmentary cross-sectional view of the respiratory mask similar to FIG. 3 showing the mask, positioned on the face of a wearer.
FIG. 5 is a cross-sectional view of the respiratory mask taken along line 5 - 5 of FIG. 2 .
FIG. 6 is a cross-sectional view of the respiratory mask taken along line 6 - 6 of FIG. 2 .
FIG. 7 is an enlarged perspective view of an upper brace of the respiratory mask.
FIG. 8 is an enlarged perspective view of a lower brace of the respiratory mask.
FIG. 9 is an enlarged and fragmentary cross-sectional view taken generally along line 9 - 9 of FIG. 1 .
FIG. 10 is an enlarged and fragmentary cross-sectional view taken generally along line 10 - 10 of FIG. 1 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
As required, detailed embodiments of the present invention are disclosed herein; however, it is to be understood that the disclosed embodiments are merely exemplary of the invention, which may be embodied in various forms. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present invention in virtually any appropriately detailed structure. The drawings constitute a part of this specification and include exemplary embodiments of the present invention and illustrate various objects and features thereof.
Certain terminology will be used in the following description for convenience in reference only and will not be limiting. For example, the words “upwardly,” “downwardly,” “rightwardly,” and “leftwardly” will refer to directions in the drawings to which reference is made. The words “inwardly” and “outwardly” will refer to directions toward and away from, respectively, the geometric center of the embodiment being described and designated parts thereof. Said terminology will include the words specifically mentioned, derivatives thereof and words of a similar import.
Referring to the drawings in more detail, the reference number 1 generally designates a respiratory mask with a mask body 2 and an improved seal or sealing assembly 3 . The mask body 2 and sealing assembly 3 are preferably constructed of silicone or other rubber-like or elastomeric material that is flexible and yet resilient and that does not cause substantial skin irritation to the user. For example it is foreseen that the mask body 2 and sealing flange assembly 3 could be formed from a thermoplastic elastomer, latex or other rubber-like materials in addition to the preferred silicone rubber. The mask body 2 is generally cup shaped and formed by a wall 7 having an inner surface 8 , an outer surface 9 and a peripheral margin, edge or boundary 10 . As best seen in FIGS. 3 and 4 , the mask body 2 forms an internal chamber or cavity 11 for receiving the nose and mouth of a wearer through the rear open side of the mask body 2 . The seal 3 includes a seal cushion or sealing cushion 14 and a sealing flange assembly 15 . The seal cushion 14 is connected to and extends from the mask body 2 generally along the peripheral margin or edge 10 of the mask body 2 and the sealing flange assembly 15 is connected to the distal end of the seal cushion 14 . The seal cushion 14 may also be referred to as a spring or a spring cushion and is formed from flexible and resilient material to both urge or bias the sealing flange assembly 15 against the wearer's face and to allow the sealing flange assembly 15 to conform to the contours or shape of the wearer's face. The seal cushion 14 is preferably formed in the shape of a compound curve, which includes at least two arc segments to form an s-shape or sinusoidal shape.
The mask 1 is held on a wearer's face by mask securing means, which in the illustrated embodiment comprises a flexible skull cap or harness 18 , adjustable securement straps 19 and strap fasteners 20 which connect to rigid braces 21 and 22 which are mounted on the outer surface 9 of the mask body 2 . The braces 21 and 22 are relatively rigid and may be formed from a rigid plastic such as a polycarbonate or acrylic plastic. An airflow tubing assembly 25 is connected to the mask body 2 in line with an airflow port or opening 26 formed in the mask body 2 at a position selected to align with the mouth of a wearer of the mask 1 . Positive pressure air is generally directed into the mask cavity 11 through the airflow tubing assembly 25 and port 26 .
Referring again to FIGS. 3 and 4 , the mask body 2 is configured to receive and cover the nose and mouth of a wearer within the internal mask cavity 11 . The mask body 2 is sized and configured such that when the mask is positioned against the face of the wearer, the peripheral margin 10 generally extends, across the bridge of the nose, down the sides of the nose, downward across the cheeks of the wearer on opposite sides of the mouth and then underneath the chin of the wearer. The seal cushion 14 is formed on the mask body 2 generally extending from the peripheral margin 10 thereof and continuously around the mask body 2 .
The seal cushion 14 , with the attached sealing flange assembly 3 , extends from the peripheral margin 10 of the mask along the portion adapted to be positioned to extend across the bridge of the nose, down the sides of the nose and downward across the cheeks on either side of the mouth. Instead of following the portion of the peripheral margin 10 adapted to extend under the chin of the wearer, the seal cushion 14 , with the attached sealing flange assembly 3 , extends across that portion of the inner surface 8 of the mask body 2 that is adapted to be positioned across and in front of the wearer's chin. The sealing cushion 14 is configured and oriented such that the sealing flange assembly 3 is oriented to generally face rearward so that the sealing flange assembly 3 can be pressed rearward against the wearer's face to facilitate formation of a seal between the flange assembly 3 and the wearer's face.
The sealing cushion 14 is preferably formed as a compound curve having at least a first arc or first section 31 that curves inward from the mask body 2 generally toward the center of the cavity 11 formed in the mask body 2 , and a second section or second arc 32 that extends from and curves in an opposite direction from the first are 31 and generally back outward away from the mask cavity 11 . As seen in FIGS. 5 and 6 , portions of the sealing cushion 14 include a third section or third arc 33 , namely all but that portion of the sealing cushion 14 that is adapted to be positioned across the chin of the wearer. The third arc 33 curves in a direction opposite of the curve of the second arc 32 . Each of the arcs 31 , 32 and 33 is preferably progressively shorter in length and radius. The sealing cushion 14 may also be described as being generally sinusoidal in shape or as forming a sinusoidal spring.
A distal end 34 of the sealing cushion 14 , whether at the end of the third arc 33 or the second arc 32 , generally faces or projects rearward relative to the front of the mask body 1 . The distal end 34 of the sealing cushion 14 is oriented to project toward the face of the wearer against which the mask 1 is to be positioned.
The sealing flange assembly 15 is integrally formed on the distal end 34 of the sealing cushion 14 and preferably includes an inner sealing flange 37 and an outer sealing flange 38 . The inner and outer sealing flanges 37 and 38 preferably extend continuously around the mask body 2 along the sealing cushion 14 . The inner sealing flange 37 projects inward toward the interior of the mask body 2 or the mask body cavity 11 . The outer sealing flange 38 projects outward and away from the interior of the mask body 2 . Along the portion of the sealing assembly 3 adapted to be positioned against the cheeks and chin of the mask wearer, both sealing flanges 37 and 38 project generally transverse to the distal end 33 of the sealing cushion 14 and then angle or curve slightly rearward relative to the front of the mask body 2 . In a preferred embodiment, the portion of the sealing flanges 37 and 38 adapted to be positioned against the cheeks and chin of the wearer generally present a concave surface, curving toward the face of the wearer.
Along the portion of the sealing assembly 3 adapted to be positioned against the sides of and across the bridge of the wearer's nose, the inner sealing flange 37 initially projects rearward relative to the front of the mask body 2 and then curves around and projects into the internal cavity 11 and toward the front of the mask body 2 . The inner sealing flange 37 is sized to be relatively wide along the portion of the sealing assembly 3 intended to extend over the nose with a slit 41 extending between the opposed inner sealing flanges along this portion to receive the wearer's nose. The portions of the inner sealing flange 37 adapted to extend over or against the nose of the wearer may be referred to as nose flaps 42 and 43 .
The inner sealing flange 37 is formed relatively thin, with a thickness of approximately 0.018 to 0.20 inches near the inner edge thereof. The thin construction of the inner sealing flange 38 allows it to more readily conform to the unique contours of the specific wearer's face. In addition when pressurized air is pumped into the mask cavity 11 , the pressurized air acts against the inner surface of the inner sealing flange 37 to urge the inner sealing flange 37 against the face of the wearer to improve the seal. The large size of the nose flaps 42 and 43 helps ensure a proper seal around the wearer's nose regardless of its size or shape, which can vary significantly.
Elastic ribs 44 are formed on the sealing assembly 3 on the outside of the seal cushion 14 and preferably at least inside the second arc 32 to provide some resistance to compression of the second arc 32 and the sealing cushion 14 . For most of the ribs 44 , a first end of the rib 44 is connected to the outer surface of the first arc 31 and a second end of the rib is connected to the outer surface of the outer sealing flange 38 to provide resistance to compression of the outer sealing flange 38 relative to the first arc 31 and the mask body 2 . In the embodiment shown, elastic ribs 44 extend along the length of the seal cushion 14 except for that portion adapted to be positioned across the chin of the wearer.
The seal cushion 14 gradually tapers or reduces in thickness from the peripheral margin 10 of the mask body to the distal end 34 of the seal cushion 14 . The distal end 34 is preferably only half or one third as thick as the peripheral margin 10 of the mask body 2 . The mask body 2 generally needs sufficient thickness to prevent excessive distortion of the shape or rupturing of the mask body 2 . However, pressing of the relatively thick-walled and rigid peripheral margin 10 of the mask body 2 against a wearer's face would rapidly cause uncomfortable wearing and possibly necrosis of the patient's skin, particularly across the bridge of the wearer's nose.
The seal cushion 14 , disclosed herein, generally positions the sealing flange assembly 15 rearward and slightly inward from the peripheral margin 10 of the mask body 2 . As the mask 1 is pressed or drawn against a wearer's face, the relatively thin walled seal cushion 14 compresses or gives to conform to the unique contours of the wearer's face. The seal cushion 14 has sufficient resiliency to resist complete compression of the seal cushion 14 to prevent the sealing flange assembly 15 from bottoming out relative to the peripheral margin 10 of the mask body 2 . The forces used to draw the mask against the wearer's face are therefore spread out over the larger surface area of the sealing flange assembly 15 and are not focused along the more rigid peripheral margin 10 of the mask body 2 , thereby reducing the development of pressure sores or the like.
The portion of the mask body 2 adapted to extend under the chin of a wearer and past the sealing assembly 3 may be referred to as a chin cup 48 . Because the chin cup 48 is formed integrally with the mask body 2 and the sealing assembly 3 , when a user lowers his or her jaw, extension or stretching of the chin cup 48 simultaneously pulls the sealing assembly 3 positioned across the chin downward with the chin to maintain the proper sealing arrangement.
As discussed above, the airflow opening or port 26 extends through the mask so as to flow communicate with the internal chamber or cavity 11 . The opening 26 is generally positioned to be aligned with the mouth of a user when the mask 5 is abuttingly positioned against the face of a user. The opening 26 is further sized so as to generally encircle the opening formed by the mouth of the user when the mouth is used for breathing during ventilatory measurement and analysis procedures. The opening 26 is defined by a grooved circular shoulder 51 , extending through the face mask 1 from the inner surface 8 to the outer surface 9 . A rim receiving groove 52 extends into the mask body 2 along the grooved circular shoulder 51 .
The airflow tubing assembly 25 is connected to the face mask 1 at the circular opening 26 by an annular connecting member 55 . The annular connecting member 55 includes a connecting rim 56 . The airflow tubing assembly 25 may be of the type including a valve to control the direction of flow of inhalation and exhalation gasses through different openings or passageways. Pressurized air can be supplied to the mask cavity 11 from a source of pressurize air 57 (shown schematically in FIG. 1 ) through the airflow tubing assembly 25 .
Each of the upper and lower rigid braces 21 and 22 is connected to the face mask 1 by first and second pairs of flexible mounting buttons 59 and 60 respectively formed on the outer surface 9 of the mask body 2 . The buttons 59 and 60 are integrally formed of the same flexible material as the rest of the mask body 2 and each comprises a cylindrical post 63 and an enlarged cylindrical head 64 .
As best seen in FIGS. 7 and 8 , each brace 21 and 22 is generally bowed inward to conform to the side to side contour of the mask body 2 . The upper brace 21 includes a relatively narrow central band 66 with enlarged mounting structure 67 formed on each end thereof. Lower brace 22 also includes a central band 71 with mounting structure 72 formed on each end thereof. The central band 66 of the upper brace 21 is positioned to extend across the portion of the mask body 2 covering the bridge of the wearer's nose. The central band 71 of the lower brace 22 is positioned to extend across the portion of the mask body 2 covering the wearer's chin.
A pair of button receiving holes 73 and 74 are formed in the mounting structures 67 and 72 respectively of each rigid brace 21 and 22 . Each of the holes 73 and 74 is preferably oblong with one axis longer than the diameter of the button head 64 and a second axis narrower than the button head 64 diameter. The gap between the head of each button 59 and 60 and the outer surface 9 of the mask body 2 is approximately equal to the thickness of the respective braces 21 and 22 . The heads 64 of each of the buttons 59 and 60 are pressed through the button receiving holes 73 and 74 to hold the braces 21 and 22 in place against the outer surface 9 of the mask body 2 .
First and second pairs of channel forming shoulders 79 and 80 are formed on the outer surface 9 of the mask body 2 above and below the opening 26 respectively. The central portion 66 and 71 of rigid braces 21 and 22 respectively are secured between the first and second pairs of channel forming shoulders 79 and 80 respectively to prevent reduce movement of the braces 21 and 22 relative to the mask body 2 .
Recesses or indentations 84 may be formed in the mask body 2 on opposite sides of the airflow opening or port 26 . The indentations 84 are preferably sized slightly wider than a wearer's fingers so that the thumb and an opposed finger of the wearer may be positioned in the indentations 84 to facilitate grasping and handling of the mask body 2 . The recesses 84 also function to reduce the volume of the internal chamber or cavity 11 in the mask body 2 , reducing dead air space and enhancing the performance of the mask for most ventilation purposes.
Receivers 85 and 86 for the strap fasteners 20 are formed in each of the mounting structures of braces 21 and 22 respectively near the distal ends thereof such that at least one strap 19 may be connected to both ends of each brace 21 and 22 . Each of the strap fasteners 20 comprises a fastener base 88 with a post 89 having a cylindrical shaft 90 and an enlarged head 91 formed on a distal end thereof projecting outward from one side of the fastener base 88 . A slot 92 is formed in the base 88 through which a strap 19 may be threaded and folded over back onto itself and secured together with hook and loop type fasteners or the like for adjustably securing the strap 19 to the fastener 20 . A grip 93 may be formed on the fastener body 88 on a side opposite the post 89 to facilitate gripping and manipulation of the fastener 20 .
The fastener receivers 85 and 86 shown are generally keyhole type openings with a wide end 95 and a narrow end 96 . The wide end 95 is wider than the diameter of the post head 90 and the narrow end 96 is narrower than the diameter of the head 90 and slightly wider than the diameter of the post shaft 90 for receiving and frictionally retaining the shaft 90 therein.
The length of the straps 19 are adjustable to allow the wearer to draw the mask 1 against there face with sufficient force to ensure a proper seal is maintained by the sealing assembly 3 . The straps 19 and the cap 18 may be formed from elastic material to accommodate movement of the wearer's face and head. As discussed previously as the mask body 2 is drawn against the face of the wearer, the seal cushion 14 compresses and generally biases the sealing flange assembly 15 against the face of the wearer.
The rigid braces 21 and 22 help resist deformation of the mask body 2 due to the pressures exerted thereon by the pumping of pressurized air into the internal chamber 11 of the mask body 2 . By reinforcing the flexible mask body 2 with rigid braces 21 and 22 the thickness of the wall 7 forming the mask body can be reduced. The added rigidity supplied by braces 21 and 22 helps maintain the sealing assembly 3 in a preferred alignment with the face of the wearer to ensure a proper and complete seal. Without the braces, the mask body 2 would tend to expand outward under the pressure of the pressurized air pumped therein, increasing the risk that the seal between the wearer's face and the sealing assembly 3 will be broken. Any break in the seal will result in uncomfortable leaks which tend to tickle the wearer or create annoying noises.
Providing receivers for the securement strap fasteners 20 on the rigid braces 21 and 22 also reduces the forces acting on the flexible mask body 2 to help the mask body 2 retain its shape. Mounting the strap fasteners directly to the flexible mask body 2 would result in the tensioning forces exerted through the strap fastener to be concentrated to that portion of the mask where the strap fasteners are connected. By connecting the strap fasteners 20 to the rigid braces 21 and 22 , the forces exerted by the strap fasteners can be more evenly distributed across the mask body 2 .
It is to be understood that while certain forms of the present invention have been illustrated and described herein, it is not to be limited to the specific forms or arrangement of parts described and shown. For example, it is to be understood that with respect to the strap fasteners 20 , the keyhole openings could be formed in each fastener base 78 and the mating posts 79 could be formed on and project outward from the rigid braces 21 and 22 . It is foreseen that the mask 1 could be utilized without the braces 21 and 22 . The location and positioning of the ribs 44 could be varied or the ribs 44 could be eliminated. The relative dimension and size of any of the components could be varied including the size of the inner and outer sealing flanges 37 and 38 .
As used in the claims, identification of an element with an indefinite article “a” or “an” or the phrase “at least one” is intended to cover any device assembly including one or more of the elements at issue. Similarly, references to first and second elements is not intended to limit the claims to such assemblies including only two of the elements, but rather is intended to cover two or more of the elements at issue. Only where limiting language such as “a single” or “only one” with reference to an element, is the language intended to be limited to one of the elements specified, or any other similarly limited number of elements. | 1a
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent application Ser. No. 14/419,140, filed Feb. 2, 2015, which is a 35 U.S.C. §371 national phase application of International Patent Application No. PCT/US2013/053609, which claims the benefit of U.S. Provisional Patent Application No. 61/679,636, filed on Aug. 3, 2012, each of which the full disclosure is herein incorporated by reference in its entirety.
[0002] The present disclosure is also related to provisional application No. 61/548,152 filed on Oct. 17, 2011, entitled “System and method for providing analysis of visual function using a mobile device with display,” the disclosure of which is herein incorporated by reference in its entirety.
INCORPORATION BY REFERENCE
[0003] All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
FIELD
[0004] The present invention relates generally to a system for analysis of visual function of a person using a mobile device with a display and communication capability, and method of use thereof. In various respects, the invention is directed to a system that allows patients to monitor their vision using a mobile device.
BACKGROUND
[0005] The use of portable devices to conduct visual acuity functions are known in the art, for example see U.S. Pat. No. 7,771,051, which is incorporated by reference in its entirety.
[0006] Additionally, the use of portable devices to conduct metamorphopsia tests using drawn inputs are known in the art, for example see U.S. Pat. No. 8,047,652, which is incorporated by reference in its entirety.
[0007] While portable devices exist, the current state of the testing methods used are time consuming. Moreover, the manner of interaction between user and device can be difficult for some users or adversely impact the accuracy of the testing. As a result there remains a need for improvement in the field of visual acuity testing.
[0008] Visual acuity testing, such as the Amsler grid, is commonly used for the detection of metamorphopsia—distortion of the image due to retinal detachment or edema. During metamorphopsia, a set of horizontal and vertical straight lines, appears wavy and parts of the grid may be absent or dim. Metamorphopsia is mainly associated with wet phase of age-related macular degeneration (i.e. choroidal neovascularization), pathological myopia, histoplasmosis syndrome, choroidal rupture and multifocal choroiditis.
[0009] During the conventional Amsler grid test patients are asked to look at the fixation point in the center of the grid, and mark the areas on the grid that appear distorted, absent, or dim. Even though the distortion is readily visible to patients, marking its location on the grid is often a very challenging task. The problem is that in some cases as soon as a person begins to draw his sight instinctively moves from the fixation point to the pen or a finger on a touch screen. This shifts the distorted area away, and the patient does not see the area he is marking as distorted anymore. Fixating away from the drawing tool (so called off-center fixation) requires significant cognitive effort which is often beyond the capabilities of the average patient affected by age-related macular degeneration. Typically, patients can easily tell whether they see distortions on the grid, but it can be hard to quantify the extent of these distortions by marking the grid. In some cases patients can have dexterity issues that make marking the grid accurately difficult or impractical.
[0010] Patients can be discouraged from taking tests on their own if the tests are difficult, time consuming, or have too many steps. As a result, it is desirable to design a test that is easy for the patient to take on their own time and that requires relatively few steps to achieve a useful result.
SUMMARY OF THE DISCLOSURE
[0011] Methods of testing visual distortions are provided herein. In some embodiments the methods can include (a) displaying a fixation point and a series of straight lines on a test area on a hand held computer device; (b) receiving a positive or negative input from a user indicating the presence or absence of distortion on the displayed series of straight lines on the test grid area; (c) removing any portions of the series of straight lines from the test area for which a negative input was received; (d) dividing the remaining positive test area into a plurality of segments; (e) sequentially displaying a fixation point and each of the plurality of segments on the hand held computer device. The steps (a)-(d) can be repeated until the segments of a predetermined minimum size are analyzed. The series of straight lines can include an Amsler grid. The method of testing distortions can be designed to test for metamorphopsia. The hand held computer device can include a mobile phone.
[0012] Examples of inputs include an auditory input or touching a discrete portion of the screen of the hand held computer device. In some embodiments the positive or negative input for presence or absence of distortion does not include touching a distorted area on the display.
[0013] The methods can also include repeating steps (a)-(d) until the visual distortion test area has been quantified with a desired level of precision to generate a visual distortion test result for the user. The methods can also include transmitting the visual distortion test results to a remote server. The methods can further include analyzing the visual distortion test results to determine a prediction of when further medical treatment is needed for the user. The methods can also include customizing the series of straight lines first presented to the user based on the user's previous visual distortion test results. In some embodiments the methods include preparing a resulting map of distortions from the visual distortion test results with segments of the predetermined minimum size.
[0014] In some embodiments dividing the remaining positive test area can include dividing the remaining positive test area by a factor of 2 or greater.
[0015] In some embodiments the series of straight lines can include moving horizontal and/or vertical lines.
[0016] In some embodiments methods of visual distortion testing are provided. The methods can include displaying a test grid area on a hand held computer device; receiving a positive or negative input from a user indicating the presence or absence of distortion on the test grid area; removing any portions of the test grid area from the test area for which a negative input was received; calculating a first remaining positive test area; dividing the first remaining positive test area into a first plurality of segments; sequentially displaying each of the first plurality of segments on the hand held computer device; receiving a negative or positive input from the user indicating the presence or absence of distortion for each of the first plurality of segments; removing any of the first plurality of segments from the first remaining positive test area for which a negative input was received; calculating a second remaining positive test area; dividing the second remaining positive test area into a second plurality of segments; sequentially displaying each of the second plurality of segments on the hand held computer device; receiving a negative or positive input from the user indicating the presence or absence of distortion for each of the second plurality of segments; and removing any of the second plurality of segments from the second remaining positive test area for which a negative input was received.
[0017] The methods can also include repeating the calculating, dividing, sequentially displaying, receiving, and removing steps until the visual distortion of the test grid has been quantified with a desired level of precision to generate a visual distortion test result for the user. The methods can further include transmitting the visual distortion test results from the hand held computing device to a remote network. The methods can also include analyzing the visual distortion test results and comparing the visual distortion test results to previous visual distortion test results. The methods can also include generating a notification message if the visual distortion test results indicate that the user may need a medical treatment.
[0018] In some embodiments dividing the remaining positive test area can include dividing the remaining positive test area by a factor of 2 or greater.
[0019] In some embodiments the visual distortion test can be customized based on the user's previous test results.
[0020] In some embodiments methods of testing visual distortions are provided. The methods can include (a) displaying a fixation point and an Amsler Grid on a hand held computer device; (b) receiving a positive or negative input from a user indicating the presence or absence of distortion on the displayed test grid area; (c) removing any portions of the grid from the test area for which a negative input was received; (d) dividing the remaining positive test area into a plurality of segments; (e) sequentially displaying a fixation point and each of the plurality of segments on the hand held computer device. The methods can also include repeating steps (a)-(d) until the segments of a predetermined minimum size are analyzed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
[0022] FIG. 1 is a flow chart of a method for performing a visual acuity test.
[0023] FIGS. 2A-2P illustrate a schematic example of screen shots of performing a sample visual acuity test.
[0024] FIGS. 3A-3K illustrate a schematic example of screen shots of performing a sample visual acuity test.
[0025] FIG. 4 illustrates a schematic example of screen shot of performing a sample visual acuity test.
[0026] FIGS. 5A-5B illustrate a schematic example of sample test results for a visual acuity test.
DETAILED DESCRIPTION
[0027] The present application discloses improved methods for administering metamorphopsia tests.
[0028] Distortions can be mapped quantitatively using an interactive computer-guided test instead of a printed grid. In this approach various parts, sections, portions, or segments of the grid appear on the screen, and the patient is only asked whether there is a distortion in the displayed segment of the grid or no distortion visible in the displayed segment. Since the patient is not asked to mark the actual position of the distortions on the screen, it is quite easy to keep his/her sight directed onto the fixation point, and just respond in a binary fashion, e.g. yes or no, whether the presented segment of the screen is distorted or not.
[0029] For mapping the whole field in this test, various segments of the grid can generally be presented in a sequence. To minimize the number of steps in this mapping procedure the size of the grid segments presented on the screen can decrease as the test progresses. Thereby large parts of the visual field that have no distortions can be quickly eliminated from further mapping.
[0030] The improved testing follows this general procedure. First, the whole grid is presented. A fixation spot (different from the rest of the grid in color or flashing or shape) is shown in the center of the grid. Next, if the patient looking at the fixation target sees no distortion, he responds by touching an area on the screen, such as a NO button (or any other label indicating the lack of distortion), or by a voice command and the test is completed. The area of the screen used to register a negative response can be a colored button or a button labeled with words indicating a negative response. If he does see a distortion he makes an affirmative response, such as by touching an area of the screen, which could be the fixation spot, a YES button, or a separate button (or section) on the screen, or by voice command. After the initial indication of distortion, any negative response to a displayed segment removes that segment from further testing. Thereafter, with every positive response the presented segment having distortion will be subsequently divided into smaller portions or segments, e.g. two halves and both of them will be presented sequentially. The divisions can be applied along the horizontal or vertical axis (or at any other direction). This way the non-distorted areas can be efficiently eliminated from the test mapping area. The distorted areas can be further tested until the distortion area is quantified with a desired level of precision or the distorted area is localized to the minimum size of the grid presented, for example, to a single square.
[0031] FIG. 1 is a flow chart of a method 100 for performing a visual acuity test in accordance with an embodiment. A first block 102 includes initiating a visual acuity test. The screen then displays a test grid 104 , for example a test grid with a dot for a fixation point. The user is then queried whether any distortion is visible on the test grid in block 106 . The user can answer by touching the screen or with an audible answer. If no distortion is visible then the test ends in block 108 . If distortion is visible in the grid then the testing continues to gather additional data about the distortion size and shape.
[0032] In block 110 , the remaining positive test area is calculated. After the first step, the remaining positive test area is the entire area or 100%. Next, the test area can be broken up into multiple segments for further analysis. Segments of the remaining test area are calculated in block 112 . In some embodiments the test area is divided into halves. In some embodiments, a factor other than one-half can be used to reduce the test area size, for example by factors of 1.5, 2.5, 3, 4, etc.
[0033] Next, the program then displays one of the segments of the remaining test area (block 114 ) and queries the user whether there is any visible distortion (block 116 ). It is to be appreciated that the testing proceeds in binary fashion by answering a question, such as “Is there any distortion in the displayed segment?” If the user responds that there is visible distortion on the segment then the segment test area is added to the positive test area (block 118 ). If the user responds that there is no visible distortion then the segment test area is removed from the areas tested in the future tests (block 120 ). Next, in block 122 the program determines if each segment of the remaining test area has been tested. If the answer is no then an additional segment of the remaining test area is displayed (block 114 ). If all of the segments for the test area have been displayed then the results are analyzed to determine if the distorted area is sufficiently quantified (block 124 ). If the distorted area is sufficiently quantified then the test is ended (block 108 ).
[0034] In another aspect greater precision or fidelity of the area of distortion may be desired under the circumstances. If the distorted area is not sufficiently quantified then the remaining positive test area is again calculated or determined (block 110 ). The remaining test area is again split into segments (block 112 ) and displayed to the user (block 114 ) with the steps repeated until the distorted area is sufficiently quantified. In some embodiments, if further resolution of the distorted space is desired then additional testing can be performed to further determine the shape of the distortion, as discussed in greater detail below with respect to FIGS. 3A-3K .
[0035] FIGS. 2A-2P illustrate a schematic example of screen shots of performing a sample visual acuity test. FIG. 2A illustrates a complete test grid 202 showing a sample distorted area 204 and with a fixation point 206 . For convenience the distorted area is represented as a shaded area 204 . Distortion is present on the test grid in FIG. 2A so the user would respond with YES to indicate that distortion is present. The positive test area is calculated. At this point in this example, the remaining positive test area is the entire area. The positive test area is then divided into multiple segments. In this example, the positive test area is divided into two segments. The first of the two segments is displayed to the user in FIG. 2B . The user would respond in the affirmative that distortion is present in FIG. 2B . The segment shown in FIG. 2B would be kept in the test area. The grid (i.e., the other of the segments) in FIG. 2C would then be presented to the user. The user would answer in the negative because no distortion is present. The test area in FIG. 2C would be removed from the test area. Next the remaining test area would be calculated and split into two segments. The two segments of the remaining area, illustrated in FIG. 2D and 2E are presented to the user. The user would answer in the affirmative that distortion is present on both FIGS. 2D and 2E . The remaining test area then includes the segments shown in FIGS. 2D and 2E . Each of the segments is divided into two, leaving four segments to be tested.
[0036] The program can determine an efficient way to present the four segments. For example, the program can assume that the distortions are continuous and potentially overlap the intersection of the test grid segments illustrated in FIGS. 2D and 2E . As a result the segments presented in FIGS. 2F and 2G are the segments that do not include the area where the segments in FIGS. 2D and 2E are likely to intersect. Here, the user would respond in the negative to the segments displayed in FIGS. 2F and 2G . The program can then assume that the distortion is present in both of the two segments that were not displayed in FIGS. 2F and 2G based on the positive responses to the segments in FIGS. 2D and 2E . The positive test area is now the area of
[0037] FIG. 2D less area of FIG. 2F and area of FIG. 2E less area of FIG. 2G . The newly calculated test area can again be divided and further segments can be presented. FIGS. 2H and 2I present segments with the outer horizontal portions of the remaining test area. Negative responses remove those segments from the remaining test area. Next, the segments in FIGS. 2J and 2K are presented to the user, with the user responding that distortion is present. The logic can assume that the distorted area is continuous between the segments shown in FIGS. 2J and 2K and save steps by not presenting the space or segment between FIGS. 2J and 2K . FIGS. 2L-2O show the remaining test area split into vertical segments and presented to the user. The user responds in the negative to the segments in FIGS. 2L and 2N and in the positive to the segments shown in FIGS. 2M and 2O . The positive test area can then be represented by the grid shown in FIG. 2P . If the positive test area is sufficiently quantified then the test ends. If further resolution of the distorted space is desired then additional testing can be performed to further determine the shape of the distortion, as discussed in greater detail below with respect to FIGS. 3A-3K .
[0038] The data on the distorted areas may be quantified using a number of different factors, such as, for example in the dimensions of an area of distribution, coordinates of all or a portion of the boundaries of a distortion area, the relative size, position or movement of a distortion area compared to prior patient data and the location relative to the fixation center, among others. The quantifying may be performed by a program operating onboard the device, by a mobile application or remotely by a server run application. Information related to test responses or the distorted area can be stored as coordinates corresponding to the grid sections covering the distorted area, as a picture, or as a percentage of the total test area. The data representing the distorted area can be stored on a mobile device and/or uploaded to a remote server or website.
[0039] The testing methods disclosed herein can be used to obtain a sufficiently precise representation of the distorted area for the purpose of evaluation of a patient condition. Generally, the size of the distortion and any information on whether the size of the distortion has changed with time is more useful to the physician than the precise size of the distortion. Typically, the size of the distortion area and/or location of the distortion correlates with the level of disease present or progression of disease or state of treatment in the user or patient. The change in the distortion area for the patient can be tracked over time to see how the patient's vision is changing and to determine whether treatment is effective or if additional treatment may be needed. The rate of change can also be used to predict when further patient treatment is needed.
[0040] The user can input the yes/no response to the test by touching the screen, by voice, by touching the screen with an object such as a stylus, or by other means. The fixation point 206 can be the area of the screen to touch to register a positive response so that the user does not have to move their eyes from the fixation point. In one aspect, a separate area of the screen can be touched to register a negative response.
[0041] As the test progresses the fixation point can shift from one position on the screen to another to allow displaying larger areas of the grid. For example, if a fixation point is shifted to the right edge of the screen, then the area displayed to the left of the fixation point is two times larger than the area available if the fixation point is presented in the center of the screen. By sequential positioning the fixation point into 4 corners of the screen a visual field 4 times larger (2.times.2) than the screen size can be mapped.
[0042] The program/logic implementing an embodiment of the metamorphopsia test described herein can be used to minimize the number of steps required to achieve a useful result. The program can make various assumptions to more efficiently determine the size and shape of the distorted area. For example, the program can assume that an area of distortion is continuous. The program can skip segments in some cases if the previous data indicates that a distortion is present. For example, after the negative responses to the segments in FIGS. 2F and 2G , the program assumed that there was a distortion in the area between the segments in FIGS. 2F and 2G based on the positive responses to the segments shown in FIGS. 2D and 2E . In this example, the program can move to block 124 or 110 from block 122 instead of continuing with block 114 to reduce steps.
[0043] The program can switch between horizontal and vertical segmentation. See for example the change in segments displayed between FIGS. 2K and 2L . The program can determine when it is efficient to switch between horizontal and vertical segmentation. Segmentation can also be performed using non-orthogonal axes. For example, using lines crossing at 60° rather than a rectangular grid.
[0044] The program can change the division factor when calculating the segments of the remaining test area in block 112 . FIGS. 2A-2P generally illustrates a division factor of 2. The division factor can vary. In some embodiments the division factor can be about 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, or any other integer. In some embodiments the division factor can be expressed as a percentage, such as 30%, 40%, 60%, or 70% depending on a number of factors. The division factor can be modified by the program during the test, such as by starting out with a lower division factor, e.g. 2, and later increasing the division factor, e.g. to about 3. Or vice-versa, the division factor can be higher during the beginning of the test and later be decreased. In some embodiments, the division factor can be optimized to achieve a sufficiently quantitative characterization of the distorted area in a relatively low number of steps. In some embodiments, the division factor can be optimized to achieve a more precise quantitative characterization of the distorted area.
[0045] In some embodiments the program can take into account patient data when determining what areas of the grid to display to patients. For example, the program can tailor the test based on the patient disease type, previous patient testing data (e.g. location or size of previous distortion and/or rate of change of the distortion size), and any other patient information. The test can be tailored to efficiently determine if the previous distortion has changed size, shape, or location. The initial presentation segment to the patient could be a larger area that excludes the area around the distorted area from the last test, for example the initially displayed segment could be ¾ of the total test area. Consider an example where prior testing indicated a distortion area is at it appears in FIG. 2A . The first test area presented 402 may be as shown in FIG. 4 . A response of “no distortion” to this screen approximates the current test result based on the prior result. Thereafter, segments may be applied as discussed above to determine whether the distortion area has changed size, shape or location within the generally known distortion area. As this example demonstrates, a test pattern modeled on prior results can remove ¾ of the test area with a negative response. Additional steps to further determine the size and shape of the distortion may follow.
[0046] In some embodiments the program can modify the distance between the horizontal lines and vertical lines to make a finer grid structure in the displayed test area. The finer grid structure can be used to increase the precision of the distorted area in comparison to using larger grid structures. The resolution of the test would correspond to the size of the squares on the grid. Adding additional lines to form a finer grid structure can increase the precision of the distorted area.
[0047] The program can be used to identify multiple distortion spots, such as the distortion spots illustrated in FIGS. 5A and 5B . If the program identifies that multiple areas may be present then the program can be used to analyze one of the distortions followed by analyzing the other distortion in sequence.
[0048] In some case it can be desirable to achieve a more precise representation of the distortion. It is harder to see distortions in small segments of straight lines so the division may stop at segments larger than a single square and an additional mapping algorithm can be applied. In this approach horizontal or vertical lines are presented in the area overlapping with the area marked as distorted. The length of these lines correspond to several periods of the grid. The line(s) shift by one period with each positive response until the distortion disappears (i.e. a negative response is obtained). This approach allows mapping the grid with the precision of one period, while the presented segments can be much longer.
[0049] If additional precision is desired for the quantitative result achieved in FIG. 2P then additional line mapping can be performed using horizontal and/or vertical lines. An example of additional mapping is shown in the flow chart illustrated in FIGS. 3A-3K . A horizontal line can move horizontally across the test area determined as distorted by previous testing. FIGS. 3A-3E illustrate a horizontal line moving across the test area between discrete points. The patient responds with an affirmative response if any distortion is present on the displayed line. The patient would respond in the negative for FIG. 3A and in the affirmative for FIGS. 3B-3E . After testing a particular horizontal latitude the distortion can be tested for a different horizontal latitude as shown in FIGS. 3F-3J . The patient would respond in the negative for FIG. 3F and in the affirmative for FIGS. 3G-3J . Additional horizontal mapping could be used to further determine the shape of the distortion. The program can continue until a sufficiently precise data is achieved.
[0050] In some embodiments vertical line mapping is used. In some embodiments horizontal line mapping is used. In some embodiments a combination of horizontal and vertical line mapping can be used. The program can be configured to use horizontal and vertical mapping to achieve a desired resolution on the distortion in a minimum number of steps. The program can also be configured to switch between horizontal and vertical modes. Lines at orientations other than horizontal or vertical can also be used. For example, a non-orthogonal set of lines (e.g. crossing at 60 degrees) can also be used.
[0051] The testing methods disclosed herein can result in improvements over current metamorphopsia tests in several aspects. First, the testing methods disclosed herein can deliver results in a form that is similar to the traditional format familiar to all ophthalmologists, and thereby is easily understood and interpreted by the doctors. Second, the algorithm is based on reduction of the segments size as the test progresses, thereby eliminating the large non-distorted sections before more refined mapping of the distorted areas is performed. This approach allows for minimizing the number of steps and time that would be required, compared to the more traditional approach of hyperacuity testing that use small segments throughout the whole visual field to map distortions. Third, the patient input can be registered by touching the fixation point or speaking the result thereby reducing foveal scanning and eye movement away from the fixation point. Fourth, the testing methods disclosed herein can leverage the familiar grid-like structure while still creating sufficient quantitative precision to detect changes in visual distortion over time using a relatively small number of steps. The testing methods can be performed on a portable device thereby allowing the patients to do the tests on their own. Periodic testing (i.e., daily or weekly or on a set schedule or frequency) can be used to track changes in the user's visual acuity over time.
[0052] The testing methods described herein can make it easier for patients to do testing on their own. The binary response, e.g. yes or no, makes the tests easier to take versus tests that require touching distorted areas or drawing over the distorted areas or choosing between three or more possible responses. The tests are also quicker than previous testing methods because the distortion can be determined without detailed mapping of the entire test area. The removal of the non-distorted areas (regions of non-interest) hastens the result and permits use of coarser segments initially with increasing segment fidelity as the region of interest becomes better defined. The reduced number of steps and quicker tests can also make the tests easier on users. Making the tests easier for the user or patient can encourage the users to periodically take the tests. The user data for a particular test over a period of time can be useful for calculating and analyzing trends in the change in the user's metamorphopsia. The trending data can be used to determine if and when additional treatment may be useful for the patient. The ability to predict when additional treatment may be useful can save the user money and time by avoiding wasted doctor visits. The trending data can also be useful to determine if the selected course of treatment is achieving the desired results or whether a different treatment schedule may be useful.
[0053] The foregoing detailed description of the technology herein has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the technology to the precise form disclosed. Many modifications and variations are possible in light of the above teaching. The described embodiments were chosen in order to best explain the principles of the technology and its practical application to thereby enable others skilled in the art to best utilize the technology in various embodiments and with various modifications as are suited to the particular use contemplated. The present invention descriptions are intended to cover such alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims and otherwise appreciated by one of ordinary skill in the art. | 1a
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BACKGROUND OF THE INVENTION
[0001] This invention relates to intraocular lenses (IOLs). More particularly, the invention relates to deformable, e.g., foldable, IOLs for placement in eyes, e.g., in the anterior chambers of eyes, and to methods of making and using such IOLs.
[0002] The human eye is susceptible to numerous disorders and diseases, a number of which attack the crystalline lens. For example, cataracts mar vision through cloudy or opaque discoloration of the lens of the eye, and can result in partial or complete blindness. When this happens, the crystalline lens can be removed and replaced with an intraocular lens, or IOL. In certain other circumstances, an IOL can be placed in an eye containing the natural crystalline lens, for example, to provide for enhanced vision in the phakic eye. A typical IOL comprises an optic body, or lens, adapted to focus light toward the retina of the eye, and one or more fixation members, or haptics, adapted to at least assist in supporting or fixating the IOL in a suitable location in the eye, such as the anterior chamber, iris, or capsular bag of the eye.
[0003] The optic and haptics may be formed as an integral unit from a single material, but in recent years the trend has been toward composite IOLs which use different materials for the various components, so that the properties of these components can be separately optimized. Examples of such composite IOLs are shown in Barrett U.S. Pat. No. 4,997,442 and Vanderbilt U.S. Pat. No. 5,217,491, both of which employ relatively flexible materials in the optic portion and more rigid materials in the haptics. The disclosure of each of these patents is incorporated in its entirety herein by reference. In both the Barrett composite IOL and the Vanderbilt composite IOL, the flexible material of the optic enables the IOL to be deformed, e.g., folded, rolled and the like, for insertion through a small surgical incision in the eye, while the relatively rigid material of the haptics enhances the stability of the optic in the eye.
[0004] In most, if not all, prior art composite IOLs, such as those disclosed by Vanderbilt and Barrett, the haptics have been configured as extremely thin, filament or loop-type members suitable for securing the optic in the posterior chamber, or capsular bag, of the eye. The slenderness of these types of fixation members to some degree compensates for the rigidity of the material from which they are made, and enables such fixation members to be curled, folded, or wound up inside a conventional inserter cartridge, without significantly interfering with the folding of the optic. However, such filament or loop type fixation members are generally not recommended for use in the anterior chamber of the eye.
[0005] More particularly, anterior chamber IOLs are subject to different conditions than posterior chamber IOLs, and thus differ significantly in their design. For instance, anterior chamber IOLs must be able to withstand the relatively high compressive forces exerted by the surrounding structure of the anterior chamber without allowing significant movement of the optic. In addition, anterior chamber IOLs should be structured to reduce the potential for complications such as pupil ovalling, endothelial cell loss and the like.
[0006] Various designs for anterior chamber IOLs are disclosed in Nigam U.S. Pat. No. 5,982,282. Other designs are disclosed in Laguette et al. co-pending U.S. patent application Ser. No. 09/908,515, Nguyen et al. co-pending U.S. patent application Ser. No. 09/847,957, Laguette co-pending U.S. patent application Ser. No. 09/847,958 and Paul co-pending patent application Ser. No. 10/225,990. Each of these co-pending applications and the present application are commonly owned. The disclosure of each of the Nigam patent and the above co-pending U.S. patent applications is hereby incorporated in its entirety by reference herein.
[0007] Although the anterior chamber IOLs disclosed in the above patent applications perform satisfactorily in most respects, they all include relatively large fixation members which, if made entirely of rigid material such as poly methylmethacrylate (PMMA), might interfere with the ability of the IOLs to be deformed for insertion into eyes through small incisions. It is advantageous to insert in an IOL though such a small incision to obtain benefits, for example, reduced surgical trauma, reduced recovery time and the like.
[0008] Accordingly, it would be advantageous to provide foldable IOLs, for example, anterior chamber IOLs, with fixation members having sufficient rigidity to maintain optic stability in the eye, while still being flexible or deformable enough to allow the IOL to be folded or otherwise deformed for insertion through a small, or even a very small, incision in the eye. In addition, it would be advantageous to provide such IOLs with configurations that are compatible for use with conventional insertion apparatus. It would also be advantageous to devise methods of manufacturing such IOLs that are relatively simple and cost-effective.
SUMMARY OF THE INVENTION
[0009] New IOLs for implantation in eyes, for example in anterior chambers of the eyes, as well as methods of making and using such IOLs have been discovered. The present IOLs are sized and structured to reduce the incidence of one or more known complications in the eye caused by prior IOLS, and to be foldable for effective and safe insertion through small or very small incisions in the eye using, for example, conventional insertion apparatus.
[0010] In accordance with one aspect of the present invention, an intraocular lens comprises an optic adapted to focus light toward a retina of an eye, and at least one fixation member configured to secure the optic in the eye. The fixation member includes a proximal portion coupled to the optic and a distal contact portion configured to be in contact with eye tissue when the intraocular lens is in use in the eye. The proximal portion of the fixation member includes at least one first area formed of a first, substantially rigid material, and at least one second area formed of a second material which is less rigid or more flexible than the first material.
[0011] In one embodiment, the fixation member is configured to secure the optic in an anterior chamber of an eye. The proximal portion of the fixation member includes at least two segments formed of the first, substantially rigid, material, preferably extending generally in a first direction and a different second direction, respectively, relative to the optic. In one useful version of this embodiment, the first segment extends generally radially with respect to the optic, and the second segment extends generally circumferentially with respect to the optic. An area between the two segments is formed of the second, more flexible material.
[0012] In a particularly useful embodiment, the optic is formed of a deformable, e.g., resiliently deformable, or foldable material, preferably a material allowing the optic to be folded or rolled for insertion through an incision measuring about 3.5 mm or less. Preferably this material is the same as the second material. In one version of this embodiment, the first and second materials are acrylic-based polymeric materials. For instance, the first material may be poly methylmethacrylate (PMMA), and the second material may be an acrylic-based polymeric material compatible with PMMA.
[0013] A method of producing an IOL according to the present invention comprises a step of forming a composite member into an intraocular lens having an optic adapted to focus light toward the retina of an eye and at least one fixation member configured to secure the optic in the eye, wherein the fixation member includes a proximal portion coupled to the optic, and a distal contact portion configured to be in contact with eye tissue when the intraocular lens is in use in the eye, and wherein the proximal portion includes at least one first area formed of a first, substantially rigid material and at least one second area formed of a second material less rigid or more flexible than the first material.
[0014] In one useful embodiment, the method further comprises a step of producing the composite member, preferably by polymerizing a first monomeric component to obtain the first material, and polymerizing a second monomeric component to obtain the second material.
[0015] In an especially useful embodiment, the step of polymerizing a first monomeric component comprises polymerizing a first acrylic-based polymeric precursor material within a mold, and the step of polymerizing a second monomeric component comprises polymerizing a second acrylic-based polymeric precursor material, compatible with the first material, within a cavity formed in the polymerized first material.
[0016] A method of correcting vision according to the present invention comprises providing an intraocular lens in a compressed configuration. The intraocular lens includes an optic adapted to focus light toward a retina of an eye, and at least one fixation member configured to at least assist in supporting the optic in an eye. The fixation member includes a proximal portion coupled to the optic and a distal portion configured to be in contact with eye tissue when the intraocular lens is in use in the eye. The proximal portion includes at least one first area formed of a first, substantially rigid material and a second area formed of a second material less rigid or more flexible than the first material. The compressed intraocular lens is inserted through a small incision in the eye, and preferably positioned within the anterior chamber, for use.
[0017] Each and every feature described herein, and each and every combination of two or more of such features, is included within the scope of the present invention provided that the features included in such a combination are not mutually inconsistent.
[0018] Additional aspects and advantages of the present invention are set forth in the following description and claims, particularly when considered in conjunction with the accompanying drawings in which like parts bear like reference numerals.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] [0019]FIG. 1 is a vertical sectional view of an eye and an exemplary anterior intraocular lens of the present invention implanted therein;
[0020] [0020]FIG. 2 is a top plan view of an intraocular lens according to the present invention;
[0021] [0021]FIG. 3 is a top plan view of a composite button from which the intraocular lens of FIG. 2 may be fabricated;
[0022] [0022]FIG. 4 is a perspective view of a precursor button created during a first step of a method of manufacturing an intraocular lens according to the present invention;
[0023] [0023]FIG. 5 is a vertical sectional view taken through the precursor button of FIG. 4;
[0024] [0024]FIG. 6 is a front side view, in perspective, showing an IOL according to the present invention positioned in an open loading cartridge of an insertion apparatus;
[0025] [0025]FIG. 7 is a front side view, in perspective, showing the loading cartridge of FIG. 6 is a closed position; and
[0026] [0026]FIG. 8 is a somewhat schematic illustration showing an IOL according to the present invention being inserted in an anterior chamber of an eye.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0027] Referring now to FIG. 1, an anterior chamber IOL 10 according to the present invention is shown implanted in an eye. For ease of illustration, the illustrated eye is aphakic; that is, the natural crystalline lens has been removed. It will be apparent to one of ordinary skill in the art, however, that an anterior chamber IOL 10 according to the present invention may also, and often will, be used in an eye having the natural crystalline lens in place—in other words, a phakic eye.
[0028] The eye 12 comprises a cornea shown to the left and an iris 16 shown in the middle of the eye. It is to be understood that the cornea 14 is at the front of the eye 12 . The iris 16 divides the eye into an anterior chamber 18 at the front of the eye and a posterior chamber 20 in front of the iris 16 . The iris 16 also defines the pupil 22 , which is an opening in the middle of the iris 16 . In front of the iris 16 is the scleral spur 24 . The scleral spur and the iris 18 delimit the ciliary band 26 .
[0029] The IOL 10 , shown in greater detail in FIG. 2, includes a central optic 28 and a pair of fixation members 30 a, b . The illustrated number and structure of the fixation members is merely exemplary, as the principles of the present invention may be applied to a large variety of anterior chamber IOLs including, but not limited to, the IOLs disclosed in Laguette et al. co-pending U.S. patent application Ser. No. 09/908,515, Nguyen et al. co-pending U.S. patent application Ser. No. 09/847,957, Laguette co-pending U.S. patent application Ser. No. 09/847,958 and Paul co-pending patent application Ser. No. 10/225,990, the contents of all of which are incorporated by reference herein.
[0030] As illustrated, each fixation member 30 a, b is sinuous in structure, and includes a proximal portion 31 and distal contact portion 40 . Each proximal portion 31 has several regions, or segments, including a proximal connector segment 32 that extends radially outwardly from the optic, an elongated intermediate segment 34 that extends generally circumferentially from a distal end of the connector portion 32 , and a distal segment or elongated member 36 that is configured to extend generally along a chordal line with respect to the ciliary band 26 when the IOL 10 is positioned in the anterior chamber 18 of eye 12 . A bridge segment 38 extends generally perpendicularly between a distal end of the intermediate segment 34 and a proximal end of the distal segment 36 . The distal contact portion 40 , also called a pod or footplate, is enlarged and somewhat bulbous, to minimize contact stress on, and reduce the potential for trauma to, the ocular tissue in the anterior chamber of the eye.
[0031] The optic 28 of the IOL 10 is advantageously made from a sufficiently flexible material to enable the IOL 10 to be resiliently deformed, e.g., folded or rolled, for insertion through a small incision, for example an incision of about 3.5 mm long or less, such as about 3.2 mm or less, or about 3.0 mm or less, and preferably no more than about 2.8 mm long. One preferred optic material meeting these requirements is the acrylic polymeric material from which the optic of an IOL marketed under the trademark SENSAR® by Advanced Medical Optics, Inc. is made. The optic of the SENSAR® IOL is made of a cross-linked acrylic polymeric material formed of copolymers of methacrylate and acrylate esters, cross-linked with a diacrylate ester to produce the cross-linked acrylic copolymer. Useful deformable cross-linked acrylic polymeric materials are disclosed in Gupta U.S. Reissue Pat. No. RE36,150, the disclosure of which is incorporated in its entirety herein by reference.
[0032] The proximal portion 31 of each of the fixation members 30 a and b includes at least one area made of a substantially rigid first material, for instance poly methylmethacrylate (PMMA), and at least one area made of a second material which is more flexible than the first material. In the illustrated embodiment, proximal connector segment 32 , intermediate segment 34 , distal segment 36 , and bridge segment 38 are all made of the first material, and regions or areas 44 , 46 , and 42 are made of the second material. The number and location of flexible areas may vary, depending on the structure of the fixation members 30 a, b . In one useful embodiment, the flexible areas are located at areas of the fixation members subject to increased stress, for example, areas where the possibility of breakage would be increased or even highest if the fixation members were made entirely of the first material. In sinuous fixation members, such high stress areas often exist at each bend or substantially sharp change in direction along the length of the fixation member. In the illustrated embodiment, there are three such bends in each fixation member 30 a, b : a first bend at the intersection between proximal portion 32 and intermediate portion 34 ; a second bend at the intersection between intermediate portion 34 and bridge portion 38 ; and a third bend at the intersection between bridge portion 38 and distal segment 36 . Thus, flexible areas 44 , 46 , and 42 are advantageously located at the first, second and third bends, respectively. These flexible areas 44 , 46 , and 42 , which also may be thought of as joints or elbows, allow the fixation members 30 a and b to be resiliently deformed, i.e. folded, thus greatly facilitating the insertion of the IOL 10 through a small incision.
[0033] In addition to being less rigid or more flexible than the first material, the second material advantageously is resilient so that the fixation members 30 a and b return quickly to substantially their original, uncompressed configurations after insertion into the eye. Advantageously, the second material is the same as the material used in the optic. It is also preferred that the second material is compatible with the first material, for example, so that the two materials can easily be co-processed and/or used effectively and safely together. For instance, the first material may be poly methylmethacrylate (PMMA), and the second material may be a deformable cross-linked acrylic material similar to the materials described in the aforementioned Gupta patent.
[0034] In the illustrated embodiment, the flexible area 42 between bridge portion 38 and distal segment 36 is bulbous and serves as a pod or footplate similar to distal contact portion 40 . Thus, in addition to facilitating folding, the flexible material in this area 42 reduces contact stresses on the surrounding ocular tissues.
[0035] Distal contact portion 40 is shown in FIG. 2 as being formed of the same material as flexible areas 44 , 46 and 42 . However, in some IOL designs, it may be preferable to make the contact portions of a more rigid material, for instance the same material as proximal connector segment 32 , intermediate segment 34 , bridge segment 38 , and distal segment 36 . Alternatively, the bridge segment 38 may be formed of the same flexible material as one or both of the distal contact portions 40 , 42 .
[0036] A method of manufacturing IOL 10 will now be described with reference to FIGS. 3 - 5 .
[0037] Initially, a first monomeric component, for instance methylmethacrylate precursor material, is poured or otherwise placed in a cylindrical mold (not shown) and polymerized to form a button 48 of substantially rigid material, such as PMMA. A cavity or hole 50 is formed in the central region of the button 48 . In the illustrated embodiment, the button 48 has a depth or axial thickness of about 5 mm, and the central cavity has a depth of about 3 to 4 mm. Several smaller, annular cavities or holes 52 , 54 , 56 are formed radially outwardly of the central cavity 50 , at the locations where flexible segments 44 , 46 and 42 are desired. These cavities 52 , 54 , 56 are illustrated herein as being continuous, concentric annular cavities, each having a radial thickness of about 0.5 to 1.0 mm, depending on the desired size of the fixation members and pods. Alternatively, the cavities 52 or 54 could be formed as discrete circular spots or holes (about 0.5 to 1.0 mm in diameter) at the desired locations.
[0038] Once the cavities 50 , 52 , 54 , 56 are formed, a second monomeric component, for instance a precursor component of a flexible or deformable cross-linked acrylic polymeric material similar to the materials described in the aforementioned Gupta patent, is polymerized within the cavities 50 , 52 , 54 and 56 to form flexible rings or spots in the button 48 . Finally, the button 48 , now having a composite composition, is processed, for example, lathed, cut or otherwise shaped, for instance along the outline 58 shown in FIG. 3, to form the optic 28 and fixation members 30 a, b of the IOL 10 . In the embodiment shown, the relatively flexible material in the cavities 50 , 52 , 54 , 56 is shaped to form the optic 28 , the joints 44 , 46 and the contact portions 42 , 40 , while the stiffer or substantially rigid material of the remainder of the button 48 is shaped to form the proximal connector segments 32 , elongated intermediate segments 34 , distal segments 36 and bridge segments 38 of the fixation members.
[0039] The IOL 10 can be effectively inserted into an anterior chamber of an eye and used to provide vision correction, for example, vision enhancement. As shown in FIG. 6, an anterior chamber IOL 10 is placed in the load chamber 60 of an IOL insertion cartridge 62 having folding leaves 64 a, b and a hollow distal tip 65 . The leaves of the cartridge 62 are then moved from their open position, shown in FIG. 6, to their closed position, shown in FIG. 7, bringing both the optic and fixation members into a folded or rolled configuration (not shown). The cartridge 62 is then placed in a suitable insertion apparatus 66 such that the distal tip 65 of the cartridge projects through an distal opening in the insertion apparatus 66 . The distal tip 65 of the cartridge is then placed in or near a very small incision 68 in the sclera or cornea of an eye 12 , and a plunger 68 or the like is advanced through the insertion apparatus, causing the IOL 10 to be passed through the outlet of the distal tip 65 into the anterior chamber 18 of the eye. Once placed in the anterior chamber 10 , the IOL may, if necessary, be repositioned using a needle or the like to obtain optimum stability and centration.
[0040] The illustrated insertion apparatus 66 is similar to an apparatus disclosed in Makker U.S. Pat. No. 5,735,858, the disclosure of which is incorporated herein by reference. However, the IOL 10 of the present invention is not limited to use with any particular insertion apparatus, and may in fact be inserted using surgical forceps or other similar devices.
[0041] While this invention has been described with respect to various specific examples and embodiments, it is to be understood that the invention is not limited thereto and that it can be variously practiced within the scope of the following claims. | 1a
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RELATED APPLICATIONS
[0001] This application relates to and claims priority to U.S. Provisional Patent Application No. 60/585,266, which was filed Nov. 9, 2006, and to U.S. Provisional Patent Application No. 60/961,773, which was filed Jul. 24, 2007. Both of which are commonly owned and incorporated herein by reference in their entireties.
FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not applicable.
FIELD OF THE INVENTION
[0003] The present invention relates to devices, kits, and methods for the capture of terrestrial and aerial arthropods based on their propensity to move towards a specific color or color combination. More specifically, this invention provides a replaceable and adjustable lighting system that allows for increased capture rates of targeted arthropods by mimicking their natural visual attractants. The lighting system also provides improved energy efficiency and enables capture traps to be adapted to various environments, conditions, and arthropods of interest.
BACKGROUND OF THE INVENTION
[0004] With the introduction of West Nile virus into the United States and the continuing presence of malaria, dengue, encephalitis viruses, and leishmania in much of the world, insect monitoring and control of vector-borne diseases is a critical healthcare need. Presently, there are approximately 550 State health departments and mosquito abatement districts throughout the United States that spend approximately 400 million dollars annually on mosquito control. Additionally, insects cause enormous agricultural damage worldwide either directly or indirectly through disease transmission.
[0005] Traps to attract insects are commonly used for surveillance and control of insect-vectored diseases or for public health research. Universal black light traps are used by the United States Department of Agriculture to monitor crop pests in fields and storage areas. Centers for Disease Control (CDC) light traps are used routinely to monitor insect populations and disease prevalence. The military uses light traps to monitor insects in and near troop encampments. In Iraq and Afghanistan, a large number of cases of leishmaniasis among U.S. troops has increased the need for effective surveillance of phlebotomine sand flies, the insect vector of leishmaniasis. Researchers interested in disease vectors (flies, mosquitoes, sand flies, and other insects and arthropods) also use light traps for collecting and monitoring.
[0006] In general, ultraviolet (UV) light traps attract more insects than similar white light traps, but power consumption is much greater for UV traps and is often a limiting factor. Further, the collection of non-target insects and arthropods in either type of trap can complicate results and analyses. Adequate public health surveillance is often impossible because of the high costs and logistical problems associated with using current CDC-traps or comparable light traps. Other limitations of known capture traps include an inability to readily adjust to different conditions or environments, irregularly shaped areas, and to target specific insects or arthropods.
[0007] A number of attempts to improve upon white light traps have used incandescent lights, fluorescent lights, or light emitting diodes (LEDs) alone or in combination, as attractants. Other insect traps use bait such as CO 2 or heat, either alone or in combination with each other or light. For example, U.S. Pat. No. 7,191,560 to Harris uses heat and light; U.S. Pat. No. 7,281,350 to Wilbanks uses a plurality of green LEDs; U.S. Pat. Nos. 7,181,885 and 6,662,489 to Spiro use blue light, preferably from at least one LED, in combination with heat, carbon dioxide, and moisture; U.S. Pat. No. 7,073,287 to Lau uses an LED emitting low intensity violet light; and U.S. Pat. No. 6,965,205 to Piepgras refers to the use of LEDs as an insect attractant and repellent.
[0008] U.S. Pat. No. 6,840,003 to Moore utilizes a combination of different forms of light from LED, ultraviolet, and fluorescent light sources and discloses that a plurality of light sources will effectuate greater trapping efficiency, but Moore teaches away from selectively using such light sources to target specific arthropods. In fact, the invention of Moore is specifically designed to attract and trap all types of insects in an area without specificity. Similar to Moore, U.S. Pat. No. 6,199,316 to Coventry utilizes a combination of ultraviolet and broad spectrum light with a light mixer, such as a prism, to produce a light attractive to a wide range of target insects. The spectrum light of Coventry is specially designed to provide a wide range of different wavelengths simultaneously.
[0009] Importantly, none of these examples provide for or teach a means of selective trapping that is crucial for reliable surveillance and pest control without damage to non-target, beneficial species.
[0010] U.S. Patent Appl. Pub. Nos. 2007/0068068 of Weiss and 2007/0056208 of Chen both teach light traps designed to specifically target mosquitoes by using a variety of light sources to produce wavelengths in the UV and visible spectra. Weiss also teaches that flickering or operating LEDs in sequence may be a useful attractant and that specific wavelengths of either the UV or visible spectrum may be used. While Weiss states that different species of mosquitoes are attracted to different wavelengths of light, Weiss does not identify those species or their respective attractant spectra. Further, neither Weiss nor any other known patent or application disclose or teach using light emitted from LEDs without a reflector or light mixer of some type. Using a reflector reduces the field of insect capture by creating blind spots behind the reflectors.
[0011] Presently, the art does not provide or teach traps that can be adjusted or programmed to selectively target a species or group of arthropods in one set of circumstances and then be adjusted to selectively target a different species or group of arthropods in another set of circumstances. It is desired that a means of easily adjusting existing non-selective traps to selectively trap targeted arthropods and simultaneously be less attractive to non-targeted arthropods be found. Further, it is desired that such methods and compositions be economical and sufficiently flexible to adjust to numerous different types of conditions. It is desired that a light trap be more energy efficient and selective under field conditions so that costs are lowered and monitoring, especially of disease-vectors or crop pests, is more sensitive and reliable.
SUMMARY OF THE INVENTION
[0012] The invention discloses compositions and methods for increasing the capture of targeted arthropods by using light systems that arrange one or more LEDs in fixed positions to emit light that mimics natural attractants or repellants. Advantageously, the lighting systems provided may be adjusted to alter the brightness, i.e. light intensity, the zone(s) of attraction, the wavelengths of light emitted, or a combination thereof of capture traps. In particular, the LEDs may be adjusted independently from one another such that different LEDs emit different wavelengths, light intensity, or combinations thereof.
[0013] In particular, the invention provides a lighting system for a capture trap that comprises at least one replaceable lighting platform and at least one supporting member. The lighting platform comprises an electrical circuit having a Zener diode, a resistor, and at least one light emitting diode (LED). The resistor regulates the voltage to the LED so that the intensity or brightness of the light emitted by the LED can be adjusted as desired. While Zener diodes are known in the electrical arts, Zener diodes are not known to be used in other light systems in traps. Herein, the Zener diode serves to protect the LEDs from reverse electrical current. A second resistor may optionally be located between a positive terminal of the electrical circuit and the Zener diode such that the second resistor regulates the current to the Zener diode to prevent prolonged reverse current from burning out the Zener diode.
[0014] The supporting member holds the LED(s) at a variable angle in a substantially rigid position. Holding the LED(s) at a fixed variable angle(s) provides several significant advantages. By allowing the light emitted from the LED(s) to be emitted directly from a trap without a reflector, light mixer, or similar structure, attractive wavelengths, especially UV and other higher energy wavelengths, are not absorbed and the attractiveness of a capture trap is increased without increasing power consumption. Further, holding the LED(s) at a variable angle allows the size and dimensions of the zone of attraction to be adjusted as needed. Using variable angle LED(s) also allows for the brightness or intensity of the light emitted to be adjusted to existing conditions (e.g. a comparatively well-lit trapping area due to moon or ambient light versus a relatively dark trapping area) so that the attractiveness is enhanced.
[0015] An exemplary preferred lighting system comprises one, two or more LEDs. The lighting system may comprise more LEDs, including 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 40, 50, 60, 75, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500 or more LEDs. The number of LEDs used will influence the amount of power required and the amount of time that the capture trap can be effectively used. In most preferred embodiments for small to mid-sized traps the lighting system comprises 1 to 12 LEDs. Large capture traps, such as encephalitis vector surveillance (EVS) or universal bucket traps, generally will require more LEDs (preferably about 10-25 LEDs) to provide an effective zone of attraction whereas broad area traps such as Shannon traps may require hundreds of LEDs to provide adequate illumination around the trap.
[0016] The invention preferably uses a plurality of LEDs to attract and trap insects and other arthropods. The LEDs are of separately adjustable color and intensity. LED lights are readily available in a variety of 5 nm wavelengths to produce a range of colors of light from ultraviolet to infrared that includes the visible light spectrum. Wavelengths emitted from LED bulbs range from about 250 nm to about 2000 nm. Further, a plurality of wavelengths may be used in combination by the invention. The specific combination(s) used will depend upon the species of arthropod(s) that is (are) to be attracted or repelled.
[0017] Supporting members may be either cylindrical or polygonal. One preferred polygonal supporting member is a polygonal circuit board, especially a printed circuit board (PCB) or embedded circuit board. An advantage of a polygonal circuit board is that one or more LEDs may be located on one or more sides of the polygonal circuit board. A preferred polygonal PCB has 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 40, 50, 60, 75, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500 or more sides. More preferably, the PCB has 2 to 12 sides and at least one LED per side. In general, it is preferred that the sides of the polygon are about equal in length.
[0018] More than one lighting platform may be used in a lighting system. These lighting platforms may be in a number of configurations such that the intensity of emitted light and/or dimensions of the zone of attraction vary. A planar or linear configuration is preferred so that LEDs and electronics may be more easily optimally arranged and secured. For example, if the supporting member is cylindrical, lighting platforms may be attached throughout the entire length of the cylinder to form a wand. Alternatively, a plurality of lighting platforms with polygonal supporting members may be used to create a variety of three-dimensional shapes, including a wand. Lighting platforms must be sufficiently separated from one another to prevent a short circuit. The number of lighting platforms that may be effectively used will be limited by the power consumption and the length of the cylindrical supporting member. Where the supporting member is polygonal, in particular a circuit board, a standoff can be used to separate the lighting platforms. Those of skill in the art will recognize that the use of standoffs to separate circuit boards is well known in the art.
[0019] The invention also provides a method of using a lighting system. Specifically, the method comprises inserting one of the described lighting systems into a capture trap and adjusting the lighting system to emit the desired wavelength(s) of light to attract one or more species of targeted arthropod. The intensity, or brightness, or the light, type(s) of wavelength emitted, and variable angle at which the LED(s) is fixed may all be adjusted to attract the desired target(s) under given environment conditions. For example, one or more LEDs may be substituted to emit any wavelength between from about 250 nm to about 2000 nm. LEDs can be of variable color, intensity, and a plurality of LEDs can be used. The resulting method increases target insect capture and electrical energy efficiency while simultaneously decreasing non-target insect capture rates. The method may be used to modify existing insect light traps, new traps, or to improve current traps without a lighting component.
[0020] Kits for adjusting the attractiveness of a capture trap and methods of using such kits are also provided by the invention. These kits, and their methods of use, may be used to replace the lighting systems in existing traps, including those that used white or UV light. Replacing such systems will improve power consumption in many of the traps so that they may be used for longer periods of time without battery replacement. If desired, these broad spectrum traps may also be adapted to LEDs to be more selective so that targeted arthropods are more likely to be attracted, or repelled, and their zones of attraction may be altered to meet environmental conditions.
[0021] Kits comprise at least one replaceable lighting platform and at least one supporting member. Preferred kits will include a plurality of lighting platforms. The lighting platform has an electrical circuit comprising at least one light emitting diode (LED), a Zener diode, and a resistor to regulate the voltage (brightness) of the LED. The addition of the Zener diode, not found in other LED traps, allows for the exchange of the lighting units into non-LED traps while still protecting against human error. Optionally, the electrical circuit included in the kit may include a second resistor between the positive terminal of the electrical circuit and the Zener diode. This second resistor regulates the current to the Zener diode to prevent a burnout from continued overload. The supporting member holds the LED(s) at a variable angle(s) in a substantially rigid position, and it may be cylindrical or polygonal. If the supporting member is polygonal, a preferred supporting member is a circuit board, more preferably an embedded circuit board. One or more LEDs may be located on one or more sides of a polygonal circuit board including in the kit. Kits that include one or more circuit boards will also include a standoff.
[0022] Methods of adjusting the attractiveness of a capture trap comprise inserting an adjustable lighting system into a capture trap. The adjustable lighting system comprises at least one replaceable lighting platform and a supporting member. The lighting platform includes an electrical circuit comprising at least one light emitting diode (LED), a Zener diode, and a resistor that regulates the voltage to the LED. The supporting member holds the LED(s) at a variable angle(s) in a substantially rigid position so that the light emitted may be adjusted to the desired wavelength(s) and/or intensity of light and to a desired three-dimensional zone of attraction.
[0023] Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein.
[0025] FIG. 1 is a cross sectional drawing from above of a lighting system where the supporting member is cylindrical.
[0026] FIG. 2 is a planar view of a lighting system where the supporting member is cylindrical. The dashed box indicates optional additional lighting platforms.
[0027] FIG. 3 is a cross sectional drawing from above of a lighting system where the supporting member is an octagonal embedded circuit board.
[0028] FIG. 4 is a planar view of a lighting system where the supporting member is an octagonal embedded circuit board and a standoff is used. The dashed box indicates optional additional lighting platforms.
DETAILED DESCRIPTION
A. Principles of Lighting Systems
[0029] The invention provides a lighting system and replacement lighting system that advantageously uses emitted light instead of reflected light, which is used in conventional LED light traps. An advantage of using emitted light is that fewer of the high energy wavelengths, like ultraviolet (UV), are absorbed by organic materials (e.g. dust and oil from skin contact) or inorganic materials as compared to systems that use a reflector to direct light in many directions. Thus, the invention allows more high energy wavelengths, such as UV, to be projected from a trap. No known traps use direct emittance because prior to the present invention, LED bulbs could not be correctly arranged to provide sufficient coverage without using excessive amounts of power or creating heavy bulky portable power units. The present invention overcomes these problems by using a novel fixed arrangement of bulbs to provide effective coverage while using relatively little power.
[0030] Conventional light traps with LEDs use one or more bulbs with light beamed at a reflector because the LEDs do not have broad viewing windows. Generally, these LEDs only had conical viewing angles of 15-30 degrees, which means that twelve bulbs are needed to make a circular beam of light with a width of 30 degrees. As a result, to achieve an effective zone of attraction, many more LEDs are required, and power consumption is relatively high. Consequently, conventional light traps that use LEDs usually include another type of attractant or source of light. Furthermore, reflectors reduce the capture field or zone of attraction by creating blind spots behind the reflectors, and reflectors tend to absorb UV light emitted from the LEDs; thus, further reducing the zone of attraction created by the LEDs and increasing the requirement for a supplemental light source.
[0031] In contrast, the lighting systems of the invention use “variable angle” LEDs to emit light. With LED technology, the greater the viewing angle of an individual LED bulb, the less distance the light is projected, which reduces the zone of attraction. In contrast, a narrow bulb angle yields greater projection of emitted light. Thus, a combination of variable angle LEDs will maximize the lighting area and zone of attraction for complete coverage for any given lighting unit. Conventional traps do not provide variable angled LEDs, and consequently, are less able to effectively maximize the lighting area and zone of attraction than the present invention.
[0032] Depending upon the specific arrangement of the LEDs in the lighting platform, the system can provide 360 degrees or more of coverage around a trap with variable angled LEDs. Desirably, the light zone projected from each LED overlap a little with the light zone(s) created by adjacent LEDs. If there is no overlap then the outer edges of the conical zone do not project as far. By overlapping the zones slightly, they will be brighter and thus project farther.
[0033] Lighting systems of the invention that incorporate a polygonal supporting member, for example a printed circuit board (PCB), advantageously emit light across the entire upper hemisphere rather than just in a downward conical radius with reflected light. This greater coverage with attractive light is important for trapping indoors, caves, or other covered areas as the hemispherical light emittance more than doubles the capture area of reflected light systems. Where this type of hemispherical-shaped coverage is desired, the polygonal shape is preferred for the supporting member.
[0034] Another advantage of the invention is that the size and shape of the attraction zone may be adjusted to meet certain conditions or target certain arthropods. For example, a trap may incorporate 8 variable angle LEDs, each of which has an effective 50 degree window to provide for 360 degree coverage in a uniform manner. (A small degree of overlap between LED ranges is desired to provide effective coverage.) Alternatively, the same trap may be adjusted so that 4 LEDs have an effective 90 degree window to, again, provide uniform 360 degree coverage. The remaining 4 LEDs may emit a different wavelength(s) of light or a narrower effective degree window. For example, the remaining 4 LEDs may have an effective 30 degree window so that they emit a brighter (higher intensity) light. This configuration allows light to be broadcast farther on the cardinal points, which would increase the field of collection along those points while maintaining the local area of capture. It also allows the number of traps needed to effectively capture arthropods in an irregularly shaped area to be reduced.
[0035] For example, a barn with 4 corridors arranged in an “X” shape would need a minimum of 2 conventional traps; however, using the invention, the same barn could be equipped with a single trap located at the center of the “X” and achieve the same results. Another example is the trapping area next to a tree or house. The invention allows the shape of the zone of attraction to be adjusted to minimize illumination of the tree or structure and maximize illumination of the open area. This ability to adjust the shape of the trapping zone improves energy efficiency, which in turn, reduces labor and costs associated with trap maintenance.
[0036] The invention also includes features to reduce the possibility of damage from reverse electrical current. Reverse electrical current is second only to battery failure as the leading cause for trap problems during field collections. Insect field collection traps commonly use 6 volt batteries or battery packs to provide power. Confusing the positive and negative terminal is a common occurrence when installing traps. The Zener diode protects the LEDs from this reverse current. Zener diodes are not used in fluorescent or incandescent light traps because fluorescent and incandescent light bulbs are not ruined by reverse current. Known LED traps do not incorporate a Zener diode because the traps are not modular, interchangeable, or adaptable; and therefore, the possibility of incorrectly inserting the positive and negative terminals is remote.
[0037] The user can control certain parameters that necessitate a plurality of lighting conditions of said device that are adjustable as desired. These parameters may include bulb replacement, that allows for insect genera specific platforms, particular trapping habitats, and different insect targets. Typical trapping habitats include caves, domestic structures, forests, and fields.
[0038] This invention encompasses systems and methods to maximize the capture of a plurality of arthropod species, preferably targeted species, by using light emitting diode (LED) technology to mimic the light frequency sensitivity(ies) of arthropod species and act as an energy efficient visual attractant to them. Advantageously, the invention provides for greater flexibility because the colors or wavelengths, viewing angles, and intensities of any or all of the LEDs may altered to suit different environments, conditions, and targeted arthropods.
[0039] The invention includes mimicking LEDs that have narrow light spectra and can be used to attract or repel insects based on the insects' innate responses to visual stimulants, including both attraction as positive phototaxis and repulsion as negative phototaxis. The energy efficient LED technology is used for monitoring, controlling, trapping, and studying arthropods and the diseases they transmit.
B. Components of Lighting Systems
[0040] The lighting systems of the invention comprise at least one replaceable lighting platform 1 and at least one supporting member 8 . The lighting platform 1 includes an electrical circuit 2 that comprises a positive terminal 3 , a Zener diode 4 that acts as a one-way gate to prevent the reverse polarity of the electrical circuit 2 , a resistor 5 , a negative terminal 6 , and at least one light emitting diode (LED) 7 . The supporting member 8 holds at least the LED 7 in a substantially rigid position. The resistor 5 regulates the voltage to the LED 7 . See FIGS. 1-4 .
[0041] It is expected that in most instances, a plurality of LEDs 7 will be desired so that sufficient brightness or combinations of wavelengths can be achieved to maximize attraction. Each LED 7 includes both a positive and negative terminal that complete the electrical circuit 2 when the LED(s) is attached to the lighting system. Those of skill in the art will recognize that a different number of LEDs may be used. For example, the number of LEDs may range from 1 to 500 or more. It is recognized that increasing the number of LEDs will increase power consumption. Preferred numbers of LEDs range from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, to 20 per lighting platform. More preferably, the numbers of LEDs range from 1 to 12 per lighting platform. The number of lighting platforms per lighting system may be varied to meet particular needs and power consumption objectives.
[0042] An advantage of the lighting system is that a plurality of lighting platforms 1 may be used simultaneously (see FIGS. 2 and 4 ). A plurality of lighting platforms 1 provides for greater flexibility for the photo spectrum emitted. For example, multiple wavelengths of light and/or increased brightness for one or more of the desired wavelengths may be easily combined by using a plurality of lighting platforms 1 . Thus, one or more arthropod species may be specifically targeted at a time. Further, the replaceable nature of the lighting system allows for the same capture trap to be used to capture one or more target species using one set of wavelengths and then later the same trap can be adjusted to capture a different target species or set of species using a completely different set of wavelength parameters. Additionally, the resistor 5 allows for the brightness to be adjusted to the trapping conditions (e.g. day, night, moon or no moon, etc.) by adjusting the voltage to the LED 7 .
[0043] In some cases, it may be desired for the lighting system to include a second resistor 9 between the positive terminal 3 and the Zener diode 4 such that the second resistor 9 regulates the current to the Zener diode 4 to prevent the Zener diode 4 from prematurely burning out (see FIG. 2 ). In some cases, it may be desired for the lighting system to include a standoff 10 to attach the lighting system to a trap or to separate two or more lighting platforms 1 from each other to prevent an electrical short and/or to place the emitted light at a particular angle and/or direction (see FIG. 4 ). Where a standoff 10 is present it is generally attached to the lighting platform 1 by a bolt 11 or other suitable fastener.
[0044] In one embodiment the supporting member 8 is cylindrical (see FIGS. 1 and 2 ). In another embodiment the supporting member 8 is polygonal, more preferably a polygonal circuit board, and most preferably a polygonal embedded circuit board ( FIGS. 3 and 4 ). An advantage of the polygonal configuration is that at least one LED may be located per slot on one or more sides of the polygon, which provides greater flexibility for emitting multiple light wavelengths and/or levels of brightness. Regardless of its configuration, the supporting member 8 may be made from a variety of materials that include metal, plastic, fiberglass, any combination thereof, or any other suitable material known in the art.
[0045] A preferred configuration for the lighting platform is linear, or planar, so that LEDs and electronics can more easily be optimized and secured to the supporting member. A linear configuration also allows additional layers of LEDs to be added (see dashed box of FIG. 2 ). Many additional levels can be added to create the desired photo spectrum by simply adding more lighting platforms.
[0046] Where the supporting member 8 is a circuit board ( FIGS. 3 and 4 ), electrical current is supplied to terminals 3 and 6 on each embedded circuit board 8 before moving to the embedded circuits 6 and 7 , which allow electrical current to flow around the circuit board to the resistor 5 , Zener diode 4 and LEDs 2 . The resistor 5 controls the brightness of each lighting platform located on a polygonal circuit board 8 by independently regulating the voltage. The resistor 5 and Zener diode 4 are soldered to the circuit board using mounting holes 14 and 15 , respectively. The LEDs 7 are soldered to mounting holes 12 and 13 . Additional LEDs 7 can be added by adding additional sides to the polygon or by adding more layers of polygons (see dashed box in FIG. 4 ).
[0047] A preferred device of this invention has an octagonal printed circuit board containing LEDs on each side to position the LEDs in an evenly arranged horizontal display. Multiple polygonal circuit boards allow for additional lighting platforms and for greater intensity of light to be emitted from a trap.
[0048] In FIGS. 1-4 each lighting platform can have a plurality of sides, each holding a plurality of LEDs 7 . Each LED 7 is independent of the other LEDs in the lighting platform and can be substituted for any viewing angle or wavelength of LED, including ultraviolet and infrared, which are invisible to human eyes.
C. Using Lighting Systems
[0049] The new lighting systems provided by the invention use ultraviolet (UV) light emitting diodes (LEDs) to increase battery life, reduce by-catch, increase trap attractiveness to con-specifics, and improve modularity (i.e. smaller and lighter batteries may be used for portable units as compared to conventional technology). Initial tests indicate that the new lighting systems will last about twelve times longer than comparable UV traps presently on the market. The trap catch composition for traps using the invention is comparable to other UV traps and is about twice as much as for incandescent light traps.
[0050] Further, the modularity of the new lighting systems allow for adjustments to color (wavelength) and LED numbers in each unit including the ability to easily convert between UV and normal light for different trapping conditions. Current traps are essentially restricted to using about 372 nm fluorescent UV light or incandescent white light of fixed intensity or brightness. In contrast, the new lighting systems can independently use any wavelength (color), combination of wavelengths (colors), brightness (intensity), or combinations thereof for each lighting unit.
[0051] The new lighting systems and replacement lighting systems based light traps are important contributions to global health because they can efficiently collect disease-vector surveillance information on major diseases in developing countries and provide a more efficient means of capturing other target arthropods. For example, initial prototypes of the disclosed lighting systems were used for surveillance of sand flies in French Guiana. During a three month period, the traps using the disclosed lighting systems captured over 400 sand flies, which was over 10-fold more than comparable conventional traps.
[0052] A direct comparison of traps is shown below in Table 1. Ultraviolet light was initially used because insects have a highly conserved UV eye pigment (rhodopsin) sensitive to around 360 nm. This visual pigment is 16 times more sensitive to photons of light than the other visual pigments. The fluorescent UV light traps collected about 1.5× as many flies as the traps using the disclosed system (LED UV replacement bulb), but the traps using the new system lasted more than 5× as long and weighed 5× less. Traps using replacement lighting systems were more effective, lasted longer, and weighed less than the incandescent white light traps.
[0000]
TABLE 1
Comparison of three types of trap lighting systems
Weight per
Avg. # of
Current (in
Batteries
Energy used
week per
Light Source
flies/night 1
milliamps) 2
needed
per week
trap
Incandescent
21.5
240 A (~4 trap
4 D-cells (17.2 Amp-hr)
8 batteries
3.2 lbs.
white light bulb
nights)
Fluorescent UV
42
610 A (~1.5
special (20.0 Amp-hr)
4 recharges
8 lbs.
light bulb 3
trap nights)
LED UV
28.25
90 A (~8 trap
4 D-cells (17.2 Amp-hr)
4 batteries
1.6 lbs.
replacement bulb
nights)
1 Four consecutive nights of trapping during the rainy season. The means are compared with non-parametric statistics (rank ordered) because environmental variation is not normally distributed.
2 The typical power arrangement for CDC light traps is a battery pack of four D-cell batteries. The trap nights are the average amount of time a trap continues to function on a battery pack as calculated from field testing. Each set of 4 batteries weighs 1.6 lbs.
3 Does not include the power needed to initiate the fluorescent tube illumination.
[0053] Field research requiring insect traps especially in developing countries is severely limited by the cost and weight of the batteries necessary to run the traps. Consequently, current surveys and surveillance techniques use incandescent white light CDC traps that require 6 volts, four D-cell batteries. The lifespan of these batteries is approximately 4 trap nights. Therefore eight D-cell batteries or 3.2 pounds of batteries are needed per trap per week.
[0054] UV light increases the number of target insects collected in the traps, but UV traps require special 8 pound, 6-volt batteries. The usage duration of these larger batteries is approximately two days before recharging is necessary which requires a power supply be present near the field sites. The LED replacement bulb uses 6.7 and 2.6 times less energy than fluorescent and incandescent bulbs respectively. The reduced power consumption prolongs battery life, decreasing weight and increasing cost effectiveness. Further, the LEDs can be exchanged or added rapidly in the field to change the emitted wavelength (color) and illumination intensity. An additional advantage is that the solid state LEDs are nearly indestructible compared to incandescent bulbs and fluorescent tubes; thus, traps equipped with the disclosed lighting systems are both more rugged and energy efficient.
D. Targeted Arthropods
[0055] Arthropods of interest in this invention include flying insects and terrestrial arthropods that are vectors of disease, such as mosquitoes, including Ochlerotatus sierrensis , vector of heartworm to cats and dogs, Culex spp., Anopheles spp., and Aedes spp., midges, sand flies, black flies, filth flies, tsetse flies, ticks, mites, spiders, lice, bed bugs, kissing bugs, and fleas, as well as, agricultural pests such as lepidopteran species, beetles, and various hemipterans. Diseases, which are either known or suspected to be transmitted by these arthropods, include, but are not limited to, malaria, dengue, filariasis, leishmaniasis, lyme disease, trypanosomiasis, chagas disease, and various encephalitis viruses.
[0056] 1. Insect Vision
[0057] New research into insect vision, physiology, and behavior has allowed for an increased understanding of positive phototaxis. Insect eyes are based on three photo-pigments, similar to human eyes, but insects see ultraviolet, blue, and green lights. Therefore, lights that are visible to humans, such as red light, are not visible to insects. Nocturnal insect eyes are ten times more efficient at capturing photos of light than diurnal insects. The wavelength of light that causes maximum stimulation of the photo-pigments, (λmax) corresponds to the brightest light an insect can visualize. The closer a wavelength light is to the λmax, the brighter the light is to the insect. It is preferred that the selected wavelength(s) of light corresponds to the maximum absorption (λmax) of one or more of the target arthropod species' three visual pigments. Examples of insect spectral sensitivities are provided in FIGS. 1-4 , Table 1, and generally discussed throughout the text of Briscoe and Chittka, “The Evolution of Color Vision in Insects”, Ann. Rev. Entomol. 46: 471-510 (2001), incorporated herein by reference. The wavelength spectra of maximum absorption of interest to the target arthropod species is comprised of photo pigments of wavelengths values in the ranges between about 320-400 nm for UV pigments, about 400-500 nm for blue, and about 500-600 nm for green depending on the arthropod species.
[0058] 2. Attractants
[0059] Insects are inherently attracted to bright lights. Positive phototaxic behavior is usually associated with the search for alimentary resources or potential mates. Sugar resources and blood meals are important for the insect's survival and reproductive needs. These resources have distinct photo spectra such as flowers, honeydew, and fruits.
[0060] Blood meals may come from mammals, lizards, and birds, which in addition to having a color, produce infrared light or heat. Potential mates for insects can be distinctive patterns on the insect or external cues such as mating leks or swarming cues. The individual insects are attracted to these areas where they compete for copulations. By mimicking the visual cues of resources and mating areas, insects will be drawn to the traps in greater number.
DEFINITIONS
[0061] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs at the time of filing.
[0062] Herein, “LED” refers to light emitting diode technology, the term is inclusive of both bulbs and chips of solid state design.
[0063] A “Zener” or “Zener diode” is a type of diode that permits current to flow in the forward direction like a normal diode, but not in the reverse direction.
[0064] In this invention, “lighting platform” refers to an arrangement of one or more LEDs, which will illuminate an area with a desired color and intensity of ultraviolet, visible and/or infrared light, and an electrical circuit. Preferably, a lighting platform comprises a plurality of LEDs that may emit similar or different wavelengths of light.
[0065] Unless otherwise specified, “insect” is used generically to refer to both insects and other arthropods (spiders, mites, centipedes, etc.) and is not limited strictly to hexapods.
[0066] “Polygonal embedded circuit board” is a preferred configuration for a supporting member of a lighting platform that can have a variable number of sides depending on the number of LED bulbs or chips used on the lighting platform.
[0067] The “viewing angle” (“viewing window”, “solid angle”, and similar terms) relates to the shape and size of the light being emitted by a single LED. The larger the angle the more diffuse the light. In general, the viewing angle is a conical shape of light projected from a LED.
[0068] A “cylindrical supporting member” refers to a cylindrical structure that rigidly holds the LEDs at fixed distances apart and at specific angles. Such structures are generally made from plastic, metal, fiberglass, or any combination thereof, but it may be comprised of other suitable materials.
[0069] A “lek” is a gathering of males, of certain animal species, for the purposes of competitive mating display.
[0070] A “standoff” is used in mechanics and electronics to separate two parts from one another. Standoffs can be many shapes and sizes and made of many different materials. Insulating standoffs may keep two parts interacting, thereby preventing an electronic short.
[0071] An “electrical network” is an interconnection of electrical elements such as resistors, inductors, capacitors, transmission lines, voltage sources, current sources, and switches. An “electrical circuit” is a network that has a closed loop, giving a return path for the current. An electrical circuit includes a positive terminal and a negative terminal.
[0072] “Zone of attraction” refers to the three dimensional area into which light is emitted by a trap. This area may be irregularly or regularly shaped and vary in cubic size. Light emitted into this area may be attractive to certain arthropods and unattractive, or even repellant, to other species of arthropods. As such, “zone of attraction” is inclusive of areas of repellence unless otherwise specified.
[0073] “Capture trap” or “trap” is inclusive of all traps used to collect arthropods, whether the arthropods are collected alive or killed by the trap (e.g. a bug zapper).
[0074] “Variable angle” means the viewing window or the angle at which light comes out of an LED bulb. This viewing window can vary from as small as a half to a quarter of a degree and produces a very narrow beam of light, such as is commonly used in laser pointers. In contrast, an LED chip has a 180 degree angle of emission (also known as solid angle). The more diffuse the angle the more dissipated the power of the LED. Thus, an LED chip generally has a more diffuse angle of emission than a comparable LED bulb with an angle of emission that is less than 180 degrees.
EXAMPLES
[0075] The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventors to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.
Example 1
Basic Lighting Systems
[0076] A lighting system was made to replace existing incandescent bulbs in Center for Disease Control (CDC) light traps for disease and insect surveillance. The system was made using from four Toyoda-Gosei UV LEDs wired in parallel with 30 ohm resistors to regulate the current in an electrical circuit and attached to a supporting member, UV resistant tubing.
[0077] The LEDs face the four cardinal points and are held in place by UV resistant tubing. The tubing allows the four LEDs to be removed and replaced as a whole by changing the entire unit or lighting platform. The tubing and individual resistors allows for additional wavelengths or LEDs to simply be added to the existing tubing or alternative units can be used. Additionally, the LEDs are protected by an added 6 volt Zener diode placed within the electrical circuit and a 200 mA fuse to protect the other electronics in the trap.
Example 2
Maximizing Brightness to Attract Terrestrial Pests to an Irregularly Shaped Area
[0078] Grain beetles have a photopigment with maximum stimulation between 350-370 nm. A decagonal lighting system is designed that contains five 350 nm LEDs with a viewing angle of 60 degrees and five 370 nm LEDs with a viewing angle of 30 degrees. The LEDs are alternated within the ten slots, one on each side of the polygon. The 350 nm light, therefore, illuminates a conical area completely surrounding the trap but only projects a few meters (<20 m) while the narrower angled 370 nm bulbs project a greater distance (at least 50 m) to attract beetles. The combination of lights, frequencies, and angles maximizes the capture area, attraction of the beetles of interest, and the brightness of the trap. The terrestrial beetles that inhabit grain silos will be attracted to the lights and be removed from the grain preventing spoilage and insect damage.
[0079] Optionally, additional lighting platforms may be added to the lighting system to increase light intensity. Such additional lighting platforms may be desired to compensate for ambient lighting conditions. For traps that are powered by non-portable power supplies or batteries, the increased power consumption by additional lighting platforms is unlikely to be a constraint on use. But, the increased power consumption, or weight by additional batteries, may be considered for traps with portable power supplies.
Example 3
A Cylindrical Replacement Lighting System
[0080] Sand flies are known to be attracted to flowers for sugar meals. Four ultraviolet 370 nm LEDs with a 90 degree viewing angle can be combined with six blue/green 500 nm LEDs with viewing angles of 60 degrees. This pattern simulates flowers on plants and is much brighter than natural flowers to the insect's photo-pigments, and therefore, appears as a giant flower.
[0081] Using a cylindrical supporting member to support a lighting platform yields a structure that is similar in shape to a conventional incandescent or fluorescent tube light. The cylindrical nature of the lighting system allows it to fit within the incandescent light mount on CDC-light traps or similar conventional traps and replace the incandescent or fluorescent light. The lighting system essentially acts as a replacement bulb and is inserted into the trap in a similar manner.
[0082] All of the compositions and methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. Those skilled in the art will appreciate that variations from the specific embodiments disclosed above are contemplated by the invention. The invention should not be restricted to the above embodiments, but should be measured by the following claims.
REFERENCES
[0083] The following references, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference.
U.S. Pat. No. 7,191,560 U.S. Pat. No. 7,281,350 U.S. Pat. No. 7,181,885 U.S. Pat. No. 6,662,489 U.S. Pat. No. 7,073,287 U.S. Pat. No. 6,965,205 U.S. Pat. No. 6,840,003 U.S. Pat. No. 6,199,316 U.S. Patent Appl. Pub. No. 2007/0068068 U.S. Patent Appl. Pub. No. 2007/0056208 Briscoe and Chittka, “The Evolution of Color Vision in Insects”, Ann. Rev. Entomol. 46: 471-510 (2001) | 1a
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BACKGROUND OF THE INVENTION
[0001] Fear of needles, belonephobia, is a very real and common condition. And even absent the more extreme condition of belonephobia, few people look forward to obtaining a shot. With modern medicine becoming more and more reliant upon the use of needles for blood tests and the administration of drugs, however, the fear of needles is becoming an increasingly important issue for health care professionals and their patients. Extreme or irrational fear of needles can keep people from receiving the medical treatment they need, which may result in serious, sometimes irreversible, damage. Topical administration of a local anesthetic agent, however, can be accomplished without needles to anesthetize the intended area for subsequent procedures. Accordingly, there is a need for a safe and effective local anesthetic composition that can be applied topically to ease pain during dermal procedures, such as venipuncture, intravenous cannulation, punch biopsy and other small incisions, vaccination, and circumcision.
[0002] Anesthesia is a partial or complete loss of sensation or feeling induced by the administration of various substances. There are many different types of anesthesia but they are usually placed into one of three groups. These groups are general anesthesia, local anesthesia, and spinal anesthesia. General anesthetics act primarily on the brain, rendering people both insensible to pain and unconscious. Local anesthetics affect only part of the body and the patient remains conscious. Local anesthetics are usually administered through a gel or cream on the surface of the skin or mucosa but can also be injected underneath the skin. When local anesthetics are applied directly to the skin or mucosa they are also referred to as topical anesthetics. Topical anesthetics are absorbed through the skin or mucosa so that they can interact with nerve endings within the dermis. Once absorbed, topical anesthetics cause a depolarization of sensory nerves within the outer dernis, which temporarily deactivates these nerves. While the anesthetic effect is present, the deactivated sensory nerves do not transmit impulses to the brain. Painful sensations within the anesthetized area are thus temporarily decreased or eliminated.
[0003] A number of topical anesthetic compositions with acceptably low concentrations of a local anesthetic agent are known to produce satisfactory results when applied specifically to mucosa. These topical anesthetic compositions typically contain local anesthetic agents such as lidocaine, which are readily absorbed from the gastrointestinal tract, from mucosa, and through damaged skin. When topically applied directly to the mucosa, these topical anesthetic compositions act rapidly and the anesthetic effects last over the duration of intended use. Absorption of the local anesthetic agent through intact skin, however, is generally poor and thus the efficacy of these topical anesthetic compositions in intact skin applications has been much less satisfactory.
[0004] Eutectic compounds have been designed to enhance membrane transport of drugs through improved solubility and absorption. A eutectic mixture of local anesthetics (EMLA), when applied topically, penetrates intact skin after an application period of one to two hours. For example, EMLA cream (Astra Pharmaceuticals, Inc., Westboro, Mass.), (U.S. Pat. No. 4,562,060 and U.S. Pat. No. 4,529,601) is a topical anesthetic product currently marketed in many countries, including the United States. Because EMLA cream contains a relatively high concentration of local anesthetic in its oil phase, it exhibits improved efficacy on intact skin compared with other conventional topical anesthetic formulations, which are effective only on mucosa.
[0005] A disadvantage of EMLA cream, however, includes the mess and inconvenience of having to apply the cream one to two hours before the anesthetic effects are realized. There also exists variability in the in the amount of anesthetic agent imparted to the intended area. Further, EMLA cream contains prilocalne, which presents the risk of methemoglobinemia, a serious condition characterized by the ferric form of hemoglobin with impaired oxygen-carrying capacity that results upon metabolization of prilocalne (B. Jakobson et al., Acta Anaesthesialogica Scandinavica 29: 453-455 (1985)). Therefore, the use of EMLA in young children has been severely restricted.
[0006] The anesthetic agent lidocaine is a widely used local anesthetic agent. Due to low permeability of lidocaine through the stratum corneum, however, the efficacy of lidocaine alone for topical application of local anesthetic agents through intact skin has been extremely disappointing to date. Conventional lidocaine creams may be readily prepared by simply dissolving lidocaine in a suitable pharmaceutical oil and emulsifying the components, but these creams can not effectively deliver lidocaine for transdermal anesthesia on intact skin. For example, in medical facilities such as hospitals, a topical anesthetic is sometimes prepared and used in accordance with a method in which an active anesthetic ingredient is blended with, for example, an agent of ointment, cream, or gel to prepare a clinically formulated topical anesthetic. The topical anesthetic is tightly sealed upon administration with an extremely air-tight resin film such as polyvinylidene chloride film. This method is referred to as the “ODT Method”; (Hifu, 34 (2), 237-242 (1992)). It takes about two hours to obtain a sufficient anesthetic effect after application of the cream using the ODT method. Efficacy can only be achieved when the concentration of lidocaine in the cream or gel for topical application is unacceptably high (e.g., greater than about 30% by weight). Such high concentrations of lidocaine pose a risk of systemic toxicity. Limited by the intrinsic solubility of lidocaine in pharmaceutical oils, lidocaine concentration in the oil phase of conventional creams cannot readily reach the concentration that is necessary for effective transdermal delivery.
[0007] Some of the clinically prepared local anesthetic compositions also have poor stability, and hence it is necessary to prepare the local anesthetic compositions just before they are to be used. This can make the local anesthetic compositions inconvenient to use. Further, some of the topical anesthetics are administered using a tape-shaped medicament, which is unsuitable to anesthetize a broad skin surface.
[0008] U.S. Pat. No. 6,429,228 (Inagi et al.) reports a local anesthetic gel for topical application having an improved efficacy. Effectiveness of the local anesthetic gel was reported as being realized 30 minutes after application on the skin of the animal being tested. The reported local anesthetic gel is formulated using an active ingredient selected from lidocaine, prilocalne, and pharmaceutically acceptable salts thereof, a fatty acid penetration enhancer having 8-18 carbon atoms such as caprylic acid and oleic acid, ethanol and/or isopropyl alcohol and water. The gel form of the local anesthetic, however, remains inconvenient to use and apply and the efficacy, while improved over EMLA cream, still requires the user to wait for 30 minutes.
[0009] Therefore, there exists a need for a topical anesthetic composition that provides fast, convenient and reliable delivery of anesthesia for minor interventions on intact skin, such as blood sampling and administration of medication by injection without the risk of systemic toxicity. Further, a topical anesthetic composition containing lidocaine but little or no prilocalne would have a significant clinical advantage over EMLA and would also expand the use of topical anesthetic compositions in children and particularly in infants and newborns.
SUMMARY OF THE INVENTION
[0010] The present invention includes a topical anesthetic composition having one or more local anesthetic agents, a penetration enhancer, and an anhydrous volatile solvent combined to provide a liquid homogenous solution. The topical anesthetic composition can be sprayed onto intact skin and can be absorbed percutaneously with greater efficacy in order to shorten the time needed for the anesthesia to take effect.
[0011] In one embodiment of the present invention, the topical anesthetic composition contains a local anesthetic agent in a concentration of from about 5 to 50 wt %, a penetration enhancer in a concentration of from about 1 to 30 wt %, an anhydrous volatile solvent in a concentration of from about 10 to 94 wt % and from about 0.01 to 20 wt % water. In an alternative embodiment of the present invention, the local anesthetic agent is lidocaine, the penetration enhancer is a fatty acid ester such as isopropyl palmitate, and the anhydrous volatile solvent is ethanol.
[0012] The amount of water is limited to minimize both occlusion and the possibility of the local anesthetic agent and/or the penetration enhancer precipitating out of solution. Therefore, in an embodiment of the present invention, the concentration of water is less than about 10 wt %. In yet another embodiment of the present invention the concentration of water is less than about 5 wt %. In yet another embodiment of the present invention, the concentration of water is 0.01 wt %.
[0013] The topical anesthetic composition of the present invention is in the form of a liquid homogenous solution that can be sprayed directly onto the exposed intact skin surface, to anesthetize the intact skin surface and ease the pain during dermal procedures, such as venipuncture, intravenous cannulation, punch biopsy and other small incisions, vaccination, and circumcision. In an alternative embodiment, the topical anesthetic composition can also be sprayed onto mucosa.
DETAILED DESCRIPTION OF THE INVENTION
[0014] A topical anesthetic composition in the form of a liquid homogeneous solution for percutaneous administration of an anesthetic having improved efficacy, convenience, and reliability and a method of anesthetizing tissue such as intact skin and mucosa are provided. In an embodiment of the present invention, the topical anesthetic composition contains a local anesthetic agent, a penetration enhancer, an anhydrous volatile solvent and water.
[0015] The term “mammal” as used herein is intended to include all warm-blooded mammals, preferably humans.
[0016] The term “mucosa” as used herein means any moist anatomical membrane or surface on a mammal such as oral, buccal, vaginal, rectal, nasal or ophthamalic surfaces.
[0017] The term “topical” or “topically” is used herein in its conventional meaning as referring to direct contact with an anatomical site or surface area on a mammal including skin, mucosa, teeth, and nails.
[0018] The term “local anesthetic agent” as used herein means an anesthetic agent that is absorbed through the skin or mucosa to interact with nerve endings within the dermis but has very little or none, to minimal, systemic effect and is not intended for systemic use.
[0019] The term “therapeutically effective” as used herein means an amount of local anesthetic agent sufficient to achieve the desired local effect or result but no or minimal systemic effect, when applied topically, over the duration of intended use.
[0020] The term “excipient” as used herein refers to an inert substance combined with an active agent such as a local anesthetic agent or penetration enhancer to prepare a convenient dosage form and vehicle for delivering the active agent.
[0021] The term “efficacy” as used herein refers to the effectiveness of the topical anesthetic composition measured by the rate at which the anesthetic effects are observed after application of the topical anesthetic composition to the intended surface.
[0022] Local Anesthetic Agent
[0023] In one embodiment of the present invention, the local anesthetic agents are provided in base form and are selected from the group of local anesthetic agents such as lidocaine (also known as lignocaine), tetracaine, benzocaine, procaine, mepivacaine, bupivacaine, etidocaine, or cocaine. The local anesthetic agent can be a single agent or a combination of agents provided the combination provides an efficacy equivalent to pure lidocaine.
[0024] Lidocaine is 2-diethylamino-N-[2,6-dimethylphenyl]acetamide and is available under the tradename XYLOCAINE. Tetracaine is 2-dimethylaminoethyl-ethyl-p-butylaminobenzoate and is available under the tradename PONTOCAINE (Abbott Laboratories, Limited, Abbott Park, Ill.). Prilocalne is 2-propylamino-N-(2-tolyl)propionamide and is available under the tradename CITANEST (Vidal). Procaine is 2-diethylaminoethyl-p-aminobenzoate and is available under the tradename of AMINOCAINE. Mepivacaine is N-(2,6-Dimethylphenyl)-1-methyl-2-piperidinecarboxamide and is available under the tradename CARBOCAINE (Vidal). Benzocaine is 4-aminobenzoic acid ethyl ester and is available under the tradename AMERICAINE. Bupivacaine is 1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide and is available under the tradename MARCAINE (Vidal). Etidocaine is 2-ethylpropylamino-2,6-butyroxylidide and is available under the tradename DURANEST (Astra Zeneca, London, United Kingdom).
[0025] In accordance with one aspect of the present invention, the local anesthetic agent is lidocaine. Lidocaine works by blocking the conduction of signals along nerve fibers. Lidocaine is more selective for the smaller fibers that cause pain so its use can prevent transmission of pain signals but retain feeling such as coarse touch and temperature, which are transmitted by the larger fibers.
[0026] The amount of local anesthetic agent to be incorporated in the topical anesthetic composition will vary depending on the particular anesthetic agent selected, the desired therapeutic effect, and the duration of intended use. In one embodiment of the present invention, the concentration of the local anesthetic agent is from about 5 wt % to 50 wt % of the total composition to deliver an effective dosage amount of about 30.0 mg/spray of the local anesthetic agent where a spray pump is held 1 inch from the intended surface to cover an area of 1 in 2 . In another embodiment of the present invention, the spray pump is held 2 inches from the intended surface to cover an area of 2 in 2 and deliver an effective amount of about 15.0 mg/spray of the local anesthetic agent. In yet another embodiment, the concentration of the local anesthetic agent is about 35 wt %.
[0027] Penetration Enhancer
[0028] Skin differs from soft and moist mucosa in that it contains a dense stratum corneum of keratinized cells, as well as the epidermal cell layer. Both act to restrain the percutaneous penetration of topically applied substances. Additionally, the skin has a superficial, cutaneous layer (the horny layer) which consists of flat, scalelike “squames” made up of the fibrous protein keratin.
[0029] Various methods such as use of penetration enhancers, prodrugs and superfluous vehicles, iontophorosis, phonophoresis and thermophoresis have been used to increase skin permeation of local anesthetic agents. In accordance with the present invention, the topical anesthetic composition has been supplemented with one or more penetration enhancers.
[0030] Suitable penetration enhancers have no irritancy or toxicity to the skin, as well as high enhancing effects. The penetration enhancers should also be physiochemically stable and not have pharmacologic effects and preferably should not have a disagreeable smell, color or taste.
[0031] An important criterion for selecting a suitable penetration enhancer is enhanced percutaneous delivery of the local anesthetic agent into the intact skin or mucosa with minimal undesired delivery of the local anesthetic agent through the intact skin or mucosa into the systemic circulation.
[0032] Penetration enhancers are described in detail in Remington's Pharmaceutical Sciences, Vol. 18, Mack Publishing Co., Easton, Pa. (1990), in particular Chapter 87, which is incorporated herein by reference in its entirety. Suitable penetration enhancers of the present invention include fatty acid esters such as isopropyl palmitate, isopropyl myristate, isopropyl laurate, diisopropyl adipate, ester derivatives of capric acid, lauric acid, leucinic acid, and neodecanoic acid including sodium laurate, sodium caprate, cetryl laurate, myristyl lactate, lauryl lactate, methyl laurate, oleic acid esters and oleic acid ester derivatives such as methyl, ethyl, propyl, isopropyl, butyl, vinyl and glycerylmonooleate, and those given in U.S. Pat. No. 5,082,866, particularly dodecyl (N,N-dimethylamino) acetate and dodecyl (N,N-dimethylamino) propionate, sodium oleate, sucrose monooleate, sorbitan esters such as sorbitan monolaurate and sorbitan monooleate, long chain alkyl esters of 2-pyrrolidone, particularly the 1-lauryl, 1-hexyl and 1-(2-ethylhexyl) esters of 2-pyrollidone, dodecyl (N,N-dimethylamino) acetate, dodecyl (N,N-dimethylamino) propionate, and combinations thereof. Additional penetration enhancers of the present invention include mentane, menthone, menthol, terpinene, terpinene, D-terpinene, dipentene, limonene, sefsol-318 (a medium chain glyceride) and combinations thereof.
[0033] Fatty acid esters enhance penetration by increasing lipid fluidity through formation of a solvation shell around polar head groups which then leads to a disruption of lipid packing, permeating into liposomal bilayers, thus increasing fluidity and promoting permeation of drug molecules and increasing diffusivity of the stratum corneum and the partition coefficient between the stratem corneum and vehicle of both drug and solvent.
[0034] The amount and rate of percutaneous absorption is dependent upon the selection of the penetration enhancer, the amount of the penetration enhancer used, and the type and condition of skin or mucosa being treated. The amount and rate of percutaneous absorption can be optimized for a particular condition. In one embodiment of the present invention, the penetration enhancer is isopropyl palmitate. In this particular embodiment, the amount of the penetration enhancer present in the total composition is from about 1 wt % to 30 wt %. In an alternative embodiment, the composition contains isopropyl palmitate in about 10 wt %.
[0035] Anhydrous, Volatile Solvent
[0036] The present invention also contains one or more anhydrous, volatile solvents as a topical excipient. The anhydrous, volatile solvent provides a convenient dosage form and vehicle for delivering the local anesthetic agent and penetration enhancer. Such anhydrous, volatile solvents are those known in the art, and are not toxic, pharmaceutically acceptable substances, preferably liquids, which do not substantially negatively affect the properties or the solubility of the local anesthetic agents at the concentrations used.
[0037] In one embodiment of the present invention, the anhydrous volatile solvent is ethanol. Ethanol, also referred to as ethyl alcohol, anhydrous alcohol or absolute alcohol, contains less than 1% water. In addition to its solvency power, ethanol can be used as a preservative. The evaporative properties of ethanol also impart a cool feel to the skin and provide quick delivery of the local anesthetic agent and penetration enhancer. In one embodiment of the present invention, the topical anesthetic composition is sprayed onto the skin or mucosa. The ethanol quickly evaporates leaving the penetration enhancer and local anesthetic agent to work on the intended tissue.
[0038] Other suitable volatile solvents include alcohols such as 2-propanol, ketones such as acetone, alkyl methyl sulfoxides such as dimethyl sulfoxide, and alkanoic acid esters such as ethyl acetate, n-propyl acetate, isobutyl acetate, n-butyl acetate isobutyl isobutyrate, hexyl acetate, 2-ethylhexyl acetate or butyl acetate, and combinations and mixtures thereof.
[0039] The amount of the solvents used in the present invention depends on the nature and amount of the other components or ingredients. In one embodiment of the present invention, the total amount of solvent used is from about 10 wt % to 94 wt %. In an alternative embodiment of the present invention, the total amount of solvent used is from about 50 to 55 wt %.
[0040] Water
[0041] Water can also be added as a topical excipient to the present invention to provide a convenient dosage form and vehicle for delivering the local anesthetic agent and penetration enhancer. Because water has occlusive properties that would undesirably enhance percutaneous transmission of the local anesthetic agent through the skin or mucosa into the systemic circulation, however, the usage and amount of water in the present invention should be minimized. Greater amounts of water will also cause the local anesthetic agent and/or penetration enhancer to precipitate from the composition.
[0042] In one embodiment of the present invention, the amount of water in the total composition is from about 0.01 to 20 wt %. In another embodiment, the amount of water is about 0.01 wt % of the total composition.
[0043] Alternatively, the topical anesthetic composition contains less than about 10 wt % water. In another embodiment of the present invention, the topical anesthetic composition contains less than about 5 wt % water.
[0044] Preparation of the Topical Anesthetic Composition
[0045] The topical anesthetic composition of the present invention may be prepared using ordinary production methods. In one embodiment, the local anesthetic agent, penetration enhancer and solvent are introduced into a standard preparation vessel and mixed to form a homogeneous solution. In an alternative embodiment, water is also added to the preparation vessel.
[0046] The solution can then be transferred to a suitable packaging container. Suitable packaging containers include a 15 ml polyethylene terephthalate (PET) cartridge with a 20 mm crimp, an 8 ml cartridge with a 13 mm crimp, and 8 ml glass cartridge with an 13 mm crimp, an 8 ml aluminum cartridge with a 13 mm crimp or an 30 ml aluminum tube cartridge with a 20 mm crimp.
[0047] A suitable spray device, such as a spray pump with an appropriately sized nozzle, capable of spraying the homogenous solution onto the intended surface can be attached to the packaging container. Spray pumps capable of delivering a constant and steady stream of the topical anesthetic composition without clogging can be used in the present invention. Examples of suitable pump sprayers include those available from Emsar S.p.A. such as the Emsar 32 MSL fragrance and crimp pump sprayer (Emsar, Chieti, Italy) and the Tenex pump sprayer (Bespak, Gary, N.C.). Both pump sprayers have a 70/130 microliter (mcl) capacity and deliver 80 to 120 mg per spray.
[0048] Application and Delivery of the Topical Anesthetic Composition
[0049] In one embodiment of the present invention, local anesthesia is obtained by topical application of the topical anesthetic composition onthe intended skin surface. Prior to application of the topical anesthetic composition, the intended surface should be cleansed with an appropriate solvent, detergent or by abrasive means. In one embodiment of the present invention, the intended surface is swabbed with an appropriate alcohol solution such as commercially available 2-propanol (also referred to as isopropyl alcohol) or ethanol. The intended surface can also be prepared using soap and water.
[0050] The topical anesthetic composition is a homogeneous liquid solution and therefore the topical anesthetic composition can be sprayed onto the intended skin surface using a suitable pump sprayer. The term spraying, as used herein, refers to dispersing the topical anesthetic composition onto an intended surface by propelling the topical anesthetic composition in a stream of droplets. The intended surface can be skin, either intact or damaged, or mucosa. The pump sprayer delivers an effective dosage amount of about 30 mg/in 2 of the local anesthetic agent where the pump sprayer is held about 1 inch from the intended surface. Alternatively, the pump sprayer delivers an effective dosage amount of about 15 mg/in 2 where the pump sprayer is held about 2 inches from the intended surface. Efficacy of the topical anesthetic composition using this application method is from about 3 to 15 minutes. In an alternative embodiment, the efficacy of the topical anesthetic composition using this application method is from about 5 to 10 minutes. The duration of the effect is sustained for about 30 minutes. In an alternative embodiment, the duration of the effect is sustained for from about 10 to 12 minutes.
[0051] Examples of procedures that can be perfommed on skin or mucosa that can be anesthetized according to the present invention include needle insertion, circumcision, incision, punch biopsy, nevi excision, dental work, toothache and relief of teething pain in infants and the like.
EXAMPLES
[0052]
EXAMPLE 1
Topical anesthetic composition
Local Anesthetic Agent:
Lidocaine Base available from
Hawkins, Inc., Minneapolis, MN
Penetration Enhancer:
Isopropyl Palmitate available
from Cognis, Cincinnati, OH
Anhydrous Volatile Solvent:
SDA-40B Ethanol available
from Aaper Alcohol,
Shelbyville, KY
SDA-39B Ethanol available
from Aaper Alcohol
190 Ethanol available from
Aaper Alcohol
200 Ethanol available from
Aaper Alcohol
Example 1
Topical Anesthetic Compositions
[0053]
Composition
(wt % of total)
Component
A
B
C
D
E
F
G
Solvent
SDA-40B Ethanol
50.0
60.0
(Excipient)
SDA-39C Ethanol
50.0
55.0
190 Ethanol
50.0
55.0
200 Ethanol
50.0
Anesthetic
Lidocaine Base
35.0
35.0
35.0
35.0
35.0
35.0
35.0
Agent
Penetration
Isopropyl
10.0
10.0
10.0
10.0
10.0
5.0
5.0
Ehanhancer
Palmitate
Water
Water
5.0
5.0
5.0
5.0
5.0
(Excipient)
Total
100.0
100.0
100.0
100.0
100.0
100.0
100.0
Example 2
Performance Results
[0054] Two sprays of Composition A were applied to intact skin on the back of the left hand to deliver 29.4 mg of lidocaine base.
[0055] A skin stick test was conducted five minutes after application of Composition A. Ten sticks were performed on intact skin on the back of the left hand using a syringe with a 28G needle. No pain was felt during the first nine sticks in the treated area where the Composition A had been applied. Only a slight sensation of pressure was observed. The tenth stick was performed outside of the treated area and pain was felt as the needle penetrated the untreated skin.
[0056] The skin stick test was repeated 30 minutes after application of Composition A. This time, five sticks were performed on intact skin on the back on the left hand using a syringe with a 28G needle. No pain was felt in the treated area where the Composition A had been applied.
[0057] A week later, a second skin stick test was conducted. Two sprays of Composition A were applied to intact skin on the back of the left hand to deliver 29.4 mg of lidocaine base.
[0058] A skin stick test was conducted three minutes after application of Composition A. No pain was felt in the treated area.
[0059] The skin stick test was repeated for Compositions B, C, and D. Each of the Compositions produced the same results as those observed for Composition A.
[0060] The skin stick test was also repeated for Compositions F and G. A skin stick test was conducted ten minutes after application of Composition F and G. No pain was felt in the treated area for either Composition F or G.
[0061] Although the present invention has been described with reference to specific embodiments. Workers skilled in the art, however, will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention. In addition, the invention is not to be taken as limited to all of the details thereof as modifications and variations thereof may be made without departing from the spirit or scope of the invention. | 1a
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BACKGROUND OF THE INVENTION
[0001] This invention relates generally to pumps, and more particularly to centrifugal pumps used in medical applications.
[0002] It is known to use centrifugal pumps as cardiac assist devices, also known as left or right ventricular assist devices (“LVAD” or “RVAD”). In such applications, the pump is implanted in the patient along with a power source and a control system. Alternatively, the power source and control system may be located externally.
[0003] A centrifugal pump includes a rotating impeller contained in a housing which defines an inlet, and an annular chamber which surrounds the impeller, which is commonly referred to as a “volute”. Fluid flow enters the impeller near its center and exits from the periphery of the impeller. The flow exiting the impeller is collected in the volute and channeled to an outlet. Conventional centrifugal pump design places the volute section in axial alignment with the outside diameter of the impeller. This results in a very short fluid residence time in the impeller and volute, and a greater residence time of recirculating fluid in the more remote sections of the pump.
[0004] When used as a blood pump for a ventricular assist system, extended residence time of blood within a pump can cause thrombus (clot) formation, and hemolysis (damage of red blood cells), both of which are undesirable.
BRIEF SUMMARY OF THE INVENTION
[0005] These and other shortcomings of the prior art are addressed by the present invention, which provides a centrifugal pump that minimizes residence time of fluids therein.
[0006] According to one aspect of the invention, a pump includes: (a) an elongated pump housing having first and second ends; (b) a primary impeller mounted in the housing for rotation about an axis, the impeller comprising a plurality of vanes whose outer tips define an impeller plane; (c) an inlet disposed in fluid communication with the primary impeller; and (d) an annular volute housing communicating with the primary impeller and with an outlet, where the volute housing is axially offset from the impeller plane.
[0007] According to another aspect of the invention, a cardiac assist device includes: (a) an elongated housing having first and second ends; (b) a primary impeller mounted in the housing for rotation about an axis, the impeller defining an impeller plane; (c) an inlet disposed in fluid communication with the primary impeller; and (d) an annular volute housing communicating with the primary impeller and with an outlet, where the volute housing is axially spaced away the impeller plane. The housing, the primary impeller, the inlet, and the volute housing are constructed from biologically compatible materials.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] The invention may be best understood by reference to the following description taken in conjunction with the accompanying drawing figures in which:
[0009] FIG. 1 is a side view of a centrifugal pump constructed according to an aspect of the present invention;
[0010] FIG. 2 is a cross-sectional view of the centrifugal pump of FIG. 1 ; and
[0011] FIG. 3 is a cross-sectional view of a prior art centrifugal pump.
DETAILED DESCRIPTION OF THE INVENTION
[0012] Referring to the drawings wherein identical reference numerals denote the same elements throughout the various views, FIGS. 1 and 2 depict a centrifugal pump 10 of the type used to pump blood or similar products. The pump 10 includes a pump housing 12 with opposed first and second ends 14 and 16 , and a central axis “A”.
[0013] In the illustrated example the pump housing 12 is split into a body 18 and a separate cover plate 20 . The cover plate 20 closes off the second end 16 and may be secured to the body 18 by one or more fasteners, for example.
[0014] A central portion of the pump housing 12 is generally cylindrical. The first end 14 of the pump housing 12 defines a centrally-located, axially-aligned inlet 22 of a conventional profile with a throat 24 and a generally conical portion 26 .
[0015] A stator housing 28 , which may be integral with the cover plate 20 , extends from the cover plate 20 into the center of the pump housing 12 . The distal end of the stator housing 28 terminates in a conical surface 30 . An electrical stator 32 comprising a plurality of coil windings is contained in the interior of the stator housing 28 . A cable 34 which penetrates the cover plate 20 provides electrical connections for power, control, and sensing functions to the stator 32 .
[0016] A rotor 36 is disposed in the pump housing 12 , surrounding the stator housing 28 . The rotor 36 is generally cylindrical with first and second ends 38 and 40 corresponding to the first and second ends 14 and 16 of the pump housing 12 . The rotor 36 includes a primary impeller 41 at its first end 38 which comprises an annular array of vanes located between the inlet 22 and the conical surface 30 . The outer tips of the vanes of the primary impeller 41 lie generally within an impeller plane, which is shown schematically at “P” in FIG. 2 . One or more permanent magnets 42 are disposed in an annular array within the walls of the rotor 36 . A secondary impeller 44 comprising an annular array of vanes is located at the second end 40 of the rotor 36 . The rotor 36 and the stator 32 operate as a brushless DC motor through the application of varying electrical currents to the stator 32 through the cable 34 , in a known manner.
[0017] All of the portions of the pump 10 which will come into contact with blood or tissue, including the pump housing 12 and the rotor 36 , are constructed from known biologically compatible materials such as titanium, medical grade polymers, and the like.
[0018] Together, the stator housing 28 and the rotor 36 are configured so as to operate as a hydrodynamic bearing for the rotor 36 in operation. Specifically, the secondary impeller 44 causes a small portion of the blood flowing through the primary impeller 41 to flow axially to the cover plate 20 , radially inward through the secondary impeller 44 , and axially towards the primary impeller 41 between the rotor 36 and the stator housing 28 . This bearing and recirculation function is explained in more detail in U.S. Pat. No. 7,189,260 to Horvath, et al.
[0019] The pump housing 12 includes an annular passage which collects the flow exiting the primary impeller 41 and channels it to a single outlet 46 (see FIG. 1 ). This passage is referred to as a “volute” or volute housing 48 . As shown in FIG. 2 , the axial position of the volute housing 48 is substantially offset away from the plane P of the primary impeller 41 and towards the cover plate 20 . The actual offset distance between the impeller plane P and the midplane “V” of the volute housing 48 , denoted “D”, is not a critical dimension, however generally the volute housing 48 is offset as much as possible towards the cover plate 20 within the physical constraints of the pump housing 12 and the walls of the volute housing 48 . In the illustrated example, the midplane V of the volute housing 48 is located approximately halfway between the impeller plane P and the second end 16 of the pump housing 12 .
[0020] This positioning of the volute housing 48 is in substantial contrast to a conventional centrifugal pump design. For Example, FIG. 3 illustrates a prior art centrifugal pump 110 having a pump housing 112 , a primary impeller 141 , and a volute housing 148 . It can be seen that the volute housing 148 and the outer vane tips of the primary impeller 141 line substantially in a single plane, denoted “P′”.
[0021] Surprisingly, it has been found that the offset position of the volute housing 48 greatly decreases fluid residence time during operation of the pump 10 . By “residence time” it is meant the duration that a specific, identifiable volume of fluid remains within the pump 10 , from the time it enters the inlet 22 until it finally exits the outlet 46 . Residence time is not necessarily related to the average mass or volume flow rate. For example, it has been found that the prior art pump 110 may exhibit a relatively long residence time. Flow visualization has revealed that peak residence time in the pump 10 is approximately cut in half as compared to the prior art pump 110 .
[0022] Despite the unconventional placement, overall pump performance is maintained across its operating range. Mechanical efficiency of the pump 10 is also virtually unchanged by moving the volute housing 48 .
[0023] The reduction in residence time is especially advantageous when using the pump 10 as an implantable blood pump for a ventricular assist system, e.g. an LVAD or RVAD, in which it is desired to minimize residence time of blood to avoid thrombus (clot) formation, and hemolysis (damage of red blood cells). However, the concepts described herein are also useful for other fluid pumping applications where the working fluid is sensitive to shear and mechanical damage, such as whole blood, plasma, serum, or other therapeutic fluids containing complex molecules.
[0024] The foregoing has described a centrifugal pump. While specific embodiments of the present invention have been described, it will be apparent to those skilled in the art that various modifications thereto can be made without departing from the spirit and scope of the invention. Accordingly, the foregoing description of the preferred embodiment of the invention and the best mode for practicing the invention are provided for the purpose of illustration only and not for the purpose of limitation. | 1a
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FIELD OF THE INVENTION
This invention relates to apparatus for producing a spray of droplets of a liquid.
BACKGROUND OF THE INVENTION
Electrostatic spraying apparatus is described in British patent specification No. 1,569,707, which apparatus comprises a spray head having a conducting or semiconducting surface; means for electrically charging the sprayhead surface to a potential of the order of 1-20 kilovolts; means for delivering spray liquid to the surface; a field-intensifying electrode mounted adjacent to the surface; and means for connecting the field-intensifying electrode to earth, the electrode being so sited relative to the surface that when the surface is charged, the electrostatic field thereat causes liquid thereon to atomise without substantial corona discharge to form electrically charged particles which are projected past the electrode.
In use of such apparatus, as the liquid leaves the surface, it is or becomes charged due to the voltage applied to the surface. The charge produces a repulsive force within the liquid, which overcomes the surface tension thereof causing the liquid to form into one or more cones, sometimes called Taylor cones, dependent on the configuration of the surface. A ligament of liquid is repelled from the tip of the or each cone. The ligament then breaks up into droplets.
The size of the droplets in the spray is distributed over a narrow range compared to other sprayers. The size of the droplets which is obtained depends on the resistivity and the viscosity of the liquid to be sprayed, on the electrical field strength at the spray head, and on the flow rate of the liquid through the spray head. The presence of the field-intensifying electrode adjacent the surface defines the electric field largely independent of the distance of the sprayhead from the target. Therefore the droplet size is largely independent of the distance from the target and can be defined by adjusting the resistivity and the viscosity of the liquid and the voltage applied to the spray head.
The production of a spray of droplets having a narrow size range can be very useful. For example the behaviour of the droplets will be more uniform if the range of sizes is narrow. There are, however, applications when the fact that the droplets are charged is unwanted. British patent specification No. 2,018,627B describes a system for producing a spray which is at least partially discharged. To do this an earthed spike is introduced near the sprayhead. In use an ionic discharge is induced from the spike which discharges the spray at least partially.
A particular application in which it would be useful to produce a non-charged spray of droplets having a narrow distribution of size, is in inhalers to administer drugs to a patient, for example for the treatment of asthma, bronchitis and emphysema. Owing to the fine tubular structure in the lungs the depth to which a particular droplet will penetrate the lungs depends on the size of the droplets. Droplets of the order of 5 microns will reach only the upper respiratory tract, which is quite satisfactory for the treatment of asthma, but for the treatment of emphysema, it is necessary for the droplets to reach the alveoli in the lower respiratory tract, and for this purpose, droplets in the range 0.5 to 2 microns are required. Current state of the art aerosol inhalers produce a wide spectrum of droplet sizes extending up to 37 microns. Current state of the art nebulizers will produce droplets of the required small size, but only in conjunction with droplets of larger sizes, so that with current nebulizers, only a proportion of an anti emphysema drug will reach the required site of action in the alveoli.
Naturally, it is desired that the spray produced be completely discharged for such an application. Charged spray would deposit in the mouth or throat, which would be unpleasant, and would not be inhaled.
In practice, we found it difficult to discharge all of the droplets produced. It was possible, using an earthed needle to discharge a large part of the spray. However, when it was attempted to discharge all the droplets, the ionic discharge (or corona) from the needle reached the cone. This discharged the cone itself which depleted or destroyed the formation of a ligament and thus of a spray.
SUMMARY OF THE INVENTION
This problem is overcome in apparatus for producing a spray of droplets of a liquid, in accordance with the invention, which apparatus comprises: a spraying edge; a shield electrode spaced from the spraying edge and having an orifice through which liquid sprayed from the edge can issue; means for producing a charge to a high potential of one polarity relative to the shield electrode in liquid at the spraying edge, to define an electric field between the edge and the shield electrode sufficient to cause the liquid to issue from the edge as at least one cone from which electrostatic forces repel through the orifice a ligament which breaks up into a spray of charged droplets; a sharp discharge electrode; means for charging the discharge electrode to a high potential of the other polarity relative to the shield electrode, such as to produce a corona to discharge the spray, the shield electrode being of sufficient overall dimensions and having a sufficiently small orifice to shield the edge and the cone of liquid from the corona.
As an example, the spraying edge may be connected to a positive output of a high voltage supply, the shield electrode to earth and the discharge electrode to a negative output. In one alternative, the spraying edge may be connected to a positive high voltage output of the supply, the discharge electrode to a lower voltage output and the shield electrode to an intermediate voltage output.
To have the desired shielding effect, the orifice in the shield electrode must be quite small. We found it surprising that the spray did not merely deposit on the shield. Indeed it will if the orifice is too small. We found it is possible to choose an orifice size which is large enough to allow the spray of droplets through without substantial deposition on the shield electrode, whilst at the same time is small enough to prevent the corona reaching the cone of liquid at the spraying edge.
The shield electrode may be constrained to earth potential or may perhaps float.
The spray itself does not present sufficient space charge to induce an ionic discharge (corona), so because the shield electrode isolates the discharge electrode from the spraying edge, an ionic discharge cannot be induced if the discharge electrode is earthed. Means are therefore provided to charge the discharge electrode to a potential of polarity suitable to discharge the spray. All the droplets in the spray can be discharged without upsetting the formation of a ligament.
In one form, the invention provides an inhaler for producing a spray of droplets of a liquid to be inhaled, comprising: walls defining with a shield electrode, a chamber having an air passage therethrough; a spraying edge, the shield electrode being spaced from the edge and having an orifice through which liquid sprayed from the edge can issue into the chamber; means for producing a charge to a high potential of one polarity relative to the shield electrode in liquid at the spraying edge, to define an electric field between the edge and the shield electrode sufficient to cause the liquid to issue from the spraying edge as at least one cone from which electrostatic forces repel through the orifice a ligament which breaks up into a spray of charged droplets; a sharp discharge electrode spaced from the shield electrode in said chamber; means for charging the discharge electrode to a high potential of the other polarity relative to the shield electrode, such as to produce a corona to discharge the spray, the shield electrode being of sufficient overall dimensions and having a sufficiently small orifice to shield the edge and the cone of liquid from the corona.
Problems can arise when it is attempted to put the spraying edge, shield electrode and discharge electrodes inside a chamber. For example, there is a tendency for the spray to deposit on the chamber walls. There is more than one mechanism which may produce this effect. Obviously there may be some deposits due to collisions between the discharged droplets and the chamber walls. A much greater deposit may be caused, however, if the spray is not completely discharged due, for example to the voltage on the discharge electrode not being high enough or being poorly directed. Any droplets remaining charged will deposit on the chamber walls. To assist the discharge of the spray, the chamber is preferably swept completely by corona to the shield electrode, so that there are substantially no pockets where droplets could escape being discharged. To this end, the discharge electrode is preferably positioned at the chamber wall and protrudes into the chamber from the wall by a small amount. The chamber wall at which the discharge electrode is positioned is also preferably concave with respect to the chamber, so that there is little or none of the chamber behind the corona.
Droplets may also be caused to deposit on the chamber walls if the walls become charged by corona from the discharge electrode. This may be caused by the discharge electrode being at too high a voltage, so that there is spare corona after the spray has all been discharged, or by the discharge electrode being poorly directed or positioned. The walls become charged oppositely to the spray, which attracts both charged and discharged droplets. The walls may become so highly charged as to produce a reduction in the corona discharge from the discharge electrode. In turn that may cause less than all of the spray to be discharged.
This effect may be reduced or prevented by choosing a material for the chamber walls which is less than completely insulating so that if corona produces unwanted charge on the walls, this can leak away. Additionally or alternatively, the shield electrode may be cup shaped, inside or forming part of the chamber walls extending towards the discharge electrode.
BRIEF DESCRIPTION OF THE DRAWINGS
An embodiment of the invention, given by way of example, will now be described with reference to the accompanying drawing, in which:
FIG. 1 shows schematically and partly in section, an inhaler embodying the invention;
FIG. 2 shows an enlarged section of part of the apparatus of claim 1;
FIG. 3 is a schematic cross section through an alternative spraying edge 7 for the apparatus of FIG. 1; and
FIG. 4 illustrates schematically the effect of discharging the spray in a prior art electrode arrangement.
DETAILED DESCRIPTION
Referring to FIGS. 1 and 2 (which are not to scale), liquid which it is desired to atomise is supplied via an insulating pipe 2 to an outlet 6 for the liquid. In the apparatus illustrated the outlet 6 is a metal capillary tube and is thus electrically conducting. The end of the outlet provides a spraying edge from which the liquid is sprayed.
Spaced from and in front of the spraying edge 7 is a shield electrode 8. The outlet 6 and the shield electrode 8 are connected to respective terminals of a high voltage generator 10 which in use charges the spraying edge 7 to a high voltage of one polarity, preferably positive, with respect to the shield electrode 8. The voltage between the spraying edge 7 and the shield electrode 8 produces a sufficient electrode field strength between them to draw a cone 11 of liquid from the spraying edge. The liquid leaving the spraying edge becomes charged, negative charge being conducted away by the conducting spraying edge 7, leaving a net positive charge on the liquid. The charge on the liquid produces internal repulsive electrostatic forces which overcome the surface tension of the liquid forming a cone of liquid from the tip of which issues a ligament 12. At a distance from the spraying edge, the mechanical forces produced on the ligament due to travelling through the air cause it to break up into charged droplets of closely similar size. The shield electrode 8 replaces the field intensifying electrode described in the above mentioned British patent specification No. 1,569,707.
In order to produce the very small droplets necessary for an inhaler, the electric field strength produced between the spraying edge and the shield electrode needs to be high. For example, the voltage between the shield electrode 8 and the spraying edge may be in the region of 5 Kv, whilst the spacing between them may be less than 5 mm, say, 2 mm. It is known that air ionises differently at the different polarities and that the threshold is higher for positive potentials. In order to produce the small droplets referred to, the electric field strength is found to be so high that if the spraying edge 7 is charged negative relative to the shield electrode 8, there is a substantial risk of corona from the spraying edge and/or the cone 11 which interferes with or destroys the stability of the ligament. We have found that suitably small droplets can be produced when the spraying edge is charged positive, without the risk of corona from the spraying edge 7 or cone 11.
The formulations used in inhalers have a resistivity which is much lower than that usually used for electrostatic spraying. In most prior art applications, say, paint spraying or spraying agricultural pesticides, in order to obtain a useful flow rate, the liquids to be sprayed usually have resistivities in the range 10 6 to 10 10 ohm cm. The formulations which might be used in an inhaler are expected to have resistivities in the range 5×10 3 to 10 8 ohm cm. Although spraying of liquids which have a resistivity at the low end of the range is known from, say, U.S. patent specification No. 1,958,406 it only works at low flow rates which have not been of much practical use. If the flow rate is too high, the ligament becomes unstable. We have found, however, that a stable ligament can be produced, and the apparatus can be made to spray satisfactorily, if the flow rate is low enough, a situation which is appropriate to inhalers, but not perhaps to agricultural or paint sprayers. It is likely that suitable formulations will have resistivities in the range 10 5 to 10 7 ohm cm. Given that a stable spray can be produced, the lower resistivities assist in the production of a small droplet size. All other parameters equal, we find that the lower the resistivity, the smaller the droplet size.
The shield electrode has an orifice 14 aligned with the spraying edge 7 and sufficiently large that the ligament or the droplets pass through, dependent on whether the ligament breaks up before or after the shield electrode, to produce a spray of droplets in a chamber 15 beyond the shield. If the orifice were too small the droplets or ligament would deposit on the shield electrode 8. Previous expectations as expressed in the above mentioned British patent specification No. 1,569,707 would have been that with the shield electrode positioned downstream of the atomising tip of the ligament, droplets would deposit on the shield electrode even with an orifice very substantially larger than illustrated. A small orifice is required in the present apparatus for reasons explained below.
In order to produce a spray which is inhalable, the droplets which issue through the orifice 14 must be discharged. This is effected by a discharge electrode in the form of a needle 16. In the embodiment illustrated, the needle is directly in the path of the spray. In alternative embodiments, one or more discharge electrodes may be positioned out of the direct path of the spray. The discharge electrode is connected to the high voltage generator 10 which, in use, charges the discharge electrode 16 to a high potential relative to the shield electrode 8 and of opposite polarity to that of the spraying edge, in this case negative. The shield electrode may be provided with a connection to earth, perhaps via a leakage path through the user of the inhaler, or may be left floating.
The discharge electrode 16 is driven to a sufficiently high voltage relative to the shield electrode 8 as to produce a corona discharge. The negative ions so produced discharge droplets in the spray issuing through the orifice 14.
The distinction between charged droplets and discharged droplets is very obvious visually. Any droplets remaining charged in the spray, are highly mobile in a predictable path. Discharged particles appear as a cloud or smoke which drifts unpredictably in the air currents.
If a prior art field intensifying electrode were used in the place of the present shield electrode, there would be considerable difficulty in discharging all the droplets in the spray. Why this is so can be understood by considering what happens as the voltage on the discharge electrode is increased from a voltage insufficient to cause ionic discharge.
FIG. 4 shows an enlarged and schematic view of what would happen. A prior art field intensifying or field adjusting electrode is illustrated at 27. At the larger scale used in FIG. 4, the ligament 12 can be seen oscillating at 28 due to mechanical disturbance of passing through the air. The ligament breaks up into droplets which separate into a spray bounded approximately by a cone indicated in broken outline at 30. Within the spray, the charged droplets are highly mobile in predictable paths generally to the right of FIG. 4. At a threshold the voltage is sufficiently high that the electric field strength around the sharp tip of the needle ionises the surrounding air leaving free negative ions. These discharge surrounding droplets in an area bounded, say, by broken line 32. The discharged droplets are easily identifiable visually. They lose their predictable mobility, becoming a drifting smoke which is very distinct from the charged droplets. As the voltage is increased droplets are discharged further from the discharge electrode, so that more of the spray is discharged as indicated by, say, broken line 34. When the voltage applied to the needle is sufficiently high that the boundary of the discharged droplets, indicated by broken line 36, reaches the edge of the spray cone 30, the spray (which is travelling to the right in FIG. 3) would be completely discharged. Unfortunately, at this point the corona uncontrollably jumps to the cone 11 and/or the spraying edge 7, which discharges the cone 11. Since it was the charge on the liquid which overcame the surface tension thereof to form the cone 11 and repel the ligament 12 therefrom, discharging the cone 11 destroys the spray.
The shield electrode 8 is arranged to shield the spraying edge 7 and the cone 11 from the corona thus enabling all the droplets in the spray to be discharged without danger of the cone being discharged. To achieve this, the orifice 14 must not be too large otherwise corona will find its way through. As mentioned above, the orifice must not be too small either, otherwise the droplets will not spray through the orifice but will deposit on the shield electrode. We have found it entirely possible to balance these conflicting requirements so that the orifice can be at the same time neither too large nor too small. With a flow rate of about 40 microliters per minute, we found that the apparatus could be made to work with a hole 14 having a diameter in the range 2 mm to 1 cm. At the small end of the range, there was a greater tendency to spray onto the shield electrode. At the large end of the range, there was a greater tendency for the corona to leak through the hole to the cone 11. Complete discharge of the spray can be ensured by adjusting the position of the needle 16 and the voltage applied thereto. We found no need in the arrangement illustrated for the voltage to be more than 10 Kv and that it could, indeed, be well below that.
The overall dimensions of the shield electrode must be sufficient to prevent corona reaching the cone 11 or spraying edge 6 round the outside of the electrode.
The shield electrode 8 may be metallic but need not necessarily be of such a good conductor as that. What is required is that the shield electrode should be sufficiently conducting to remove any charge which may accumulate due to the ionic discharge.
The outlet 6, shield electrode 8 and discharge electrode 16 are contained within a capsule 50 having a volume of about 200 ml, defining the walls of the chamber 15. In order to reduce interference with the electrical fields produced between the spraying edge and the shield electrode on the one hand, and the discharge electrode and the shield electrode on the other hand, the capsule is made of an insulating or semi-insulating material. Polyethylene plastics is an example of a very highly insulating material. In order that any charge received by the capsule may leak away, it may be preferred to use a less insulating material for example polycarbonate, polyethylene terephthalate or polyacetal. The shield electrode may be cup shaped extending inside the walls towards the discharge electrode, or may form part of the walls.
Two holes 52 and 54 provide an air passage through the chamber 15 transverse to the direction in which the spraying edge sprays. The discharged spray can thus be removed in an airstream across the chamber and inhaled. The airstream may be produced by the user inhaling or, if necessary or preferred, by a fan (not shown).
The discharge electrode 16 has a sharp tip which just projects into the chamber 15. The wall containing the discharge electrode is concave with respect to the chamber. Both these features are intended to reduce the volume of the chamber which is behind (to the right in FIG. 2) of the corona discharge. It is desired that the corona discharge sweeps as much of the chamber 15 as possible without being so directed as to charge the walls of the chamber which would be both wasteful and could charge the walls so interfering with the formation of corona as mentioned above.
To facilitate the user inhaling the discharged spray, the air passage communicates with a face mask 36 as shown in FIG. 1. A non return valve, for example a flap (not shown), may be placed between the face mask and the capsule to prevent exhaled breath blowing the discharged droplets out through the hole 54.
Also shown in FIG. 1 is a supplies pack 38, which in this case is shown separate. The liquid supply tube 2 and the high voltage electrical leads are bundled together as indicated schematically. A mobile emphysema patient, for example, can put the supplies pack in a pocket and move about whilst using the mask. The supplies pack contains the high voltage generator 10 and delivery means 40 for supplying metered amounts of the liquid to be inhaled.
The flow rate of the liquid supplied to the outlet 6 is required to be very accurate. Accuracy is required both so that the patient gets the correct dose, and so that the droplet size remains accurate.
In order to achieve the required accurate flow rate, the delivery means 40 comprises a syringe 42 containing the liquid. The syringe is replaceable when empty. The syringe has a plunger 44, which is driven directly by a friction wheel 45. This is driven by a stepping motor and reduction gearbox 46 controlled by an electrical controller 48 which may include means for setting the rate, or alternatively the rate may be fixed. This general arrangement is already used in a metered pump for administering successive doses of insulin. The pump is manufactured by Muirhead Vactric Components Ltd. of Beckenham, Kent.
Although the outlet capillary tube 6 is metallic in the above example, it is possible to use an insulating tube, especially when the liquid to be atomised has a resistivity towards the lower end of the range. In this case an electrode contacts the liquid upstream of the spraying edge. The liquid is itself sufficiently conducting to carry the charge to the spraying edge so to define the electric field between the spraying edge and the shield electrode 8. The lower the resistivity of the liquid the further upstream contact can be made with the liquid.
Although illustrated as one integral piece the capsule 50 may be formed as two separable parts to facilitate cleaning.
A further form of spraying edge is illustrated in FIG. 3. This spraying edge comprises an outer insulating tube 18 tapered externally at one end 20. A conducting core 22 is connected to the high voltage generator 10 by a lead 23. The core 22 tapered to a point 24 at one end. The point 24 projects slightly beyond the outer insulating tube so defining an annular orifice 26 therewith. The arrangement produces a single ligament from the tip of the projecting point of the core.
All the examples of spraying edges described above are arranged to produce a single ligament principally because of the very low flow rate which may be required in the particular application of an inhaler. In applications where higher flow rates may be required, it may be appropriate to use a spraying edge which produces a plurality of ligaments. One form of spraying edge which produces a plurality of ligaments is a linear nozzle (not shown). In this form liquid is fed to a a linear edge at which the intense electric field is formed. The linear edge may be fed with liquid from a slot at or spaced from the edge. A linear nozzle is illustrated in British patent specification No. 1569707. If the edge is plane, ligaments from along its length at intervals determined by various factors including the field strength and the flow rate. It is possible to position the ligaments to some extent by means of irregularities in the edge, for example teeth, which provide local intensification of the field from which the ligaments issue.
To illustrate the use of a linear nozzle, FIG. 2 could still be considered a cross section through the apparatus, the outlet 6, shield electrode 8 and discharge electrode 16 all extending linearly at right angles to the plane of the paper. In effect the outlet would be a slot feeding a linear edge. It is possible to space the slot back from the edge, as would be the case if the arrangement of FIG. 3 were considered to be a section through a linear nozzle. The spraying edge would then be a linear edge instead of a point described above, and the annular orifice would be a slot above and below the edge. The edge could be fed from a slot on just one side. In such arrangements the orifice 14 in the shield electrode is in the form of a slot and the discharge electrode is either in the form of an edge or a row of discrete points as that illustrated.
Formulations suitable for use with an inhaler embodying the invention, are likely to have a resistivity in the range 5×10 3 to 10 8 ohm cm.
Predominantly aqueous formulations are not completely satisfactory, since the droplet size is so small that evaporation takes place very quickly. Water also has a high surface tension which makes it difficult to spray. Suitably the formulation comprises an acceptable organic diluent and the amount of water, if present, comprises not more than about 50% of the total diluent, more suitably less than 20% and preferably less than 10%.
The formulation consists of a suitable, pharmaceutically acceptable, solvent e.g. dimethyl isosorbide, glycerol, propylene glycol and polyethylene glycol of average molecular weight up to about 600 admixed with water or ethanol. In addition the formulations may contain a suitable pharmaceutically acceptable surfactant e.g. polyethoxy-ethylated castor oils ("Cremophors"), polyoxyethylene-polyoxypropylene block copolymers ("Pluronics", "Synperonics"), polyoxyethylene sorbitan derivatives ("Tweens"), polyoxyethylene oleyl ethers ("Brijs") and sorbitan esters of fatty acids ("Spans"). Such materials are preferably present at not more than 1% concentration.
An inhaler embodying the invention is suitable for the administration to a patient of any drug which can be administered via the lungs, either to have a direct effect on the lungs, for example for the treatment of asthma, emphysema or bronchitis, or for absorption from the lung into the bloodstream in order to produce a systemic therapeutic effect elsewhere in the body. Examples of drugs which have a direct effect on the lung for the treatment of asthma, emphysema or bronchitis are bronchospasm relaxants such as adrenaline, isoprenaline, orciprenaline, ephedrine, phenylephrine, diphenhydramine, terbutalene, isoetharine, etafedrine, methoxyphenamine, theophylline, aminophylline, salbutamol, sodium cromoglycate, ipratropium bromide, beclomethasone, betamethasone valerate, fenoterol reproterol, pirbuterol, budesonide, ketotifen and compounds as defined and claimed in published European patent specification No. 189 305, particularly those compounds defined in claims 4, 5 and 6. Examples of drugs which can be administered systemically via the lungs include polypeptide drugs, for example luteinising hormone-releasing hormone, and synthetic analogues thereof.
Suitably the active ingredient is in the formulation in a concentration range of 0.1 to 20%, and preferably 5 to 10%, but the required concentration depends, naturally, upon the potency of the particular drug being used. | 1a
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FIELD OF THE INVENTION
[0001] The present invention relates to an operation management technique of a mobile-type X-ray apparatus for executing X-ray imaging by making the rounds in hospitals, particularly to a technique for monitoring power consumption amount of batteries provided to a mobile-type X-ray apparatus.
DESCRIPTION OF RELATED ART
[0002] Battery-driven devices are generally provided with the function to detect and display available power supply at the present point (remaining battery power) (for example, refer to Patent Document 1). Mobile-type X-ray apparatuses that are movable for making the rounds in hospitals to execute X-ray imaging also use batteries as a drive source for X-ray irradiation. Thus they also have a function which displays remaining battery power to indicate the timing for exchanging batteries and the remaining time for operating the device.
PRIOR ARTS
[0000]
Patent Document 1: Japanese Patent No. 3078286
[0004] However, since power consumption of a battery is different in each imaging condition, it is difficult to predict whether or not the remaining power of battery is able to complete the entire scheduled imaging by referring only to the remaining battery power. Particularly a mobile-type X-ray apparatus often uses a battery not only as the drive source for X-ray imaging but also as the power source for moving, which makes it more difficult to predict the timing for recharging the battery. This problem sometimes causes the condition that the battery is expended after moving the X-ray apparatus. In order to avoid such situations, an extra amount of battery power needs to be consistently charged up which often incurs waste.
[0005] The object of the present invention is to provide a technique to support determining if the remaining amount of battery power is enough to execute desired quantity of imaging by using a mobile-type X-ray apparatus driven by a mounted battery, considering the above-mentioned problem.
BRIEF SUMMARY OF THE INVENTION
[0006] The present invention, based on the imaging list of the scheduled imaging and the pre-stored power consumption information for each target region, calculates the predictive amount of battery power consumption for completing the entire imaging on the imaging list and displays the calculated amount along with the remaining battery power to an operator.
[0007] In concrete terms, it provides the mobile-type X-ray apparatus provided with a battery for executing X-ray imaging, comprising:
[0008] remaining battery power detecting means configured to detect remaining power of a battery;
[0009] predictive power consumption calculating means configured to calculate predictive battery power consumption based on an imaging list for making the rounds; and
[0010] display means configured to display the remaining power and the predictive battery power consumption.
[0011] In accordance with the present invention, it is possible to easily determine if the entire planned imaging can be executed by a mobile-type X-ray apparatus using a battery as its drive source.
BRIEF DESCRIPTION OF THE DIAGRAMS
[0012] FIG. 1 is a block diagram of a substantial part in the mobile-type X-ray apparatus related to an embodiment of the present embodiment.
[0013] FIG. 2 is a functional block diagram of a power consumption controller in an embodiment of the present embodiment.
[0014] FIG. 3 is a hardware block diagram of the power consumption controller in an embodiment of the present invention.
[0015] FIG. 4 is for explaining an imaging list in an embodiment of the present invention.
[0016] FIG. 5 is for explaining a power consumption table by target region related to an embodiment of the present invention.
[0017] FIG. 6 is for explaining an example of a display screen related to an embodiment of the present invention.
[0018] FIG. 7 is a flowchart showing a process for displaying predictive battery power consumption related to an embodiment of the present invention.
[0019] FIG. 8 is a functional block diagram for correcting the power consumption controller related to an embodiment of the present invention.
[0020] FIG. 9 is a functional block diagram for updating the moving power consumption in the power consumption controller related to an embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0021] An embodiment related to the present invention will be described below referring to the attached diagrams. In all the diagrams, the same function parts are represented by the same reference numerals, and the duplicative description thereof is omitted.
[0022] FIG. 1 is a block diagram of a substantial part of mobile-type X-ray apparatus 100 in the present embodiment. Mobile-type X-ray apparatus 100 of the present embodiment comprises motor- or manually-driven mobile carriage 106 , wheels 107 , rechargeable battery 108 , X-ray generator 102 for irradiating X-rays, main body 101 for supporting the X-ray generator via an arm, imaging controller 109 for controlling imaging, input unit 103 , display unit 104 and power consumption controller 105 , as shown in the diagram.
[0023] In the present embodiment, the predictive power consumption of rechargeable battery 108 is calculated in power consumption controller 105 . FIG. 2 is a functional block diagram of power consumption controller 105 of the present embodiment. Power consumption controller 105 comprises imaging list controller 201 , remaining battery power detecting unit 204 , predictive battery power consumption calculating unit 205 and display unit 206 , calculates predictive battery power consumption 250 using imaging list 210 , power consumption table by target region 220 and moving power consumption 230 and detects remaining battery power 240 .
[0024] As shown in FIG. 3 , power consumption controller 105 comprises central processing unit (CPU) 301 for controlling operation of the respective components, RAM 302 for temporarily storing data etc. for CPU 301 to execute processing, ROM 303 for storing various data or control program, display unit 304 for displaying the processing result, and input device 305 for receiving the input of various commands.
[0025] The above-described respective functions are achieved by loading the control program stored in ROM 303 to RAM 302 to be executed by CPU 301 . Display device 304 and input device 305 of power consumption controller 105 may be configured to be used also as display unit 104 and input unit 103 of mobile-type X-ray apparatus 100 . Also, mobile-type X-ray apparatus 100 may comprise the device having configuration connectable to a network in hospitals (for example, a CR device or FPD device).
[0026] Imaging list controller 201 controls imaging list 210 which is inputted via input device 305 and stored in ROM 303 . Imaging list 210 contains the list of imaging examinations planned for one round, and a target region to be imaged for each patient and the number of imaging times are registered. FIG. 4 is for explaining imaging list 210 . On the imaging list 210 , the information for specifying the imaging order (order information) 211 , the information for specifying the patient (patient information) 212 , the information for specifying the imaging target region (target region information) 213 and the number of imaging times 214 are registered as imaging data for each imaging as shown in FIG. 4 . In patient information 212 , patient ID 212 a for uniquely specifying the respective patients is registered. Also, imaging list controller 201 notifies predictive battery power consumption calculating unit 205 when imaging list 210 is newly inputted or updated. In the case that mobile-type X-ray apparatus 100 has a device having configuration connectable to a network in hospitals, imaging list 210 may be configured to be inputted or updated via the device. Further, imaging list 210 may be comprised in the foresaid device.
[0027] Imaging list controller 210 , upon receiving the notification from imaging controller 106 that a certain imaging is completed, deletes the imaging data of the completed imaging and updates imaging list 210 . At this time, imaging order information 211 of the imaging data after the deleted imaging is moved forward one by one. Also, when new imaging is added, imaging data added in the assigned imaging order is inserted, and imaging order information 211 of the imaging data after the inserted imaging is to be moved down for the number of the inserted imaging data. Such control process is to be continued, for example until the command to end the rounds is received via input device 305 .
[0028] In power consumption table 220 for each region, the power consumption according to the imaging target region is registered. FIG. 5 is for explaining power consumption table 220 for each target region. In power consumption table 220 by target region, an available power consumption of mobile-type X-ray apparatus 100 to execute imaging for each imaging region 221 (battery power consumption information) 222 is stored. As for battery consumption information 222 , for example tube voltage (kV) and tube current time integration (mAs) to be required upon imaging each target region are registered. Also, power consumption table 220 by target region is stored in ROM 303 in advance. In the case that mobile-type X-ray apparatus 100 comprises the device connectable to a network in a hospital, power consumption table 220 may be stored outside of mobile-type X-ray apparatus 100 .
[0029] The electric energy to be consumed upon moving among patients (moving power consumption) is controlled as moving power consumption 230 . The pre-set values are registered in ROM 303 as moving power consumption 230 .
[0030] Remaining battery power detecting unit 204 detects the sufficient electric energy which rechargeable battery 108 can supply being set off by predetermined time intervals or occurrence of a predetermined event, stores the detected energy in ROM 303 as remaining battery power 240 , and notifies it to display processor 206 . For detection of remaining battery amount 240 , a commonly known method for detecting remaining battery amount is to be used. For example, sufficient power supply amount is calculated by detecting the output current from rechargeable battery 108 .
[0031] Predictive battery power consumption calculating unit 205 , when receiving the command from the user or the notification from imaging list controller 201 that imaging list 210 is updated, calculates the power consumption for executing the entire imaging registered in imaging list 210 as predictive battery power consumption 250 . Predictive battery power consumption 250 is a sum of the predictive imaging power consumption to be consumed in imaging itself and predictive moving power consumption to be consumed in moving mobile-type X-ray apparatus 100 among imaging examinations.
[0032] For calculating predictive imaging power consumption, power consumption for the number of scanning times for each patient or target region is calculated and summed, using power consumption information 222 stored in power consumption table by target region 220 corresponding to target 221 which accords with target region information 213 on imaging list 210 . Also, predictive moving power consumption is to be obtained by multiplying the number of patients registered in imaging list 210 by moving power consumption 230 . The number of patients is to be counted using patient ID 212 a in imaging list 210 . Predictive battery power consumption calculating unit 205 notifies the calculated predictive battery power consumption 250 to display processing unit 206 .
[0033] Display processing unit 206 generates display data for displaying remaining battery power 240 and predictive battery power consumption 250 on display unit 304 . FIG. 6 is for explaining an example of display screen 600 formed by display data. Display screen 600 comprises first display section 601 and second display section 602 . Remaining battery power 240 is displayed on first display section 601 and predictive battery power consumption 250 is displayed on second display section 602 respectively. The display of remaining battery power 240 and predictive battery power consumption 250 are updated respectively upon receiving the notification. These figures are displayed, for example on percentage (0%˜100%) with respect to the electric energy in the case that rechargeable battery 108 is recharged 100%.
[0034] Display device 304 may comprise command button 603 for receiving the command to switch the content of display. Display processing unit 206 receives the command to change the display via command button 603 and changes, for example remaining battery amount 240 and predictive battery power consumption 250 from the above-mentioned numeric display to a chart display. The method for displaying remaining battery amount 240 and predictive battery power consumption 250 are not limited thereto. Any display pattern that is easy for the user to capture the amount values visually may be used such as graph display, meter display or digital display.
[0035] Next, predictive battery power consumption 250 of the present embodiment is calculated and displayed. The processing flow for displaying the predictive battery power consumption by power consumption controller 105 will be described. Here, the case that starts the process on the basis of the registration of imaging list 210 will be exemplified. FIG. 7 is a flowchart showing the display process of predictive the battery power consumption. Here, the case that calculates predictive battery power consumption 250 for every update of imaging list 210 will be exemplified. It also may be configured such that the above-mentioned calculation is executed only when the command from the user is received. Also, remaining battery power 240 is to be detected separately at predetermined intervals.
[0036] Upon receiving the input of an imaging list via input device 305 (step 701 ), imaging list controller 201 registers imaging list 210 in ROM 303 (step 702 ), and notifies the list to predictive battery power consumption calculating unit 205 . Upon receiving the notification, predictive battery power consumption calculating unit 205 calculates predictive battery power consumption 250 referring to imaging list 210 (step 703 ). Then it notifies the calculation result to display processing unit 206 . Display processing unit 206 generates display data using the most updated remaining battery power 240 stored in remaining battery detecting unit 204 and the notified predictive battery power consumption 250 (step 704 ), and displays the generated data on display device 304 (step 705 ). After that, imaging list controller 201 monitors if imaging list 210 is updated, and also monitors the command from the user to end the rounds at predetermined timings (steps 706 and 707 ). When the list is updated the process returns to step 702 , and when the command to end the rounds is received the process is to be ended.
[0037] Also, in the case that mobile-type X-ray apparatus 100 is the kind in which imaging list is stored in advance such as a CR device or FPD device, for example power consumption controller 105 executes the above-mentioned step 703 and subsequent steps thereof being set off by receiving of the command from the user to start calculating the predictive battery power consumption via input device 305 .
[0038] As mentioned above, in accordance with the present embodiment, not only the remaining battery power at the present time but also the predictive battery power consumption planned to be consumed in the subsequent imaging examinations is displayed on the display unit. The approximate estimate of the power consumption to be consumed by moving of mobile-type X-ray apparatus 100 in rounds is also included in the predictive battery power consumption. Therefore, it is possible to acquire the predictive battery power consumption calculated with high accuracy. Also, the user can easily determine whether to execute the imaging registered in the imaging list or to recharge the battery by comparing the remaining battery power and the predictive battery power consumption.
[0039] Also, the predictive battery power consumption is updated in accordance with the update of the imaging list. Therefore, even in the situation such as addition of imaging, requirement for re-imaging or emergency imaging occurs, it is possible to identify accurate predictive battery power consumption which leads to quick response to the change of examination plan.
[0040] While the above-described embodiment calculates and displays predictive battery power consumption 250 of along with remaining battery power 240 , the display content is not limited thereto. For example, it may be configured to display the predictive power supply that rechargeable battery 108 can supply (predictive remaining battery amount) after executing the entire imaging registered in imaging list 210 . Predictive remaining battery power is calculated, after calculating predictive battery power consumption 250 by predictive battery power consumption calculating unit 205 , by subtracting predictive battery power consumption 250 from remaining battery power 240 at the present time point. Then display processing unit 206 displays the predictive remaining battery power on display device 304 along with remaining battery power 240 . Also, when the predictive battery power becomes minus, the information indicating “shortage” may be displayed.
[0041] Also, it may be configured to display the information indicating up to which point in imaging list 210 can be imaged (available imaging list) with remaining battery power 240 at the present time. In this case, predictive battery power consumption calculating unit 205 repeats subtracting from remaining battery power 240 the battery power consumption necessary for executing the imaging and subtracting the moving power consumption each time the patient information is changed in the order of imaging list 210 , until the result ends up as minus. When the result ends up as minus, predictive battery power consumption calculating unit 205 determines that the imaging can be executed until the imaging data just before the power runs out and notifies, for example order number information 211 of the imaging data just before the power runs out to display processing unit 206 . In the case that the result does not reach minus when the entire list in imaging list 210 is processed, the information indicating that the entire imaging can be executed is notified to display processing unit 206 . Display processing unit 206 displays the available imaging list along with remaining battery power 240 .
[0042] As for the display pattern of the available imaging list, for example the entire imaging data available to be imaged from among imaging list 210 may be displayed, the imaging data determined as available to be imaged may be displayed in an identifiable manner, or the maximum number from among order number information 211 of the imaging data determined as available to be imaged may be displayed.
[0043] Also, the number of image pieces available to be imaged for each target region (the available imaging pieces by target region) may be calculated and displayed using not the predictive battery power consumption based on imaging list 210 but by remaining battery power 240 . Predictive battery power consumption calculating unit 205 calculates the number of available imaging pieces for each target region using power consumption information 222 for each target region stored in power consumption table 220 for each target region. Display processing unit 206 displays the number of available imaging pieces for each target region on display device 304 . The electric consumption energy to be consumed in imaging is different by each target region. Therefore, obtaining the number of available imaging pieces for each target region facilitates the user to easily change the plan for the rounds by using the obtained information as a guide.
[0044] Mobile-type X-ray apparatus 100 of the present embodiment may have the configuration capable of calculating and displaying one or more items from among predictive battery power consumption 250 , predictive remaining battery power, available imaging list and available number of imaging pieces for each region. Also, it may have the configuration that enables the user to select which items are to be displayed. By having the capability to display a plurality of items, the user can identify whether or not he/she can execute the imaging on an imaging list more easily.
[0045] Further, it may be configured that a predictive remaining battery power, available imaging list and available number of imaging pieces for each region are calculated and displayed also when remaining battery power 240 changes more than a predetermined value from the previous calculation, in addition to when receiving a command from the user or imaging list 210 is updated. This configuration is provided with the function to store the remaining battery power at the time of calculation, and to compare the remaining battery power at the time of update with the stored remaining battery power. In this manner, when there is a significant change in the remaining battery power, for example in the cases that no imaging is executed while mobile-type X-ray apparatus 100 is running or an unexpected long distance movement is required, more accurate calculation result can be obtained.
[0046] Further, the present embodiment may be configured capable of executing various corrections upon calculation of the above-mentioned various items by predictive battery power consumption calculating unit 205 . Also, the corrections to be considered may be selected by a user. Here, the case will be exemplified that correction can be made on operating time, temperature at the environment of usage, degradation, and device type of rechargeable battery 108 . The additional configuration to power consumption controller 105 required to execute these corrections is shown in FIG. 8 .
[0047] Power consumption controller 105 comprises correcting selection receiving unit 810 , temperature measuring unit 802 and temperature correcting unit 820 for making correction due to the temperature at the environment of usage, degradation degree detecting unit 803 and degradation degree correcting unit 830 for making correction due to degradation of battery, device type input unit 804 and device type correcting unit 840 for making correction due to the type of the device being used, and time measuring unit 805 and time correcting unit 850 for making correction due to operating time (passage of operating time). Correcting selection receiving unit 810 gives command to the respective units via input device 305 to execute only the selected correction.
[0048] Generally, available energy capacity of a battery changes according to the temperature at the environment of usage. When the temperature drops, available energy capacity decreases and remaining battery power 240 also decreases. In order to measure the temperature of rechargeable battery 108 at the environment of usage, temperature measuring device 802 is placed in the vicinity of rechargeable battery 108 . As for temperature measuring device 802 , for example a thermistor is used. When the command to consider correction due to temperature is received by correcting selection receiving unit 810 , temperature correcting unit 820 calculates the correction value for correcting remaining battery power 240 using the temperature measured by temperature measuring device 802 . The correction value is calculated using correlative information between the temperature and the change in battery capacity and correlative information between the battery capacity and the available electric power that are stored in advance. Then the correction value is notified to remaining battery power detecting unit 204 . Remaining battery power detecting unit 204 corrects the detected remaining battery power 240 detected using the correction value.
[0049] Also, generally a battery deteriorates as being used. In accordance with the degradation of battery, the battery power consumption also varies. When the command to consider the correction due to degradation of battery is received by correcting selection receiving unit 810 , degradation detecting unit 803 detects the voltage or current at the time of high-load usage such as during imaging or moving. Degradation degree detecting unit 830 compares the power consumption calculated from the detected voltage or current and the pre-stored power consumption at the time of high-load condition, determines the degradation degree of rechargeable battery 108 , calculates the correction value for correcting the remaining battery power, and notifies the calculated power to remaining battery power detecting unit 204 . Remaining battery power detecting unit 204 corrects the remaining battery power 240 using the correction value.
[0050] In the case that mobile-type X-ray apparatus 100 has the function besides the imaging function such as for connecting to a network in a hospital, for example a CR device or FPD device, the electric power consumption increases for the amount to operate those functions. When the command to consider the correction due to the type of device is received by correcting selection receiving unit 810 , type input unit 804 receives the information to specify the type of device via input device 305 . Type correcting unit 840 stores the information to specify the increase of electric power consumption according to the respective devices, and extracts the electric power consumption (increasing portion) according to the received type of device. Then it notifies the extracted increasing portion of the electric power consumption to predictive battery power consumption calculating unit 205 . Predictive battery power consumption calculating unit 205 adds the received increasing portion to the calculated predictive battery power consumption 250 to make it zero.
[0051] Type input unit 804 may be configured to input not only the type of device but also the information for specifying a user. In this case, type correcting unit 840 stores the variation portion of the electric power consumption according to a user, and notifies the obtained increasing portion to predictive battery power consumption calculating unit 205 .
[0052] When mobile-type X-ray apparatus 100 is running without imaging for a long period of time, the output of rechargeable battery 108 decreases. However, predictive battery power consumption calculating unit 205 does not execute the process unless imaging list 210 is updated or the command from a user is received. Therefore, when one kind of calculation is executed from among the calculations for predictive remaining battery power, available imaging list or the number of available imaging piece for each region, there is a possibility that the accuracy of these calculation results is lowered. When the command to consider the correction due to passage of time is received by correcting selection receiving unit 810 , time measuring unit 805 measures the passage of time from the previous calculation executed by predictive battery power consumption calculating unit 205 . Time correcting unit 850 monitors the measurement by time measuring unit 805 , and when determination is made that more time has passed than a predetermined time, gives the command to predictive battery power consumption calculating unit 205 to execute re-calculation. Then it makes the correction by replacing predictive battery consumption 250 with the obtained result. By employing the above-described correction, it is possible to reflect the lowering of a battery output on a timely basis in the case that the imaging is not executed for a long period of time while mobile-type X-ray apparatus 100 is running.
[0053] As described above, by providing with the configuration capable of executing various types of correction, predictive battery power consumption can be presented to a user with a higher accuracy, and the timing for recharging a battery can also be determined more accurately.
[0054] The present embodiment also may be configured as capable of selecting whether or not to consider the predictive moving power consumption. When the command to consider the predictive moving power consumption is received via input device 305 is selected, power consumption controller 105 causes predictive battery power consumption calculating unit 205 to calculate also the predictive moving power consumption. Also, moving power consumption 230 does not have to be provided. In this case, predictive battery power consumption calculating unit 205 calculates only the predictive power consumption for imaging as the predictive battery power consumption. For example, in the case that mobile-type X-ray apparatus 100 is mainly moved manually, it is possible to obtain sufficiently accurate information with such easy processing.
[0055] Also, the present embodiment may be configured capable of correcting moving power consumption 230 according to the used facility (hospital). This is because the moving distance per patient differs largely depending on the size of the facility.
[0056] Also, the present embodiment may be configured as capable of updating moving power consumption 230 . That is, the moving power consumption is calculated from the actual moving power consumption and the calculated power consumption is to be replaced with the newest calculation result at each round.
[0057] In order to achieve the above-mentioned function, electric consumption controller 105 comprises moving power consumption controller 203 that updates moving power consumption 230 as shown in FIG. 9( a ). Moving power consumption 203 comprises moving power consumption measuring unit 901 for measuring the actual power consumption at the time of moving from the variation etc. of the remaining battery power, actual measurement database 902 for storing the actual moving power consumption wherein the measured power consumption is divided by the number of patients who received imaging examination for a portion of the predetermined previous numbers of measuring times, and first moving power consumption calculating unit 903 for calculating the average of the stored actual moving power consumption as the updated moving power consumption 230 .
[0058] Also, when the power consumption according to the unit moving distance is clarified, the present embodiment may be configured to update the moving power consumption based on the average moving distance for making one round. In order to achieve the above-mentioned configuration, moving power consumption controller 203 is to be placed in the vicinity of wheel 107 of moving carriage 106 , and comprises moving distance detecting unit 911 for detecting the moving distance from the number of rotations of wheel 107 , moving distance database 912 for storing the moving distance detected by moving distance detecting unit 911 for the predetermined previous numbers of imaging times, and second moving power consumption calculating unit 913 for calculating moving power consumption 230 by calculating the average of the moving distances stored in moving distance database 912 , multiplying the calculated average value by the electric power consumption according to the above-mentioned unit moving distance and dividing the multiplied value by the number of patients who received an imaging examination in the rounds, as shown in FIG. 9( b ).
[0059] As described above, by providing the configuration capable of updating moving power consumption 230 , accuracy in calculating the predictive moving power consumption can be further improved.
[0060] Further, while the above-described embodiment is configured to update the content to be displayed on display device 304 according to the command from command button 603 , the present embodiment is not limited thereto. For example, in the case that display device 304 is used also as display unit 104 for setting and displaying the imaging condition of mobile-type X-ray apparatus 100 , it may be configured to display the information related to rechargeable battery 108 such as remaining battery power 240 and predictive battery power consumption 250 while the apparatus is moving and to execute usual display while the apparatus is not moving.
[0061] In this case, for example the present embodiment comprises a brake-release detecting unit for detecting release of a break and a display data switching unit, and switches the display data on display unit 104 when the break-release detecting unit detects that the break is released.
[0062] By comprising the above-described configuration, it is possible to obtain the necessary information at necessary situations with simple configuration.
DESCRIPTION OF REFERENCE NUMERALS
[0063] 100 : mobile-type X-ray apparatus, 101 : main body, 102 : X-ray generator, 103 : input unit, 104 : display unit, 105 : electric consumption controller, 106 : moving carriage, 107 : wheel, 108 : rechargeable battery, 109 : imaging controller, 201 : imaging list controller, 204 : remaining battery power detecting unit, 205 : predictive battery power consumption calculating unit, 206 : display processing unit, 210 : imaging list, 211 : order information, 212 : patient information, 212 a : patient ID, 213 : region information, 214 : number of imaging pieces, 220 : power consumption table for each region, 221 : region, 222 : power consumption information, 230 : moving power consumption, 240 : remaining battery power, 250 : predictive battery power consumption, 301 : CPU, 302 : RAM, 303 : ROM, 304 : display device, 305 : input device, 600 : display screen, 601 : first display section, 602 : second display section, 603 : command button, 802 : temperature measuring unit, 803 : degradation degree detecting unit, 804 : type input unit, 805 : time measuring unit, 810 : correcting selection receiving unit, 820 : temperature correcting unit, 830 : degradation degree correcting unit, 840 : type correcting unit, 850 : time correcting unit, 901 : moving power consumption measuring unit, 902 : actual measurement database, 903 : first moving power consumption calculating unit, 911 : moving distance detecting unit, 912 : moving distance database, 913 : second moving power consumption calculating unit | 1a
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PRIORITY
[0001] This application claims priority to U.S. Provisional Patent Application Ser. No. 61/348,275, entitled “Methods and Devices for Regulating the Activation of Ghrelin Hormones within a Stomach,” filed May 26, 2010, the disclosure of which is incorporated by reference herein.
FIELD OF INVENTION
[0002] The present invention relates to methods and devices for regulating the activation of ghrelin hormones within a stomach.
BACKGROUND OF THE INVENTION
[0003] Ghrelin is a hormone produced mainly by P/D1 cells lining the majority of the human stomach. These cells are distributed throughout the stomach and portions of the duodenum, but are highly concentrated in the area of the fundus and along the greater curvature of the stomach. Ghrelin, commonly called the hunger hormone, is associated with eating and fasting cycles in the body. It has been found that ghrelin levels increase before meals and decrease after meals. Further, it has been discovered that ghrelin levels in the plasma of obese individuals are typically lower than those in leaner individuals, while those suffering from the eating disorder anorexia nervosa typically have high plasma levels of ghrelin compared to both the constitutionally thin and normal-weight controls. These findings suggest that ghrelin plays a role in weight disorders.
[0004] Additionally, increased Ghrelin levels have been linked to enhanced learning and memory, a reduction in stress-induced depression, and shorter sleep durations.
[0005] Accordingly, there remains a need for methods and devices for regulating the activation of ghrelin hormones within a stomach in order to treat weight disorders, to promote learning and memory functions, to treat stress-induced depression, and to promote healthy sleep duration.
SUMMARY OF THE INVENTION
[0006] The present invention generally provides methods and devices for regulating the activation of ghrelin hormones within a stomach in order to treat weight disorders, to promote learning and memory functions, to treat stress-induced depression, and to control sleep duration. Through recent research, it has been discovered that the enzyme Ghrelin-Octanoyl Acyl-Transferase (GOAT) mediates the control of ghrelin activation within the stomach. While dietary lipids serve as a substrate for GOAT which is used for acylation of circulating ghrelin, ghrelin acylation by GOAT may depend on the presence of specific dietary lipids. GOAT/ghrelin is a gastrointestinal lipid sensing system, yet the secretion and activation of ghrelin are two independently regulated processes. It is believed that the primary means for activating ghrelin is through the contact of the ghrelin producing cells of the stomach and/or intestines with stomach contents carrying the GOAT enzyme and dietary lipids necessary for activating ghrelin. The activated ghrelin, Human-Acyl-Ghrelin, moves from the stomach and/or intestines into the blood stream and its levels may be measured in the blood through known testing procedures. It has been found through testing that the Human Acyl-Ghrelin levels present in the blood stream decrease under fasting conditions. Accordingly, increased Human Acyl-Ghrelin levels in the blood stream may not reflect an empty stomach as previously thought; rather these increased Human Acyl-Ghrelin levels in the blood stream may actually be a signal indicating the availability of specific dietary lipids which may prepare the body for optimal nutrient partitioning and storage.
[0007] By blocking GOAT's access to ghrelin, ghrelin may be maintained in a non-activated state within the stomach, and may thereby reduce or eliminate hunger, promote learning and memory functions, treat stress-induced depression, and promote healthy sleep duration. Inversely, by facilitating GOAT's access to ghrelin, ghrelin may be maintained in an activated state within the stomach, and may thereby increase hunger or appetite, and alter healthy sleep duration. As may be appreciated, proper regulation of the activation of ghrelin hormones within a stomach may be utilized to treat or cure metabolic disorders, obesity, anorexia, depression, insomnia, learning or attention disorders, memory loss and the like.
[0008] In one embodiment, a method for regulating activation of ghrelin hormones within a stomach comprises a means for isolating ghrelin producing cells from food content and dietary lipids within the stomach is provided. These means for isolating may take any number of forms and may comprise one or more of a surgical procedure, an implanted device, or an ingestible substance.
[0009] In an exemplary method, the stomach may be partitioned into a first and second chamber; the first chamber containing and permitting flow therethrough of food content and dietary lipids; and the second chamber containing the bulk of the ghrelin hormone producing cells. Partitioning may be accomplished via a surgical procedure such as a Magenstrasse and Mill (M&M) procedure or the like, through the implanting of a device such as a gastric sleeve or the like, or through a combination of a surgical procedure and an implanted device. The Magenstrasse and Mill (M&M) procedure is an evolving gastroplasty technique wherein the greater curvature of the stomach is separated (e.g., stapled and cut) from the path of food, leaving a tube of stomach, the Magenstrasse, which is comprised of the lesser curvature. This procedure is similar to Vertical Banded Gastroplasty (VBG) except that the longitudinal separation line of the stomach extends further along the lesser curvature and into the antrum. The theory behind leaving the antral “mill” is that it will continue to serve its normal function of mixing, grinding, retropulsion, and well-orchestrated expulsion of chyme into the duodenum. Non-limiting disclosures of the M&M procedure can be found in U.S. patent application Ser. No. 12/242,381, filed Sep. 30, 2008, entitled “Methods and Devices for Performing Gastroplasties Using Multiple Port Access”, and U.S. patent application Ser. No. 12/242,353, filed Sep. 30, 2008, entitled “Methods and Devices for Performing Gastrectomies and Gastroplasties” which are incorporated herein by reference. A non-limiting study on the operation is incorporated herein by reference in its entirety (Johnston et. al. The Magenstrasse and Mill Operation for Morbid Obesity; Obesity Surgery 13, 10-16). Non-limiting disclosure of the implanting of a bariatric sleeve devices can be found in U.S. Pat. No. 7,476,256 B2 to Meade et al., U.S. Pat. No. 7,347,875 B2 to Levine et al., U.S. Pat. No. 7,329,285 B2 to Levine et al., U.S. Pat. No. 7,267,694 to Levine et al., U.S. Pat. No. 7,122,058 B2 to Levine et al. and U.S. Pat. No. 7,025,791 B2 to Levine et al., which are hereby incorporated by reference in their entirety. The method further includes providing a means for preventing dietary lipids from contacting ghrelin producing cells, thus preventing GOAT from utilizing the dietary lipids to activate the ghrelin. The means for preventing dietary lipids from contacting ghrelin producing cells may be accomplished by at least one of a surgical procedure and an implanted device. The surgical procedure for preventing dietary lipids from contacting ghrelin producing cells may comprise creating a passive biological one-way valve via tissue folding and/or removal. The implanted device for permitting controlled evacuation of non-activated ghrelin hormones contained within the second stomach chamber may comprise an elongate tubular device having an internal bore; the device may further include a valve assembly. Exemplary valve assemblies may comprise at least one of a duck bill valve, a ball valve, a one-way osmotic membrane, and the like.
[0010] Other means for isolating ghrelin producing cells from food content and dietary lipids within the stomach, such as introducing a substance within the stomach which substantially regulates the activation of ghrelin producing cells, or performing an ablation procedure on at least some ghrelin producing cells present within the stomach and/or intestines are also contemplated. These means may be provided alone or in concert with any other means for regulating activation of ghrelin producing cells within a stomach and/or intestines disclosed herein, in order to achieve the desired effect of treating or curing weight disorders, promoting learning and memory functions, treating stress-induced depression, and/or promoting healthy sleep duration.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] The invention will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which:
[0012] FIG. 1 is a schematic view of a human stomach.
[0013] FIG. 2 is a schematic view of a human stomach following a Magenstrasse and Mill (M&M) surgical procedure.
[0014] FIG. 3 is schematic partially transparent view of a human stomach following a Magenstrasse and Mill (M&M) surgical procedure and implantation of a controlled evacuation device.
[0015] FIG. 4 is a schematic view of a human stomach following a Magenstrasse and Mill (M&M) surgical procedure and creation of a passive biological one-way valve.
[0016] FIG. 5A is a schematic partially transparent view of a human stomach following the implantation of a gastric sleeve.
[0017] FIG. 5B is a schematic partially transparent view of a human stomach following the implantation of a gastric sleeve.
[0018] FIG. 6A is a cross-sectional view of a passive biological one-way valve in an open position.
[0019] FIG. 6B is a cross-sectional view of a passive biological one-way valve in a closed position.
[0020] FIG. 7 is a schematic partially transparent view of a controlled evacuation device comprising a duck bill valve.
[0021] FIG. 8 is a schematic partially transparent view of a controlled evacuation device comprising an internal ball valve.
[0022] FIG. 9 is a schematic partially transparent view of a controlled evacuation device comprising an osmotic membrane.
[0023] FIG. 10A is a schematic view of a human stomach at a first step of a modified Magenstrasse and Mill (M&M) type surgical procedure.
[0024] FIG. 10B is a schematic view of a human stomach at a second step of a modified Magenstrasse and Mill (M&M) type surgical procedure.
[0025] FIG. 10C is a schematic view of a human stomach at a third step of a modified Magenstrasse and Mill (M&M) type surgical procedure.
[0026] FIG. 10D is a schematic view of a human stomach at a forth step of a modified Magenstrasse and Mill (M&M) type surgical procedure.
[0027] FIG. 10E is a schematic view of a human stomach at a fifth step of a modified Magenstrasse and Mill (M&M) type surgical procedure.
[0028] FIG. 11 is a schematic partially transparent view of a human stomach following the implantation of a duodenal sleeve.
[0029] FIG. 12 is schematic partially transparent view of a human stomach following a Magenstrasse and Mill (M&M) surgical procedure and implantation of a controlled evacuation device and a duodenal sleeve.
[0030] FIG. 13 is schematic partially transparent view of a human stomach following a sleeve gastrectomy procedure and implantation of a duodenal sleeve.
[0031] FIG. 14A is schematic view of a unitary implantable hydrophilic foam barrier.
[0032] FIG. 14B is schematic view of a segmented ingestible hydrophilic foam barrier prior to suturing.
[0033] FIG. 14C is schematic view of a segmented ingestible hydrophilic foam barrier after suturing.
[0034] FIG. 15A is a schematic partially transparent view of a human stomach following a first step in a transoral introduction and laparoscopic fixation of a barrier.
[0035] FIG. 15B is a schematic partially transparent view of a human stomach following a second step in a transoral introduction and laparoscopic fixation of a barrier.
[0036] FIG. 15C is a schematic view of a human stomach following a third step in a transoral introduction and laparoscopic fixation of a barrier.
[0037] FIG. 15D is a schematic view of a human stomach following a transoral introduction and laparoscopic fixation of a barrier and details thereof.
[0038] FIG. 15E is a cross sectional view of a human stomach following a transoral introduction and laparoscopic fixation of a barrier and details thereof.
[0039] FIG. 15F is a schematic partially transparent view of a human stomach following a transoral introduction and laparoscopic fixation of a barrier illustrating a water path within the stomach.
[0040] FIG. 15G is a schematic partially transparent view of a human stomach following a transoral introduction and laparoscopic fixation of a barrier illustrating a lipid path within the stomach.
DETAILED DESCRIPTION OF THE INVENTION
[0041] Certain exemplary embodiments will now be described to provide an overall understanding of the principles of the structure, function, manufacture, and use of the devices and methods disclosed herein. One or more examples of these embodiments are illustrated in the accompanying drawings. Those skilled in the art will understand that the devices and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments and that the scope of the present invention is defined solely by the claims. The features illustrated or described in connection with one exemplary embodiment may be combined with the features of other embodiments. Such modifications and variations are intended to be included within the scope of the present invention.
[0042] FIG. 1 is a schematic view of a human stomach 100 . Esophagus 102 , which meets stomach 100 at antrum 104 , serves as an inlet for ingested food content. At the uppermost region of stomach 100 resides fundus 106 . Fundus 106 is the region of the stomach where most of the ghrelin hormone producing cells reside. Stomach 100 is generally defined by greater curvature 108 and lesser curvature 110 , and is bound by anterior wall 112 . At the lowermost region of the stomach reside angular notch 114 , pylorus 116 and duodenum 118 . Together, angular notch 114 , pylorus 116 and duodenum 118 serve as an outlet for the contents of the stomach to pass into the intestines (not shown); the digestive process being aided by gall bladder 122 . Ghrelin expression zones 120 are defined within stomach 100 in areas generally defined by fundus 106 and duodenum 118 .
[0043] FIG. 2 is a schematic view of human stomach 100 following a Magenstrasse and
[0044] Mill (M&M) surgical procedure. The M&M surgical procedure is generally accomplished by creating a vertical transection, division or separation 200 of the gastric cavity of stomach 100 generally along lesser curvature 110 from antrum 104 to a point roughly 4-6 cm from pylorus 116 . A transorally delivered bougie (not shown) is often placed into the pylorus. The bougie is pressed against lesser curvature 110 with a stapling device (not shown) and helps determine the location of separation 200 . The size of the bougie chosen by the surgeon aids in determining the size of the lumen of first stomach chamber 202 . The bougie also helps the surgeon create a lumen in chamber 202 that is uniform in diameter. As may be appreciated, the performance of an M&M surgical procedure serves the function of partitioning stomach into a first chamber 202 and a second chamber 204 . First chamber 202 contains and permits flow therethrough of food content and dietary lipids (not shown). Second chamber 204 contains the bulk of the ghrelin hormone producing cells present in stomach 100 . It should be appreciated that similar procedures for separating the stomach, whether physically or virtually are contemplated and may be performed in place of or in concert with the M&M surgical procedure disclosed herein. Details of such a procedure are disclosed herein with respect to FIGS. 10A-10E .
[0045] FIG. 3 is schematic partially transparent view of human stomach 100 following a Magenstrasse and Mill (M&M) surgical procedure and implantation of a controlled evacuation device 300 . In this particular embodiment, controlled evacuation device 300 is an implanted device having a tubular configuration with an internal bore passing therethrough, thereby defining an inlet 302 and an outlet 304 . In this particular embodiment, controlled evacuation device 300 is illustrated as a conical or funnel shaped device where inlet 302 substantially surrounds the space between vertical separation 200 and the bottom portion of anterior wall 112 to substantially create a seal between first chamber 202 and second chamber 204 , although it should be understood that various other shapes may be employed by one having ordinary skill in the art without departing from the scope of the present invention. Accordingly, in this embodiment, controlled evacuation device 300 may prevent contact within the stomach of the non-activated ghrelin cells and dietary lipids of first chamber 202 in order to induce or maintain a fat burning metabolic state, thereby causing weight loss in an obese patient. As will be discussed in greater detail later herein, controlled evacuation device 300 may comprise a valve which is functional to provide controlled one-way fluid flow therethrough, and to prevent retrograde flow of food content and dietary lipids through controlled evacuation device 300 by way of peristaltic stomach motions. As may be appreciated, controlled evacuation device 300 may have alternate forms and placements within stomach 100 without departing from the scope of the present invention.
[0046] FIG. 4 is a schematic view of human stomach 100 following a Magenstrasse and Mill (M&M) surgical procedure and creation of a passive biological one-way valve 400 . In this particular embodiment, passive biological one-way valve 400 is functional to regulate the contact between dietary lipids of first chamber 202 and the non-activated ghrelin cells contained within second chamber 204 in order to achieve a desired effect. Passive biological one-way valve 400 may be formed, for example, via tissue folding or tissue removal. Cross-sectional views of a passive biological one-way valve taken along section line A-A will be discussed in greater detail later herein with respect to FIGS. 6A and 6B . Further, passive biological one-way valve 400 may also include an implantable prosthetic device such as a one-way osmotic membrane. As may be appreciated, passive biological one-way valve 400 may have alternate forms and placements within stomach 100 without departing from the scope of the present invention.
[0047] FIGS. 5A and 5B are schematic partially transparent views of human stomach 100 following the implantation of a gastric sleeve 500 . In these particular embodiments, gastric sleeve 500 is an implanted device having a tubular configuration with an internal bore passing therethrough, thereby defining an inlet 502 and an outlet 504 . In these particular embodiments, gastric sleeve 500 is secured at its inlet 502 to esophagus 102 near antrum 104 via anchoring stent 506 . In FIG. 5A , outlet 504 extends to a point beyond pylorus 116 , but terminates prior to ghrelin expression zone 120 of duodenum 118 . In FIG. 5B , outlet 504 extends to a point beyond ghrelin expression zone 120 of duodenum 118 . In this manner, the length of gastric sleeve 500 may be tailored to the specific needs of the patient, as determined by their physician without departing from the scope of the present invention. Accordingly, food content and dietary lipids are effectively separated from the ghrelin hormone producing cells present in fundus 106 and/or duodenum 118 , thereby preventing activation of ghrelin by the enzyme Ghrelin-Octanoyl Acyl-Transferase (GOAT). This isolation may aid in reducing or eliminating hunger sensations, as well as inducing or maintaining a fat burning metabolic state, thereby causing weight loss in an obese patient. As may be appreciated, gastric sleeve 500 may have alternate forms and placements within stomach 100 with the primary function remaining as separating food content and dietary lipids from the ghrelin hormone producing cells present in fundus 106 . Further, it should be understood that known gastric sleeves and sleeve gastrectomy methods may be employed, without changing or altering the scope of the present invention.
[0048] FIG. 6A is a cross-sectional view of a passive biological one-way valve 400 in an open position, as taken along section line A-A of FIG. 4 . As disclosed previously herein, passive biological one-way valve 400 may be formed, for example, via tissue plication or tissue removal. Accordingly, in this particular embodiment, passive biological one-way valve 400 includes a first tissue fold 602 and a second tissue fold 604 which cooperate to form a valve which separates second chamber 204 of stomach 100 from the formed outlet chamber 606 . In the open position of FIG. 6A , the stomach fluids contained within second chamber 204 are free to be evacuated into outlet chamber 606 , and subsequently through outlet passage 608 . As may be appreciated, passive biological one-way valve 400 may have alternate forms (e.g., one or more plications may be created to obtain the desired effect) and placements within stomach 100 with the primary function remaining as controlling evacuation of stomach fluids from second chamber 204 .
[0049] FIG. 6B is a cross-sectional view of a passive biological one-way valve 400 in a closed position, as taken along section line A-A of FIG. 4 . As disclosed previously herein, passive biological one-way valve 400 may be formed, for example, via tissue plication or tissue removal. Accordingly, in this particular embodiment, passive biological one-way valve 400 includes a first tissue fold 602 and a second tissue fold 604 which cooperate to form a valve which separates second chamber 204 of stomach 100 from the formed outlet chamber 606 . In the closed position of FIG. 6B , the stomach fluids contained within second chamber 204 are collected before being evacuated into outlet chamber 606 , and subsequently through outlet passage 608 . In this embodiment, dietary lipids are prevented from contacting the ghrelin producing cells in second chamber 204 . As may be appreciated, passive biological one-way valve 400 may have alternate forms and placements within stomach 100 with the primary function remaining as controlling evacuation of stomach fluids from second chamber 204 .
[0050] FIG. 7 is a schematic partially transparent view of a controlled evacuation device 700 comprising a duck bill valve. In this particular embodiment, controlled evacuation device 700 is an implanted device having a tubular configuration with an internal bore passing therethrough, thereby defining an inlet 702 and an outlet 704 . Within the internal bore resides a duck bill valve formed by a first elongated member 706 and a second elongated member 708 . First elongated member 706 and a second elongated member 708 are resiliently biased to a normally closed configuration as seen in FIG. 7 , but allow for passage of materials therethrough. In one embodiment, the material passing therethrough is the stomach fluids contained within second chamber 204 as described previously herein with respect to FIG. 3 .
[0051] FIG. 8 is a schematic partially transparent view of a controlled evacuation device 800 comprising an internal ball valve. In this particular embodiment, controlled evacuation device 800 is an implanted device having a tubular configuration with an internal bore passing therethrough, thereby defining an inlet 802 and an outlet 804 . Within the internal bore resides a ball valve formed by a first elongated member 806 and a second elongated member 808 which interact with a ball 810 . Ball 810 may be resiliently biased to a normally closed configuration as seen in FIG. 8 , but allow for passage of materials therethrough. In one embodiment, the material passing therethrough is the stomach fluids contained within second chamber 204 as described previously herein with respect to FIG. 3 . As may be appreciated, ball 810 may be constructed of a suitable material such as Polyetheretherketone (PEEK) or silicone and have a suitable size and shape for use within a human stomach.
[0052] FIG. 9 is a schematic partially transparent view of a controlled evacuation device 900 comprising an osmotic membrane. In this particular embodiment, controlled evacuation device 900 is an implanted device having a tubular configuration with an internal bore passing therethrough, thereby defining an inlet 902 and an outlet 904 . Within the internal bore resides an osmotic membrane 906 . Osmotic membrane 906 allows for one-way fluid passage therethrough. In one embodiment, the fluid passing therethrough is the stomach fluids contained within second chamber 204 as described previously herein with respect to FIG. 3 .
[0053] FIGS. 10A-10E illustrate a schematic view of human stomach 100 undergoing the basic steps of a modified Magenstrasse and Mill (M&M) type surgical procedure. In FIG. 10A , a first division or separation 1000 is created in stomach 100 . In FIG. 10B , a second division or separation 1002 is created in stomach 100 . In FIG. 10C , first division or separation 1000 is separated to create two distinct stomach chambers; first stomach chamber 202 and second stomach chamber 204 . In FIG. 10D , second division or separation 1002 is also separated to further define first stomach chamber 202 and second stomach chamber 204 . In FIG. 10E , second stomach chamber 204 is secured to inert structural tissue 1004 in the abdominal cavity of the patient by sutures 1006 or the like. In this manner, narrow passage 1008 between first division or separation 1000 and second division or separation 1002 serves as the only fluid communication passage between first stomach chamber 202 and second stomach chamber 204 , thereby controlling the fluid communication between the dietary lipids contained within first stomach chamber 202 and the ghrelin hormone producing cells present second stomach chamber 204 . This in turn prevents activation of the non-activated ghrelin cells which will induce or maintain a fat burning metabolic state, thereby causing weight loss in an obese patient. As may be appreciated, passage 1008 may further include a valve means (not shown) which may, for example, comprise either an implanted mechanical device or a surgically created biological one-way valve which have been detailed previously herein in other embodiments.
[0054] FIG. 11 is a schematic partially transparent view of human stomach 100 following the implantation of a duodenal sleeve 1100 . In this particular embodiment, duodenal sleeve 1100 is anchored at its inlet 1108 by anchoring stent 1102 within duodenum 118 . In these particular embodiments, duodenal sleeve 1100 is an implanted device having a tubular configuration with an internal bore passing therethrough, thereby defining an inlet 1108 and an outlet 1110 . In FIG. 11 , outlet 1110 of duodenal sleeve 1100 extends to a point beyond ghrelin expression zone 120 of duodenum 118 (see FIG. 1 ). In this manner, the length of duodenal sleeve 1100 may be tailored to the specific needs of the patient, as determined by their physician without departing from the scope of the present invention. Accordingly, food content and dietary lipids 1104 pass through duodenal sleeve 1100 in a direction indicated by flow arrow 1106 and are effectively separated from the ghrelin hormone producing cells present in duodenum 118 , thereby preventing activation of ghrelin by the enzyme Ghrelin-Octanoyl Acyl-Transferase (GOAT). This isolation may aid in reducing or eliminating hunger sensations, as well as inducing or maintaining a fat burning metabolic state, thereby causing weight loss in an obese patient. As may be appreciated, duodenal sleeve 1100 may have alternate forms and placements within duodenum 118 with the primary function remaining as separating food content and dietary lipids from the ghrelin hormone producing cells present in duodenum 118 . Further, it should be understood that known duodenal sleeves and sleeve gastrectomy methods may be employed, without changing or altering the scope of the present invention.
[0055] FIG. 12 is schematic partially transparent view of human stomach 100 following a Magenstrasse and Mill (M&M) surgical procedure and implantation of a controlled evacuation device 1200 and a duodenal sleeve 1100 . Controlled evacuation device 1200 includes an inlet 1202 and an outlet 1204 and comprises a valve which is functional to provide controlled one-way fluid flow therethrough, and to prevent retrograde flow of food content and dietary lipids through controlled evacuation device 1200 by way of peristaltic stomach motions. Accordingly, in this embodiment, controlled evacuation device 1200 may prevent contact within the stomach of the non-activated ghrelin cells and dietary lipids of first chamber 202 in order to induce or maintain a fat burning metabolic state, thereby causing weight loss in an obese patient. As may be appreciated, controlled evacuation device 1200 may have alternate forms (e.g., a passive biological one-way valve as in FIG. 4 above) and placements within stomach 100 without departing from the scope of the present invention. The M&M procedure of FIG. 12 is equivalent to that of the M&M procedure detailed previously herein with respect to FIG. 2 . The implantation of duodenal sleeve 1100 is equivalent to that of the procedure detailed previously herein with respect to FIG. 11 .
[0056] FIG. 13 is schematic partially transparent view of human stomach 100 following a sleeve gastrectomy procedure and implantation of a duodenal sleeve 1100 . In FIG. 13 , a division or separation 1302 is created in stomach 100 in order to create two distinct stomach portions; first portion 1304 and second portion 1306 . In this embodiment, second portion 1306 comprising fundus 106 is excised leaving stomach 100 having portion 1304 as its new effective volume. In this manner, the ghrelin producing portions of fundus 106 are removed from the body and are therefore incapable of being contacted by the dietary lipids and food content within stomach 100 . Non-limiting disclosures of the sleeve gastrectomy procedure can be found an example of this is disclosed in US2005/0131386A1, Jun. 16, 2005 “METHOD AND DEVICE FOR MINIMALLY INVASIVE IMPLANTATION OF BIOMATERIAL”, which is hereby incorporated by reference in their entirety. The implantation of duodenal sleeve 1100 is equivalent to that of the procedure detailed previously herein with respect to FIG. 11 .
[0057] FIGS. 14A-C are schematic views of hydrophilic foam barrier 1400 . In FIG. 14A , hydrophilic foam barrier 1400 is a unitary implantable device, whereas in FIGS. 14B and 14C barrier 1400 is a segmented ingestible device. In these figures, barrier 1400 is constructed from multiple smaller sections 1402 . Each section 1402 would be small enough to pass in the expanded state shown. One embodiment of a construction method would be to hold the sections together with bioabsorbable suture 1404 . That way, barrier 1400 could be implanted in one easily maneuverable piece, but would break up into passable sections in the unlikely event that it becomes dislodged from the gastric fixturing means (discussed below). The idea described in this document uses a moist barrier to repel lipids from areas of the stomach or small bowel that contain GOAT. In one embodiment, barrier 1400 is a highly hydrophilic and is constructed of a porous material.
[0058] FIGS. 15A-C are schematic partially transparent views of human stomach 100 following a transoral introduction and laparoscopic fixation of hydrophilic foam barrier 1400 . FIG. 15A illustrates a first step in the process wherein barrier 1400 is rolled, compressed and inserted into stomach 100 orally. FIG. 15B illustrates a second step in the process wherein barrier 1400 is unrolled and positioned in fundus 106 using a flexible endoscope with standard tools (not shown). FIG. 15C illustrates a third step in the process wherein using a laparoscopic device 1500 , the anterior and posterior layers of stomach 100 are forced into contact with barrier 1400 , not compressing the barrier fully. Fasteners 1502 are inserted through the anterior stomach layer, barrier 1400 and the posterior stomach layer in order to hold barrier 1400 in place.
[0059] FIGS. 15D-E are a schematic view and cross sectional view respectively of human stomach 100 following a transoral introduction and laparoscopic fixation of an hydrophilic foam barrier 1400 and details thereof. As shown and described previously herein with respect to FIGS. 15A-C , FIG. 15D illustrates barrier 1400 fastened between the anterior stomach layer and the posterior stomach layer via fasteners 1502 and further includes a section line A-A. FIG. 15E as taken along section line A-A illustrates barrier 1400 fastened between the anterior stomach layer and the posterior stomach layer via fasteners 1502 in order to be better understood.
[0060] FIGS. 15F-G is are schematic partially transparent views of human stomach 100 following a transoral introduction and laparoscopic fixation of a barrier illustrating a water path and a lipid path respectively within stomach 100 . In FIG. 15F a portion of water 1504 introduced by ingestion is retained in barrier 1400 . Also, secretions from fundus area 106 of stomach 100 can pass through barrier 1400 for drainage, because they are water based. However, as seen in FIG. 15G , ingested lipids 1506 are repelled by barrier 1400 due to the fact that the porous material is engorged with water 1504 , and lipids 1506 are hydrophobic. Therefore, it is ensured that lipids 1506 do not contact the GOAT containing tissue within fundus 106 . This isolation may aid in reducing or eliminating hunger sensations, as well as inducing or maintaining a fat burning metabolic state, thereby causing weight loss in an obese patient.
[0061] One skilled in the art will appreciate further features and advantages of the invention based on the above-described embodiments. Accordingly, the invention is not to be limited by what has been particularly shown and described, except as indicated by the appended claims. All publications and references cited herein are expressly incorporated herein by reference in their entirety. | 1a
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This application claims the benefit of Provisional application Ser. No. 60/126,656, filed Mar. 29, 1999.
BACKGROUND OF THE INVENTION
This invention relates to an improved formulation and process methodology of Coenzyme Q 10 in producing soft gel capsules of this formulation. Coenzyme Q 10 (CoQ 10 or Ubiquinone) is a large molecular weight (863.63 grams) lipid compound that is produced in the liver and perhaps other body organs. The total body content is estimated to be 1.4 to 1.8 grams, depending on the age and the physical fitness of the individual. Although CoQ 10 is found in the mitochondria and other organelles of every living cell, it appears to be most abundant in tissues with a high number of mitochondria and a high level of metabolic activity. For example, in the metabolically inactive blood there is approximately 4 mg, in the heart, and in the skeletal muscle 1000 mg. The blood acts as a CoQ 10 reservoir and transport media between endogenous CoQ 10 synthesis in the liver, exogenous CoQ 10 absorption from digested food substances in the intestinal tract, and the body cells. Endogenous synthesis appears to be responsible for 56 percent and exogenous sources for 44 percent of the body's CoQ 10 requirements. These numbers are currently being studied and endogenous CoQ 10 synthesis may be significantly deficient in the elderly. These deficiencies are not related to the total caloric intake, but rather to the vitamin content of ingested foods. The body requires multiple vitamins for the synthesis of CoQ 10 .
CoQ 10 requirements of the body are also variable between individuals and are dependent on age, physical activity, and disease. It is estimated that the body CoQ 10 utilization is between 5 and 9 mg per day. Intercellular CoQ 10 is required for the synthesis of energy and therefore essential for life. Energy synthesis occurs in the mitochondria, where CoQ 10 provides an electron for the electron transport chain in the cytochrome system, in which adenosine tripohosphate (ATP) is synthesized. As CoQ 10 gives up an electron for ATP synthesis, it gets oxidized. If CoQ 10 is used as an antioxidant, it gets oxidized and is no longer available to provide electrons and function in the synthesis of ATP. Under conditions of high metabolic stress, endogenous sources may become inadequate to meet the body's CoQ 10 requirement for ATP synthesis. Under such conditions, dietary CoQ 10 supplementation has been shown to be an effective source. An improved soft gel formulation and process of CoQ 10 soft gel capsule manufacturing has uses to treat heart failure, chronic fatigue and patients with psoriasis and planter warts. In all cases, it has been found that the improved soft gel formulation at ingestion rates of 30-100 mg/day of CoQ 10 have been proven to be superior to commercially available 60 mg dry powder capsules, and existing 100 mg/day CoQ 10 soft gel formulations.
An appropriate CoQ 10 dosage for a normal individual compared to the dosage necessary for a diseased individual has been difficult to ascertain. Recommended doses of 10 to 30 mg/day were found to be ineffective for patients with significant CoQ 10 deficiencies. In the past 15 years, it has become generally accepted that poor intestinal absorption of certain CoQ 10 formulations limits their effective use. For this reason, 50 and 150 mg CoQ 10 containing tablets or capsules are commercially available to the consumer, at a considerably higher cost.
Folkers et al (U.S. Pat. No. 4,824,669) addresses a soft gel capsule with CoQ 10 and at least one vegetable oil. This formulation was determined to increase blood CoQ 10 levels to 2.5 μg/ml compared to 1.6 μg/ml for an equivalent 100 mg dose of dry powder CoQ 10 . Many different CoQ 10 formulations have appeared which are claimed to increase intestinal absorption. However, intestinal absorption data, collected under near basal conditions, which compare CoQ 10 alone in oil with dry powder CoQ 10 , are conclusive that oil is a better delivery agent.
SUMMARY OF THE INVENTION
The present invention comprises a stable and nontoxic soft gel Coenzyme Q 10 formulation and process methodology of Coenzyme Q 10 for maximum Coenzyme Q 10 levels in the human body for a given input. A preferred soft gel formulation includes Coenzyme Q 10 (hereinafter CoQ 10 ), Vitamin E, beta-carotene, bee's wax, medium chain triglycerides available as MCT Myglyol S12, and rice bran oil formulated to maximize the body's absorption by maintaining the CoQ 10 in what may be a supersaturated solution in easily absorbed materials, that can provide healthful effects, as opposed to just fillers. It is important as much of the supplied CoQ 10 be absorbed, rather than just taking megadoses at frequent intervals as the wholesale cost of CoQ 10 dry powder in quantity is as much as $2000 per kg. Not only is a relatively large percentage of the CoQ 10 absorbed, but the volume of the soft gel capsule is minimized, making it easier to swallow and requiring smaller shipping and storage space. Recent studies indicate the preferred soft gel CoQ 10 formulation should be administered twice a day in dosages of about 30 mg CoQ 10 in 220 mg capsules, as that amount of CoQ 10 is about the maximum the body of a healthy sedentary adult can use for maintenance of a preferred blood level. For those who have deficiencies of CoQ 10 , studies have shown that twice a day administration of about 60 mg CoQ 10 in 435 mg capsules is advantageous. In special instances of CoQ 10 deficiency, twice a day ingestion of 100 mg CoQ 10 containing soft gel capsules can be tolerated.
It is therefore an object of the present invention to provide a soft gel formulation of CoQ 10 and a methodology of formulation processing that produce a significantly greater bioavailability percentage of ingested CoQ 10 than existing soft or dry formulations.
Another object of the present invention is to provide a soft gel formulation of CoQ 10 and methodology of administration that produces greater absorption of CoQ 10 into the intestine.
Another object is to minimize the ingested volume required to maintain a given CoQ 10 blood content.
Another object is to provide a process that keeps CoQ 10 in solution in readily absorbed materials, that themselves have beneficial effects.
These and other objects and advantages of the present invention will become apparent to those skilled in the art after considering the following detailed description of the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The unique formulation of the present invention of a stable and non-toxic soft gel Coenzyme Q 10 where the amount of Coenzyme Q 10 is balanced with antioxidants and absorption agents to maximize the percentage of Coenzyme Q 10 in a capsule of a given size, that is delivered to the blood stream from the intestines. The formulation includes: Coenzyme Q 10 , Vitamin E, beta-carotene, bee's wax, medium chain triglycerides (MCT) such as MCT Myglyol S12, and rice bran oil. The preferred soft gel Coenzyme Q 10 formulation of the present invention is prepared in accordance with the following sequence of ingredients and process.
Rice bran oil, a carrier suspension agent for soft gel formulation useful for absorption of lipophilic ingredients such as Coenzyme Q 10 , is heated to 50 to 60° C. Bee's wax is then added. 50° C. is above the melting point of bee's wax and the wax and oil is mixed until a uniform mixture is formed. Bee's wax thickens the rice bran oil and acts as a suspension agent for subsequent ingredients. Without bee's wax, the other ingredients, which are to be suspended inside a transparent gel capsule, might separate or congregate under the effect of gravity, and appear faulty or spoiled to the consumer.
Subsequently, the mixture is cooled to 35 to 45° C. Coenzyme Q 10 , beta-carotenes including alpha and beta carotenes, cryptoxanthin, lutein and zeaxanthin (available commercially as Betatene, available from Cognis Nutrition), Vitamin E, and medium chain triglycerides (MCT) are then simultaneously added to the oil-wax mixture under a vacuum (to eliminate oxidation) and mixed together for one to two hours beta-carotenes improves the solubility and adds antioxidant value. Vitamin E is an antioxidant preservative that prevents peroxidation of the final product, adds antioxidant value, and is fat soluble. Although Vitamin E is available commercially in 30 IU, 100 IU, 200 IU, 400 IU, and 1000 IU concentrations for the present invention concentrations from 350 IU to 400 IU are usable, with 372 IU being the preferred concentration, which results in a concentration from 30 to 100 IU in the soft gel capsule. Medium chain triglycerides are fatty acids that improve the lipid environment and enhance absorbability like the rice bran oil. The bee's wax primarily increases viscosity to keep insoluble components from settling to one side of the soft gel capsule, but it also improves solubility. For instances where viscosity (and in turn gel capsule cosmetics) is not a concern, it can be eliminated.
The resultant mixture is cooled to 25 to 30° C. A nitrogen gas blanket is introduced to shield the mixture for oxygen and the pressure is returned to atmospheric. The mixture is then encapsulated in a soft gel capsule.
Formula 1
Ingredient
Amount Range
% in formula
1.
Vitamin E 372 IU
0.161 g-2.50 g
37%-51%
2.
Beta Carotene
0.00525 g-0.118 g
1.2%-2.5%
(20% from D. salina)
3.
MCT Myglyol 812
0.5 g-1.0 g
12%-21%
4.
Rice Bran Oil
0.193 g-.50 g
10%-44%
5.
Yellow Bee's Wax
0.015 g-.2 g
1%-4%
6.
CoQ 10
0.5-2.0 g
10%-15%
Formula 2
Ingredient
Amount Range
% in formula
1.
Vitamin E 372 IU
0.161 g-2.50 g
38.5%-53%
2.
Beta Carotene
0.00525 g-0.118 g
1.25%-2.6%
(20% from D. salina)
3.
MCT Myglyol 812
0.5 g-1.0 g
12%-22%
4.
Rice Bran Oil
0.193 g-.50 g
10%-46%
5.
CoQ 10
0.5-1.0 g
11%-16%
The bioavailability or intestinal absorption of CoQ 10 has been a major controversy in the international CoQ 10 research community. Previous data indicate that only 1 to 3 percent of dry powder CoQ 10 formulations are absorbed through the lacteals in the intestines and appear in the blood over a twelve hour interval. In general, blood levels of 1.2 to 1.6 μg/ml have been reported, when taking 30 to 60 mg/day dry powder CoQ 10 formulation for 30 days. It has been reported that when a dry powder CoQ 10 formulation is taken with a fat, such as peanut butter, steady-state blood levels of 2.0 to 2.8 μg/ml are measurable.
Multiple clinical trials were conducted in the United States and Europe using the Folkers (U.S. Pat. No. 4,824,669) soft gel. With a dosage of 100 mg/day, multiple investigators have reported group mean blood levels of 2.3 to 3.5 μg/ml depending on the laboratory conducting the measurement.
As observed in recent trials, the bioavailability results found for the present soft gel indicate it provides approximately 50 percent, and with two 30 mg CoQ 10 containing capsules, 100 percent, of the daily CoQ 10 requirements of a normal sedentary individual. It would take at least three of the dry powder 30 mg CoQ 10 capsules to produce the same effects as one soft gel, and six to produce the same effect as two 30 mg CoQ 10 containing soft gel capsules of the present invention. Regardless of the absorption mechanism, the significantly higher basal blood CoQ 10 levels (167%) and the 273% greater absorption rate were found in previous studies to establish that the present soft gel formulation is indeed a superior product to dry CoQ 10 formulations. This may be particularly true for those individuals whose daily CoQ 10 requirement is elevated due to high physical activity, an increased use of CoQ 10 as an antioxidant, and disease associated with known CoQ 10 deficiencies.
Cellular CoQ 10 content is a function of the number and quality of the cellular mitochondria. For example, the failing heart muscle has 2.2 μg CoQ 10 per mg of tissue and a blood CoQ 10 deficiency of 0.3-0.5μg/ml. The normal hearts conditioned heart has 6.3 μg/gm per mg of tissue, and a low basal blood level of 0.5-0.6 μg/ml. These results indicate that supplemental CoQ 10 enters the cell. This observation has also been reported for skeletal muscles of trained and non-trained athletes.
The subjective and objective responses to supplemental CoQ 10 in the normal individual appear more rapidly compared to that of the physically unfit or the diseased individual with a CoQ 10 deficiency. The most probable reason for this observation is that the metabolic machinery (mitochondria) is viable in the non-diseased normal volunteer, whereas the mitochondria are atrophied in the cells of deconditioned and/or diseased individuals. Therefore, it takes time in the diseased individual to build up the mitochondria to a more normal activity level and to normalize their distribution in the organ system involved.
In summary, studies have statistically proven that the present soft gel CoQ 10 formulation used at 60 mg CoQ 10 /day is superior to dry powder CoQ 10 formulations, and prior art soft gel formulations.
Thus, there has been shown novel formulations, which fulfill all of the objects and advantages sought therefor. Many changes, alterations, modifications and other uses and applications of the subject invention will become apparent to those skilled in the art after considering the specification. All such changes, alterations and modifications which do not depart from the spirit and scope of the invention are deemed to be covered by the invention which is limited only by the claims that follow. | 1a
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CROSS-REFERENCE TO RELATED APPLICATIONS
This is a continuation of U.S. patent application Ser. No. 11/368,783, which was filed on Mar. 6, 2006 and claims priority to U.S. Provisional Patent Application No. 60/659,227, filed on Mar. 7, 2005, the entireties of which are incorporated by reference herein.
FIELD OF THE INVENTION
The present invention relates generally to external fixation devices, and more particularly to an external fixation device for use in the reconstruction of acute, chronic and traumatic injuries to the upper and lower extremities.
BACKGROUND OF THE INVENTION
In the medical field, patients can suffer from acute, chronic, and/or traumatic injuries to the upper and lower extremities. In such circumstances, it is often desirable to stabilize and reconstruct the bones of the afflicted area. To that end, systems have been developed to help stabilize and reconstruct injured bones. One type of system employed in the past is an external fixation system.
All bone injuries are not the same. As a result, the best mode of treatment for a bone injury can vary significantly depending on the size of the person, size of the injured bone, and type of bone injury. Specifically, it is often times desirable to have an external fixation device that is capable of accommodating a wide variety of pin placements. However, it is simultaneously desirable to have a relatively simple system that can be readily taught to practitioners in the field. Further, it is also necessary to have a stable system that effectively treats the bone injury. Finally, it is desirable to have a cost effective system. It is therefore desirable to have an external fixation device that allows for versatile pin placement, is relatively simple, stable, and cost effective.
SUMMARY OF THE INVENTION
The present invention comprises an external fixation device (“fixator”) for use in the reconstruction of acute, chronic and traumatic injuries to the upper and lower extremities. The fixator's functions include, but are not limited to, immobilization, compression, joint realignment, arthrodesis, bone distraction and lengthening, fracture reduction/stabilization, and treatment of Charcot arthropathy. More specifically, potential uses for the fixator include acute stabilization and chronic reconstruction of bones, particularly those of the hand or foot. Advantages of using the fixator include, but are not limited to, the ability to gradually correct over time, to fixate away from the injury site if necessary, to provide additional manipulation or additional correction, and to provide assistance in interpositional bone grafting.
The fixator can be used in multi-planar and multi joint correction, is percutaneous and, therefore, minimally invasive, and can provide additional stability and mobility when compared to fixation devices currently in use. Additional advantages of the present invention over existing devices include the design and adjustability to easily assemble and disassemble components of the system without disturbing pins already set into the patient's bone or the rest of the system itself.
BRIEF DESCRIPTION OF THE DRAWINGS
The features of the present invention which are believed to be novel are set forth with particularity in the appended claims. The drawings may not be to scale. The invention may best be understood by reference to the following description taken in conjunction with the accompanying drawings, in the several figures of which like reference numerals identify like elements, and in which:
FIG. 1 is a side perspective view of one embodiment of the fixator.
FIG. 2 is a side perspective view of a second embodiment of the fixator.
FIG. 3 is a side and top view of one embodiment of a clamp system.
FIG. 4 is a side view of one embodiment of the fixator.
FIG. 5 is a top view of one embodiment of the fixator.
FIG. 6 is an angled view of one embodiment of parts of the clamp system.
FIG. 7 is a side view of one embodiment of the clamp system.
DETAILED DESCRIPTION OF THE INVENTION
While the present invention is susceptible of embodiments of various forms, there is shown in the drawings, and will hereinafter be described some exemplary and non-limiting embodiments, with the understanding that the present disclosure is to be considered an exemplification of the invention. It is not intended to limit the invention to the specific embodiments listed.
As can be seen in FIGS. 1-7 , in one embodiment of the present invention, a fixator 10 comprises a rail 12 , at least one clamp system 14 , and a pin 16 . Generally, the clamp system 14 is configured to attach to both the rail 12 and the pin 16 , which is connected to the bone 40 for fixation and stabilization. The fixator 10 may further include compression and distraction nuts 18 functionally connected to the fixator 10 to allow for additional manipulation of bone healing and growth. The clamp systems 14 can be splined to receive and hold rails 12 and pins 16 .
The rails 12 may be any size or shape, and persons of skill in the art will recognize that different application require rails 12 of many differing sizes or shapes, all of which are contemplated herein. The rails 12 may, for example, have a circular, oblong, square, rectangular, or other-shaped cross section. Typically, however, the rails 12 have a round or circular cross-section and are sized in a manner suitable for fixation of small bones 41 , such as those of the foot or hand. The rails 12 may be composed of many materials including, for example, carbon fiber or high density plastic, which allows the rod to be radiolucent. Optionally, the rails 12 may also be threaded to allow for attachment of clamp systems 14 , distraction/compression nuts 18 , or other components of a fixator 10 .
In one embodiment of the present invention, the rail 12 has a “negative” thread pattern, in which the threads 22 are grooves in the surface of the rail 12 rather than protrusions. In this specification, reference to a threaded component will be a disclosure of both a positive and negative thread. The negative thread pattern allows, for example, the clamp system 14 to easily slide up and down the rail 12 , while still allowing for the attachment of compression nuts 18 or other components which could be threaded onto the rail 12 . In such situations, the corresponding component, such as a compression nut 18 , will have a positive thread pattern. In a preferred embodiment, the rail 12 has a thread pitch of approx 1 mm so one revolution of around the threaded rail 12 produces 1 mm of linear movement. In another embodiment, the rail 12 can be geared. In such an embodiment, the rail has a rack and pinion design 20 that allows for compression or distraction. This geared version can have a scale 24 indicating the amount of compression or distraction.
As can be seen more specifically in FIGS. 6 and 7 , in a preferred embodiment, the clamp system 14 comprises a first clamp area 32 and a second clamp area 42 . Preferably, the first clamp area 32 comprises a pin clamp 34 while the second clamp area 42 comprises a rail or bar clamp 44 . Preferably, the first clamp area 32 is functionally connected to the second clamp area 42 such that the object held by the different clamp areas, either pins 16 or rails 12 , can lie in different planes.
Preferably, the first clamp area 32 is a pin clamp 34 that can comprise a pin clamp top 36 , a pin clamp bottom 38 and a first clamp bolt 40 . The pin clamp top 36 and bottom 38 are each configured to allow the first clamp bolt 40 to pass through them. In one embodiment, the first clamp bolt 40 is threaded, and the pin clamp top 36 and pin clamp bottom 38 have internal, threaded holes configured to receive the threaded first clamp bolt 40 . When held by the first clamp bolt 40 , the pin clamp top 36 and bottom 38 can be thought of as a set that together define at least one pin passage 33 capable of receiving the pin 16 . Preferably, the pin clamp top and bottom 36 , 38 each have inner surfaces 35 that together define two distinct pin passages 33 each capable of receiving the pin 16 . It is preferred that the inner surfaces 35 of the pin passages 33 be textured to allow for more secure engagement of the pin 16 . For example, the inner surfaces 35 may have a 2× diamond face with grooves 90 degrees to each other. In addition to the inner surfaces 35 being textured, other surfaces of the pin clamp top and bottom 36 , 38 may be textured where a more secure engagement is desired.
In one embodiment, the two distinct pin passages 33 are configured to receive the same size pin 16 . In another embodiment, one pin passage 33 is configured to receive one size pin 16 , for example a half pin, while the other pin passage 33 is configured to receive a second size pin 16 , for example a transfixing pin. It is contemplated that the pin passage 33 will extend in a direction substantially perpendicular to the first clamp bolt 40 . In one embodiment, the pin clamp top and bottom 36 , 38 can be rotated around the first clamp bolt 40 such that the pins 16 can be orientated in any direction in the plane perpendicular to the first clamp bolt 40 .
In a preferred embodiment, the first clamp area 32 further comprises another pin clamp 34 or a rail clamp 44 . An example of a first clamp area 32 with at least two pin clamps can be found in FIG. 7 . As can be seen in FIG. 7 , two sets of pin clamp top and bottom clamps 36 , 38 can be arranged proximate each other on the pin clamp bolt 40 . In such a set up, four distinct pin passages 33 , each capable of receiving a pin 16 , can be defined by the pin clamp top and bottoms 36 , 38 . In a preferred embodiment, the first clamp area 32 further comprises springs 46 which are functionally attached to the first clamp area 32 and that exert pressure on some of the pin clamp tops and bottoms 36 , 38 . In such a configuration, the pin clamps 34 can be “snap in.” That is, one can exert force on the pin clamp top and/or bottom 36 , 38 . When so doing, the pin clamp top and/or bottom 36 , 38 will push against the springs 46 and thereby be in a position that defines an opening 48 leading into the pin passage 33 capable of allowing the pin 16 to be pressed into that pin passage 33 . When the force is released, the springs 46 again exert full pressure on the pin clamp top and/or bottom 36 , 38 , causing the pin clamp top and bottom 36 , 38 set to clamp on the pin 16 and hold it in a fixed position. In addition, a nut 52 can then be tightened to more securely hold the rail 12 or pin 16 in place.
In another embodiment, the first clamp area further comprises a rail clamp 44 . The rail clamp 44 comprises a rail clamp top 46 , a rail clamp bottom 47 and a rail clamp bolt 49 . The rail clamp top and bottom 46 , 47 are each configured to allow the rail clamp bolt 49 to pass through them. In one embodiment, the rail clamp bolt 49 is threaded, and the rail clamp top and rail clamp bottom 46 , 47 have internal, threaded holes configured to receive the threaded rail clamp bolt 49 . When held by the rail clamp bolt 49 , the rail clamp top and bottom 46 , 47 can be thought of as a set that together define at least one rail passage 54 capable of receiving the rail 12 . It is contemplated that the inner surfaces 56 of the rail passage 54 can be textured to allow for more secure engagement of the rail 12 . For example, the inner surfaces 56 may have a 2.times. diamond face with grooves 90 degrees to each other. In addition to the inner surfaces 56 being textured, other surfaces of the rail clamp top and bottom 46 , 47 may be textured where a more secure engagement is desired. As seen in FIG. 5 , the first clamp area 32 can comprise a rail clamp 44 and a pin clamp 34 . In such cases, the rail passage 54 can be in a different plane than the pin passage 33 . The first clamp area 32 can be configured to allow for the rail 12 in the rail passage 54 to be disposed in a different direction than the pin 16 in the pin passage 33 . For example, the pin 16 may extend at an angle generally perpendicular to the bone or bones 41 to be fixed so that it can be anchored in the bone 41 while the rail 12 may extend at an angle generally parallel to the bone or bones 41 to be fixed.
In one embodiment, a hinge 60 is attached to the first clamp bolt 40 proximate to either a pin or rail clamp bottom 38 , 47 . In a preferred embodiment, the hinge 60 has a male element 62 and a female element 64 . The use of the terms male and female elements 62 , 64 is not meant to suggest a certain structure, but only to disclose that the two elements are configured to work together to provide a hinged connection. The male element 62 has a first section 66 and a second section 68 that are connected to each other. The first section and the second section 66 , 68 can be disposed at about a 90 degree angle in relation to each other. Preferably, the first section 66 is configured to receive the first clamp bolt 40 by having a hole therethrough. The hole may be threaded. It is also preferred that the surface 69 of the first section 66 proximate the pin clamp 34 be textured. For example, the surface may have a 2× diamond face with grooves 90 degrees to each other. Preferably, the second section 28 is configured to receive a hinge bolt 70 by having a hole therethrough. The hole may be threaded.
The female element 64 can have a first section 72 that is connected to a second section 74 , preferably at about a 90 degree angle in relation to each other. The first section 72 of the female element 64 is preferably configured to receive a rail clamp bolt 49 by having a hole therethrough. The second section 74 of the female element 64 can have a hole therethrough that is able to accommodate the hinge bolt 70 . The female element 64 is hingedly connected to the male element 62 . In a preferred embodiment, both the female element 64 and the male element 62 are disposed on the hinge bolt 70 , and are held thereon by a hinge retaining washer or nut 76 . When the hinge bolt 70 and retaining washer or nut 76 are loose, the female element 64 can be rotated in relation to the male element 62 , and vice versa. To stabilize the connection, the hinge bolt 70 is tightened, thus holding the male element 62 against the female element 64 . The surfaces 78 of the female and male elements 62 , 64 that come into contact with each other may be textured to increase friction and create a more stable connection. In addition, washers 80 may be employed to ensure a stable connection.
In a preferred embodiment, the first clamp area 32 is connected via the hinge 60 to the second clamp area 42 . The second clamp area 42 can comprise a pin clamp 34 , a rail clamp 44 , or a combination of pin and rail clamps, 32 , 44 . Preferably, each clamp system 14 allows for multi-planar attachment of rails 12 and pins 16 .
In another embodiment, the clamp system 14 comprises one clamp area. In such a system, the one or more pin clamps 32 and one or more rail clamps 34 can be linearly attached to the same bolt 82 . For example, as can be seen in FIG. 3 , such a clamp system comprises one or more pin clamp tops 36 held in spaced relation to one or more corresponding pin clamp bottoms 38 . Together, the pin clamp top and bottom 36 , 38 define a pin passage 33 that can accept a pin 16 . The pin clamp tops and bottoms 36 , 38 are configured with a hole therethrough that accepts a pin clamp bolt 82 . The pin clamp tops and bottoms 36 , 38 can be loosened and tightened to accept a pin 16 and then securely attach to that pin 16 . This embodiment of a clamp system 14 further comprises a clamp body 84 that preferably is configured with a hole therethrough that can accept the pin clamp bolt 82 . The clamp body 84 can further define a rail passage 86 that is capable of accepting a rail 12 . The clamp body 84 can further comprises a device, such as a bar clamp bolt 88 , that is capable of being screwed into the rail passage 86 to secure the rail 12 .
The pins 16 can be half pins or transfixing pins. In practice, one part of the pin 90 is set into a patient's bones while a second part of the pin 92 is attached to a clamp area 32 , 42 . The configuration of the fixator 10 allows for such pins 16 to be placed prior to, during, or after assembly of the other parts of the fixator 10 without comprising the accuracy of the fixation.
As can be seen in FIGS. 1 , 2 , 4 , and 5 , it is contemplated that the fixator 10 comprise more than one clamp system 14 . A first clamp system 14 is preferably attached to a bone 41 at a first location. A second clamp system 14 is preferably attached to a bone 41 , either the same bone, or a different bone, at a second location. The two clamp systems 14 are connected by a rail 12 , to which both clamps systems 14 are attached via the rail clamp 44 . More than one clamp system 14 and more than one rail 12 can be utilized. In one embodiment, a first clamp system 14 has a rail clamp 44 attached to a first rail 12 and a pin clamp 34 attached to two pins 16 . The pins 16 are attached to a bone 41 at a first location. A second clamp system 14 has a rail clamp 44 attached to the first rail 12 , and a pin clamp 34 attached to two different pins 16 , which are attached to a bone 41 at a second location. The second clamp system 14 also has a second rail clamp 44 attached to a second rail 12 . A third clamp system 14 has a rail clamp 44 attached to the second rail 12 and a pin clamp 34 attached to two pins 16 . These two pins 16 are attached to either the same bone 41 , or a different bone. As can be seen, the fixator 10 described herein, with each clamp system 14 capable of being comprised of one or more adjustable rail or pin clamps 44 , 34 , allows for a wide range of fixator 10 configurations that allow for effective treatment of a number of injuries.
The clamps systems 14 are adjustable with respect to the rail 12 in that each clamp system 14 can slide up or down the rail 12 and also rotate around the rail 12 freely. Once the optimum position for each clamp system 14 is obtained, the clamp system 12 may then be fixed securely in place by simply tightening the rail clamp 44 . Moreover, additional clamp systems 14 may be added to or removed from the fixator 10 easily, both prior to fixation and stabilization and at any point during the healing process, and any number of rail or pin clamps 44 , 34 may be used, depending upon the number of rails or pins 12 , 16 necessary for a given treatment.
The pins 16 can be placed independently of the fixator 10 because of the snap-in functionality of the clamp systems 14 and the ability of the fixator 10 to correct in all planes due to the multi-planar movement of the clamp systems 14 .
In a further embodiment of the present invention, compression nuts and distraction nuts 18 can attached to the rails 12 and used in conjunction with the clamp systems 14 to further adjust bone healing and growth. The nuts 18 may be used to move the clamp systems 14 incrementally along the rail 12 without moving the pins 16 or other components of the fixator 10 , thus providing additional correction on a minute scale during the healing or growth process. The compression nuts 18 are preferably attached on the rail 12 such that, when moved, they will force two clamp systems 14 to move closer to each other. The distraction nuts 18 are preferably attached on a rail 12 between two clamp systems 14 such that when the distraction nut 18 is moved, it will force one clamp system 14 away from the other. Preferably, more than one compression and or distraction nuts 18 can be attached to the same rail 12 to allow for compression or distraction, i.e., the movement of one or more than one clamp systems 14 in either direction along the rail 12 . Optionally, the compression and distraction nuts 18 may have built in washers. Further, the compression and distraction nuts 18 may have a positive thread and can be used in conjunction with a round rail 12 having a negative thread, as described previously.
In a further embodiment of the present invention, the fixator 10 may be easily modified in many ways, such as for example to accommodate pins 16 of multiple diameters and lengths. Additionally, many various sizes and shapes of clamps systems 14 , rails 12 , and/or compression/distraction devices may be employed without detracting from the spirit of the invention. Clamp systems 14 , pins 16 , and rails 12 can be easily reproduced, for example, for medium and large applications as well, such as for use on long bones of the leg or arm.
Because of the exceptional adjustability of the fixator 10 , the fixator described herein can be connected to various parts of the foot or other body parts without being limited by the configuration of the device. Further, the clamp systems 14 also have the mechanical ability to interconnect with other rails and fixation systems, allowing for multiple-rail systems or more complex applications.
In further embodiments of the present invention, for example, the fixator can be used in conjunction with foot plate (“U ring”) attachments, wires, Ilizarov fixators, or any other compatible external fixator device (none of which are shown) through the use of pins, wires (not shown), and/or transfixing pins.
The fixator 10 can be comprised of a wide variety of materials. In a preferred embodiment, the components of the fixator 10 are composed of anodized aluminum, stainless steel, or composite polymer. Specifically, the pins 16 can be manufactured from 316L stainless steel and are preferably 2 mm, 2.5 mm, or 3 mm in length. | 1a
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This is a divisional of application Ser. No. 08/718,774, filed Sep. 24, 1996 now U.S. Pat. No. 5,772,677.
FIELD OF THE INVENTION
The invention relates to an apparatus for providing a skin incision in order to cause bleeding and more particularly to a disposable device which provides a precisely controlled incision in the skin of the patient, can be automatically assembly, and can have its spring wound during final assembly.
BACKGROUND OF THE INVENTION
Disposable skin incision devices have been produced and marketed for many years. In a majority of these skin incision devices, a trigger is pushed which causes a blade to project out of a slot in the housing and then to retract back into the housing. The skin incision device has a spring or a flexural member which upon triggering produces the force to project the blade out of the housing into the skin and retract the blade. A skin incision device having a spring is described in U.S. Pat. No. 4,643,189 entitled "Apparatus for Implementing A Standardized Skin Incision" which issued to Mintz on Feb. 17, 1987, and is incorporated herein by reference.
In skin incision devices which use a spring, the spring must be tensioned or cocked in order to achieve the desired result. In assembling the skin incision device, the spring must be tensioned and then held in tension while the skin incision device is being assembled.
It would be desirable to assemble the spring in the skin incision device in a non-tension position and then tension the spring at a later time.
SUMMARY OF THE INVENTION
This present invention is directed to an apparatus for implementing a skin incision and a method of assembling the apparatus. The apparatus has a housing having a pair of housing sections. Each of the housing sections has a base and a plurality of walls. The housing defines an inner space and an exterior. A pivot arm is pivotally mounted to a base of a housing section. The pivot arm is guided between a first position and a second position by a follower in a cam carried by the housing. A torsion spring carried by a spring post is coupled to the arm to exert a spring force on the arm in the first position. The housing has an indentation with a raised level and a lower groove on the base for receiving a portion of the spring post. The opening through the base extends from the lower groove. The spring post has a cylindrical base portion adapted to be received by the indentation in the base and a detent portion. The detent portion has a circular segment detent portion and a turn element accessible from the exterior of the housing. The circular segment detent portion is adapted to engage the raised level of the indentation in the install position and be retained in the lower groove in the loaded position. A trigger mechanism is received in the housing and acts with the pivot arm when activated whereby the arm moves from the first position to the second position due to the spring energy.
One object, feature, and advantage resides in the housing having an indentation with a raised level and a lower groove on the base for receiving a portion of the spring post, and the circular segment detent portion of the spring post adapted to engage the raised level of the indentation in the install position and be retained in the lower groove in the loaded position. Another object, feature, and advantage resides in the torsion spring having a circular core and a pair of legs, the circular core of the torsion spring encircling the spring post, and the spring post having a slot for receiving one of the legs of the spring. Further objects, features, and advantages of the present invention will become more apparent to those skilled in the art as the nature of the invention is better understood from the accompanying drawings and detailed descriptions.
BRIEF DESCRIPTION OF THE DRAWINGS
For the purpose of illustrating the invention, there is shown in the drawings a form which is presently preferred; it being understood, however, that this invention is not limited to the precise arrangements and instrumentalities shown.
FIG. 1A is a rear view of a skin incision apparatus, according to the invention
FIG. 1B is a front view of the skin incision apparatus. Selected parts are shown in hidden line.
FIG. 2 is a bottom plan view of the apparatus;
FIG. 3A is an inside view of a first housing section of the apparatus;
FIG. 3B is a sectional view taken along the line 3B--3B in FIG. 3;
FIG. 3C is a sectional view taken along the line 3C--3C in FIG. 3A;
FIG. 4A is an inside view of a second housing section of the apparatus;
FIG. 4B is a section view taken along the line 4B--4B in FIG. 4A;
FIG. 4C is a sectional view taken along the line 4C--4C in FIG. 4A;
FIG. 5A is a front view of a pivot arm and a cutting edge employed in this invention;
FIG. 5B is a rear view of the pivot arm and the cutting edge;
FIG. 6A is a front view of a trigger mechanism or plunger employed in this invention;
FIG. 6B is a bottom view of the trigger mechanism;
FIG. 7 is an enlarged front view of a torsion spring;
FIG. 8A is a side view of a spring post;
FIG. 8B is a front view of the spring post;
FIG. 8C is a rear view of the spring post;
FIG. 9A is an inside view of a first housing section with the pivot arm, and the spring and the spring post installed in an installation position;
FIG. 9B is a section view taken along the line 9B--9B in FIG. 9A;
FIG. 9C is a sectional view taken along the line 9C--9C in FIG. 9A;
FIG. 10A is a front view of the apparatus with a portion of the base of the front housing section broken away to show the interior;
FIG. 10B is a sectional view taken along the line 10B--10B in FIG. 10A; and
FIG. 11 is a top view of a turntable for automatically assembly with various components shown broken away or in hidden line.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now the drawings, wherein like numerals indicate like elements, there is illustrated in FIG. 1 a rear view of an apparatus for skin incision which has been identified by the numeral 20.
The skin incision apparatus 20 has a housing 22 having a pair of housing sections 24 and 26, only one section, the rear section 24, seen in FIG. 1. A trigger mechanisms 28 of and for activating the skin incision apparatus 20 projects through an opening 30, as best seen in FIGS. 3A and 4A, formed between the two section 24 and 26 of the housing 22. The trigger mechanism 28 is also referred to as a plunger. The rear section 24 of the housing 22 has a hole 32 through which a portion of a spring post 34 projects.
The skin incision apparatus 20 has a keeper or safety device 38 which can be removed from a safety position surrounding a portion of the trigger mechanism 28 to prevent inadvertent operation. The keeper 38 is shown removed in FIG. 1A.
The front housing section 26 with the surface configuration not shown and selected components of the skin incision apparatus 20 are shown in hidden line is seen in FIG. 1A. The skin incision apparatus 20 has, in addition to the housing 22, the trigger mechanism 28, and the spring post 34, not seen in FIG. 1A, a pivot arm 40 which carries a blade 42, and a torsion spring 44. The pivot arm 40, the spring post 34, and the torsion spring 44 are located in an inner space 46 defined by the housing sections 24 and 26. When the trigger mechanism 28 is pushed/pressed inwardly, to the left in FIG. 1A, the trigger mechanism 28 releases the pivot arm 40 and the torsion spring 44 rotates the pivot arm 40 such that the blade 42 passes through a slot 48, as seen FIG. 2, and retracts back into the housing 22.
In order to gain some insight into the dimensions of an actual unit, a typical unit has a height A of approximately 1.19 inches with a bottom length B of 1.125 inches; the top length being slightly less than the bottom length. The unit has width C, as seen in FIG. 2, of about 0.4375 inches.
Each of the housing sections 24 and 26 has a base 50 and four walls 52, 54, 56, and 58 projecting from the base 50. The bottom wall 54 of each of the housing sections 24 and 26 is shown in FIG. 2. The bottom wall 54f and 54r are joined together to define the slot 48, through which the blade 42 passes during operation or when activated.
The base 50r and the four walls 52r, 54r, 56r and 58r projecting from the base 50r of the rear housing section 24 are seen in FIG. 3. The four walls 52r, 54r, 56r, and 58r and base 50r define a portion of the inner space 46. Located generally where two walls join to form a corner is an opening 60.
Referring to FIGS. 3A and 3B, the rear housing section 24 has a raised portion or bulkhead 62 projecting from the base 50r. The raised portion 62 defines a convoluted cam channel 64. Located between the convoluted cam channel 64 and the slot 48, defined by the bottom wall 54, is a circular boss 66 which surrounds an extending rod 68. The post 68, as explained below, acts as a pivot point for the pivot arm 40 containing the blade 42.
Referring to FIG. 3A and 3A, the rear housing section 24 has a second circular boss 70 defining an indentation 72 for receiving a portion of the spring post 34. The indentation 72 has a bi-level surface 74 at the base 50r; the bi-level surface includes a raised level 76 on either side of a lower groove 78. In the center of the lower groove 78 is the hole 32 seen in FIG. 1.
Still referring to FIG. 3A, the rear housing section 24 has a post 80 that projects upwards. The post 80 engages the base 50f of the front housing section 26 as described below. The base 50r, in addition, forms a ridge 82 upon which the trigger mechanism 28 slides. The top wall 58r of the housing section 24 has a projecting member 84, a stop member, which projects into the inner space 46 for limiting movement of the trigger mechanism 28.
The base 50f and the four walls 52f, 54f, 56f, and 58f projecting from the base 50r of the front housing sections 26 are seen in FIG. 4A. The four walls 52f, 54f, 56f, and 58f and base 50f define a portion of the inner space 46. Located generally in the locations where two walls join to form a corner are pins 86, as seen in FIGS. 4A, 4B, and 4C, which are received by the openings 60 in the rear housing section 24.
Referring to FIG. 4A and 4B, the front housing section 26 has a semi-circular boss 88 for holding the pivot arm 40 containing the blade 50 in position, as explained below.
The top wall 58f of the housing section 26 has a projecting member 84, a stop member, which projects into the inner space 46 for limiting movement of the trigger mechanisms 28. The front housing section 26 has a circular boss 90 defining an indentation 92 for receiving a portion of the spring post 34 as seen in FIGS. 4A and 4C. The indentation 92 has a raised protrusion 94 at the base 50f.
Still referring to FIG. 4A, the front housing section 26 has a dimple 96 for receiving the tip of the post 80 that projects from the rear housing section 24. The base 50f, in addition, forms a ridge 82 upon which the trigger mechanism 28 slides.
Referring to FIG. 5A, the pivot arm 40 has a shoulder 98 defined by two different level surfaces. The shoulder 98 is engaged by the torsion spring 44, as defined below. A recess 100 is formed for part of the shoulder 98, and is shown in hidden line. The blade 42, a triangular blade with a cutting edge 102 and a sharpened apex 104 is coupled to the pivot arm 40. The blade 42 may be secured to the pivot arm 40 by any conventional means and is scalpel-like in appearance and function. Located on the top of the pivot arm 40 is a keeper section 106 which acts with the end of the trigger mechanism 28 to retain the pivot arm 40 in a first position prior to actuation of the skin incision apparatus 20.
Referring to FIG. 5B, the pivot arm 40 has an extended cam follower rod 108 which extends into the convoluted cam channel 64. The convoluted cam surface of the cam channel 64 controls the movements of the pivot arm 40 and, therefore, of the cutting edge 102 of the blade 42 when the skin incision apparatus 20 is activated. A raised boss 110 projects from the pivot arm 40 to define an elongated aperture 114.
The trigger mechanism 28 has a sloping front end 116 as seen in FIG. 6A which acts with the keeper section 106 of the pivot arm 40 during operation. The trigger mechanism 28 also contains a top channel 118 which abuts against the stop member 84 of the housing 22. Referring to FIG. 6B, the trigger mechanism 28, also referred to as a plunger member, has a hallow section 120 through which the keeper section 106 of the pivot arm 40 passes as it moves, as explained below.
FIG. 7 is an enlarged side view of the torsion spring 44. The spring 44 has a core 122 and a pair of legs 124 and 126. The first leg 124 projects inwardly and bisects the core 122. The second leg 126 extends generally out at a tangent from the core 122. The second leg 126 has a bend or jog 128, which facilitates assembly as discussed below.
Referring to FIGS. 8A, 8B, and 8C, the spring post 34 is adapted to carry the spring 44. The spring post 134 generally has a cylindrical shape and includes a cylindrical base portion 130, a raised detent portion 132, and a reduced diameter cylindrical portion 134. The raised detent portion 132 projects from the cylindrical base portion 130 to a first end 136. The raised detent portion 132 has a circular segment detent portion 138 projecting from the cylindrical base portion 130. A cylindrical guide portion 140 projects from the detent portion 138. The cylindrical guide portion 140 has an outside diameter no greater than the width of the circular segment detent portion 138 and is received by the hole 32 in the rear housing section 24, as seen in FIGS. 1 and 3. A turn element 142 for setting or loading the spring 34, as described below, projects from the end of the cylindrical guide portion 140. The turn element 142, similar to the circular segment detent portion 138, has a pair of parallel edges 144 spaced by circular arc edges, in a preferred embodiment, as best seen in FIG. 8B.
The reduced diameter cylindrical portion 134 of the spring post 34 extends from the base portion 130 to a second end 146. A slot 148 in the reduced diameter cylindrical portion 134 extends from the second end 146 to approximately the cylindrical base portion 130. The intersection of the base portion 130 with the reduced diameter cylindrical portion 134 defines a shoulder 150.
Referring to FIGS. 9A and 9B, the skin incision apparatus 20 is assembled by placing the pivot arm 40 in the rear housing section 24 such that the extended cam follower rod 108 is received by the convoluted cam channel 64 and the elongated aperture 114 defined by the raised boss 110, as best seen in FIGS. 9B and 5B, receives the extending rod 68 of the rear housing section 24. The pivot arm 40 is positioned in the first position, the actuation position, with the keeper section 106 to the left in FIG. 9A.
Prior to installing the torsion spring 44 and the spring post 34, the leg 124 is received by the slot 148 in the reduced diameter cylindrical portion 134 of the spring post 34, such that the core 122 of the spring 44 encircles the reduced diameter portion 134 of the post 34. The spring 44 is located on the shoulder 150 defined by the base portion 130 and the reduced diameter cylindrical portion 134. Referring to FIG. 9A and 9C, the spring post 34 is positioned on the rear housing section 24 so that the raised detent portion 132 of the spring post 34 is received by the second circular boss 70 on the base 50 of the rear housing section 24. The circular segment detent portion 138 is positioned so that it does not align with the lower groove 78 of the bi-level surface 74, as best seen in FIG. 9C. The turn element 142, in a preferred embodiment, is located in the hole 32 in the base 50 of the rear housing section 26. The second leg 128 is received by the shoulder 98 in the pivot arm 40. The bend or jog 128 in the leg 126 of the spring 44 reduces the chance of interference with the front housing section 26 during assembly.
The trigger mechanism 28 is installed on the ridge 82. The sloping front end 116 is positioned to engage the keeper section 106 of the pivot arm 40. The top channel 118 is positioned to receive the stop member 84. The keeper or safety device 38 can be installed on the trigger mechanism 28 at this time.
Referring to FIGS. 10A and 10B, the front housing section 26, is positioned on top of the rear housing section 24 such that the pins 86, as seen in FIG. 4A, are received by the openings 60, as seen in FIG 9A, in the rear housing section 24. The semi-circular boss 88 of the front housing section 26 is positioned above the pivot arm 40, in proximity to where the blade 42 is mounted to the pivot arm 40. The reduced diameter cylindrical portion 134 of the spring post 34 is received in the indentation 92 defined by the circular boss 90 of the front housing section 26. The slot 148 is not aligned with the raised protrusion 94 in the circular boss 90, at least initially. The position of the slot 148 is shown in FIG. 9A.
With the circular segment detent portion 138 of the spring post 34 not located in the lower groove 78 of the bi-level surface 74 of the second circular boss 70 of the rear housing section 24 and the raised protrusion 94 on the front housing section 26 not received by the slot 148 of the spring post 34, the walls 52, 54, 56, and 58 of the two housing sections 24 and 26 do not engage completely, specifically walls 54 and 56 which are close to the spring post 34.
With the two housing sections 24 and 26 held together, the turn element 142 is rotated using a tool 154, as seen in FIG. 11, which complements the shape of the turn element. The turn element 142 is turned clockwise as seen in FIGS. 9 and 10A, and counterclockwise as seen in FIG. 1. The rotation of the turn element 142 rotates the spring post 34, therein moving the first leg 124 of the spring 44 which is received by the slot 148 in the reduced diameter cylindrical portion 134 of the spring post 34. In the assembly, the first leg 124 is the movable end or leg to tension the spring 44. The second leg 126, which is received by the shoulder 98 of the pivot arm 40, is the stationary end. The turn element 142 is rotated until the circular segment detent portion 138 of the spring post 34 aligns with the lower groove 78 of the bi-level surface 74 of the second circular boss 70 of the rear housing section 24 and the raised protrusion 94 on the front housing section 26 is received by the slot 148 of the spring post 34. With the alignment, the walls 52, 54, 56, and 58 of the two housing sections 24 and 26 do mesh, as shown in FIG. 10B.
With the spring 44 wound and the housing 22 closed, the skin incision apparatus 20 is ready to operate. The keeper 38 is removed from the trigger mechanism 28. The trigger mechanism 28 is pushed inward, to the left in FIG. 1A. As the trigger mechanism 28 is pushed, the sloping front end 116 pushes the pivot arm 40 towards the left until the pivot arm 40 clears the sloping front end 116 of the trigger mechanism 28. With the pivot arm 40 cleared, the spring 44 pivots the entire pivot arm 40. As the spring rotates the pivot arm 40, the second leg 126 rotates and is the movable end, and the first leg 124, the stationary end, is held by the spring post 34 which is held by the bi-level surface 74 of the rear housing section 24 and the raised protrusion 94 of the front housing section 26.
The pivot arm 40 moves with the extended cam follower rod 108 following the convoluted cam channel 64. The shape of the convoluted cam channel 64 converts the generally arcuate motion of the pivot arm 40 into a linear portion for a segment of the motion of the blade 42. The operation is such that the apex 104 of the blade 42 punctures the skin and thereafter the cutting edge 102 incises the skin. At the end of the travel, the blade 42, including the apex 104, is withdrawn from the skin back into the housing 22.
It is recognized that assembly could occur without assistance of humans, such as on a turntable 156 as shown in FIG. 11. The turntable 156 has a plurality of orifices 158 which are of a shape similar to that of the rear housing section 24, with an additional notch for the placing of the keeper 38. In a preferred embodiment, the turntable 156 has eight (8) orifices 158. The turntable 158 has a plate 160, shown in hidden line, which is generally annular and underlies all of the orifices 158, except one as explained below, for retaining the skin incision apparatus 20.
The rear housing section 24 slides into an orifice 158 from a ramp 162 at station I. The turntable is rotated, by a motor mechanism 164 shown in hidden line, to the next position, or station. While the next rear housing section 24 is being loaded into the next orifice 158, the pivot arm 40 is loaded by a robotic arm, not shown, at the next station (station II) into the rear housing section 24. In the next station (station III), after rotation of the turntable 156, the trigger mechanism 28 and keeper 38 are loaded as a unit. The keeper 38 is loaded on the trigger mechanism 28 prior to installation in station III.
Prior to installing the torsion spring 44 and the spring post 34, the leg 124 of the spring 44 is received by the slot 148 in the reduced diameter cylindrical portion 134 of the spring post 34, such that the core 122 of the spring 44 encircles the reduced diameter portion 134 of the post 34. The spring 44 is located on the shoulder 150 defined by the base portion 130 and the reduced diameter cylindrical portion 134. The spring post 34 is positioned on the rear housing section 24 (in station IV) so that the raised detent portion 132 of the spring post 34 is received by the second circular boss 70 on the base 50 of the rear housing section 26, similar to that described above with reference FIGS. 9A and 9C. The second leg 128 is received by the shoulder 98 of the pivot arm 40.
With all the parts located on the rear housing section 24, the front housing section 26 is positioned on the rear housing section 24 in station V. The pins 86, as seen in FIG. 4A of the front housing section 26 are received by the openings 60 in the rear housing section 24. As indicated above, the walls 52, 54, 56, and 58 of the two housing sections 24 and 26 do not engage completely. The turntable rotates moving the housing sections 24 and 26 under a spring loaded plate 166, which urges the front housing section 26 into engagement with the rear housing section 24. The spring loaded plate 166 overlies stations VI and VII. In a preferred embodiment, no operation occurs at station VI.
At the next station (Station VII), a tool 154, shown exploded away in FIG. 11, moves into engagement with the turn element 142 of the spring post 34, as seen in FIG. 1 and (C, rotates the spring post 34, therein moving the first leg 124 of the spring 44 which is received by the slot 148 in the reduced diameter cylindrical position 134 of the spring post 34. The turn element 142 is rotated until the circular segment detent portion 138 of the spring post 34 aligns with the lower groove 78 of the bi-level surface 74. The spring loaded plate 166 urges the front housing section into engagement with the rear housing section.
The turntable 156 rotates to a final station (station VIII) where the underlying plate 160 is not located. The skin incision apparatus 20 drops to a chute 168 or a conveyor, to move to a packaging section, not shown. It is recognized that the turntable 156 could have fewer or more stations. It is also recognized that multiple parts could be loaded at one station or a plurality of stations could have the same operation being performed and the turntable turns a plurality of orifices at one time. In addition, it is recognized that there are other methods of assembling the skin incision apparatus 20 automatically.
The present invention may be embodied in other specific forms without departing from the spirit or essential attributes therefore and, accordingly, references should be made to appended claims, rather than to the foregoing specification, as indicating the scope of the invention. | 1a
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CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 10/425,093 filed Apr. 28, 2003, the entirety of which is hereby incorporated by reference into this application.
FIELD OF INVENTION
[0002] The present invention is concerned with providing completely solubilized hydroxyapatite (calcium phosphate) and zinc citrate in water in order to enhance their bioavailability and absorption. More particularly, the present invention provides completely solubilized hydroxyapatite (calcium phosphate) and zinc citrate, in a clear water beverage from which calcium, phosphorus and zinc all in ionized form, are completely bioavailable immediately after ingestion.
BACKGROUND OF THE INVENTION
[0003] Calcium is an essential mineral with a wide range of biological actions. Apart from being a major component of bones and teeth, calcium is crucial for muscle contraction, nerve conduction, beating of the heart, blood coagulation, glandular secretion, energy production and the maintenance of immune function.
[0004] Calcium exists in bones and teeth primarily as hydroxyapatite (calcium phosphate). Almost 99% of the total body calcium is found in bones and teeth.
[0005] Calcium has anti-osteoporotic activity as well as anti-carcinogenic, anti-hypertension and hypocholesterolemic functions. A number of studies also suggest that calcium may reduce the risk of colorectal cancer ( N. Engl J Med. 1993; 313:1381-1384, N. Engl J Med. 1999; 340:101-107). Calcium supplementation has been shown to have a modest affect on the reduction of systolic blood pressure in people with hypertension ( Ann. Intern. Med. 1996; 124:825-831, Arch. Fam. Med. 2000; 9:31-39). Still other studies have found calcium supplementation to lower serum cholesterol levels ( Arch. Fam. Med. 1992; 152:2441-2444).
[0006] In findings by the Heritage Family Study, it is reported that calcium deficiency leads to abdominal adiposity. Another study reported that obese people on a 24-week, low calorie diet who received 800 mg of calcium per day lost more weight than those on placebo ( Vitamin Retailer February 2005).
[0007] The absorption of calcium varies throughout the life span, being highest during infancy and decreasing during adulthood. In post-menopausal women, fractional absorption of calcium declines about 0.21% annually.
[0008] Absorption efficiency varies with different calcium salts and complexes, being about 35% for calcium citate and 29% from milk. In a study using radio-labeled calcium, it has been shown that the absorption efficiency (measured as bone deposition) for calcium sulfate was 49%, for calcium phosphate was 31% and for calcium carbonate was 30%. All these calcium salts were administered as tablets.
[0009] The inefficiency of calcium absorption has been recently highlighted by The New England Journal of Medicine. It reported very little difference in the fracture rate of women who have been taking calcium supplements for seven years. This Women's Health Initiative study involved 36,000+women over a seven-year period.
[0010] The combination of calcium and phosphorus is optimal for healthy bone development. The medical community has for a long time known the benefits of calcium for healthy bones and soft tissues and has now shown that the mineral phosphorus also plays an equally important role ( Ann. Rev. Nutr. 1988; 8:121-148).
[0011] Researchers at Creighton University Medical Center in Omaha, Nebr. conducted a study to determine the role of phosphorus in bone growth and development. They were able to demonstrate the consequences of phosphorus deficiency and the co-dependence on calcium and phosphorus for bone growth. They concluded that in any growth situation, both calcium and phosphorus are needed to support an increase in bone mass. ( Bone 32 (2003), 532-540).
[0012] Phosphorus intake in a normal diet is usually sufficient to meet standard nutritional guidelines. However, phosphorus deficiencies are prevalent. Phosphorus deficiency is generally treated with phosphorus supplements such as calcium phosphate.
[0013] Phosphorus is an integral part of many organic compounds and plays an important role in energy and protein metabolism. Phosphorus is a component of adenosine triphosphate (ATP), a fundamental energy source in living things. Almost every biochemical reaction that occurs within the human body involves phosphorus. It is found in complex organic compounds in the blood, muscles, nerves and in calcium phosphate (hydroxyapatite), the principal material that gives rigidity and strength to bone and teeth ( Int. J. Sport Nutr. 1992; 2:20-47).
[0014] Zinc is also an important element in human and animal nutrition. Zinc possesses catalytic, structural and regulatory roles in the more than 200 zinc metalloenzymes previously identified in biological systems. Metalloenzymes are mainly involved in nucleic acid and protein metabolism and the production of energy. Zinc also plays a structural role in the formation of so-called zinc fingers, which are exploited by transcription factors for interacting with DNA and regulating the activity of genes ( Science 1996; 271-108 1-1085). Additionally zinc is involved in the maintenance of the integrity of biological membranes and guards against oxidative injury.
[0015] Zinc is present in all of the body organs, tissues, fluids and secretions. Zinc is vital for growth and development, sexual maturation and reproduction, dark vision adaptation, olfactory and gustatory activity, insulin storage and for a variety of host immune defenses ( J. Nutr. 2000; 130 (5S Suppl); 1378S-1383S). Publicized claims that zinc is efficacious in preventing and ameliorating symptoms of the common cold are also supported by Nutrition Reviews ( Nutr Rev. 1988; 106:192-198).
[0016] Additionally, research suggests that iron and zinc stores are important not just in performance but also exercise-related health problems. Researchers report that exercise-induced menstrual dysfunction may be due to different levels of iron and zinc, both of which adversely affect bone health.
[0017] Nutritional supplement products containing calcium have been and continue to be available mostly in solid dosage formulations. However, of late calcium as different calcium salts but primarily calcium carbonate have been added to fortify beverages, yogurts, milks, and other foods. The required daily amount of elemental calcium is 1000 mg for adults and children over 4 years. Each calcium supplement tablet provides up to about one-half of the required daily amount. These tablets are usually large and hard to swallow. Consumers, especially older women and children, usually avoid such large tablets or take them with difficulty. Chewable forms available leave a gritty, chalky mouthfeel. The size of the tablet is dictated by the calcium salts used and marketing constraints that demand fewest tablets to be taken per day. The amount of elemental calcium available is highest in calcium carbonate at 40% and lowest in calcium gluconate at 9.3%. Calcium carbonate is the primary source of calcium in almost all supplements, fortified foods and beverages because of cost considerations and its highest elemental calcium content.
[0018] As described above, phosphorus is almost always present as calcium phosphate, which is essentially used as a delivery form of calcium or as a filler/binder in making tablets. The phosphorus content of calcium phosphate is about 25%. The required daily amount of phosphorus is 1000 mg. The amount of phosphorus available from calcium phosphate that is used as filler/binder does not exceed 250 mg. Therefore, while the required daily amount of calcium (1000 mg) is provided by 3-4 tablets, same is not true for phosphorus.
[0019] Zinc is available in a host of nutritional products. It is present in almost all multivitamin/mineral formulations, in tablets with calcium and magnesium and as lozenges. Dosage contents vary from 5 mg to 50 mg. The required daily amount of zinc is 15 mg.
[0020] As described above, the absorption of calcium from solid forms varies between 30% and 50%, being about 30% from calcium carbonate which is the primary source of calcium. Therefore, even though 3-4 tablets supplying 1000 mg of elemental calcium may be used, the total amount dissolved and available for absorption is at best 300-500 mg. In order to obtain the full amount of daily requirement of calcium, it is necessary to (1) increase the number of tablets to more than 15 per day or (2) increase the bioavailability/absorption of calcium. Since it is not practical to take 15 or more supplement tablets daily and technology does not exist to significantly increase the bioavailability and absorption of calcium from existing formulations, the present invention provides the method of solubilizing and the method of delivering completely bioavailable and absorbable bone minerals.
[0021] Many attempts have been made at increasing the solubility of calcium from solid forms.
[0022] U.S. Pat. No. 5,151,274 describes nutritional improvements in calcium supplements that can be used in conjunction with foods and beverages or taken as an oral solid or liquid supplement. Mineral calcium citrate malate in powder form is used in tablets, capsules, granules and bulk powders or added to a juice-containing beverage or other beverages. The solubility and absorption of calcium from calcium citrate malate powder is limited.
[0023] U.S. Pat. No. 3,949,098 describes a nutritious orange drink concentrate that contains whey protein. The patent suggests other nutrients which include various cupric salts, manganese salts, zinc salts, as well as calcium salts.
[0024] U.S. Pat. No. 4,497,800 describes a nutritionally complete ready-to-use liquid diet for providing total patient nourishment. The diet contains free amino acids, and small peptides, a carbohydrate source and nutritionally significant amounts of all essential vitamins and minerals and stabilizers. The minerals include calcium, copper, zinc and manganese, among others. Most of these minerals are given as a gluconate salt.
[0025] U.S. Pat. No. 4,214,996 discloses dispersible mineral compositions. These compositions contain calcium, phosphorus, zinc as well as manganese, as powders.
[0026] U.S. Pat. No. 6,235,322 discloses mineral compositions that have been mixed in solution with an acid, solubilized at high concentrations, dried and ground. Powdered mineral salts are thus formed which can be reconstituted in various vehicles. This patent teaches that compositions of calcium alone with acids were tried and they failed. The calcium fell out of solution within a short time.
[0027] It is known that salts of calcium alone formed with food grade acids such as, but not limited to, phosphoric acid, lactic acid, citric acid, ascorbic acid, malic acid are mostly insoluble in water. When added to water these calcium salts, either immediately or shortly thereafter will separate out of the solution.
[0028] Calcium has been used in the treatment and prevention of osteoporosis. However, none of the references of which Applicant is aware discloses the use, requirement or inclusion of phosphorus in required daily amounts as an equally important mineral for the prevention of osteoporosis.
[0029] It is desirable to provide a formulation of solubilized hydroxyapatite (calcium phosphate) and zinc citrate in aqueous solution which can be bottled, containing the Required Dietary Allowance of fully bioavailable calcium, phosphorus and zinc (when present) in easily consumable and palatable quantities.
SUMMARY OF THE INVENTION
[0030] The present invention relates to providing completely solubilized and bioavailable bone mineral calcium phosphate (hydroxyapatite) and zinc citrate in aqueous solution and the methods of producing and delivering the same. Hydroxyapatite, commonly referred to as calcium phosphate, constitutes the mineral portion of the bone and is a therapeutically important mineral in bones. Hydroxyapatite is critical in maintaining bone density and strength and to prevent osteoporosis. More particularly, the present invention provides completely solubilized hydroxyapatite (calcium phosphate) and zinc citrate, in a clear water beverage from which calcium, phosphorus and zinc all in ionized form, are completely bioavailable immediately after ingestion. This obviates the necessity and time-consuming steps of disintegration and complete dissolution that must first occur from conventional solid dosage supplements or the complete dissolution of conventional powdered calcium compounds from beverages because the body will only absorb calcium and other minerals in completely dissolved form.
[0031] Bones are composed of both calcium and phosphorus. These minerals are present in the form called hydroxapatite, also known as calcium phosphate. Hydroxyapatite gives bones strength and rigidity. When the body draws calcium from the bones into the blood for other functions performed by calcium, described above it must be replenished. If not done on a continuous basis, bones weaken which leads to low bone mass and fractures. Conventional supplements are available that supply calcium. Due to limited solubility of these supplements, only about one-third of the elemental calcium contained therein dissolves into ionic form that can be absorbed. This leaves a continuing deficiency of calcium in the body. Additionally, little or no phosphorus is provided by these supplements leaving the bones vulnerable to weakness and fragility. The present invention provides ingredients, the methods of processing and delivery of completely solubilized and bioavailable hydroxyapatite (calcium phosphate) and optionally zinc citrate to help keep bones strong and healthy.
[0032] An additional and unexpected benefit of the present invention is the management of body weight. It is believed that the weight control affect of the present invention may be due to availability of fully solubilized and absorbable calcium which is not available from supplements to the same extent.
[0033] In an alternate embodiment, a composition of powdered ingredients of the present invention can be consumed by adding the powder to commercially available aqueous beverages. The present invention preferably is used per se in aqueous solution to which, after completion of an effervescent reaction, has been added suitable flavor(s), sweetener(s), acidulent(s) and preservatives. One or more water soluble vitamins, plus vitamin D, folic acid; herbal ingredients and/or extracts thereof can also be added. The addition of some of these additional ingredients imparts some turbidity to the otherwise clear aqueous solution.
[0034] Preservatives can be added to prevent microbiological growth but more preferably the aqueous solution is sterilized by heating. Colorants can be added to match the flavor or for aesthetic reasons. It is however, preferred to retain the natural color of the aqueous beverage.
[0035] The present invention also provides for combining stoichiometric ratios zinc carbonate and glycine citrate and adding to a proper amount of water, such as 16 fluid ounces of water. The aqueous solution resulting from the effervescent reaction, contains completely solubilized zinc citrate and glycine.
[0000] Definitions
[0036] As used herein, the term “flavors” includes both fruit and botanical flavors. The term “fruit flavors” refers to those flavors derived from the edible reproductive part of a seed plant, especially one having a sweet pulp associated with the seed. Also included within the term “fruit flavors” are synthetically prepared flavors made to simulate fruit flavors derived from natural sources. The term “botanical flavors” refers to flavors derived from parts of a plant other than the fruit, i.e., derived from beans, nuts, bark, roots and leaves. Also included within the term “botanical flavors” are synthetically prepared flavors made to simulate botanical flavors derived from natural sources. Examples of such flavors include cocoa, chocolate, vanilla, coffee, cola, tea and the like. Botanical flavors can be derived from natural sources such as essential oils and extracts, or can be synthetically prepared.
[0037] As used herein, the term “sweeteners” includes both natural and artificial sweeteners. Sweeteners include, but are not limited to, sucralose, acesulfame potassium, aspartame, saccharin, sucrose, glucose, fructose, high fructose corn syrup, invert sugars, sugar alcohols including sorbitol, mannitol and mixtures thereof.
[0038] As used herein, the term “acidulents” includes, but is not limited to, citric acid, lactic acid, malic acid, sodium citrate, potassium citrate.
[0039] As used herein, the term “preservatives/antimicrobial agents” includes, but is not limited to sodium benzoate, potassium benzoate, benzoic acid, ethylparaben, methylparaben, propylparaben, sorbic acid.
[0040] As used herein, the term “herbal ingredients” includes, but is not limited to Echinacea, goldenseal, soy, teas, citrus aurantium and/or extracts thereof.
DETAILED DESCRIPTION OF THE INVENTION
[0041] The invention relates to an aqueous beverage for bone health and prevention or treating osteoporosis, to processes therefor and a composition of powdered ingredients for preparing an aqueous beverage.
[0042] The reaction of acidic compositions, hereinafter referred to as the “acid factor,” with bicarbonate or carbonate-containing compositions, hereinafter referred to as the “carbonate factor,” in an aqueous environment, such as a solution, to produce or release carbon dioxide is well known in the art and will hereinafter be referred to as an “effervescent reaction.” Products that undergo the effervescent reaction upon use normally comprise a dry, solid mixture of an acid factor and a carbonate factor, the mixture being hereinafter referred to as an “effervescent composition.” The acid factor and the carbonate factor in the effervescent compositions are normally dry solids and are water soluble, at least in the presence of each other. Additionally, the acid and carbonate factors utilized must be compatible with their intended use, i.e., they must be physiologically acceptable.
[0043] An effervescent composition of calcium carbonate, glycine phosphate and glycine citrate provides an aqueous beverage for bone health and preventing or treating osteoporosis upon adding the effervescent composition to a proper amount of water. The effervescent composition causes an effervescent reaction when added to water. Upon completion of the effervescent reaction, the aqueous beverage contains completely solubilized and bioavailable calcium phosphate, calcium citrate and glycine.
[0044] Optionally, the effervescent composition can include zinc carbonate. Upon completion of the effervescent reaction, the aqueous beverage also contains completely solubilized and bioavailable zinc citrate.
[0045] The calcium component of the present invention is derived from calcium carbonate. The phosphorus moiety comes from glycine phosphate (phosphoglycine). Optionally, zinc is obtained from zinc carbonate. Glycine citrate (citroglycine) is added not only as a critical reactant but also to aid complete solubilization of calcium carbonate, calcium citrate, zinc carbonate and zinc citrate. Calcium citrate and optionally, zinc citrate are reaction products, along with calcium phosphate (hydroxyapatite), glycine, carbon dioxide and water.
[0046] The inclusion of zinc carbonate as a reactant or zinc citrate as a reaction product in the aqueous solution of this invention is not needed to enhance solubility of calcium carbonate or enhance bioavailability or stability of the solubilized hydroxyapatite (calcium phosphate). The mineral zinc imparts its own therapeutic properties. The use of zinc is therefore optional.
[0047] Stoichiometric ratios of the effervescent composition of calcium carbonate, glycine citrate and glycine phosphate and optionally zinc carbonate, are added to a proper amount of water, such as 20 fluid ounces of water at room temperature in a suitable stainless steel or glass vessel with moderate mechanical stirring. Water can be tap water or it can be purified, deionized, carbonated or distilled. More preferably, reverse osmosis purified water is used. The effervescent reaction begins which lasts for 30-60 minutes. Mixing at moderate speed is maintained and can be stopped anytime during this time period. More preferably, mixing is maintained for 45 minutes. Stoichiometric ratios of the reactants are calculated to provide 500 mg of elemental calcium, 350 mg of elemental phosphorus and 7.5 mg of elemental zinc, when present, in each 20 fluid ounces of the aqueous solution of the present invention.
[0048] Next, sweetener(s), acidulents(s) and other nutritional and/or herbal ingredients, when used are added. Mixing is continued at moderate speed for 15-30 minutes, more preferably for 20 minutes. Flavor(s) are then added and mixing at moderate speed is continued preferably for 10 minutes.
[0049] The aqueous solution of the present invention containing completely solubilized and bioavailable hydroxyapatite (calcium phosphate) and optionally zinc citrate preferably provides 50% of the Recommended Daily Intake (RDI) of calcium, 35% of phosphorus and optionally 50% of zinc in each 20 fluid ounce serving. Two servings supply 100% of the RDI of calcium, 70% of phosphorus and 100% of zinc. Serving size can be reduced or increased. Serving sizes of 12 fluid ounces and up to 24 fluid ounces are common and acceptable. The preferred serving size of the present invention is 20 fluid ounces. Recommended Daily Intake of calcium and phosphorus and optionally zinc can be reduced by up to 50% or increased by up to 50% for the preferred serving size. Reducing the RDI would require more servings to be consumed per day. However, consumers may be averse to drinking more than two 20 fluid ounce servings daily. Not consuming the full servings would leave consumers deficient in the essential bone building minerals and thus negate the advantage inherent in the aqueous beverage of the present invention. Increasing the RDI of these minerals in the preferred serving size renders the aqueous beverage less palatable and thus less acceptable.
[0050] The aqueous solution of the present invention containing 50% RDI of calcium, 35% RDI of phosphorus and optionally 50% RDI of zinc in each 20 fluid ounce serving and after addition of other ingredients and further treatment as described above can be packaged in larger volume containers for ease of handling and cost savings. Containers of half gallon and one gallon size may be appropriate, bearing labels specifying directions for use as necessary.
[0051] The present invention also provides for combining stoichiometric ratios of zinc carbonate and glycine citrate and adding to a proper amount of water, such as 16 fluid ounces of water. The aqueous solution resulting from the effervescent reaction, contains completely solubilized zinc citrate and glycine.
[0052] Stoichiometric ratios are calculated to provide 100% of the RDI of zinc which is 15 mg. Serving size may vary between 12 and 20 fluid ounces. Preferred serving size is 16 fluid ounces. To this aqueous solution are added flavor(s), sweetener(s) and acidulent(s). Other ingredients that may be added, methods of processing and packaging are same as above.
[0053] The aqueous beverage containing completely solubilized hydroxyapatite (calcium phospate), optionally zinc citrate and other ingredients can be sterilized. Sterilization can be accomplished by the incorporation of preservatives/antimicrobial agents or heat. More preferably, sterilization is accomplished by heating. Heating can be accomplished in a heat exchanger or jacketed steam kettles. More preferably, heat exchanger is used to provide for faster and continuous processing. The aqueous solution is heated to between 140° F. and 200° F. More preferably to 195° F. and maintained at this temperature for 20-60 seconds, but more preferably for 30 seconds. The aqueous beverage is allowed to cool to 186° F. and bottled at this temperature. The pH of the aqueous beverage is in the range of 2.8 and 4.8. Prior to heating, the aqueous beverage of the present invention can be carbonated. More preferably, the aqueous beverage is maintained in the still, non-carbonated form.
[0054] When preservatives/antimicrobial agents are used, the heating step is by-passed. Preservatives/antimicrobial agents are added along with flavor(s), sweetener(s), acidulent(s) and other ingredients and the process continued as described above.
[0055] The aqueous beverage of the present invention containing completely solubilized and bioavailable hydroxyapatite (calcium phosphate) and optionally zinc citrate in flavored, sweetened, palatable form can be packaged in tightly capped polyethylene terephthalate (PET) or glass bottles or jugs but more preferably in PET bottles/jugs. The caps (lids) have tamper-evident rings that detach when bottles/jugs are opened. PET bottles/jugs can be clear or tinted.
[0056] Processed and packaged by the methods of the present invention, the aqueous beverage of the present invention containing completely solubilized and bioavailable hydroxyapatite (calcium phosphate), and optionally zinc citrate and other ingredients has been found to be stable with no change in taste, appearance, chemical or physical properties after two years.
[0057] In an alternate embodiment, the effervescent composition of the present invention can be used in powder form. In this embodiment, the ingredients used in the effervescent composition of calcium carbonate, glycine phosphate (phosphoglycine), glycine citrate (citroglycine), and optionally zinc citrate in their stoichiometric ratios, flavor(s), sweetener(s), acidulents(s) and other ingredients are mixed together and packaged in sachets for reconstitution. The stoichiometric ratios will yield the same RDI of each mineral as if they were to be used in water. The contents of the sachets are added to a predetermined amount of water, such as 20 fluid ounces of commercially available aqueous beverages. The aqueous beverages used for reconstitution of the sachet contents include, but are not limited to Seven-Up®, Seltzer Waters, Sprite®, plain bottled water and ice tea. The sachet contents can be added to less than 20 fluid ounces or more than 20 fluid ounces of the reconstitution beverage. Adding to less than 20 fluid ounces appreciably altered the taste and flavor which were not acceptable. Adding to more than 20 fluid ounces was acceptable but required that the entire volume be consumed in one day to derive the intended bone health benefit. The preferred volume of the reconstitution beverage is 20 fluid ounces.
[0058] After the sachet contents are added to a container of the aqueous beverage, the container can be closed and shaken lightly for 30 seconds. Within a minute, the cap can be removed to allow escape of the evolved carbon dioxide gas. The resulting beverage now also contains completely solubilized and bioavailable hydroxyapatite (calcium phosphate) and optionally zinc and is ready for consumption as such or after refrigeration.
[0059] The effervescent composition of the present invention can also be combined with commercially available powdered drink mixes prior to their reconstitution in water. The powdered drink mixes utilized for combining with the effervescent composition of the present invention include, but are not limited to, Kool-Aid®, Crystal Light®, Ice Tea To-Go® and Green Tea To-Go®, following the reconstitution directions on the packages of these powdered drink mixes.
[0060] In both cases above of reconstitution of the sachet contents of the present invention in commercial aqueous beverages or combining with other commercially available powdered drink mixes, the flavor(s), sweetener(s) and acidulents(s) concentrations in the sachet contents may need to be changed. More preferably, the amounts of these additives may need to be reduced as commercially available aqueous beverages and powdered drink mixes may already contain these additives in adequate amounts.
EXAMPLE
Comparative Bioavailability and Effect on Bone Density
[0061] A laboratory study was conducted to compare the relative affects of the aqueous beverage of this invention and calcium carbonate powder on bone development in young, growing rats. Ten male weanling Sprague-Dawley derived albino rats weighing 70-80 g were used in each group. All animals were fed the same basal diet. Control group received calcium from calcium carbonate powder incorporated in the diet. Drinking water was provided ad-libitum. Test group was provided the aqueous beverage of this invention containing completely solubilized hydroxyapatite (calcium phosphate) and calculated to contain the same amount of elemental calcium as the control group. The calculated volume was lower than the volume of drinking water consumed by the control group. The difference was made up by mixing drinking water with it. Food consumption, volume of drinking water, volume of the aqueous beverage of this invention and animal weights were recorded daily. At the end of 30 days the animals were sacrificed and both femurs from each animal were removed for evaluation. Results show that bone mineral density, tensile strength, femur ash, femur calcium and phosphorus were all much higher for the test group compared to the control. Bone density and bone strength numbers were 2.5-3 times greater for test group than the control. On day 30, the individual mean body weight gain for the test group was almost 15% lower.
[0062] It is to be understood that the above-described embodiments are illustrative of only a few of the many possible specific embodiments, which can represent applications of the principles of the invention. Numerous and varied other arrangements can be readily devised in accordance with these principles by those skilled in the art without departing from the spirit and scope of the invention. | 1a
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[0001] This application is Continuation-in-Part of application Ser. No. 13/291,345, filed on Nov. 8, 2011, and currently pending. The present invention is directed to a training device to enhance hand-eye coordination, in the field of sport training devices, applicable to particular sports in which hand-eye coordination comes into play. Examples include tennis, racquetball, baseball, and others.
BACKGROUND OF THE INVENTION
[0002] Many individuals participate in sports both as a pastime, as well as a hobby. As can be appreciated, it is important when participating in a particular sport to develop a proper technique in playing the sport to increase an individual's level of skill, as well as to prevent injuries.
[0003] Therefore, many techniques have been developed for assisting an individual in improving their skill level. With respect to a sport involving hitting a ball, a number of different devices have been developed to enable an individual to better improve his or her performance. For example, and with respect to a racquet sports such as tennis, racquetball or squash, U.S. Pat. No. 2,003,558 to An teaches the use of a training device provided with a uni-directional flexible spinner. This device includes a ball mounted on a flexible support column. In use, the individual strikes the ball at a top most position, forcing the ball away from the individual. Once the ball provided on the support column reaches a first position away from the top-most position, it returns from this position to a position closer to the individual. At this point, the ball then oscillates back and forth until it again reaches the top-most position. During the use of this training device, the individual endeavors to strike the ball when it returns to the top-most position. This type of device allows an individual to practice his or her technique in properly striking the ball without the necessity of including a partner in the training technique. However, the device described in the An patent does not afford the individual with any indication that the ball was properly struck.
SUMMARY OF THE INVENTION
[0004] The present invention relates to a training device to enhance hand-eye coordination.
[0005] It is, therefore, an object of the present invention to provide a sport training device, such as a reciprocating ball sports trainer, to assist an individual practice hitting a ball with an implement, such as, but not limited to a tennis racket.
[0006] It is a further object of the present invention to provide a sport training device including an illumination device for determining the proper time for the individual to strike the ball and to collect practice information for later evaluation.
[0007] It is yet another object of the present invention to provide a sport training device with various sensors for determining whether the ball has been properly struck.
[0008] The present invention addresses the deficiencies of the prior art by providing a sport training device, such as a reciprocating ball sports trainer, allowing an individual to practice hitting a ball with an implement such as a racket or bat, as well as providing an immediate indication whether the ball has been properly struck. In addition, the individual is provided with a record of his or her performance which can be reviewed by themselves or a professional. This is accomplished by providing a reciprocating ball sports trainer including a ball affixed to a flexible support assembly, and allowing the support and the ball which is attached thereto to reciprocate or pivot when the ball has been struck. The location of the ball is constantly monitored each time the ball is struck. The amount of force applied to the ball when struck by an individual or implement can also be determined. Information relating to the manner in which the ball has been struck is recorded and is analyzed in real time or after a practice session has been completed. The reciprocating ball sports trainer is fitted with wheels, skid pads or traction pads, allowing the sport training device to be steered, freewheeled, braked or slid after each impact with the ball. The direction and amount of travel of the sport training device can be controlled by varying the degrees of the wheels and/or the amount of resistance to movement.
[0009] A ball motor/generator is located in proximity to the ball. The ball motor/generator detects rotation of the ball. This is accomplished by monitoring pulses created by the rotation of the ball. Thereafter, the speed and direction of movement of the ball can be calculated. In addition, the motor/generator can assist the individual to spin the ball and create the effect of top or back spin. The amount of spin produced by hitting the ball is augmented or reduced through the use of a spin retarder placed in proximity with the motor/generator.
[0010] The present invention also includes a timing light providing a light which illuminates a lens when the ball has reached the exact point at which it should be hit by the user, for example, the top dead center point. The timing light uses a light source located in the bottom of the flexible support assembly such as a hollow spring that also holds the ball. When the ball reaches the top of its arc, the timing light illuminates the lens or opaque cover provided at the top of the flexible support assembly resulting from the light passing unimpeded from the bottom of the flexible support assembly to the top of the flexible support assembly. This indicates that the ball has reached the top of the arc at the top dead center position. As the flexible support assembly bends past the top dead center, the light is no longer illuminating the lens or cover due to the bending of the flexible support assembly which blocks light transmission, thereby indicating to the individual that it would not be the proper time to strike the ball. This action is repeated each time the ball passes the top dead center point.
[0011] A timing sensor is provided producing a signal when the individual strikes the ball. The timing sensor includes an illumination device provided in the base of the flexible support assembly and a reflector provided at the top of the flexible support assembly in a direct line with the illumination device. Since the timing sensor is in direct line with the reflector, light impinges on the reflector only when the flexible support assembly is at the top dead center position. Light impinging upon the reflector is reflected back to the bottom of the flexible support assembly to be received by a photo detector. Therefore, if the ball is struck when the flexible support assembly is at the top dead center position, a signal is produced indicating that the ball was struck at the proper time. However, if the ball is struck when the flexible support assembly is not at the top dead center position, a signal is produced indicating that the ball was not struck correctly or at the proper time. A controller provided with a microprocessor and memory is used to calculate and store the number of “good hits” and the number of “bad hits.” Additionally, an audio signal is produced when a “good hit” has been struck.
[0012] Information produced by the timing light and timing sensor, as well as sensed by the ball motor/generator is transmitted to the microprocessor within the base of the reciprocating ball sports trainer. The microprocessor includes a memory in which information generated by the reciprocating ball sports trainer is stored. This information, along with the output from the ball motor/generator is utilized to analyze the manner in which the user has struck the ball. The microprocessor provides real time, or post time information produced by the device. In addition, the device can display information relating to future goals, times, percentages, averages, correct and incorrect hits, impact velocity, as well as position data and any other information appropriate to the technique being developed by the individual. The reciprocating ball sports trainer can be internally or externally powered, recharged via external sources or internal such as kinetic energy generators, solar devices or other means. Real time monitoring by the user allows for real-time feedback, as well as possible interfacing to other interactive or storage devices such as a computer or some other user in real time with a like device such as a Wii. Information relating to the manner in which the individual is performing can be provided in a display included at the base of the sport training device.
[0013] Other objects and advantages of the present invention will become apparent from the following detailed description when viewed in conjunction with the accompanying drawings, which set forth certain embodiments of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] Preferred exemplary embodiments of the invention are illustrated in the accompanying drawings which the reference numerals represent like parts throughout in which:
[0015] FIG. 1 a is a front perspective view of the reciprocating ball sports trainer;
[0016] FIG. 1 b is a side perspective view of the reciprocating ball sports trainer;
[0017] FIG. 2 a is a side view of the sport training device;
[0018] FIG. 2 b is a rear view of the sport training device;
[0019] FIG. 3 is an exploded side view showing various components of the reciprocating ball sports trainer;
[0020] FIG. 4 is a detailed perspective view showing the top of the reciprocating ball sports trainer;
[0021] FIG. 5 a is a side perspective view of the reciprocating ball sports trainer showing the use of a skid attached to the base of the reciprocating ball sports trainer;
[0022] FIG. 5 b shows details of height adjustment of the device;
[0023] FIG. 6 shows various components of the reciprocating ball sports trainer;
[0024] FIG. 7 is a detailed view showing the base of the reciprocating ball sports trainer;
[0025] FIG. 8 is a side view of the reciprocating ball sports trainer showing the motion of the ball;
[0026] FIG. 9 is a perspective view of the reciprocating sports trainer showing the use of skids;
[0027] FIG. 10 shows an end cutaway view of the ball motor generator of the present invention;
[0028] FIG. 11 shows a side cutaway view of the ball motor generator;
[0029] FIG. 12 shows a schematic representation of the electrical circuitry of the present invention; and
[0030] FIG. 13 shows a schematic representation of further electrical circuitry details.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0031] The detailed embodiment of the present invention is disclosed herein. It should be understood, however, that the disclosed embodiment is merely exemplary of the invention, which may be embodied in various forms. Therefore, the details disclosed herein are not to be interpreted as limiting, but merely as a basis for teaching one skilled in the art how to make and/or use the invention.
[0032] As previously explained, the purpose of the inventive training device 10 is to allow an individual to practice hitting a ball 12 with any sort of implement, such as, but not limited to a tennis racquet, racquetball racquet, squash racquet and baseball bat. However, for purposes of simplicity, the present invention will be explained with respect to training an individual to properly strike a tennis ball with a tennis racket.
[0033] The reciprocating ball sports trainer 10 ( FIGS. 1 a and 1 b ) includes a ball 12 attached to a flexible support assembly 11 including a first vertical spring 18 and a second vertical spring 20 parallel to the first vertical spring 18 , as well as a first housing 22 and a second housing 24 . A ball 12 is attached to a U-shaped ball mount 14 ( FIGS. 1 a and 3 ) with a portion of the ball 12 extending beyond the end of the ball mount 14 ( FIGS. 2 a and 5 a ) in such a manner to allow the ball 12 to rotate when struck by the tennis racket. One or more bolts 50 ( FIG. 4 ) secure a back plate 49 to the ball mount 14 , with the tops of the springs 18 , 20 provided between the back plate 49 and the ball mount 14 . As shown in FIGS. 1 a and 2 a , a portion of the springs 18 , 20 will extend to, but not into the separate housings 22 , 24 , respectively. However, as shown in FIG. 5 a , the housings 22 , 24 can be eliminated. Both the vertical springs 18 , 20 as well as the housings 22 , 24 are hollow. The length of each housing 22 , 24 is not crucial to the operation of the present invention and could extend very close to the top ball mount 14 , or be provided a relatively large distance from the ball mount 14 . Housing 22 includes a top outer tube portion 23 and a bottom inner tube portion 27 . Housing 24 includes a top outer tube portion 25 and a bottom inner tube portion 29 . A tightening ring 19 secures the bottom of spring 18 to the top of the top outer tube portion 23 and a tightening ring 21 secures the bottom of spring 20 to the top of top outer tube portion 25 . Since individuals utilizing the reciprocating ball sports trainer 10 will be of different heights, it is important that the height of the ball 12 with respect to the individual could be adjusted so as to be the proper height for each individual. Therefore, the exterior of the housing 22 is provided with a first height adjustor 46 and the exterior of the housing 24 is provided with a second height adjustor 48 . Movement of each of the height adjustors 46 , 48 changes the height of each housing 22 , 24 as well as the height of each of the springs 18 , 20 . Therefore, the height of the ball 12 and the ball mount 14 with respect to the individual user is adjustable to accommodate children as well as adults of varying heights. Both of the housings 22 , 24 are attached to a base assembly 74 through the use of a spring clamp 72 and bolt 70 as shown in FIG. 7 .
[0034] The height of the housing 22 or 24 is changed by telescoping the bottom inner tube portion 27 or 29 , respectively, into or out of the top outer tube portion 23 or 25 , respectively. In one example, the height adjustors 46 , 48 are conical split rings which overlie the bottom inner tube portions 27 , 29 , respectively. As the height adjustor 46 is squeezed by a threaded sleeve 101 , the split 109 narrows and it tightens the bottom tube 27 around the upper tube 23 . Similarly, the length of housing 24 is changed by telescoping the upper inner tube portion 25 into or out of the lower outer tube portion 29 . The height adjustor 48 is a ring with a split 111 which overlies the bottom inner tube portion 27 . As the height adjustor 48 is squeezed by threading down sleeve 105 , the split 111 narrows and it tightens the top outer tube portion 25 around the bottom inner tube portion 27 . As can be appreciated, the height of both of the housings 22 , 24 should be equal to one another during use of the reciprocating ball sports trainer 10 .
[0035] With further reference to FIG. 5 b , in more detail, it is seen that the rings 46 and 48 are conical in nature and have respective external threads 113 and 115 on their outer surfaces. Each ring is also split, with the ring 46 having a split 109 and the ring 48 having a split 111 . With respect to the telescoping tubes 23 , 27 , a threaded locking sleeve 101 has internal threads 103 designed to enmesh with the threads 113 of the ring 46 . As the sleeve 101 is rotated so that it descends over the ring 46 , the conical nature of the ring 46 results in the split 109 narrowing, causing the ring 46 to clamp radially inwardly to therefore lock the vertical position of the tube 23 with respect to the tube 27 . The respective upper tube portions 23 , 25 may telescope within the respective lower tube portions 27 , 29 or vice-versa as desired.
[0036] In the case of the tubes 25 and 29 , similarly, the ring 48 is conical with external threads 115 . The locking sleeve 105 has internal threads 107 that enmesh with the threads 115 of the ring 48 . As the sleeve 105 is rotated to descend over the ring 48 , the conical nature of the ring 48 results in the split 111 narrowing, causing the ring 48 to clamp down radially inwardly to lock the vertical position of the tube 25 with respect to the tube 29 .
[0037] A first base assembly 74 ( FIG. 1 a ) is mounted upon two longitudinal members or skids 26 which diverge from the base assembly point 74 as illustrated in FIGS. 1 a - 3 . The base arms 26 act as a base to support the springs 18 , 20 , the housings 22 , 24 and the electronics and illumination devices used to operate the reciprocating ball sports trainer 10 . Each of the base arms 26 is provided with separate handles 28 , 30 for ease of moving the reciprocating ball sports trainer 10 from one location to another location. FIG. 1 includes a wheel or roller 38 attached to the ends of each of the base legs 26 at the end opposite the handles 28 , 30 . A butterfly nut 68 (or similar device) as shown in FIG. 3 attaches the wheel or roller 38 to the connection point of the base legs. As illustrated in FIG. 5 , a skid pad 56 or similar device can be substituted for rear wheel or roller 38 . As can be appreciated, striking the ball 12 with the roller 38 attached to the base legs 26 causes the reciprocating ball sports trainer 10 to move more easily than having the skid pad 56 attached to the skids 26 .
[0038] As shown in FIG. 7 , two load cells 32 , 34 are provided on or immediately above the base assembly 74 for use in determining whether a ball 12 is properly struck by the individual. One load cell 32 measures the lateral motion of the springs 18 , 20 and the second load cell 34 measures any reciprocating movement of the springs 18 , 20 when the ball 12 is struck. The load cells are mounted to the bottom base plate of the device with one on top of the other. The lower load cell 34 is mounted vertically and the upper load cell 32 is mounted horizontally. The lower load cell 34 detects the amount of front 120 to back 122 torque applied to the base 74 when the ball is hit, and the upper load cell 32 detects the amount of rotational, or side 124 to side 126 torque applied to the ball 12 and upper assembly tubes 22 , 24 . The load cells are able to measure the amount of torque and the rate at which it is applied. The electrical signals from the two load cells are sent to the microprocessor 129 ( FIGS. 12-13 ) via their own wiring harness. That signal will then be used to calculate the amount of energy applied when the ball 12 was struck. By continually monitoring this information, the microprocessor 129 will be able to determine how hard the ball was hit, the direction, and where in the arc the ball is located. This information will also be used to calculate what the trajectory, and velocity of the ball would have been, if the ball 12 were in free play. Calculations within the microprocessor graph the movement of the ball like that of a sinusoidal wave and the zero line is referenced as the zero point of the arc. A graphic representation of the movement of the head looks very much like that of an EKG, or cardiac strip used by a doctor or a paramedic to monitor a Heartbeat. This “STRIP” as it's called, is used to evaluate the player's performance. These same measurements are also transmitted (option set via the control panel by the user) to a website, or any other electronic device. This information along with the other data can be used for interactive games, or coaching. It is also used for Live Interactive Tele-Present Coaching, or “Tele-Coaching.” For Example, a student purchases a device, and that student has an internet connection. The student is able to send a live video stream of them, from a remote camera linked with the device. That video and data are then streamed from the device to a coach at a remote location. The coach can then monitor and give real time feedback to the student. Another example is going on vacation and still getting one's tennis lesson while half a world away.
[0039] FIGS. 3 , 6 and 7 illustrate the reciprocating ball sports trainer 10 of the present invention with various components removed from an operational reciprocating ball sports trainer 10 for ease of illustration. As shown in FIGS. 1 and 4 , the ball 12 is provided between the two arms 13 , 15 of the ball mount 14 . A ball motor/generator 42 is provided in the interior of the ball 12 . The ball motor/generator 42 is designed to allow the direction of rotation as well as the speed of rotation of the ball 12 to be detected and measured. The ball motor/generator 42 includes an armature and rotor mounted within a small tube provided within the ball 12 itself. The two ends 42 a , 42 b of the ball motor/generator 42 secure the ball 12 to the ball mount 14 through the use of two end caps 16 , allowing the ball 12 to rotate between the two arms 13 , 15 of the ball mount 14 .
[0040] With particular reference to FIGS. 6 and 10 - 11 , the ball motor generator 42 is a small DC electric motor/generator located within the axle shaft of the ball. It consists of an armature or rotor 130 (outer portion of the shaft attached to the ball) and a stator 134 (inner portion) having plural windings 136 and mounted on the ball mount 14 . Brushes 138 on the armature 130 are spring biased ( 139 ) to engage the support shaft 140 . Armature 130 includes permanent magnets 142 , 144 . Ball bearings 146 facilitate rotation of the armature 130 with respect to the stator 134 . When the ball 12 spins, the rotation of the armature 130 begins inducing a voltage into the stator 134 . The output voltage and polarity of the ball motor generator 42 are determined by the speed, and direction of rotation and reproducibly represent values of speed and direction of rotation. This information is continually sent to and monitored by the microprocessor 129 to determine whether top or backspin was applied to the ball and how much. The polarity of that output voltage determines the direction of spin, and the amount of voltage used to determine the speed of rotation and amount of spin. The microprocessor 129 captures the voltage levels, and the electrical power that is generated is even re-used via a capacitor. The electrical energy stored in the capacitor bank is then used to recharge the batteries 141 ( FIGS. 12-13 ). Additional recharging capabilities come from the solar panels 143 ( FIG. 13 ) under the display panel. The energy generated is used to power the device, which upon external “spin control” commands via the Wi-Fi interface making the ball spin in either direction. This technique is for a trainer to change the ball dynamics which provides the student with another level of interaction with the device. By being able to place a spin on the ball, a trainer can provide an additional level of interactive game play, or practice session.
[0041] The electrical energy that travels to and from the ball motor generator is done through electrical conductors 160 , 161 ( FIG. 6 ) on both ends of the axle that contains the ball motor generator. From the ball motor generator 42 , electrical conductors 160 , 161 or wires transmit the electrical signals to the microprocessor 129 at the base 74 of the unit. The same wiring harness provides connectivity with the LEDs and a photoelectric cell located alongside the LEDs within the base. That wiring harness then connects to the main control box and is wired directly into the onboard microprocessor 129 .
[0042] Once the ball 12 is struck by the tennis racket or other device, the ball 12 moves about an arc 76 , 78 as shown in FIG. 8 through the pivoting movement of springs 18 , 20 . If desired, the tension of the springs 18 , 20 may be adjusted in a manner well known by those skilled in the art for slow, medium, or fast return flexing. However, the housings 22 , 24 are fixed in place but slightly flex in both a traverse and/or lateral direction based upon the manner in which the ball 12 has been struck. At this time, as will be explained, the rotation, direction, as well as speed of acceleration and deceleration of the ball 12 are detected by the motor generator 42 . This information is transferred to the microprocessor 129 ( FIGS. 12-13 ) provided in the base assembly 74 of the device. In operation, the rotor 134 is fixed and the armature 130 spins around the rotor of the ball motor/generator 42 ( FIGS. 10-11 ). The rotor is connected to the end cap 16 and two small wire 160 , 161 ( FIG. 6 ) transmit the electrical signal sent by the ball motor/generator 42 to the rear 17 of the ball mount 14 to which the two small wires are connected to small electrical contacts. These electrical contacts allow the electrical connection to be transferred from the ball motor generator 42 down through the flexible support assembly 11 to the microprocessor 129 provided in the first base assembly 74 . Two additional electrical contacts are connected directly to the microprocessor 129 allowing the processing of the motor/generator signals to take place. Additionally, as will be subsequently explained, signals from the ball motor/generator 42 as well as signals received from a timing light and the load cells (or sensors) 32 , 34 are also processed and stored within the microprocessor 129 . As best shown in FIG. 7 , the lateral load cell 32 is provided between the springs 18 , 20 , at a small distance above the base assembly 74 . Similarly, the reciprocating load cell 34 is also provided between the base of the springs 18 , 20 and immediately above the top of the base assembly 74 .
[0043] The lateral load cell 32 and the reciprocating load cell 34 are designed to determine the positioning of the ball 12 by measuring the amount of load that is applied to the base assembly 74 of the reciprocating ball sports trainer 10 . The reciprocating load cell 34 determines the position of the ball 12 with respect to vertical by determining the amount of pressure that is applied either in a forward or reverse direction from the center portion of the ball 12 based upon the torque that is sensed by the load cell 34 . When the ball 12 is in the zero position, the springs 18 , 20 are perfectly aligned straight up and down from the ball mount 14 to the base assembly 74 . When the ball 12 is struck, the ball 12 , the ball mount 14 , and the springs 18 , 20 will move away from the point of impact in a positive direction 78 as shown in FIG. 8 . As the ball 12 moves further from the zero position to the furthest point away (direction 76 ) from the center of the arc as shown in FIG. 8 , the amount of torque applied to the reciprocating load cell 34 increases. As this distance increases in the positive direction 78 , the pressure on the base assembly 74 as well as the load cell 34 is also increased. The reciprocating load cell 34 measures the torque and provides a reading to the microprocessor 129 to determine approximately how far the ball 12 has traveled from the zero point. This measurement allows for the determination of the approximate amount of energy that has been applied to the ball 12 to determine how far and how fast the ball 12 would have traveled from the point of impact, if the ball 12 were not attached to the reciprocating ball sports trainer 10 .
[0044] As the ball 12 starts to come back toward the center or zero point, the amount of torque applied to the reciprocating load cell 34 decreases which is detected. Once the ball 12 reaches the top dead center or zero point and passes into the negative portion of the arc 76 , this motion is detected by the reciprocating load cell 34 to measure how long it took for the ball 12 to cycle, as well as to what speed the ball 12 was traveling as it passed over the zero point. Once the ball 12 has reached its maximum travel distance across the arc and into the negative territory 76 , the reciprocating load cell 34 determines how far past the center point into the negative portion of the arc the ball 12 has traveled. As the ball 12 begins to travel back toward the zero point once again, the reciprocating load cell 34 detects this movement as well.
[0045] Once the ball 12 reaches the zero point for the second time, it will then travel into the positive portion 78 of the arc and begin to return toward the zero point for the third time. When the ball 12 reaches the top dead center point or zero point for the third time, this is the precise moment of the desired impact by the user. By calculating whether or not there was a positive or negative force, or no force at all upon the ball 12 at the time of impact, the system can determine whether or not the ball 12 was struck early, late or precisely at the optimum point of contact, which is the zero point. By monitoring each individual impact as well as the oscillation of the ball 12 and the ball mount 14 ; the present invention itself determines whether or not the user is contacting the ball 12 early, late or exactly as desired.
[0046] When the ball 12 is struck the first time, it moves to the maximum forward position in the arc. As it returns towards the top dead center for the first time, the user does not have enough time to get the racket in place again to hit it before it reaches to top dead center for the first time. As it passes top dead center for the first time, it is moving toward the maximum negative point in the arc. Once it reaches that point, the ball 12 then starts to travel towards the positive side of the arc. Once it reaches the top dead center for the second time, it is traveling in the same direction as the user would be swinging. However, the user would not have enough time to swing at the ball 12 a second time. As the ball 12 reaches the maximum forward point of the arc for the second time, and the ball 12 has now passed the top dead center twice, the user can then begin their next swing. The goal is to have the user's racket hit the ball 12 at the exact same time that the ball 12 reaches the top dead center for the third time which is when the ball 12 is traveling in the opposite direction as the racket, and a solid hit can be applied to the ball 12 .
[0047] If no lateral roll is sensed by the reciprocating ball sports trainer 10 , particularly by the load cell 32 , this means that the user has struck the ball 12 so that it has traveled without any angle with respect to the user. However, during a tennis match, there are many instances in which the player might wish to strike the ball 12 so that it would angularly move left or right with respect to the player.
[0048] The lateral load cell 32 is used to determine the amount of lateral roll or angulation from vertical, if any, has been produced when the user impacts, as well as the side spin sensed in conjunction with the ball motor/generator 42 the ball 12 . This is done by calculating the amount of torque applied to the ball 12 in a left or right direction, as opposed to the normal arc of travel as shown in FIG. 8 . As shown in FIG. 4 , the bolts 50 attach the back plate 49 to the ball mount 14 in a manner in which the ball 12 is not angled with respect to the back plate 49 . However, additional holes (not shown) may be provided in the rear of the ball mount 14 to allow the ball mount 14 to be adjusted at a particular angle, such as, but not limited to, 45 degrees to the left or to the right. This is accomplished by attaching the bolts 50 to the back plate 49 using holes provided in the back plate 49 to the left or right of center of the back plate 49 . When the ball mount 14 and thus the ball 12 is adjusted either to the left or to the right, and the user attempts to put side spin, back spin or top spin on the ball 12 , the lateral load cell 32 is able to detect the amount of side torque or twisting of the ball 12 in the left or right direction. By measuring and calculating the amount of force that is applied, the present invention will determine whether the user is hitting the ball 12 correctly, as well as how much lateral movement from the normal arc shown in FIG. 8 , a particular swing has provided. In addition, each impact can be registered and recorded by remote electronic devices or later reviewed by the user or an instructor. In addition, the function buttons 58 shown in FIG. 7 allow the user to change the amount and type of information which is measured and recorded. In addition, some of this information is directly provided to the user by the digital display 60 .
[0049] In addition to sensing when an individual has properly struck the ball 12 as well as to determine various other parameters of the ball striking ability of the individual, the present invention assists the individual hitting the ball 12 at the proper location, i.e., the sensor zero point. In FIG. 6 , the base assembly 74 is provided with a first illumination device including a light emitting diode 62 provided directly under the housing 24 . The illumination produced by the light emitting diode 62 is directed upward through the housing 24 and the hollow spring 18 to a timing light lens 52 ( FIGS. 4 and 6 ) attached to the top of the spring 20 . The light emitting diode 62 shines up through the spring and impacts the bottom of the timing light lens 52 only when the spring 20 is perfectly vertical with respect to the base assembly 74 . The lens 52 has a reflective coating on its bottom surface that reflects much of the light back down toward the LED 62 , however, when light strikes the lens 52 , enough light shines through the reflective coating that the lens illuminates, the illumination clearly visible to the user and signifying that the spring 20 is perfectly vertical, the optimal orientation at which to strike the ball 12 . When the ball 12 is struck by the individual, springs 18 , 20 move in positive and negative directions away from the zero point. When this occurs, at times when the spring 20 is not perfectly vertical above the base assembly 74 , the light emitted by the light emitting diode 62 is blocked by the bending of the spring 18 and thus the illumination of the light emitting diode 62 no longer strikes the timing light lens 52 and thus is not reflected back down the tube assembly to be detected by the photo electric detector 66 . As the ball 12 travels back to the zero position and comes into perfect alignment with the light emitting diode 62 in the base assembly 74 , the path of the light produced by the light emitting diode 62 is no longer blocked by the spring 20 and the timing light lens 52 becomes illuminated again by direct line of sight by the emitting diode 62 located within the base assembly 74 . Again, the light hitting the timing light lens 52 , visible to the user, indicates to the user the proper time to strike the ball 12 which is when the ball passes over the zero point of the arc.
[0050] A second illumination device including a light emitting diode 64 ( FIG. 6 ) is provided in the bottom of the base assembly 74 and is aligned with the housing 22 and the spring 18 . The top of the spring 18 is provided with a timing light reflector 54 ( FIGS. 4 and 6 ). The reflector 54 reflects light from the LED 64 back toward the LED 64 . When the reflected light reaches the base, it is detected by photo transistors located beside and shielded from the LEDs such as the detector 66 ( FIG. 6 ) shielded by the tube 65 . This electrical signal is constantly monitored by the microprocessor and compared to other signal inputs from the device in real time. Similar to the light emitting diode 62 , light emitting diode 64 produces a beam of light directed from the base assembly 74 up through the housing 22 and the spring 18 which strikes the timing reflector 54 only when the spring 18 is vertical with respect to the first base 74 . As is the case with the lens 52 , the timing reflector 54 allows enough light to shine through its reflective coating so that it glows and indicates to the user that the spring 18 is perfectly vertical. Since the springs 18 and 20 are perfectly vertical simultaneously, use of phototransistors adjacent the light source 62 is optional. The lens 52 and reflector 54 are both provided so that regardless of whether the user is right handed or left handed, they can clearly see the glowing of at least one of them when the ball 12 is perfectly vertical. Therefore, the light produced by the light emitting diode 64 only strikes and illuminates the timing light lens 52 when the spring 18 is in the zero position. The first base assembly 74 is provided with an illumination sensing device including a photo detector 66 provided in a cylinder 65 in proximity with the light emitting diode 64 . The purpose of the cylinder 65 is to prevent cross-contamination of the light between the light emitting diode 64 and the photo detector 66 . The main purpose of this timing light is to determine if the user has struck the ball 12 at the proper time when the ball 12 passes near the zero point within the arc. It is noted that both the timing light lens 52 and the timing light reflector 54 illuminates the top of the springs 18 , 20 at the same time and the tops of the springs 18 , 20 become dark at the same time.
[0051] To determine whether the ball 12 has been properly struck on its return arc toward the zero point prior to impact, the microprocessor 129 of the present invention is looking for signals from the lateral load cell 32 , the reciprocating load cell 34 , as well as the zero point detector associated with spring 18 . If the present invention detects an impact of the ball 12 without detecting the pulse from the photo cell 66 , the impact was not correct and would not be considered a good hit. If the system of the present invention detects the pulse received from the photo cell 66 and no impact is detected for a period of time before and after this pulse is detected, then it would be determined that this hit was not correct. The proper correlation between the impact of the ball 12 and the detection by the photo cell 66 also indicate whether the hit was late or early. The amount of impact as well as the amount of time passing between the impact sensed and the zero point is detected, can be programmed or changed within the unit to determine a window of what would be considered a good or bad hit. The present invention is able to determine whether an impact at the zero point or any degree positive or negative of that zero point can be determined as to what would be considered as a good hit.
[0052] As shown, for example, in FIGS. 1 and 2 , a roller or wheel 38 is located at the point the longitudinal members of the leg base 26 converge together. The purpose of the wheels or rollers 38 is to allow the user to move the device around the training area. Additionally, although a single roller wheel 38 is shown in FIGS. 1 and 2 , the unit can be provided with additional rollers to best achieve the amount of movement and direction of movement required by the user. Each time the ball 12 is struck, the impact carries through the base unit and propels the unit forward based upon the amount of energy applied to the ball 12 by the impact. The roller or rollers on the base of the unit have a resistance capability that can be adjusted to allow for the amount of roll desired by the user. This resistance is created by loosening or tightening the butterfly nut 68 . In addition to the amount of roll, the direction of each of the rolls so as to allow the device to roll in a particular direction each time the unit is impacted by the user. This will make it necessary for the user to reposition himself or herself next to the device each time the user wishes to impact the device or swing at the device. The rollers can be used by themselves or in combination with a pad or skid 56 as shown in FIG. 5 . The use of the pad 56 prevents the unit from moving after each impact or moving very little in combination with a roller or the pad 56 . The pad 56 can be placed on the bottom of the unit to allow it to slide on different types of surfaces such as tennis courts, pavement, wooden floors, carpeting or any other type of flooring or ground material. The pad 56 may be made of any suitable material such as plastic, wood, metal and may, if desired, be covered with a cover or coating to facilitate the desired degree of friction. The device shown in FIG. 5 a utilizes elongated springs 31 , 33 extending from between the ball mount 14 and the back plate 49 and the base 74 instead of the springs 18 , 20 and the housings 22 , 24 shown in FIG. 3 . Additionally, as shown in FIG. 9 , skid pads 80 , 82 can be provided at the end of each skid 26 which would also affect the manner in which the training device would move when the ball 12 is struck.
[0053] As previously explained, FIGS. 6 and 7 show the use of the first base assembly 74 providing a digital display 60 as well as a plurality of function buttons 58 . The function buttons 58 may be arranged in multiple rows including rows above and below the display 60 . Function buttons 58 may be pushed to control on/off of device, on/off of WiFi connection, synchronization with WiFi, dump data to the USB port 188 ( FIG. 12 ), control operation of the speaker 183 ( FIG. 12 ), clear stored data, control operation of the microphone 184 ( FIG. 13 ), cause data to be displayed on the display 60 , cause training data to be stored in the CPU 129 ( FIG. 13 ), to control operation of the USB port 188 , control operation of the Wii port 196 ( FIG. 13 ), and control connection to an external device such as an X Box via the port 200 ( FIG. 13 ). The display 60 can display items including amount of practice time elapsed, total hits, total good hits, remaining practice time, whether ball spin has been initiated, indicate on/off status and/or provide a system ID. This first base assembly 74 is attached to the longitudinal base legs 26 at points 90 , 92 , the longitudinal base legs 26 forming a second base assembly. The microprocessor 129 for controlling operation of the present invention is also housed in the base assembly 74 as well as being powered by one or more batteries or similar devices stored in power pack 88 shown in FIG. 9 . The present invention has a variety of different capabilities and functions and can provide a wide range of information not only to the user, but to a coach or instructor as well as uploading information to a website via the Internet. The present invention can be provided with an I-O port that is capable of being interfaced with a wide variety of different electronic devices or components, for example, the I-O port can be plugged into a home computer or a device such as a Wii such that remote information and remote players can be interfaced to the unit such that a semi-reality practice match with professionals or other players in other locations can be conducted utilizing the microprocessors. The present invention can also be interfaced with a home game station so that users can practice against computer-generated professionals to help hone their skills. As previously indicated, the present invention can count the number of good hits, bad hits, total number of hits, as well as a percentage of good or bad hits. The present invention can run software programs and allow the unit to provide lessons and determine if the user has reached a skill level that can be programmed by the user or instructor.
[0054] With particular reference to FIGS. 12-13 , the microprocessor 129 connects to all of the electronics in the device. There are several Input/Output (I/O) signals and ports on the device such as a Pulse Width Modulation (PWM) I/O 181 signal, an Audio Output (Speaker) 183 , as well as for Video Output 185 , and Data signal outputs. The device will also have multiple wireless capabilities, such as Bluetooth or Wi-Fi wireless connections 187 to routers. These interfaces with other electronic devices provide for remote interaction, training, and programming. The main function is to monitor and record all inputs, calculate that raw information, and provide real-time feedback. A “Good Hit” is determined by only one thing, and that is the ball being hit when it is in the top dead center position. The device has several ways of detecting this. First, reflected light 62 , 64 must be detected. Second, the shock of an impact is detected at the same time, and the load cells 32 , 34 show that the head has changed to the forward direction at the top dead center, and it is moving at a greater velocity than when it entered that position. The level of force applied to the ball is also considered when calculating a Good Hit. That level, along with all other I/O's can be adjusted in the programming. The device can be programmed by the user or remotely to have goals, and what type of information to be displayed. This information will consist of percentages, number of good or bad hits, numbers of hits needed, times, dates, calories burned, temperature, and solar, and voltage levels. It can also remind you to put on sunscreen. This is achieved by monitoring the input voltage level from the solar panel 143 . The voltage output from the solar panel 143 is designed to be sufficient to facilitate relatively rapid recharge of the batteries 141 . It will also tell you if it is not getting enough sun to recharge, and can even sound an alarm to remind you of your tennis lesson. This can be programmed via any of the aforementioned ways. It can also be synched to your calendar book. The device can be set up via the control panel to also email, and have performance records remotely printed. In addition to being able to provide pre-recorded voice responses, it has a speech recognition function that will allow the user to speak their requests rather than have to key them in. All inputs can be done from the touch screen, the control buttons, via tablets or smart phone devices and gaming stations through the internet (global computer network) interface (Wi-Fi) (via means for so connecting) or by voice commands. Voice commands, sound prompts, and other audio signals are pre-programmed into the device as well. These are triggered by how well the student is performing. All of these parameters will be programmed into different levels, and multiple voice responses will randomly be given via speaker 183 for the same result. i.e.: “Well done”, “Good job”, “That's the way”, “Way to go”, and several others, will be pre-programmed audio type responses generated from the device for a good hit. A microphone 184 ( FIG. 13 ) may be provided to allow communications between a user and the microprocessor 129 . A USB port 188 ( FIG. 13 ) is provided to allow easy transfer of data stored in the microprocessor 129 . The microprocessor 129 may be coupled to an “X Box” or Nintendo device as desired, wirelessly or directly.
[0055] The display 192 allows display of data resulting from use of the inventive device in a suitable format for easy viewing and understanding. The data to be displayed can include amount of time practiced, total hits, total good hits, remaining practice time, direction of ball spin, an indicator showing that the device is operable as well as log-in information. Also associated with the microprocessor 129 is a keypad 194 allowing inputting of commands to the microprocessor 129 . A Wi-Fi interface 196 ( FIGS. 12-13 ) allows wired connection to the Internet while a wireless connection 187 also has an antenna 198 to facilitate wireless Wi-Fi connection. These Wi-Fi connections permit communications with remote teachers.
[0056] As illustrated in FIG. 4 , the present invention is provided with a spin retarder 40 . The spin retarder is used to decrease the amount of rotation of the ball 12 once impacted by the user. The spin retarder 40 is composed of two opposed discs provided between the end cap 16 and the ball 12 , each disc provided on either side of the ball 12 . These discs apply friction to the rotation of the ball 12 . As the amount of friction is increased by adjusting the pressure on the two discs, the amount of rotation of the ball 12 is retarded. The purpose of the ball spinner retarder is to allow the user to increase the amount of top spin or back spin applied to the ball 12 with each hit. If little or no friction is applied to the ball 12 , can spin freely makes it very difficult to determine how much top spin or back spin was applied to the ball 12 each time it was hit. As the amount of resistance is increased, the amount of rotation decreases and allows for the user to determine whether they are applying a substantial or significant amount of top spin or back spin to the ball 12 with each hit of the ball 12 .
[0057] While the preferred embodiments have been shown and described, it will be understood that there is no intent to limit the invention by such disclosure, but rather, is intended to cover all modifications and alternate constructions falling within the spirit and scope of the invention. | 1a
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FIELD OF THE INVENTION
This invention relates, generally, to an improved air-operated, low air loss, active feedback patient support system. More particularly, it relates to an improved self-contained corrective, low air loss, dynamic patient body weight air support system which has active feedback pressure sensing and real time automatic pressure correction capabilities for use on a sleeping surface and/or as a wheelchair therapeutic pressure relief system.
BACKGROUND OF THE INVENTION
The capillary occlusion pressure threshold is 32 mm Hg. Pressures above 32 mm Hg result in capillary closure which occludes blood flow to the tissue. Decubitus ulcers occur when the blood flow through the skin capillaries is occluded due to the compression of tissue for a prolonged period of time. Decubitus ulcers, which are also referred to as pressure ulcers, pressure sores and bedsores, are a pervasive problem in the health care field. The most crucial factors in the formation of decubitus ulcers are the intensity and duration of the pressure being applied to the area of the patient's body.
There are a variety of systems available that are intended to reduce the formation of decubitus ulcers. These systems are either static devices or dynamic devices. Static devices include foam mattresses and gel and/or air cushions and/or mattresses which attempt to redistribute support pressure away from bony prominences. For example, static air mattresses include those disclosed in U.S. Pat. No. 4,685,163 to Quillen et al., U.S. Pat. No. 5,369,828 to Graebe and U.S. Pat. No. 5,282,286 to MacLeish. Static devices are undesirable because they require frequent turning and repositioning of the patient by health care workers and do not maintain pressure relief below the 32 mm Hg capillary occlusion pressure threshold.
Dynamic devices, such as alternating air mattresses, function by alternately shifting support pressure. Generally, these devices can be divided into two general types, no air loss devices which are made of an air and liquid impervious material and are, therefore, airtight, and those which are made of materials or supplied with additional manifolds to provide for low air loss from the device.
No air loss air devices include, for example, those disclosed in U.S. Pat. No. 5,509,155 to Zigarac et al., U.S. Pat. No. 4,833,614 to Saitoh et al., U.S. Pat. No. 4,864,671 to Evans, U.S. Pat. No. 5,500,965 to Hannagan et al., U.S. Pat. No. 5,010,608 to Barnett et al., U.S. Pat. No. 5,243,721 to Teasdale, U.S. Pat. No. 4,953,247 to Hasty, U.S. Pat. No. 4,852,195 to Schulman, U.S. Pat. No. 4,796,948 to Paul et al., and U.S. Pat. No. 4,175,297 to Robbins et al. These devices, while alternately shifting support pressure are problematic due to the build up of heat and moisture at points of interface between the mattress and a patient, which leads to skin maceration and ultimately decubitus ulcer formation.
Low air loss devices, for example, are disclosed in U.S. Pat. No. 5,003,654 to Vrzalik, U.S. Pat. No. 5,267,364 to Volk, U.S. Pat. No. 5,103,518 to Gilroy et al., U.S. Pat. Nos. 5,193,237, 5,379,471 and 5,533,217 to Holdredge. Low air loss devices have been found to be particularly useful because these mattresses prevent the build up heat and moisture at points of interface between the mattress and a patient, which prevents skin maceration.
However, all of these devices have various shortcomings. For example, static devices require turning and repositioning of the patient. Alternating devices attempt to alleviate the problem of turning and repositioning by alternately inflating and deflating individual air sacks or groups of air sacks based on cyclic preselected time intervals. However, these devices, due to their alternating nature, produce areas of concentrated high pressure on the patient's body at the interface with the inflated portions and areas of little or no support on the patient's body at the deflated portions. Further, none of these devices provide a low air loss device which simultaneously prevents skin maceration due to the build up of heat and moisture at points of interface between the device and the patient, and is an active feedback system which provides for real time adjustments to the inflation pressure of the air mattress in response to an increase in the compressive pressure on a part of the mattress from shifting of the patient's weight or other causes.
Thus, what is needed then is a corrective, low air loss, dynamic patient body weight air support system which has active feedback pressure sensing and real time automatic pressure correction capabilities.
In view of the prior art as a whole at the time the present invention was made, it was not obvious to those of ordinary skill in the pertinent art how the needed dynamic patient body weight air support system could be provided. Further, it was not obvious to those of ordinary skill in the pertinent art how a dynamic patient body weight air support system having active feedback pressure sensing and real time automatic pressure correction capabilities could be provided which maintained pressures below the 32 mm Hg capillary occlusion pressure given the reduced surface area of a wheelchair seat.
SUMMARY OF THE INVENTION
In accordance with the present invention, a patient body weight air support system which has a plurality of elongated independently sealed, air impermeable, inflatable chambers arranged in a longitudinally proximal side-by-side relationship is disclosed. Each of the inflatable chambers has a bottom surface, a top body weight supporting surface and a longitudinal axis. In addition, the top body weight supporting surface has venting means to provide for low air loss from the plurality of inflatable chambers. The inflatable chambers are arranged in a first group of chambers which are in spaced relationship with each other and a second group of chambers which are in a spaced relationship with each other and in an alternating proximal spaced relationship with the first group to form the plurality of chambers. A first conduit means is connected to the first group of inflatable chambers and a second conduit means is connected to the second group of inflatable chambers.
The system is also provided with a pump means for inflating the plurality of inflatable chambers. The pump means is in open communication with and connected to the first and second conduit means. A profile means for storing a compendium of data based upon projected patient body weight having a correlation to a desired internal pressure value for the plurality of inflatable chambers is provided. A pressure sensor means including means for detecting in real time the actual internal air pressure of the plurality of inflatable chambers is also provided. Further the device has a control means including comparator means for comparing the desired internal pressure value of the plurality of inflatable chambers with the actual internal air pressure of the plurality of inflatable chambers and further includes a pressure compensation means for adjusting pump means operation. The control means is activated by active feedback data derived from the comparator means for maintaining the desired internal pressure value of the plurality of inflatable chambers. The control means actuates the pressure compensation means for adjusting pump means operation to maintain the desired internal pressure value of the plurality of inflatable chambers. The pump means simultaneously adjusts the inflation of the first and second groups of inflatable chambers. The control means is connected to the first and second conduit means and the pump means.
The control means is programmed to monitor the profile means for storing a compendium of data based upon projected patient body weight having a correlation to a desired internal pressure value for the plurality of inflatable chambers, monitor the pressure sensor means including means for detecting in real time the actual internal air pressure of the plurality of inflatable chambers, actuate the indicator means to reflect the current state of the system, and actuate the pump means including means for venting the plurality of inflatable chambers for adjusting the inflation of the plurality of inflatable chambers corresponding to active feedback signals received from the comparator means to simultaneously adjust inflation of the first and second groups of inflatable chambers.
The invention accordingly comprises the features of construction, combination of elements and arrangement of parts that will be exemplified in the description hereinafter set forth, and the scope of the invention will be indicated in the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
For a fuller understanding of the nature of the invention, reference should be made to the following detailed description, taken in connection with the accompanying drawings, in which:
FIG. 1 is a top view of the control unit connected to the wheelchair cushion of the present invention;
FIG. 2 is an open internal view of the control unit of the present invention;
FIG. 3 is a top view of the wheelchair seat cushion of the present invention;
FIG. 4 is a bottom view of the wheelchair seat cushion of the present invention;
FIG. 5 is a cross-sectional view of the wheelchair seat cushion of the present invention; and
FIG. 6 is a top view of the mattress of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
Referring now to the drawings, in which like numerals refer to like elements thereof, FIG. 1 shows the control unit 10 of the novel patient body weight air support system of the present invention. As shown in FIG. 2, the control unit 10 has two pumps 22 and 24 for pumping air to the either the seat cushion 100 or the mattress 200. These pumps have a standard construction and any pump device commonly used by those skilled in the art is suitable for use in the present invention. Pumps 22 and 24 are arranged and connected in series. In this manner pumps 22 and 24 are connected to solenoids 32 and 34. Solenoids 32, 34 have ports 142, 140 respectively which are connected to tubing to form part of the active feedback circuit of the present invention. These solenoids have a standard construction and any solenoid device commonly used by those skilled in the art is suitable for use in the present invention. As shown in the drawing external hoses 18 and 20 are adapted to readily connect to the ports 88 and 90 of the control unit, respectively. These external hoses and ports have a standard construction and any such devices commonly used by those skilled in the art are suitable for use in the present invention. Tubing 38, 36 connects the ports 90, 88 respectively, with the ports 92, 96 respectively located on the solenoid base 84. As is known by those skilled in the art solenoid base 84 is readily constructed from commonly available materials and is in open communication with solenoids 32 and 34. Pumps 22, 24 have ports 98, 110 and 112, 114 respectively, which are connected via various tubing to form part of the active feedback circuit of the present invention. For purposes of the present invention and for use throughout the entire construction of the present invention any suitable tubing known in the art is useful.
The electronic control unit 30 is made up of two electronic circuit boards 146 and 28. Circuit boards 146, 28 are readily available and are commonly used in the art. Circuit boards 146, 28 are connected by a standard electronic connector 144 which is known in the art. Board 146 has contained thereon pressure transducer 26. Transducers useful in the present invention are commonly known in the art. Transducer 26 has port 118 which is connected in series to pumps 22, 24 to form part of the active feedback circuit. A manifold construction comprising connectors 42, 46, 50, 56, and 60 and tubing 44, 48, 52 and 58 also make up part of the active feedback circuit. Connectors 42, 46, 50, 56, and 60 are known in the art. Specifically, the following are connected in open communication: Pump 22 via port 98 and tubing 40 are connected to the manifold construction comprising connectors 42, 46, 50, 56, and 60 and tubing 44, 48, 52 and 58, connector 60 is connected to tubing 62 which is in turn connected to port 114 of pump 24; port 112 of pump 24 in connected to connector 42 via tubing 72; port 110 of pump 22 is connected to connector 60 via tubing 66; port 142 of solenoid 32 is connected to connector 56 via tubing 68, while port 140 of solenoid 34 is connected connector 46 via tubing 70; connector 50 of the manifold construction is connected to tubing 64 which is, in turn connected to port 118 of transducer 26; port 92 of solenoid base 84 is connected to port 90 via tubing 38 which in turn is connected to a seat cushion 100 or mattress 200 of the present invention via tubing 20, while port 96 of solenoid base 84 is connected to port 88 via tubing 36 which in turn is connected to a wheelchair seat cushion 100 or mattress 200 of the present invention via tubing 18. Pumps 22 and 24 are in communication with electronic control unit 30 via conduits 80 and 74, respectively. Further solenoids 32 and 34 are in communication with electronic control unit 30 via conduits 76 and 78, respectively. Conduits 80, 74, 76, and 78 are known in the art.
According to the present invention back pressure from the cushion 100 or the mattress 200 is sampled frequently, such as, every 11 seconds through the output of the transducer 26. As is known in the art this signal is then amplified and, subsequent to amplification the signal is converted from an analog to a digital signal. This converted signal is then fed to the comparator means which is part of the electronic control unit 30. The comparator means compares the transducer signal to a preset preprogrammed pressure profile which was determined by the initial pressure profile determined for that particular patient. If a pressure variation from the preset pressure profile is sensed by the comparator means the control means which is part of the electronic control unit 86 will cause an interrupt signal and will halt the scan mode and either cause the solenoids 32, 34 to open thus venting air to lower the internal pressure of the chambers or turn on the pumps 22, 24 to add pressure to the plurality of chambers. This process of pressure correction can occur up to 327 times per hour. In this way, the present invention constantly maintains the interface pressure to below 32 mm Hg.
As shown in FIG. 1 the control unit display panel is represented as a whole by numeral 10. The display panel at 302 indicates the mode of operation of the device, while at 304 override functions are represented and the power switch and indicator is indicated at 306.
FIGS. 3 and 4 show the wheelchair seat cushion 100 according to the present invention, while FIG. 6 shows the mattress 200 according to the present invention. The wheelchair seat cushion 100 and the mattress 200 as shown in the drawings are comprised of a plurality of inflatable chambers represented by numeral 12. A first group of inflatable chambers (A) are connected a first conduit means 14. A second group of inflatable chambers (B) are connected a second conduit means 16. As shown in the drawings each alternating inflatable chamber 12 has a vent means 122 for the purpose of venting air continuously against the inside layer of a vapor permeable, fluid impermeable nylon cover, not shown. The first group of inflatable chambers has a connector 130 for connection to tubing 18. The second group of inflatable chambers has a connector 132 for connection to tubing 20.
FIGS. 1 and 3, taken together, depict how each individual chamber of the wheelchair seat cushion is mounted. The lowermost edge of each of the four sidewalls of each chamber is formed integrally with a common bottom wall 11, and a space 13 is provided between each pair of contiguous chambers. Thus, when a chamber is independently inflated, each of its four side walls is disposed in a substantially upstanding configuration relative to bottom wall 11. In this way, each chamber, whether an A chamber or a B chamber, is independently secured to the bottom wall and is held in its operable position relative to said bottom wall.
Note further that conduit means 14 and 16 are formed integrally with bottom wall 11, thereby eliminating separate pipes and other conduit means of the type heretofore employed in connection with low air loss support systems.
As is known in the art numerous methods and devices can be utilized to make the vent means 122. In a preferred embodiment every A chamber of the wheelchair seat cushion 100 and the mattress 200 has a single venting means for continuously venting air, however, a plurality of vents are also contemplated. The vent means is useful in accelerating evaporation of moisture which accumulates under the patient and to maintain a cooler environment by dissipating heat through the evaporation process. As is known in the art, the vent means will be appropriately sized to accomplish these evaporation and cooling processes without interfering with the operation of the control means.
EXAMPLES
The following examples are presented to illustrate the invention, which is not intended to be in any limited thereto, since numerous modifications and variations therein will be apparent to one skilled in the art. Actual experimental data was obtained as follows:
Example 1
Interface pressure point testing was conducted on the corrective, low air loss, patient body weight air support bed mattress system according to the present invention. A Talley Oxford Pressure Monitor--Model MKII was used for this analysis. The mattress was placed directly on a standard hospital spring unit. The test methods employed for this analysis were based on sound laboratory practices. Precautions were employed to position the sensor correctly in each case. The pressure monitor was calibrated before and after each series of measurements.
Ten subjects were used for the analysis and selected according to specific weight and height ranges. The subjects were dressed in an appropriate size cotton sweat suit to ensure proper placement of the 4"×5" sensor pad. Positioning of the sensor pad was accomplished by both the subject and experimenter. The sensor pad was placed under the appropriate body part between the subject and the mattress. The control unit was individually programmed, as known in the art, for each subject in order to achieve optimum pressure displacement. It should be noted that in normal operation the system is preprogrammed with data based on projected patient body weights which are correlated to a desired internal pressure value for the mattress. Consequently, in normal operation the mattress automatically adjusts to an optimum desired internal pressure value without any programming by the user based upon these preprogrammed values. Three replications were conducted on each subject. The subject's height, weight, and gender are listed in Table 1 below.
TABLE 1______________________________________Subject Height Weight Sex______________________________________1 5'3" 105 lbs F2 5'7" 125 lbs F3 5'5" 125 lbs F4 5'9" 135 lbs F5 5'6" 140 lbs F6 5'8" 145 lbs M7 5'6" 160 lbs M8 5'9" 175 lbs M9 5'8" 190 lbs M10 6'1" 195 lbs M______________________________________
The pressure measurements for various body parts for each of the subjects listed in Table 1 above are shown in Table 2 below.
TABLE 2__________________________________________________________________________(Low Air Loss Dynamic Mattress)Average Pressure (mm Hg) ± S.D.#1 #2 #3 #4 #5 #6 #7 #8 #9 #10 Ave. ± S.D.__________________________________________________________________________Scapula 11 11 8 12 13 17 9 11 12 11 11 ±3.9Sacral 15 14 13 13 11 14 10 13 10 11 12 ±5.3ProminenceHeel 8 6 6 10 8 6 6 10 7 8 7 ±6.9Trochanter 25 28 22 24 23 30 28 21 19 33 25 ±7.4__________________________________________________________________________
As shown in Table 2 an air mattress in accordance with the present invention maintains interface pressures below the capillary closure pressure of 32 mm Hg. Further, the mattress of the present invention responded to the subject's weight and anatomical structure. A summary of the results shown in Table 2 are shown in Table 3 below.
TABLE 3______________________________________(Low Air Loss Dynamic Mattress)Average Pressure (mm Hg)-All Subjects (10) ± S.D.Position mm Hg ± S.D.______________________________________Scapula (Shoulder Blade) 11 ± 3.9Sacral Prominence (Tailbone) 12 ± 5.3Heel (Values cut off below 2 mm) 7 ± 6.9Trochanter (Hip) 25 ± 7.4______________________________________
Example 2
Interface pressure point testing was conducted on the corrective, low air loss, patient body weight air support seat cushion system according to the present invention. The Talley Oxford Pressure Monitor--Model MKII used in Example 1 above was also used for this analysis. The seat cushion was placed in the collapsible seat of a Ventura Theradyne wheelchair. The cushion was covered with a nylon cover and had a 1" polyurethane foam base. Again, the test methods employed for this analysis were based on sound laboratory practices. Precautions were employed to position the sensor correctly in each case. The pressure monitor was calibrated before and after each series of measurements.
The subjects, listed in Table 1 above, were dressed in an appropriate size cotton sweat suit to ensure proper placement of the 4"×5" sensor pad. Positioning of the sensor pad was accomplished by both the subject and experimenter. The sensor pad was placed under the appropriate body part between the subject and the cushion. The control unit was individually programmed, as known in the art, for each subject in order to achieve optimum pressure displacement. Again, in normal operation the system is preprogrammed with data based on projected patient body weights which are correlated to a desired internal pressure value for the mattress. Consequently, in normal operation the cushion automatically adjusts to an optimum desired internal pressure value without any programming by the user based upon these preprogrammed values. Three replications were conducted on each subject. The subject's height, weight, and gender are listed in Table 4 below.
TABLE 4______________________________________(Low Air Loss Dynamic Wheelchair Cushion)Average Pressure (mm Hg) ± S.D.#1 #2 #3 #3 #4 #5 #6 #7 #8 #9 #10 Ave. +S.D.______________________________________Right 30 25 27 28 25 35 32 35 39 34 31 ±6.4 Is- chial Tuber- osity Left 33 29 25 30 27 34 34 30 33 38 31 ±5.4 Is- chial Tuber- osity Sacral 25 27 32 28 28 30 31 27 34 30 29 ±6. 3 prom- inence (Coc- cyx)______________________________________
As shown in Table 4 an air seat cushion in accordance with the present invention maintains interface pressures below the capillary closure pressure of 32 mm Hg. Further, the seat cushion of the present invention responded to the subject's weight and anatomical structure. A summary of the results shown in Table 4 are shown in Table 5 below.
TABLE 5______________________________________(Low Air Loss Dynamic Wheelchair Cushion)Average Pressure (mm H9)-All Subjects (10) ± S.D.Position mm Hg ± S.D.______________________________________Right Ischial Tuberosity 31 ± 6.4Left Ischial Tuberosity 31 ± 5.4Sacral Prominence (Coccyx) 29 ± 6.3______________________________________
These results clearly show the unexpected advantages of this invention over the prior art devices. This invention maintains interface pressures below the capillary closure pressure while providing low air loss to prevent skin maceration. Further, the system automatically adjusts the internal pressure of the mattress to maintain interface pressures below the capillary closure pressure based on real time internal pressure measures.
The advantages of the present invention will thus be seen, and those made apparent from the foregoing description, are efficiently attained. Since certain changes may be made in the foregoing description without departing from the scope of the invention, it is intended that all matters contained in the foregoing description shall be interpreted as illustrative and not in a limiting sense.
It will thus be seen that the objects set forth above, and those made apparent from the foregoing description, are efficiently attained and since certain changes may be made in the foregoing construction without departing from the scope of the invention, it is intended that all matters contained in the foregoing construction or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.
It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described, and all statements of the scope of the invention which, as a matter of language, might be said to fall therebetween.
Now that the invention has been described, | 1a
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This patent claims the benefit of U.S. provisional patent No. 61/946,685 filed on Feb. 28, 2014, which is herein incorporated by reference.
[0000]
U.S. PATENT DOCUMENTS
5,490,784
February 1996
Carmein
Virtual reality system with enhanced sensory
434/55
apparatus
6,629,896
October 2003
Jones
Nimble virtual reality capsule using rotatable
472/60
drive assembly
8,939,455
January 2015
Terry
Ride-on vehicle and game seat for infants
180/19.1
and young children
14/096,986
December 2014
Batten
Children's ride-on vehicle with computer-
tablet display and child supervision
62/117,491
February 2015
Batten
Self-Pivoting Drive for Spherical-Form
Motion Simulators
OTHER PUBLICATIONS
[0002] www.sincraft.com Simcraft web page
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0003] Not applicable
REFERENCE TO SEQUENCE LISTING, A TABLE, OR A COMPUTER PROGRAM LISTING COMPACT DISC APPENDIX
[0004] Not applicable
BACKGROUND OF THE INVENTION
[0005] 1. Field of the Invention
[0006] The purpose of this invention is providing a low-cost motion simulator to be used in homes and other venues. The invention can be adapted for children or adults.
[0007] The invention has a seat which moves in response to signals from a smart phone or smart tablet, hereinafter referred to as “computer tablet.” The nature of the motion is determined by application-specific software (an “app”) in the computer tablet. The computer tablet's display is used to display motion-related images. The seat can rotate about any axis. Pitch and roll are limited, but the range of each is sufficient for many simulations. Yaw is unlimited.
[0008] 2. The Prior Art
[0009] Many motion simulators have been developed. A well-known early one was the Link Trainer, which had an analog control system and a mechanical arrangement based of pneumatic devices. There are many modern motion simulators using digital computers for control. Some are large and very expensive, so they are used only by such persons as professional aircraft pilots.
[0010] One marketed by Simcraft is small enough for nonprofessional use. It has a seat mounted on gimbals, so any rotation is possible. The control system is a conventional digital computer with application-specific software. There seem to be no patents for this device.
[0011] U.S. Pat. Nos. 5,490,784 and 6,629,896 describe large simulators with spherical moving platforms, supported by drive wheels which move the sphere by friction. These inventions are not suitable for home use.
[0012] In contrast, the present invention is small enough to be used in homes. Since it uses a computer tablet as the main control device, a family can purchase a basic physical unit, then use an already-owned computer tablet for the control. Thus the physical units can be sold inexpensively.
BRIEF SUMMARY OF THE INVENTION
[0013] This invention relates generally to game seats with motion simulation, and motion simulators in general. Related information appears in the U.S. Pat. No. 8,939,455 and U.S. patent application Ser. No. 14/096,986, which describe the mechanical, electrical, control, and communication aspects of a base vehicle. The present invention is as a stationary unit with a moving platform for a human rider, but it does use some electrical, control, and communication features that are similar to ones in those patents.
[0014] The invention comprises a base unit and a moving platform. See FIG. 1 . The moving platform has an exterior shell which is supported by a freely moving ball and two assemblies with drive wheels for rotating the platform. FIG. 3 shows the baseplate with the drive wheels and ball. The axes of the drive wheels rotate so they can produce any rotation of the moving platform. Pitch and roll are limited: typically, pitch and roll angles can be at least −15 to +15 degrees, which is enough to be useful for many simulations. Yaw rotation is unlimited.
[0015] The invention includes a fixed-position retainer plate 7 between the exterior and interior shells. See FIG. 2 . That plate prevents tipping, which might happen, for example, when a rider climbs on board. The retainer plate can be made so that it does not touch any part of the moving platform under normal conditions; this avoids certain frictional losses that would otherwise occur with any rotation.
[0016] Electrical signals from an electronics module (not shown in the figures) mounted on the base unit power the drive wheels and determine the direction and rotational speed of the wheels. The electronics module carries out some basic computations for control, but the motion plan is determined by a computer tablet in the moving platform. The computer tablet is mounted on a bracket that holds it in view of the human rider, so the computer tablet display becomes part of the simulation. The bracket is moved out of the way when a different display (e.g., a large, wall-mounted display) is used.
[0017] Control signals, mostly descriptions of required rotations, are sent from the computer tablet to the electronics module in the base unit through a bidirectional wireless link. That link also carries moving-platform position information from the electronics module to the computer tablet. Thus, there are no wires between the base unit and the moving platform; the invention does not need slip rings or other moving electrical connections.
[0018] The computer tablet touch screen can be used as a control for interactive simulations. Alternatively, other controls—joystick, steering wheel, switches, etc.—can be used if they are linked to the computer tablet. Wireless links are preferred. One advantage of this arrangement is that controls can be switched easily, so each type of simulation can have a simulation-specific set of controls.
[0019] Under some conditions it might be useful to mount the invention on a steerable base unit with powered wheels, and to provide controls so the rider could drive the unit from place to place. It that case it might be appropriate to apply the concepts taught in U.S. Pat. No. 8,939,455 and U.S. patent application Ser. No. 14/096,986.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0020] FIG. 1 shows a partial section of the ride as viewed from one side.
[0021] FIG. 2 is the retainer plate 7 as viewed from the top.
[0022] FIG. 3 is the base plate 15 as viewed from the top.
[0023] FIG. 4 is a view of a drive wheel mechanism.
[0024] FIG. 5 is a diagram showing various points, lines, and vectors, including a rotation vector R.
[0025] FIG. 6 is a block diagram showing a possible arrangement of the control system.
[0026] The figures use the following reference identifiers:
1 Outer shell. 4 Inner shell. 7 Retainer plate. 8 Ball supporting outer shell 1 . 9 Mount for the outer shell support ball 8 . 10 Wheels driving movements of outer shell 1 . 11 Mount and drive motors for wheels 10 . 13 Mount for the retainer plate 7 . 15 Base plate as seen from above. 16 Floor surface. 17 Shroud. 18 Edge of clearance opening in outer shell 1 . 21 Seat. 22 Seat mounting bracket. 26 Joy stick (or other control device). 27 Armrest-mounted controls. 28 Support for the mount and drive motors 11 . 36 Bracket for the computer tablet. 37 Alternate position of bracket 36 . 38 Shell closure and support for inner shell 4 . 40 Great circle through the center C of the spherical surface and wheel contact points. 41 Circle showing rotation corresponding to the vector R. 50 Pivoting frame supporting the drive wheels 52 . 51 Fixed frame for the motors and angle sensor. 52 Drive wheel. 72 Mounting plate. 79 Surface of the outer shell.
DETAILED DESCRIPTION OF THE INVENTION
[0054] A fundamental mechanical element of this invention is the spherical surface of outer shell 1 , the motion of which is driven by the wheels of two assemblies. Each such assembly comprises a single wheel, or a pair of wheels, frictionally contacting the spherical surface; associated motors; and a mounting arrangement. The mounting arrangement provides for the wheel axis direction to be changed, thereby changing the direction of motion of the sphere. Outer shell 1 supports the entire moving platform.
[0055] FIG. 1 is a partial sectional view with some parts rotated into the plane of the view as is commonly done in good drafting practice. It shows outer shell 1 resting on freely-rotating ball 8 in its mount 9 , and one of the drive wheels 10 on its mechanism and mount 11 . FIG. 3 shows the ball and drive wheels arranged in a triangular pattern on the base plate 15 . Drive wheel 10 and its mechanism 11 have controlled bidirectional motors and gears that drive the rotation of each wheel about its axis, and set the direction of the wheel axis, hence the direction of wheel action. U.S. Pat. No. 5,490,764 shows three arrangements for mechanisms of this type (in that patent's FIGS. 4 , 5 , and 6 ).
[0056] FIG. 4 shows another arrangement for the wheel mechanism. In that figure, wheels 10 are mounted on freely pivoting frame 50 . The axles of the wheels have a common centerline. Motors driving the wheels are in fixed frame 51 . Mounting plate 72 supports the mechanism. The wheels frictionally contact outer surface 79 of outer shell 1 and drive the shell's motion. The direction of wheel action is determined by controlled differential rotation of the two wheels 10 , which causes freely pivoting frame 50 to rotate. This mechanism is described in more detail in U.S. patent application Ser. No. 62/117,491.
[0057] One unique feature of this invention is retainer plate 7 , which is rigidly mounted on base plate 15 using mount 13 . The retainer plate prevents tipping of outer shell 1 , hence that of the moving platform. Mount 13 passes through a clearance opening, shown as edge 18 , in outer shell 1 . While the retainer plate and its mount limit the range of motion of the outer shell, a preferred arrangement will allow sufficient motion for the intended applications. For the configuration shown in FIG. 1 , roll and pitch can range at least from −15 to +15 degrees. Yaw is unlimited.
[0058] Shroud 17 encloses the movement mechanism. Base plate 15 rests on floor surface 16 .
[0059] In the moving platform, inner shell 4 , which separates the rider space from retainer plate 7 , is attached to outer shell 1 by shell closure 38 . FIG. 1 shows inner shell 4 as a spherical section, but the shape is not important as long as it provides clearance for retainer plate 7 , and structural support for seat 21 and the rider. Seat 21 , which is mounted on seat mounting bracket 22 , has a movable bracket 36 to support the computer tablet within view of the rider. FIG. 1 shows the alternate position 37 of bracket 36 when it has been moved to an out-of-the-way position. Various rider-operated controls 27 , including, for example, a joystick 26 , are be mounted on the seat. The computer tablet is bidirectionally linked, preferably by wireless connections, to controls that are not part of the computer tablet and to an electronics module (not shown in the figures) in the base unit. That electronics module produces the electrical signals powering the motors of the drive-wheel assemblies.
Mathematics of the Rotation
[0060] It is useful to have some mathematical notations for describing control of the drive wheels. To that end, identify each wheel assembly with a number 1 or 2 , wheel assembly 1 being the first one encountered in moving from the support ball in a counterclockwise direction around the center of base 15 as seen from above, and wheel assembly 2 being the other one. In the following, k will denote either wheel number, and “sphere” will mean the sphere of the exterior surface of outer shell 1 .
[0061] Let u k be the unit vector pointing from the center C of the sphere toward wheel assembly k. More specifically, u k points toward a point P k defined as follows: if wheel assembly k has a single wheel, then P k is the point at which the wheel contacts the spherical surface; if wheel assembly k has a pair of wheels, P k is midway between the points at which the two wheels contact the spherical surface. See FIG. 5 .
[0062] The two vectors u 1 and u 2 and the center C determine a plane P. Let w denote the unit vector orthogonal to P and pointing in the direction of motion of a right-handed screw rotating about C from P 1 to P 2 . In conventional vector notation, w=(u 1 ×u 2 )/|u 1 ×u 2 |, where × is the usual vector cross product, and the denominator is the length of u 1 ×u 2 . Let v k =w×u k . Then u k , v k , and w are unit basis vectors for a right-handed coordinate system.
[0063] FIG. 5 shows the plane P and the sphere's great circle 40 intersection with P. The great circle has its center at C, and it passes through wheel points P 1 and P 2 . The figure also shows a rotation vector R and the circle of rotation 41 associated with R. Coordinate vectors u 1 , u 2 , v 1 , v 2 , and w (the latter in two places) are shown moved to the corresponding wheel points P 1 and P 2 .
[0064] Let R 1 , and R 2 be the rotation vectors associated with sphere rotation due to the drive wheels at P 1 , and P 2 , respectively. Since each of these is orthogonal to the corresponding u k , these can be expressed as follows:
[0000] R 1 =β 1 v 1 +γ 1 w , and
[0000] R 2 =β 2 v 2 +γ 2 w ,
[0000] where β 1 , γ 1 , β 2 , and γ 2 are numbers. The vectors γ 1 w and γ 2 w represent rotations in the plane P. In order that there be no conflict (i.e., jamming) between drive wheels at P 1 and P 2 , these must be equal, so
[0000] R 1 =β 1 v 1 +γw , and
[0000] R 2 =β 2 v 2 +γw , (1)
[0000] where γ is the common value of γ 1 and γ 2 .
[0065] The vector β 1 v 1 represents a rotation orthogonal to the plane P. That rotation must have P 2 as a fixed point because drive-wheel friction will block non-zero motion there (unless the drive-wheel motion at that point is identical to that caused by the rotation β 1 v 1 ). The only way that this can be guaranteed is for the line through C and P 2 , the axis of this rotation, to be parallel to v 1 . The same argument can be applied to β 2 v 2 , mutatis mutandis, of course.
[0066] Thus, P 1 and P 2 must be positioned so that u 1 and u 2 are orthogonal. This is the same as requiring that the lines from C to each of P 1 and P 2 be orthogonal, which is assumed henceforth.
[0067] The overall rotation, represented by the vector R, is a combination of R 1 and R 2 . It is the sum of the orthogonal in-plane components and the out-of-plane component:
[0000] R=β 1 v 1 +β 2 v 2 +γw. (2)
[0068] The first step in controlling sphere motion is determining β 1 , β 2 , and γ from a given R. Then those values are used to set the direction and speed of the drive wheels. Since v 1 , v 2 , and w are mutually orthogonal, this is just a matter of computing vector dot products:
[0000] β 1 =v 1 ·R,
[0000] β 2 =v 2 ·R, and
[0000] γ= w·r. (3)
[0000] Drive wheel rotations R w1 and R w2 at P 1 and R 2 , respectively, are
[0000] R w1 =−ρ(β 1 v 1 +γw ), and
[0000] R w2 =−ρ(β 2 v 2 +γw ), (4)
[0000] where ρ is the ratio of sphere radius to drive wheel radius, and the minus sign arises from the fact that wheel rotation is opposite to the corresponding sphere rotation.
Control
[0069] The timed sequence of rotations generated by the computer tablet are sent through the wireless link to the electronics module in the base unit. That module receives the required rotations, and converts them to signals controlling the motors of the drive-wheel assemblies.
[0070] The electronics module also determines the position of the moving unit, for example using an optical or magnetic sensor and corresponding marks on or magnets in the outer shell, and sends the position information back to the computer tablet in the moving unit. Methods for doing this will be apparent to persons knowledgeable of the relevant art.
[0071] FIG. 6 shows a possible organization for control. The dashed line separates the part in the moving platform from that in the base unit. The part in the moving platform centers on the Computer Tablet, which communicates with Other Controls, preferably by wireless links. Control commands are communicated through the Wireless Module of the Computer Tablet to the Wireless Module in the electronics module of the base unit. The most common command is to rotate the sphere according to rotation vector R to a particular position, as indicated by the angle θ. Consecutively arriving values of the pair <R, θ> are pushed into the first-in, first-out register (FIFO). They are passed on at appropriate times.
[0072] FIG. 6 shows one other type of command, the Align command. The pitch and roll positions of the moving platform are estimated using accelerometers in the Computer Tablet or Other Controls. Yaw position is determined by integrating the rotation rate obtained from drive wheel rotation and direction. Each of these positions is subject to drift, integration errors, or changing of the position of the computer tablet, so it is necessary to realign the moving platform occasionally. The electronics module has an Alignment Timeout unit which issues an Align command at appropriate times. The OR element combines commands so that an Align command is issued to the Alignment Control unit if the command is received from either the Wireless Module or the Alignment Timeout element.
[0073] When the Alignment Control unit receives an Align command, it issues a Reset signal to the Alignment Timeout unit, thereby starting the time interval to the next timeout; then it begins issuing rotation pairs <R, θ>. The Select by Priority unit passes the <R, θ> pairs to the Compute β 1 , β 2 , γ unit, with commands from Alignment Control having priority over those from FIFO. The values of β 1 , β 2 , and γ are passed to the Wheel Motor Control, which generates signals to the motors of the drive-wheel assemblies.
[0074] The electronics module has a Position Sensing unit which supplies some information about the sphere position to the Alignment Unit and, through the wireless connection, to the Computer Tablet. In a preferred embodiment, the Position Sensor uses optical or magnetic means to determine sufficient information for homing (realigning) the moving platform. For example, an optical means might sense only a few optically contrasting marks on the sphere. One such mark is sufficient to establish a home position for yaw. A single optical sensor can be used for homing as follows: if yaw is moved to the home position first, a mark across the yaw mark is sufficient for homing pitch; roll can then be homed by using small movements of the sphere to test the orientation of the yaw mark. More complex optical patterns can be used if more complete position information is needed. The possibility of using more marks and/or optical sensors to obtain more complete position information will be apparent to persons familiar with the relevant art.
[0075] The Computer Tablet generates commands for whatever motion simulation is being done. A single installation of this invention can be used for such activities as aircraft flight simulation, auto driving simulation, space trip simulation, etc. Each kind of simulation has a corresponding app. The exact nature of such apps is not a part of this invention, but persons familiar with the relevant art would be able to develop apps for particular applications.
[0076] It will be apparent to persons familiar with the relevant art that a freely rotating ball can be replaced by a caster or a drive-wheel assembly. In the latter case, the electronics module must coordinate rotation of all drive wheels. | 1a
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CROSS REFERENCE TO RELATED APPLICATIONS
The present application is a 35 U.S.C. 371 National Application of PCT/EP2010/053433 filed Mar. 17, 2010, which claims priority to European Patent Application No. 09003805.0, filed Mar. 17, 2009, the entire contents of which are incorporated entirely herein by reference.
FIELD OF THE INVENTION
The invention relates to a trigger mechanism for a drug delivery device comprising at least one energy-storing element and to a drug delivery device with such a trigger mechanism.
BACKGROUND OF THE INVENTION
Drug delivery devices, such as inhalers or injection devices, that can be easily operated by a patient himself are well known in the art. Generally, such devices have trigger mechanisms to actuate drug dispensing.
For instance, there are trigger mechanisms designed as breath-actuation mechanisms in mechanically powered inhalers, such as a dry powder inhaler (DPI), an aqueous droplet inhaler (ADI) and/or a metered dose inhaler (MDI).
US 2004 020486 A1 discloses an inhaler for delivery of medicament from a canister which is compressible to deliver a dose of medicament. The inhaler comprises a housing for holding a canister. The housing having a mouthpiece for inhalation of a dose of medicament delivered by the canister. Furthermore the inhaler includes a breath-actuated actuation mechanism for compressing a canister held in the housing in response to inhalation at the mouthpiece. The actuation mechanism includes a locking mechanism arranged to lock the canister in a compressed state. The locking mechanism has a vane in the form of a flap and being responsive to the inhalation at the mouthpiece to release the canister when the level of inhalation at the mouthpiece falls below a predetermined threshold. It is necessary for the user to take e deep breath to ensure proper inhalation of the medicament so the delay for reset of the canister is sufficient long.
U.S. Pat. No. 6,405,727 B1 discloses a dosing device comprising a dispensing means for dispensing a dose material, a first biasing means for engaging with the dispensing means, and a dose activating mechanism. The dose activating mechanism comprises a deflectable member moveable by airflow, and a series of at least two moveable elements which transmit movement of the first element in the series to the last element in the series by a cascade effect, such that movement of the deflectable member is transferred to the first element of the series and a second biasing means communicates with one the at least two moveable elements. As movement is transferred between the moveable elements, energy stored in the second biasing means is released to increase the force associated with the movement of the moveable elements.
US 2007 118094 A1 discloses a needle-less injector device for delivering a dose of fluid intradermally, subcutaneously or intramuscularly to an animal or human. The device includes an inner housing having opposed ends. A syringe is disposed in one end of the inner housing. The syringe includes a nozzle for delivering a dose of fluid held within the syringe. A plunger is movably disposed within the syringe. A spring-powered hammer is movably disposed within the inner housing. The hammer cooperates with the plunger to drive the dose of medicament from the nozzle. An injection delivery spring for powering the hammer is positioned and compressed between the other vend of the inner housing and the spring powered hammer. An outer housing slideably supports the inner housing. A skin tensioning spring is mounted between the inner housing and the outer housing, the skin tensioning spring biasing the nozzle of the syringe against the animal or human. A trigger mechanism is disposed in the outer housing, the trigger mechanism cooperating with the spring powered hammer to release the injection delivery spring, wherein the size of the injection delivery spring and the length of the hammer dictate the amount of dose delivered and whether the dose is delivered intradermally, subcutaneously or intramuscularly to an animal or human.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an improved trigger mechanism for a drug delivery device, in particular to actuate drug dispensing, and an improved drug delivery device.
The object is achieved by a trigger mechanism according to claim 1 and by a drug delivery device according to claim 9 .
Preferred embodiments of the invention are given in the dependent claims.
According to the present invention there is provided a trigger mechanism for a drug delivery device comprising at least one energy storing element, an actuation element and a series of cascaded trigger elements. The trigger elements are pre-stressed with increasing pre-stressing and coupled to the at least one energy storing element such that the trigger elements, upon exerting a sufficient actuation force on the actuation element, cause a cascaded release of increasing portions of energy stored in the at least one energy storing device. Thereby at least one of the trigger elements is equipped with a latch element directly coupling at least two trigger elements such that the latch element restrains at least one of these trigger elements to its pre-stressed state before exerting the actuation force.
The cascaded release of increasing portions of stored energy has the advantage that a large amount of energy can be released through a relatively small actuation force. This is particularly useful for drug delivery devices that are to be actuated by very small amount of trigger energy, for example for an inhaler that is to be actuated by a flap that is moved by a flow of inhaled air or a device to be actuated by a button pressed by a finger or an autoinjector that is actuated by pressing against a patients body.
The cascaded release of increasing portions of stored energy by a cascaded series of trigger elements thereby advantageously solves the problem that stored energy usually creates resistance to the movement of a trigger, typically in the form of friction. This resistance therefore limits the amount of stored energy that a trigger can release. Using a cascade of trigger elements, one trigger element in the series can trigger a subsequent trigger element in the series using a portion of stored energy, thereby increasing successively the portion of stored energy that can be released by trigger elements.
Equipping trigger elements with latch elements directly coupling trigger elements in the series simplifies the cascaded trigger mechanism as compared to indirect couplings, e.g. through intermediate coupling elements, and reduces both the manufacturing expense and the size of the trigger mechanism. Furthermore it can reduce the probability of a malfunction of the trigger mechanism due to the reduction of the number of components, which is particularly desirable when the trigger mechanism is used in drug delivery devices for life-saving drugs. In addition it can simplify the procedure to reset the trigger mechanism after drug delivery, again due to the reduction of the number of components and to the simplification of the couplings between the trigger elements.
In a preferred embodiment at least one of the trigger elements is a pivoted lever.
Pivoted levers are particularly suited as trigger elements as the can be easily coupled to one another and are cheap and simple components.
When using pivoted levers as trigger elements, preferably at least one latch element is a protrusion, in particular designed as a ring segment, and located at a pivot of a pivoted lever.
A protrusion located at a pivot of a pivoted lever is particularly suited to a cascaded coupling of trigger elements as it can restrain another trigger element from moving, and decouple this trigger element from the lever as the lever rotates, thereby supporting the cascade effect in a simple and effective manner.
Furthermore, in preferred embodiment the pivots of all pivoted levers are preferably located in the same plane.
This enables a particularly simple and effective construction of the trigger mechanism by a chain of pivoted levers.
In another preferred embodiment, at least one latch element is a notch in the surface of a trigger element.
A notch in the surface of a trigger element is another suitable means to couple two trigger elements in a simple and effective manner by engaging one trigger element in the notch of a neighbouring trigger element and disengaging it within the cascade effect.
Preferably at least one energy-storing element is a spring.
Springs are particularly suited as energy storing elements for the trigger mechanism for they are simple and cheap components that can store energy effectively and that can be easily reset and connected to trigger elements.
Furthermore, preferably the trigger elements correspond one-to-one to energy storing elements and each trigger element is coupled to the corresponding energy storing element.
In this way each trigger element is coupled precisely to one energy-storing element. This makes it particularly easy to realize a cascaded release of increasing portions of stored energy as each trigger element in the series can control its “own” energy storing element and trigger the release of energy stored in it during the cascade effect.
Preferably the actuation element is equipped with a latch element directly coupling it to one of the trigger elements.
In this way the actuation of the cascade effect can be easily realized by making the actuation element effectively part of the series of trigger elements.
Furthermore, in a preferred embodiment the cascaded release of increasing portions of stored energy amplifies an actuation force exerted on the actuation element to a force exertable through one of the trigger elements.
An amplification of the actuation force is particularly advantageous in drug delivery devices which the force required for drug delivery exceeds the actuation force exertable on the actuation element.
According to the present invention, there is further provided a drug delivery device equipped with a trigger mechanism according to any one of these embodiments, in which the trigger mechanism is a release mechanism to actuate and release delivery of a dose of a drug stored in the drug delivery device.
A preferred embodiment of such a drug delivery device is an inhaler, in particular an inhaler whose actuation element is a pivoted actuation flap movable by gas or fluid flow.
Another preferred embodiment of such a drug delivery device is an autoinjector.
The trigger mechanism is particularly suited as a release mechanism for drug delivery through inhalers and autoinjectors as these devices are typically actuated by an actuation force that is smaller than the force required for drug delivery.
In a preferred embodiment of a drug delivery device at least one of the trigger elements is a piston by means of which a pressure is exertable to the drug.
The use of a piston as a trigger element is particularly advantageous when the drug to be delivered by the drug delivery device is a fluid or a gas because such drugs may be best delivered by a pressure exerted to the drug.
BRIEF DESCRIPTION OF THE DRAWINGS
These and other objects, features, aspects, and advantages of the present invention will become more apparent from the following detailed description of preferred embodiments and accompanying drawings, in which
FIGS. 1A through 1D illustrate schematically a first embodiment of a trigger mechanism for an inhaler to actuate delivery of a dose of a drug,
FIGS. 2A and 2B illustrate schematically a second embodiment of a trigger mechanism for an inhaler to actuate delivery of a dose of a drug, and
FIGS. 3A through 3D illustrate schematically a third embodiment of a trigger mechanism for an autoinjector to actuate delivery of a dose of a drug.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
FIGS. 1A through 1D illustrate a first embodiment of a trigger mechanism according to the invention. The trigger mechanism is used in an inhaler 1 to actuate delivery of a dose of a drug stored in the inhaler 1 , for example a dry powder, aqueous droplet or metered dose inhaler. Successive stages of an actuation process for drug delivery are shown to explain the operation of the trigger mechanism.
The trigger mechanism comprises an actuation flap 11 , a first lever 12 , a second lever 13 , a first spring 14 and a second spring 15 .
The actuation flap 11 is located in a breathing channel 10 through which a user inhales. The actuation flap 11 and the levers 12 , 13 are pivoted around pivots 111 , 121 , 131 at one of their ends respectively. The actuation flap 11 is equipped with a first ring segment 112 located at its pivot. The first lever 12 is equipped with a second ring segment 122 located at its pivot. The ring segments 112 , 122 extend about one third of a circle around the centre of the respective pivot 111 , 121 and extend from the surface of the respective pivot 111 , 121 .
The pivots 111 and 121 of the actuation flap 11 and of the first lever 12 are separated by a distance L 1 corresponding to a length of the first lever 12 . The pivots 121 and 131 of the levers 12 , 13 are separated by a distance L 2 corresponding to a length of the second lever 13 . The pivots 111 , 121 , 131 are located in a common plane. Hence, when the actuation flap 11 and the levers 12 , 13 are rotated to this plane and likewise oriented from their respective pivots 111 , 121 , 131 as shown in FIG. 1A , the first lever 12 extends to the pivot 111 of the actuation flap 11 , and the second lever 13 extends to the pivot 121 of the first lever 12 . Furthermore, in this position the first ring segment 112 restrains the first lever 12 from rotating upwards while the second ring segment 122 restrains the second lever 13 from rotating downwards.
The first lever 12 is coupled to the first spring 14 near to the pivot 111 of the actuation flap 11 at a distance X 1 to the pivot 121 of the first lever 12 . The second lever 13 is coupled to the second spring 15 near to the pivot 121 of the first lever 12 at a distance X 2 to the pivot 131 of the second lever 13 . Thereby the first spring 14 is located below the first lever 12 while the second spring 15 is located above the second lever 13 . The stiffness of the second spring 15 exceeds the stiffness of the first spring 14 .
FIG. 1A shows an initial state of the trigger mechanism with the actuation flap 11 and the levers 12 , 13 located in the same plane as described above. In this state both springs 14 , 15 are compressed, the second spring 15 storing more energy than the first spring 14 . When no force is acting on the actuation flap 11 , a rotation of the actuation flap 11 and the levers 12 , 13 are restrained by the ring segments 112 , 122 respectively. The levers 12 , 13 are thus pre-stressed by the springs 14 , 15 respectively, the pre-stressing of the second lever 13 exceeding the pre-stressing of the first lever 12 .
FIG. 1B shows the trigger mechanism when a user just has started to inhale. The inhaling causes an airflow B and a pressure drop P which suffices to rotate the actuation flap 11 downwards. A detailed quantitative discussion of this mechanism is given below.
FIG. 1C shows the trigger mechanism when the actuation flap 11 has been rotated sufficiently so that the first ring segment 112 releases the first lever 12 . As a consequence, the first spring 14 expands and rotates the first lever 12 upwards. This mechanism is also discussed in detail below.
FIG. 1D shows the trigger mechanism when the first lever 12 has been rotated sufficiently so that the second ring segment 122 releases the second lever 13 . As a consequence, the second spring 15 expands and rotates the second lever 13 downwards.
During the actuation process illustrated by the FIGS. 1A through 1D an actuation force Fa exerted by the pressure drop P on the actuation flap 11 releases energy stored in the first spring 14 which in turn is used to release energy stored in the second spring 15 . Thereby the actuation force Fa can be considerably amplified to forces exerted by the springs 14 , 15 . This will be shown in the following quantitative analysis of the trigger mechanism described qualitatively above.
With A denoting the area of the actuation flap 11 , the actuation force Fa exerted by the pressure drop P on the actuation flap 11 is Fa=P·A. The actuation force Fa exerts an actuation torque Ta=P·A·Z on the actuation flap 11 where Z is the distance between the pivot 111 of the actuation flap 11 and the effective application point of the actuation force Fa.
Denoting the spring force exerted by the first spring 14 on the first lever 12 by F 1 , a reaction force Y 1 at the pivot 111 is Y 1 =(X 1 /L 1 )·F 1 . In the initial state of the trigger mechanism shown in FIG. 1A , the rotation of the actuation flap 11 is restrained by a static friction between the first ring segment 112 and the corresponding end of the first lever 12 . This static friction is mue Y 1 =μ·(X 1 /L 1 )·F 1 with μ a friction coefficient. Denoting the radius of the first ring segment 112 from the centre of the pivot 111 by R 1 , the rotation of the actuation flap 11 is thus restrained by a first restraining torque T 1 =R 1 ·μ·(X 1 /L 1 )·F 1 .
In order for the trigger mechanism to operate according to FIG. 1B , i.e. in order to rotate the actuation flap 11 , this first restraining torque T 1 must be exceeded by the actuation torque Ta, i.e. T 1 <Ta and thus R 1 ·μ·(X 1 /L 1 )·F 1 <Z·P·A. Therefore, the force F 1 of the first spring 12 that can be restrained by the trigger mechanism, and still released by actuation flap 11 is restricted by
F 1< Z·P·A· ( L 1 /X 1 )/( R 1 ·μ). [1]
and the maximal amplification of the actuation force Fa provided by the first spring 14 is restricted by
F 1/ Fa<Z· ( L 1 /X 1 )/( R 1 ·μ). [2]
Inserting typical values A=100 mm 2 , Z=5 mm, P=1 kPa, L 1 =40 mm, X 1 =20 mm, R 1 =1 mm and μ=0.5, this results in
F 1<2 N [3]
and
F 1/ Fa< 20. [4]
An analogous consideration applies to the coupling of the first lever 12 to the second lever 13 through the second ring segment 122 .
Denoting the spring force on the second lever 13 due to the second spring 15 by F 2 , a reaction force Y 2 at the pivot 121 is Y 2 =(X 2 /L 2 )·F 2 . The rotation of the first lever 12 is restrained by a static friction between the second ring segment 122 and the corresponding end of the second lever 13 . This static friction is μ·Y 2 =μ·(X 2 /L 2 )·F 2 . Denoting the radius of the second ring segment 122 from the centre of the pivot 121 by R 2 , the rotation of the first lever 12 is restrained by a second restraining torque T 2 =R 2 ·μ·(X 2 /L 2 )·F 2 .
In order for the trigger mechanism to operate according to FIG. 1C , i.e. in order to rotate the first lever 12 , the second restraining torque T 2 must be exceeded by the torque X 1 ·F 1 provided by the first spring 14 on the first lever 12 , i.e. R 2 ·μ·(X 2 /L 2 )·F 2 <X 1 ·F 1 .
Therefore, the additional force amplification F 2 /F 1 is restricted by
F 2/ F 1< X 1·( L 2 /X 2 )/( R 2 ·μ). [5]
Inserting the same typical values as above with X 1 =X 2 =20 mm, L 1 =L 2 =40 mm, R 1 =R 2 =1 mm, μ=0.5, this yields
F 2/ F 1<80 [6]
and
F 2<160 N. [7]
F 2 could thus be up to about 160 N. This is a significant force and the energy released from the springs 14 , 15 can indeed be used dose delivery through the inhaler 1 . Additional cascaded trigger elements and springs could be added to enhance the force amplification even further.
A further use for the trigger mechanism could be that each lever 12 , 13 could be connected to a separate part of the inhaler mechanism. For example, the first lever 12 could trigger opening of a dose container, the second lever 13 could trigger dose delivery. By adding damping to either the first lever 12 or the second lever 13 it would also be possible to introduce a time delay between the initial breath actuation of the actuation flap 11 and the release of the second lever 13 . This could be used to introduce a “staged” response to the breath actuation.
After the levers 12 , 13 have been released the user would have to reset both levers 12 , 13 before the trigger mechanism could be used again. The reset action could occur simultaneously when the user performs some other action with the inhaler 1 , for example opening it to remove an empty dose container or load a new dose container, or in a priming action of the inhaler 1 prior to use. The limit of how far a force could be amplified by the trigger mechanism is likely to be how much energy the user can put back into the system when resetting the trigger mechanism.
The embodiment shown in FIGS. 1A through 1D has the disadvantage that the springs 14 , 15 have to be reset in opposite directions. This disadvantage is overcome by an alternative embodiment of the trigger mechanism shown in FIGS. 2A and 2B . Again, the trigger mechanism is used in an inhaler 1 .
A difference of this embodiment as compared to the first embodiment is that the levers 12 , 13 are arranged such that they are stacked one above the other in an initial state of the trigger mechanism shown in FIG. 2A . Furthermore, the first lever 12 is fixed to the actuation flap 11 , both having the same pivot 111 so that they can only rotate simultaneously. The springs 14 , 15 are located on the same side of the levers 12 , 13 , and the second lever 13 is equipped with a third ring segment 133 of the same type as the ring segments 112 , 122 of the first embodiment. The first lever 12 now extends from its pivot 111 to the pivot 131 of the second lever 13 . Again, the pivot 111 is equipped with a first ring segment 112 (not visible in the FIGS. 2A and 2B ) to which the second lever 13 extends in its initial position.
In the initial state of the trigger mechanism shown in FIG. 2A , the third ring segment 133 restrains the actuation flap 11 and the first lever 12 from rotating through the friction between the third ring segment 133 and the corresponding end of the first lever 12 and the first ring segment 112 restrains the second lever 13 from rotating through the friction between the first ring segment 112 and the corresponding end of the second lever 13 .
When a user exerts a sufficient actuation force Fa on the actuation flap 11 through inhaling, the levers 12 13 are released and both rotate upwards as shown in FIG. 2B .
In order to reset the trigger mechanism both levers 12 , 13 are pushed downwards to reengage the ring segments 112 , 133 .
FIGS. 3A through 3D illustrate a third embodiment of a trigger mechanism according to the invention. The trigger mechanism is used in an autoinjector 2 to actuate delivery of a dose of a drug 242 stored in a cartridge 24 through a dispensing element 243 of the autoinjector 2 located at the bottom of the cartridge 24 . The cartridge 24 is sealed by plug 241 .
The trigger mechanism comprises a manually operated actuation lever 21 , an intermediate lever 22 , a piston 23 , a first spring 26 and a second spring 25 .
The actuation lever 21 is pivoted around a pivot 211 at one of its ends and is equipped with a trigger button at its opposite end. The distance between the centres of the pivot 211 and of the trigger button is denoted by X 5 . The actuation lever 21 is equipped with a first ring segment 212 which is located at the pivot 211 and is of the same type as the ring segments 112 , 122 , 133 of the first and second embodiment.
The intermediate lever 22 is hook-shaped with a bend located at the pivot 211 of the actuation lever 21 . A first end of the intermediate lever 22 is directed towards the piston 23 , the second end contains a pivot around which the intermediate lever 22 is pivoted. The intermediate lever 22 is connected to the first spring 26 at a distance X 3 from its pivot. The distance between the bend and the pivot of the intermediate lever 22 is denoted by X 4 .
One end of piston 23 is directed towards the plug 241 of the cartridge 24 , the other end is connected to the second spring 25 . The surface of the piston 23 is equipped with a notch in which the first end of the intermediate lever 22 can engage.
The operation of the trigger mechanism is now described first qualitatively with reference to FIGS. 3A through 3D and afterwards analysed quantitatively.
FIG. 3A shows an initial state of the trigger mechanism. Both springs 25 , 26 are compressed. The first end of the intermediate lever 22 engages in the notch of the piston 23 and prevents the piston 23 from moving towards the plug 241 . The bend of the intermediate lever 22 is coupled to the first ring segment 212 which restrains the intermediate lever 22 from rotating.
FIG. 3B shows the trigger mechanism when a user presses the trigger button of the actuation lever 21 sufficiently so that the actuation lever 21 is rotates around its pivot 211 . As the actuation lever 21 rotates, the first ring segment 212 eventually disengages and releases the intermediate lever 22 .
FIG. 3C shows the trigger mechanism after the intermediate lever 22 has been released. The first spring 26 expands and rotates the intermediate lever 22 . The first end of the intermediate lever 22 disengages from the notch in the surface of the piston 23 which releases the piston 23 . The piston 23 is now free to move towards the plug 241 under the action of the fourth spring 25 .
FIG. 3D shows the trigger mechanism after the piston 23 has been released. The piston 23 has moved to the plug 241 and pressed it towards the bottom of the cartridge 24 . Thereby it exerts a pressure on the drug inside the cartridge 24 which forces delivery of the drug through the dispensing element 243 .
To discuss the trigger mechanism quantitatively the spring forces of the third spring 26 and of the fourth spring 25 exerted on the intermediate lever 22 and the piston 23 in the initial state of the trigger mechanism are denoted by F 3 and F 4 respectively.
Assuming that the thickness of the intermediate lever 22 thickness is negligible compared to its length, the approximate reaction force provided by the first spring 26 between the intermediate lever 22 and the second ring segment 212 in the initial state of the trigger mechanism is F 3 ·(X 3 /X 4 ). A third restraining torque T 3 caused by friction between the intermediate lever 22 and the fourth ring segment 212 is therefore approximately T 3 =R 3 ·μ·F 3 ·(X 3 /X 4 ) where R 3 is the radius of the first ring segment 212 from the centre of the pivot 211 .
A user must provide a sufficient actuation force U to the trigger button to overcome this resistance. The actuation torque resulting from U is U·X 5 .
The actuation lever 21 starts to rotate when this torque exceeds the third retraining torque T 3 , i.e. when U·X 5 >R 3 ·μ·F 3 ·(X 3 /X 4 ). Hence, for the actuation lever 21 to rotate, the force F 3 of the third spring 26 is restricted by
F 3<( X 4 ·X 5 /X 3 )· U /( R 3 ·μ). [8]
In order to release the piston 23 the force F 3 ·(X 3 /X 4 ) provided by the first spring 26 at the bend of the intermediate lever 22 must overcome the friction between the piston 23 and the intermediate lever 22 which is μ F 4 . Therefore, the piston 23 is released if F 3 ·(X 3 /X 4 )>μ·F 4 . Hence, for the trigger mechanism to operate, the force F 4 of the second spring 25 is restricted by
F 4< F 3·( X 3 /X 4 )/μ. [9]
Inserting typical values X 5 =25 mm, X 3 =15 mm, X 4 =30 mm, μ=0.5, R 3 =2.5 mm and U=1 N, one obtains
F 4<40 N. [10]
As compared to the actuation force U=1 N this gives a force amplification up to a factor of 40. The amplification can be further enhanced by different arrangements of the intermediate lever 22 and/or the use of further intermediate levers and springs and/or a “rolling” coupling of the intermediate lever 22 to the piston 23 in place of the coupling through the notch in the surface of the piston 23 .
LIST OF REFERENCES
1 inhaler
10 breathing channel
11 actuation flap
12 , 13 , 22 lever
14 , 15 , 25 , 26 spring
111 , 121 , 131 , 211 pivot
112 , 122 , 133 , 212 ring segment
2 autoinjector
21 actuation lever
22 intermediate lever
23 piston
24 cartridge
241 plug
242 drug
243 dispensing element
X 1 ,X 2 ,X 3 ,X 4 ,X 5 ,L 1 ,L 2 ,Z distance
B air flow
P pressure drop
Fa, U actuation force
F 1 ,F 2 ,F 3 ,F 4 spring force
Y 1 ,Y 2 reaction force
Ta actuation torque
T 1 ,T 2 ,T 3 restraining torque
R 1 ,R 2 ,R 3 radius
μ friction coefficient | 1a
|
RELATED APPLICATIONS
This application is a divisional of U.S. application Ser. No. 09/274,825, filed Mar. 23, 1999 now U.S. Pat. No. 6,165,764. This application also claims benefit of U.S. Provisional Patent Application No. 60/107,691 filed Nov. 9, 1998.
FIELD OF THE INVENTION
This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, the invention relates to polynucleotides and polypeptides of the trmD (tRNA methyl transferases) family, as well as their variants, herein referred to as “trmD,” “trmD polynucleotide(s),” and “trmD polypeptide(s)” as the case may be.
BACKGROUND OF THE INVENTION
The Streptococci make up a medically important genera of microbes known to cause several types of disease in humans, including, for example, otitis media, conjunctivitis, pneumonia, bacteremia, meningitis, sinusitis, pleural empyema and endocarditis, and most particularly meningitis, such as for example infection of cerebrospinal fluid. Since its isolation more than 100 years ago, Steptococcus pneumoniae has been one of the more intensively studied microbes. For example, much of our early understanding that DNA is, in fact, the genetic material was predicated on the work of Griffith and of Avery, Macleod and McCarty using this microbe. Despite the vast amount of research with S. pneumoniae , many questions concerning the virulence of this microbe remain. It is particularly preferred to employ Streptococcus genes and gene products as targets for the development of antibiotics.
The frequency of Streptococcus pneumoniae infections has risen dramatically in the past few decades. This has been attributed to the emergence of multiply antibiotic resistant strains and an increasing population of people with weakened immune systems. It is no longer uncommon to isolate Steptococcus pneumoniae strains that are resistant to some or all of the standard antibiotics. This phenonenon has created an unmet medical need and demand for new antimicrobial agents, vaccines, drug screening methods, and diagnostic tests for this organism.
Moreover, the drug discovery process is curreny undergoing a fundamental revolution as it embraces “functional genomics,” that is, high throughput genome- or gene-based biology. This approach is rapidiy soperseding earlier approaches based on “positional cloning” and other methods. Functional genomics relies heavily on the various tools of bioinformatics to identify gene sequences of interest from the many molecular biology databases now available as well as from other sources. The is a continuing an significant need to identify and characterize further genes and other polynucleotides sequences and their related polypeptides, as targets for drug discovery.
Clearly, there exists a need for polynucleotides and polypeptides, such as the trmD embodiments of the invention, that have a present benefit of, among other things, being useful to screen compounds for antimicrobial activity. Such factors are also useful to determine their role in pathogenesis of infection, dysfunction and disease. There is also a need for identification and charaction of such factors and their antagonist and agonist to find ways to prevent, ameliorate or correct such infection, dysfunction and disease.
SUMMARY OF THE INVENTION
The present invention relates to trmD, in particular trmD polypeptides and trmD polynucleotides, recombinant materials and methods for their production. In another aspect, the invention relates to methods for using such polypeptides and polynucleotides, including treatment of microbial diseases, amongst others. In a further aspect, the invention relates to methods for identifying agonists and antagonists using the materials provided by the invention, and for treating microbial infections and conditions associated with such, infections with the identified agonist or antagonist compounds. In a still further aspect, the invention relates to diagnostic assays for detecting diseases associated with microbial infections and conditions associated with such infections, such as assays for detecting trmD expression or activity.
Various changes and modifications with in the spirit and scope of the disclosed invention will become readily apparent to those skilled in the art from reading the following descriptions and from reading the other parts of the present disclosure.
DESCRIPTION OF THE INVENTION
The invention relates to trmD polypeptides and polynucleotides as described in greater detail below. In particular, the invention relates to polypeptides and polynucleotides of a trmD of Streptococcus pneumoniae , that is related by amino acid sequence homology to B. subtilis trmD polypeptide. The invention relates especially to trmD having a nucleotide and amino acid sequences set out in Table 1 as SEQ ID NO:1 and SEQ ID NO:2 respectively. Note that sequences recited in the Sequence Listing below as “DNA” represent an exemplification of the invention, since those of ordinary skill will recognize that such sequences can be usefully employed in polynucleotides in general, including ribopolynucleotides.
TABLE 1
trmD Polynucleotide and Polypeptide Sequences
(A) Streptococcus pneumoniae trmD polynucleotide sequence
[SEQ ID NO:1].
5′-
atgaagattgatattttaaccctctttccagagatgttttctccactggagcactcaatcgttggaaaggct
cgagaaaa
agggctcttggatatccagtatcataattttcgagaaaatgctgaaaaggcccgtcatgtagatgatgagcc
ctacggag
gcggtcagggcatgttgctcagagcacaacctattttcaattcctttgatgctattgaaaagaaaaatccgc
gcgttatt
ctcctcgatcctgctggaaagcagtttgatcaggcttatgctgaagatttggctcaagaggaagagctaatc
tttatctg
tgggcactatgagggttatgatgagcgcattaagaccttggtaacagatgagatttccctaggcgactatgt
cctcactg
gtggagaattggcagctatgaccatgattgatgctacagttcgcctgattccagaagtgattggcaaggagt
ctagccac
caagatgatagtttttcttcaggtcttttagaatatcctcagtacacacgtccctatgattatcgaggcatg
gtcgtgcc
agatgtattgatgagtggccaccatgaaaagattcgtcagtggcgattgtacgagagtttaaagaaaaccta
cgagcgca
gaccagatttacttgaacattatcaactgacagtagaagaagaaaaaatgctggcagaaatcaaagaaaaca
aagaataa
-3′
(B) Streptococcus pneumoniae trmD polypeptide sequence deduced from a
polynucleotide sequence in this table[SEQ ID NO:2].
NH 2 -
MKIDILTLFPEMFSPLEHSIVGKAREKGLLDIQYHNFRENAEVDDEPYGGGQGMLL
RAQPIFNSFDAIEKKNPRVI
LLDPAGKQFDQAYAEDLAQEEELIFICGHYEGYDERIKTLVTDEISLGDYVLTGGELAAM
TMIDATVRLIPEVIGKESSH
QDDSFSSGLLEYPQYTRPYDYRGMVVPDVLMSGHHEKIRQWRLYESLKKTYERRPDLLEH
YQLTVEEEKMLAEIKENKE
-COOH
Deposited Materials
A deposit comprising a Streptococcus pneumoniae 0100993 strain has been deposited with the National Collections of Industrial and Marine Bacteria Ltd. (herein “NCIMB”), 23 St. Machar Drive, Aberdeen AB2 1RY, Scotland on Apr. 11, 1996 and assigned deposit number 40794. The deposit was described as Streptococcus pneumoniae 0100993 on deposit.
On Apr. 17, 1996 a Streptococcus pneumoniae 0100993 DNA library in E. coli was similarly deposited with the NCIMB and assigned deposit number 40800. The Streptococcus pneumoniae strain deposit is referred to herein as “the deposited strain”or as “the DNA of the deposited strain.”
The deposited strain comprises a full length trmD gene. The sequence of the polynucleotides comprised in the deposited strain, as well as the amino acid sequence of any polypeptide encoded thereby, are controlling in the event of any conflict with any description of sequences herein.
The deposit of the deposited strain has been made under the terms of the Budapest Treaty on the International Recognition of the Deposit of Micro-oganism for Purposes of Patent Procedure. The deposited strain will be irrevocably and without restriction or condition released to the public upon the issuance of a patent. The deposited strain is provided merely as convenience to those of skill in the art and is not an admission that a deposit is required for enablement, such as that required under 35 U.S.C. §112. A license may be required to make, use or sell the deposited strain, and compounds derived therefrom, and no such license is hereby granted.
In one aspect of the invention there is provided an isolated nucleic acid molecule encoding a mature polypeptide expressible by the Streptococcus pneumoniae 0100993 stain, which polypeptide is comprised in the deposited strain. Further provided by the invention are trmD polynucleotide sequences in the deposited strain, such as DNA and RNA, and amino acid sequences encoded thereby. Also provided by the invention are trmD polypeptide and polynucleotide sequences isolated from the deposited strain.
Polypeptides
TrmD polypeptide of the invention is substantially phylogenetically related to other proteins of the trmD (tRNA methyl transferases) family.
In one aspect of the invention there are provided polypeptides of Streptococcus pneumoniae referred to herein as “trmD” and “trmD polypeptides” as well as biologically, diagnostically, prophylactically, clinically or therapeutically useful variants thereof and compositions comprising the same.
Among the particularly preferred embodiments of the invention are variants of trmD polypeptide encoded by naturally occurring alleles of a trmD gene.
The present invention further provides for an isolated polypeptide that: (a) comprises or consists of an amino acid sequence that has at least 95% identity, most preferably at least 97-99% or exact identity, to that of SEQ ID NO:2 over the entire length of SEQ ID NO:2; (b) a polypeptide encoded by an isolated polynucleotide comprising or consisting of a polynucleotide sequence that has at least 95% identity, even more preferably at least 97-99% or exact identity to SEQ ID NO:1 over the entire length of SEQ ID NO:1; (c) a polypeptide encoded by an isolated polynucleotide comprising or consisting of a polynucleotide sequence encoding a polypeptide that has at least 95% identity, even more preferably at least 97-99% or exact idenitity, to the amino acid sequence of SEQ ID NO:2, over the entire length of SEQ ID NO:2.
The polypeptides of the invention included a polypeptide of Table 1 [SEQ ID NO:2] (in particular a mature polypeptide) as well as polypeptides and fragments, particularly those that has a biological activity of trmD, and also those that have a least 95% identity to a polypeptide of Table 1 [SEQ ID NO:2] and also include portions of such polypeptides with such portion of the polypeptide generally comprising at least 30 amino acids and more preferably at least 50 amino acids.
The invention also includes a polypeptide consisting of or comprising a polypeptide of the formula:
X—(R 1 ) m —(R 2 )—(R 3 ) n —Y
wherein, at the amino terminus, X is hydrogen, a metal or any other moiety described herein for modified polypeptides, and at the carboxyl terminus, Y is hydrogen, a metal or any other moiety described herein for modified polypeptides, R 1 and R 3 are any amino acid residue or modified amino acid residue, m is an integer between 1 and 1000 or zero, n is an integer 1 and 1000 or zero, and R 2 is an amino acid sequence of the invention, particularly an amino acid sequence selected from Table 1 or modified forms thereof. In the formula above, R 2 is oriented so that its amino terminal amino acid residue is at the left, covalently bound to R 1 , and its carboxy terminal amino acid residue is at the right, covalently bound to R 3 . Any stretch of amino acid residues denoted by either R 1 or R 3 , wh m and/or n is greater than 1, may be either a heteropolymer or a homopolymer, preferably a heteropolymer. Other preferred embodiments of the invention are provided where m is an integer between 1 and 50, 100 or 500, and n is an integer between 1 and 50, 100, or 500.
It is most preferred that a polypeptide of the invention is derived from Streptococcus pneumoniae , however, it may preferably be obtained from other organisms of the same taxonomic genus. A polypeptide of the invention may also be obtained, for example, from organisms of the same taxonomic family or order.
A fragment is a variant polypeptide having an amino acid sequence that is entirely the same as part but not all of any amino acid sequence of any polypeptide of the invention. As with trmD polypeptides, may be “free standing,” or comprised within a larger polypeptide of which they form a part or region, most preferably as a single continuous region in a single larger polypeptide.
Preferred fragments include, for example, truncation polypeptide having a portion of an amino acid sequence of Table 1 [SEQ ID NO:2], or of variants thereof, such as a continuous series of residues that includes an amino- and/or carboxyl-terminal amino acid sequence. Degradation forms of the polypeptides of the invention produced by or in a host cell, particularly a Streptococcus pneumoniae , are also preferred. Further preferred are fragments characterized by structural or functional attributes such as fragments that comprise alpha-helix and alpha-helix forming regions, beta-sheet and beta-sheet-forming regions, turn and turn-forming regions, coil and coil-forming regions, hydrophilic regions, hydrophobic regions, alpha amphipathic regions, beta amphipathic regions, flexible regions, surface-forming regions, substrate binding region, and high antigenic index regions.
Further preferred fragments include an isolated polypeptide comprising an amino acid sequence having at least 15, 20, 30, 40, 50 or 100 contiguous amino acids from the amino acid sequence of SEQ ID NO:2, or an isolated polypeptide comprising an amino acid sequence having at least 15, 20, 30, 40, 50 or 100 contiguous amino acids truncated or deleted from the amino acid sequence of SEQ ID NO:2.
Fragments of the polypeptides of the invention may be employed for producing the corresponding full-length polypeptide by peptide synthiesis; therefore, these variants may be employed as intermediates for producing the full polypeptides of the invention.
Polynucleotides
It is an object of the invention to provide polynucleotides that encode trmD polypeptides, particularly polynucleotides that encode a polypeptide herein designated trmD.
In a particularly preferred embodiment of the invention the polynucleotide comprises a region encoding trmD polypeptides comprising a sequence set out in Table 1 [SEQ ID NO:1] that includes a full length gene, or a variant thereof. The Applicants believe that this full length gene is essential to the growth and/or survival of an organism that possesses it, such as Streptococcus pneumoniae.
As a further aspect of the invention there are provided isolated nucleic acid molecules encoding and/or expressing trmD polypeptides and polnucleotides, partcularly Streptococcus pneumoniae trmD polypeptides and polynucleotides, including, for example, unprocessed RNAs, ribozyme RNAs, mRNAs, cDNAs, genonic DNAs, B- and Z-DNAs. Further embodiment of the invention include biologically, diagnostically, prohylactically, clinically or therapeutically useful polynucleotides and polypeptides, and variants thereof, and compositions comprising the same.
Another aspect of the invention relates to isolated polynucleotides, including at least one full length gene, that encodes a trmD polypeptide having a deduced amino acid sequence of Table 1 [SEQ ID NO:2] and polynucleotides closely related thereto and variants thereof.
In another particularly preferred embodiment of the invention there is a trmD polypeptide from Streptococcus pneumoniae comprising or consisting of an amino acid sequence of Table 1 [SEQ ID NO:2], or a variant thereof.
Using the invention provided herein, such as a polynucleotide sequence set out in Table 1 [SEQ ID NO:1], a polynucleotide of the invention encoding trmD polypeptide may be obtained using standard cloning and screening methods, such as those for cloning and sequencing chromosomal DNA fragments from bacteria using Streptococcus pneumoniae 0100993 cells as starting material, followed by obtaining a full length clone. For example, to obtain a polynucleotide sequence of the invention, such as a polynucleotide sequence given in Table 1 [SEQ ID NO:1], typically a library of clones of chromosomal DNA of Streptococcus pneumoniae 0100993 in E. coli or some other suitable host is probed with a radiolabeled oligonucleotide, preferably a 17-mer or longer, derived from a partial sequence. Clones carrying DNA identical to that of the probe can then be distinguished using stringent hybridization conditions. By sequencing the individual clones thus identified by hybridization with sequencing primers designed from the original polypeptide or polynucleotide sequence it is then possible to extend the polynucleotide sequence in both directions to determine a full length gene sequence. Conveniently, such sequencing is performed, for example, using denatured double stranded DNA prepared from a plasmid clone. Suitable techniques are described by Maniatis, T., Fritsch, E. F. and Sambrook et al., MOLECULAR CLONING, A LABORATORY MANUAL , 2nd Ed.; Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989). (see in particular Screening By Hybridization 1.90 and Sequencing Denatured Double-Stranded DNA Templates 13.70). Direct genornic DNA sequencing may also be performed to obtain a full length gene sequence. Illustrative of the invention, each polynucleotide set out in Table 1 [SEQ ID NO:1] was discovered in a DNA library derivied from Streptococcus pneumoniae 0100993.
Moreover, each DNA sequence set out in Tale 1 [SEQ ID NO:1] contains an open reading frame encoding a protein having about the number of amino acid residues set forth in Table 1 [SEQ ID NO:2] with a deduced molecular weight that can be calulated using amino acid residue molecular weight values well known to those skilled in the art. The polynucleotide of SEQ ID NO:1, between nucleotide number 1 and the stop codon that begins at nucleotide number 718 of SEQ ID NO:1, encodes the polypeptide of SEQ ID NO:2.
In a further aspect, the present invention provides for an isolated polynucleotide comprising or consisting of: (a) a polynuclectide sequence that has at least 95% identity, even more preferably at least 97, still more preferably at least 99%, yet still more preferably at least 99.5% or exact identity to SEQ ID NO:1 over the entire length of SEQ ID NO:1, or the entire length of that portion of SEQ ID NO:1 which encodes SEQ ID NO:2; (b) a polynucleotide sequence encoding a polypeptide that has at least 95% identity, even more preferably at least 97, still more preferably at least 99%, yet still more preferably at least 99.5% or 100% exact, to the amino acid sequence of SEQ ID NO:2, over the entire length of SEQ ID NO:2.
A polynucleotide encoding a polypeptide of the present invention, including homologs and orthologs from species other than Streptococcus pneumoniae , may be obtained by a process that comprises the steps of screeaing an appropriate library under stringent hybridization conditions with a labeled or detectable probe consisting of or comprising the sequence of SEQ ID NO:1 or a fragment thereof, and isolating a full-length gene and/or genoric clones comprising said polynucleotide sequence.
The invention provides a polynucleotide sequence identical over its entire length to a coding sequence (open reading frame) in Table 1 [SEQ ID NO:1]. Also provided by the invention is a coding sequence for a mature polypeptide or a fragment thereof, by itself as well as coding sequence for a mature polypeptide or a fragment in reading frame with another coding sequence, such as a sequence encoding a leader or secetory sequence, a pre-, or pro- or prepro-protein sequence. The polynucleotide of the invention may also comprise at least one non-coding sequence, including for example, but not limited to at least one non-coding 5′ and 3′ sequence, such as the transcribed but non-translated sequences, termination signals (such as rho-dependent and rho-independent termination signals), ribosome binding sites, Kozak sequences, sequences that stabilize mRNA, introns, and polyadenylation signals. The polynucleotide sequence may also comprise additional coding sequence encoding additional amino acids. For example, a marker sequence that facilitates purification of a fused polypeptide can be encoded. In certain embodiments of the invention, the marker sequence is a hexa-histidine peptide, as provided in the pQE vector (Qiagen, Inc.) and described in Gentz et al., Proc. Natl. Acad. Sci., USA 86: 821-824 (1989), or an HA peptide tag (Wilson et al., Cell 37: 767 (1984), both of that may be useful in purifying polypeptide sequence fused to them. Polynucleotides of the invention also include, but are not limited to, polynucleotides comprising a structural gene and its naturally associated sequences that control gene expression.
A preferred embodiment of the invention is a polynucleotide of consisting of or comprising nucleotide 1 to the nucleotide immediately upstream of or including nucleotide 718 set forth in SEQ ID NO:1 of Table 1, both of that encode a trmD polypeptide.
The invention also includes a polynucleotide consisting of or comprising a polynucleotide of the formula:
X—(R 1 ) m —(R 2 )—(R 3 ) n —Y
wherein, at the 5′ end of the molecule, X is hydrogen, a metal or a modified nucleotide residue, or together with Y defines a covalent bond, and at the 3′ end of the molecule, Y is hydrogen, a metal, or a modified nucleotide residue, or together with X defines the covalent bond, each occurrence of R 1 and R 3 is independently any nucleic acid residue or modified nucleic acid residue, m is an integer between 1 and 3000 or zero, n is an integer between 1 and 3000 or zero, and R 2 is a nucleic acid sequence or modified nucleic acid sequence of the invention, particularly a nucleic acid sequence selected from Table 1 or a modified nucleic acid sequence thereof. In the polynucleotide formula above, R 2 is oriented so that its 5′ end nucleic acid residue is at the left bound to R 1 , and its 3′ end nucleic acid residue is at the right, bound to R 3 . Any stretch of nucleic acid residues denoted by either R 1 and/or R 2 , where m and/or n is greater than 1, may be either a heteropolymer or a homopolymer, preferably a heteropolymer. Where, in a preferred embodiment, X and Y together define a covalent bond, the polynucleotide of the above formula is a closed, circular polynucleotide, that can be a double-stranded polynucleotide wherein the formula shows a first strand to which the second strand is complementary. In another preferred embodiment m and/or n is an integer between 1 and 1000. Other preferred embodiment of invention are provided where m is an integer between 1 and 50, 100 or 500, and n is an integer between 1 and 50, 100, or 500.
It is most preferred that a polynucleotide of the invention is derived from Streptococcus pneumoniae , however, it may preferably be obtained from other organisms of the same taxonomic genus. A polynucleotide of the invention may also be obtained, for example, from organisms of the same taxonomic family or order.
The term “polynucleotide encoding a polypeptide” as used herein encompasses polynucleotides that include a sequence encoding a polypeptide of the invention, particularly a bacterial polypeptide and more particularly a polypeptide of the Streptococcus pneumoniae trmD having an amino acid sequence set out in Table 1 [SEQ ID NO:2]. The term also a polynucleotides that include a single continuous region or discontinuous regions encoding the polypide (for example, polynucleotides interrupted by intergrated phage, an integrated insertion sequence, an integrated vector sequence, an integrated tansposon sequence, or due to RNA editing or genomic DNA reorganization) together with additional regions, also may comprise coding and/or nono-coding sequences.
The invention further relates to variants of the polynucleotides describe herein that encode variants of a polypeptide having a deduced amino acid sequence of Table 1 [SEQ ID NO:2]. Fragments of polynucleotides of the invention may be used, for example, to synthesize full-length polynucleotides of the invention.
Further particularly preferred embodiments are polynucleotides encoding trmD variants, that have the amino acid sequece of trmD polypeptide of Table 1 [SEQ ID NO:2] in which several, a few, 5 to 10, 1 to 5, 1 to 3, 2, 1 or no amino acid residues are substituted, modified, deleted and/or added, in any combination. Especially preferred among these are silent substitutions, additions and deletions, that do not alter the properties and activities of trmD polypeptide.
Preferred isolated polynucleotide embodiments also include polynucleotide fragments, such as a polynucleotide comprising a nuclic acid sequence having at least 15, 20, 30, 40, 50 or 100 contiguous nucleic acids from the polynucleotide sequence of SEQ ID NO:1, or an polynucleotide comprising a nucleic acid sequence having at least 15, 20, 30, 40, 50 or 100 contiguous nucleic acids truncated or deleted from the 5′ and/or 3′ end of the polynucleotide sequence of SEQ ID NO:1.
Further preferred embodiments of the invention are polynucleotides that are at least 95%, 97% or 99.5% identical over there entire length to a polynucleotide encoding trmD polypeptide having an amino acid sequence set out in Table 1 [SEQ ID NO:2], and polynucleotides that are complementary to such polynucleotides. Most highly preferred are polynucleotides that comprise a region that is at least 95% are especially preferred. Furthermore, those at least 97% are highly preferred among those with at least 95%, and among these those with at least 98% and at least 99% are particularly highly preferred, with at least 99.5% being the more preferred.
Preferred embodiments are polynucleotides encoding polypeptides that retain substantially the same biological function or activity as a mate polypeptide encoded by a DNA of Table 1 [SEQ ID NO:1].
In accordance with certain preferred embodiments of this invention the are provided polynucleotides that hybridize, particularly under it conditions, to trmD polynucleotide sequence, such as those polynucleotides in Table 1.
The invention further relates to polynucleotides that hybridize to the polynucleotide sequences provided herein. In this regard, the invention especially relates to polynucleotides that hybridize under stringent conditions to the polynucleotides described herein. As herein used, the terms “stringent conditions” and “stringent hybridization conditions” mean hybridization occurring only if there is at least 95% and preferably at least 97% identity between the sequences. A specific example of stringent hybridization conditions is overnight incubation at 42° C. in a solution comprising: 50% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH7.6), 5×Denhardt's solution, 10% dextran sulfate, and 20 micrograms/ml of denatured, sheared salmon sperm DNA, followed by washing the hybridization support in 0.1×SSC at about 65° C. Hybridization and wash condition are well known and exemplified in Sambrook, et al., Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor, N.Y., (1989), particularly Chapter 11 therein. Solution hybridization may also be used with the polynucleotide sequences provided by the invention.
The invention also provides a polynucleotide consisting of or comprising a polynucleotide sequence obtained by screening an appropriate library comprising a complete gene for a polynucleotide sequence set forth in SEQ ID NO:1 under stringent hybridization conditions with a probe having the sequence of said polynucleotide sequence set forth in SEQ ID NO:1 or a fragment thereof; and isolating said polynucleotide sequence. Fragments useful for obtaining such a polynucleotide include, for example, probes and primers fully described elsewhere herein.
As discussed elsewhere herein regarding polynucleotide assays of the invention, for instance, the polynucleotides of the invention, may be used as a hybridization probe for RNA, cDNA and genonic DNA to isolate full-length cDNAs and genomic clones encoding trmD and to isolate cDNA and genomic clones of other genes that have a high identity, particularly high sequence identity, to a trmD gene. Such probes generally will comprise at least 15 nucleotide residues or base pairs. Preferably, such probes will have at least 30 nucleotide residues or base pairs and may have at least 50 nucleotide residues or base pairs. Particularly preferred probes will have at least 20 nucleotide residues or base pairs and will have least than 30 nucleotide residues or base pairs.
A coding region of a trmD gene may be isolated by screening using a DNA sequence provided in Table 1 [SEQ ID NO:1] to synthesize an oligonucleotide probe. A labeled oligonuceotide having a sequence complementary to that of a gene of the invention is then used to screen a library of cDNA, genoic DNA or mRNA to determine which members of the library the probe hybridizes to.
There are several methods available and well known to those skilled in the art to obtain full-length DNAs, or extend short DNAs, for example those based on the method of Rapid Amplification of cDNA ends (RACE) (see, for example, Frobman, et al., PNAS USA 85: 8998-9002, 1988). Recent modifications of the technique, exemplified by the Marathon™ technology (Clonech Laboratories Inc.) for example, have significantly simplified the search for longer cDNAs. In the Marathon™ technology, cDNAs have been prepared from mRNA extracted from a chosen tissue and an ‘adaptor’ sequence ligated onto each end. Nucleic acid amplification (PCR) is then carried out to amplify the “missing” 5′ end of the DNA using a combination of gene specific and adaptor specific oligonucleotide primers. The PCR reaction is then repeated using “nested” primers, that is, primers designed to anneal within the amplified product (typically an adaptor specific primer that anneals further 3′ in the adaptor sequence and a gene specific primer that anneals further 5′ in the selected gene sequence). The products of this reaction can then be analyzed by DNA sequencing and a full-length DNA constructed either by joining the product directly to the existing DNA to give a complete sequence, or carrying out a separate full-length PCR using the new sequence information for the design of the 5′ primer.
The polynucleotides and polypeptides of the invention may be employed, for example, as research reagents and materials for discovery of treats of and diagnostics for diseases, particularly human diseases, as further discussed herein relating to polynucleotide assays.
The polynucleotides of the invention that are oligonuciotides derived from a sequence of Table 1 [SEQ ID NOS:1 or 2] may be used in the processes herein as described, but preferrably for PCR, to determine whether or not the polynucleotides identified herein in whole or in part are transcribed in bacteria in infected tissue. It is recognized that such sequences will also have utility in diagnosis of the stage of infection and type of infection the pathogen has attained.
The invention also provides polynucleotides that encode a polypeptide that is a mature protein plus additional amino or carboxyl-terminal amino acids, or amino acids interior to a mature polypeptide (when a mature form has more than one polypeptide chain, for instance). Such sequences may play a role in processing of a protein from precursor to a mature form, may allow protein transport, may lengthen or shorten protein half-life or may facilitate manipulation of a protein for assay or production, among other things. As generally is the case in vivo, the additional amino acids may be processed away from a mature protein by cellular enzymes.
For each and every polynucleotide of the invention there is provided a polynucleotide complementary to it. It is preferred that these complementary polynucleotides are fully complementary to each polynucleotide with which they are complementary.
A precursor protein, having a mature form of the polypeptide fused to one or more prosequence may be an inactive form of the polypeptide. When prosequences are removed such inactive precursors generally are activated. Some or all of the prosequences may be removed before activation. Generally, such precursors are called proproteins.
As will be recognized, the entire polypeptide encoded by an open reading frame is often not required for activity. Accordingly, it has become routine in molecular biology to map the boundaries of the primary structure required for activity N-treminal and C-treminal deletion experiments. These experiments utilize exonuclease digestion or commit restriction sites to cleave coding nucleic acid sequence. For example, Promega (Madison, Wis.) sell an Erase-a-base™ system that uses Exonuclease III designed to facilitate analysis of the deletion products (protocol available at www.promega.com). The digested endpoints can be repaired (e.g., by ligation to synthetic linkers) to the extent necessary to preserve an open reading fame. In this way, the nucleic acid of SEQ ID NO:1 readily provides contiguous fragments of SEQ ID NO:2 sufficient to provide an activity, such as an enzymatic, binding or antibody-inducing activity. Nucleic acid sequences encoding such fragments of SEQ ID NO:2 and variants thereof as described herein are within the invention, as are polypeptides so encoded.
In sum, a polynucleotide of the invention may encode a mature protein, a mature protein plus a leader sequence (which may be referred to as a preprotein), a precursor of a mature protein having one or more prosequences that are not the leader sequences of a preprotein, or a preproprotein, that is a precursor to a proprotein, having a leader sequence and one or more prosequences, that generally are removed during processing steps that produce active and mature forms of the polypeptide.
Vectors, Host Cells, Expression Systems
The invention also relates to vectors that comprise a polynucleotide or polynucleotides of the invention, host cells that are genetically engineered with vectors of the invention and the production of polypeptides of the invention by recombinant techniques. Cell-free translation systems can also be employed to produce such proteins using RNAs derived from the DNA costructs of the invention.
Recombinant polypeptides of the present invention may be prepared by process well known in those skilled in the art from genetically engineered host cells comprising expression systems. Accordingly, in a further aspect, the present invention relates to expression systems that comprise a polynucleotide or polynucleotides of the preset invention, to host cells that are genetically engineered with such expression systems, and to the production of polypeptides of the invention by recombinant techniques.
For recombinant production of the polypeptides of the invention, host cells can be genetically engineered to incorporate expression systems or portions thereof or polynucleotides of the invention. Introduction of a polynucleotide into the host cell can be effected by methods described in many standard laboratory manuals, such as Davis, et al., BASIC METHODS IN MOLECULAR BIOLOGY , (1986) and Sambrook, et al, MOLECULAR CLONING: A LABORATORY MANUAL , 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989), such as, calcium phosphate transfection, DEAE-dextran mediated transfection, transvection, microinjection, cationic lipid-mediated transfection, electoporation, transduction, scrape loading ballistic introduction and infection.
Representative examples of appropriate hosts include bacterial cells, such as cells of streptococci, staphylococci, E. coli , streptomyces, cyanobacteria, Bacillus subtilis , and Streptococcus pneumoniae ; fungal cells, such as cells of a yeast Kluveromyces, Saccharomyces, a basidiomycete, Candida albicans and Aspergillus; insect cells such as cells of Drosophila S2 and Spodoptera Sf9; animal cells such as CHO, COS, HeLa C127, 3T3, BHK, 293, CV-1 and Bowes melanoma cells; and plant cells, such as cells of a gymnosperm or angiosperm.
A great variety of expression systems can be used to produce the polypeptides of the invention. Such vectors include, among other, chromosomal-, episomal- and virus-derived vectors, for example, vetors derived from bacterial plasmids, from bacteriophage, from transposons, from yeast episomes, from insertion elements, from yeast chromosomal elements, from viruses such as baculoviruses, papova viruses, such as SV40, vaccinia viruses, adenoviruses, fowl pox viruses, pseudorabies viruses, picornaviruses and retroviruses, and vectors derived from combinations thereof, such as those derived from plasmid and bacteriophage genetic elements, such as cosmids and phagemids. The expression system constructs may comprise control regions that regulate as well as engender expression. Generally, any system or vector suitable to maintain, propagate or express polynucleotides and/or to express a polypeptide in a host may be used for expression in this regard. The appropriate DNA sequene may be inserted into the expression system by any of a variety of well-known and routine techniques, such as, for example, those set forth in Sambrook et al., MOLECULAR CLONING, A LABORATORY MANUAL , (supra).
In recombinant expression systems in eukaryotes, for secretion of a translated protein into the lumen of the endoplasmic reticulum, into the periplasmic space or into the extracellular environment, appropriate secretion signals may be incoporated into the expressed polypeptide. These signals may be endonous to the polypeptide or they may be heterologous signals.
Polypeptides of the invention can be recovered and purified from recombinant cell cultures by well-known methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography, and lectin chromatography. Most preferably, high performance liquid chromatography is employed for purification. Well known techniques for refolding protein may be employed to regenerate active conformation when the polypeptide is denatured during isolation and or purification.
Diagnostic, Prognostic, Serotyping and Mutation Assays
This invention is also related to the use of trmD polynucleotides and polypeptides of the invention for use as diagnostic reagents. Detection of trmD polynucleotides and/or polypeptides in a eukaryote, particularly a mammal, and especially a human, will provide a diagnostic method for diagnosis of disease, staging of disease or response of an infectious organism to drugs. Eukaryotes, particularly mammals, and especially humans, particularly those infected or suspeted to be infected with an organism comprising the trmD gene or protein, may be detected the nucleic acid or amino acid level by a variety of well known techniques as well as by methods provided herein.
Polypeptides and polynucleotides for prognosis, diagnosis or other analysis may be obtained from a putatively infected and/or infected individual's bodily materials. Polynucleotides from any of these sources, particularly DNA or RNA, may be used directly for detection or may be amplified enzymatically by using PCR or any other amplification technique prior to analysis. RNA, particularly mRNA, cDNA and genomic DNA may also be used in the same ways. Using amplification, characterization of the species and strain of infectious or resident organism present in an individual, may be made by an analysis of the genotype of a selected polynucleotide of the organism. Deletions and insertions can be detected by a change in size of the amplified product in comparison to a genotype of a reference sequence selected from a related organism preferably a different species of the same genus or a different strain of the same species. Point mutations can be identified by hybridizing amplified DNA to labeled trmD polynucleotide sequence. Perfectly or significantly matched sequences can be distinguished from imperfectly or more significantly mismatched duplexes by DNase or RNase digestion, for DNA or RNA resctively, or by detecting differences in melting temperatures or renaturation kinetics. Polynucleotide sequence differences may also be detected by alterations in the electrophoretic mobility of polynucleotide fragments in gels as compared to a reference sequence. This may be carried out or without denaturing agents. Polynucleotide may also detected by direct DNA or RNA sequencing. See, for example, Myers et al., Science , 230: 1242 (1985). Sequence changes at specfic locations also may be revealed by nuclease protection assays, such as RNase, V 1 and S 1 protection assay or a chemical cleavage method. See, for example, Cotton et al., Proc. Natl. Acad. Sci. USA , 85: 4397-4401 (1985).
In another embodiment, an array of oligonucleotides probes comprising trmD nucleotide sequence or fragments thereof can be constructed to conduct efficient screening of, for example, genetic mutations, serotype, taxonomic classification or identification. Array technology methods are well known and have general applicability and can be used to address a variety of questions in molecular genetics including gene expression, genetic linkage, and genetic variability (see, for example, Chee et al., Science , 274: 610 (1996)).
Thus in another aspect, the present invention relates to a diagnostic kit that comprises: (a) a polynucleotide of the present invention, preferably the nucleotide sequence of SEQ ID NO:1, or a fragment thereof; (b) a nucleotide sequence complementary to that of (a); (c) a polypeptide of the present invention, preferably the polypeptide of SEQ ID NO:2 or a fragment thereof; or (d) an antibody to a polypeptide of the present invention, preferably to the polypeptide of SEQ ID NO:2. It will be appreciated that in any such kit, (a), (b), (c) or (d) may comprise a substantial component. Such a kit will be of use in diagnosing a disease or susceptibility to a Disease, among others.
This invention also relates to the use of polynucleotides of the present invention as diagnostic reagents. Detection of a mutated form of a polynucleotide of the invention, example, SEQ ID NO:1, that is associated with a disease or pathogenicity will provide a diagnostic tool that can add to, or define, a diagnosis of a disease, a prognosis of a course of disease, a detection of a stage of disease, or a susceptibility to a disease, that results from under-expression, over-expression or altered expression of the polynucleotide. Organisms, particularly infectious organisms, carrying mutations in such polynucleotide may be detected at the polynucleotide level by a variety of techniques, such as those described elsewhere herein.
The differences in a polynucleotide and/or polypeptide sequence between organisms possessing a first phenotype and organisms possessing a different, second different phenotype can also be determined. If a mutation is observed in some or all organisms possessing the first phenotype but not in any organisms possessing the second phenotype, then the mutation is likely to be the causative agent of the first phenotype.
Cells from an organism carrying mutations or polymorphisms (allelic variatons) in a polynucleotide and/or polypeptide of the invention may also be detected at the polynucleotide or polypeptide level by a variety of techniques, to allow for serotyping, for example. For example, RT-PCR can be used to detect mutations in the RNA. It is particularly preferred to use RT-PCR in conjunction with automated detection systems, such as, for example, GeneScam RNA, cDNA or genomic DNA may also be used for the same purpose, PCR. As an example, PCR print complementary to a polynucleotide encoding trmD polypeptide can be used to identify and analyze mutations. The invention further provides these primers 1, 2, 3 or 4 nucleotides removed from the 5′ and/or the 3′ end. These primers may be used for, among other things, amplifying trmD DNA and/or RNA isolated from a sample derived from an individual, such as a bodily material. The primers may be used to amplify a polynucleotide isolated from an infected individual, such that the polynucleotide may then be subject to various techniques for elucidation of the polynucleotide sequence. In this way, mutations in the polynucleotide sequence may be detected and used to diagnose and/or prognose the infection or its stage or course, or to serotype and/or classify the infectious agent.
The invention further provides a process for diagnosing, disease, preferably bacterial infections, more perferably infections caused by Streptococcus pneumoniae , comprising determining from a sample derived from an individual, such as a bodily material, an increased level of expression of polynucleotide having a sequence of Table 1 [SEQ ID NO:1]. Increased or decreased expression of a trmD polynulceotide can be measured using any on of the methods well known in the art for the quantitation of polynucleotides, such as, for example, amplification, PCR, RT-PCR, RNase protection, Northern blotting, spectrometry and other hybridization methods.
In addition, a diagnostic assay in accordance with the invention for detecting over-expression of trmD polypeptide compared to normal control tissue samples may be used to detect the presence of an infection, for example. Assay techniques that can be used to determine levels of a trmD polypeptide, in a sample derived from a host, such as a bodily material, are well-known to those of skill in the art. Such assay methods include radioimmunoassays, competitive-binding assays, Western Blot analysis, antibody sandwich assays, antibody detection and ELISA assays.
Antagonists and Agonists—Assays and Molecules
Polypeptides and polynucleotides of the invention may also be used to assess the binding of small molecule substrates and ligands in, for example, cells, cell-free preparations, chemical libraries, and natural product mixtures. These substrates and ligands may be natural substrates and ligands or may be structural or functional mimetics. See, e.g., Coligan et al., Current Protocols in Immunology 1(2): Chapter 5 (1991).
Polypeptides and polynucleotides of the present invention are responsible for many biological functions, including many disease states, in particular Diseases herein mentioned. It is therefore desirable to devise screening methods to identify compounds that agonize (e.g., stimulate) or that antagonize (e.g., inhibit) the function of the polypeptide or polynucleotide. Accordingly, in a further aspect, the present invention provides for a method of screening compounds to identify those that agonize or that antagonize the function of a polypeptide or polynucleotide of the invention, as well as related polypeptides and polynucleotides. In general, agonists or antagonists (e.g., inhibitors) may be employed for therapeutic and prophylactic purposes for such Diseases as herein mentioned. Compounds may be identified from a variety of sources, for example, cells, cell-free preparations, chemical libraries, and natural product mixtures. Such agonists and antagonists so-identified may be natural or modified substrates, ligands receptors, enzymes, etc., as the case may be, of trmD polypeptides and polynucleotides; or may be structural or functional mimetics thereof (see Coligan et al., Current Protocols in Immunology 1(2):Chapter 5 (1991)).
The screening methods may simply measure the binding of a candidate compound to the polypeptide or polynucleotide, or to cells or membranes bearing the polypeptide or polynucleotide, or a fusion protein of the polypeptide by means of a label directly or indirectly associated with the candidate compound. Alternatively, the screening method may involve competition with a labeled competitor. Further, these screening methods may test whether the candidate compound results in a signal generated by activation or inhibition of the polypeptide or polynucleotide, using detection systems appropriate to the cells comprising the polypeptide or polynucleotide. Inhibitors of activation are generally assayed in the presence of a known agonist and the effect on activation by the agonist by the presence of the candidate compound is observed. Constitutively active polypeptide and/or constitutively expressed polypeptides and polynucleotides may be employed in screening methods for inverse agonists, in the absence of an agonist or antagonist, by testing whether the candidate compound results in inhibition of activation of the polypeptide or polynucleotide, as the case may be. Further, the screening methods may simply comprise the steps of mixing a candidate compound with a solution comprising a polypeptide or polynucleotide of the present invention, to form a mixture, measured trmD polypeptide and/or polynucleotide activity in the mixture, and comparing the trmD polypeptide and/or polynucleotide activity of the mixture to a standard. Fusion proteins, such as those made from Fc portion and trmD polypeptide, as herein described, can also be used for high-throughput screening assays to identify antagonists of the polypeptide of the present invention, as well as of phylogenetically and and/or functionally related polypeptides (see D. Bennett et al., J Mol Recognition, 8:52-58 (1995); and K. Johanson et al., J Biol Chem, 270(16):9459-9471 (1995)).
The polynucleotides, polypeptides and antibodies that bind to and/or interact with a polypeptide of the present invention may also be used to configure screening methods for detecting the effect of added compounds on the production of mRNA and/or polypeptide in cells. For example, an ELISA assay may be constructed for measuring secreted or cell associated levels of polypeptide using monoclonal and polyclonal antibodies by standard methods known in the art. This can be used to discover agents that may inhibit or enhance the production of polypeptide (also called antagonist or agonist, respectively) from suitably manipulated cells or tissues.
The invention also provides a method of sounds to identify those that enhance (agonist) or block (antagonist) the action of trmD polypeptides or polynucleotides, particlarly those compounds that are bacteristatic and/or bactericidal. The method of screening may involve high-throughput techniques. For example, to screen for agonists or antagonists, a synthetic reaction mix, a cellular compartment, such as a membrane, cell envelope or cell wall or a preparation of any thereof, comprising trmD polypeptide and a labeled substrate or ligand of such polypeptide is incubated in the absence or the presence of a candidate molecule may be a trmD agonist or antagonist. The ablity of the candidate molecule to agonize or antagonize the trmD polypeptide is reflected in deceased binding of the labeled ligand or decreased production of product from such substate. Molecules that bind gratuitously, i.e., without inducing the efects of trmD polypeptide are most likely to be good antagonists. Molecules that bind well and, as the case may be, increase the rate of product production from subsrate, increase signal transduction, or increase chemical channel activity are agonists. Detection of the rate or level of, as the case may be, production of product from substrate, signal transduction, or chemical channel activity may be enhanced by using a reporter system. Reporter systems that may be useful in this regard include but are not limited to colorimetric, labeled substate converted into product, a reporter gene that is responsive to changes in trmD polynucleotide or polypeptide activity, and binding assays known in the art.
Polypeptides of the invention may be used to identify membrane bound or soluble receptors, if any, for such polypeptide, through standard receptor binding techniques known in the art. These techniques include, but are not limited to, ligand binding and crosslinking assays in which the polypeptide is labeled with a radioactive isotope (for instance, 125 I), chemically modified (for instance, biotinylated), or fused to a peptide sequence suitable for detection or purification, and incubated with a source of the putative receptor (e.g., cells, cell membranes, cell supernatants, tissue extracts, bodily materials). Other methods include biophysical techniques such as surface plasmon resonance and spectroscopy. These screening methods may also be used to identify agonist and antagonist of the polypeptide that compete with the binding of the polypeptide to its receptor(s), if any. Standard methods for conducting such assays are well understood in the art.
The fluorescence polarization value for a fluorescently-tagged molecule depends on the rotational correlation time or tumbling rate. Protein complexes, such as formed by trmD polypeptide associating with another trmD polypeptide or other polypeptide, labeled to comprise a fluorescently-labeled molecule will have higher polarization values than a fluorescently labeled monomeric protein. It is preferred that this method be used to characterize small molecules that disrupt polypeptide complexes.
Fluorescence energy transfer may also be used characterize small molecules that intefere with the formation of trmD polypeptide dimers, trimers, tetramers or higher order structures, or structures formed by trmD polypeptide bound to another polypeptide. TrmD polypeptide can be labeled with both a donor and acceptor fluorophore. Upon mixing of the two labeled species and excitation of the donor fluorophore, fluorescence energy transfer can be detected by observing fluorescence of the acceptor. Compounds that block dimerization will inhibit fluorescence energy transfer.
Surface plasmon resonance can be used to monitor the effect of small molecules on trmD polypeptide self-association as well as an association of trmD polypeptide and another polypeptide or small molecule. TrmD polypeptide can be coupled to a sensor chip at low site density such that covalently bound molecules will be monomeric. Solution protein can then passed over the trmD polypeptide-coated surface and specific binding can be detected in real-time by monitoring the change in resonance angle caused by a change in local refractive index. This technique can be used to characterize the effect of small molecules on kinetic rates and equilibrium binding constants for trmD polypeptide self-association as well as an association of trmD polypeptide and another polypeptide or small molecule.
A scintillation proximity assay may be used to characterize the interaction between an association of trmD polypeptide with another trmD polypeptide or a different polypeptide. TrmD polypeptide can be coupled to a scintillation-filled bead. Addition of radio-labeled trmD polypeptide results in binding where the radioactive source molecule is in close proximity to the scintillation fluid. Thus, signal is emitted upon trmD polypeptide binding and compounds that prevent trmD polypeptide self-association or an association of trmD polypeptide and another polypeptide or small molecule will diminish signal.
In other embodients of the invention there are provided methods for identify compounds that bind to or otherwise interact with and inhibit or activate an activity or expression of a polypeptide and/or polynucleotide of the invention comprising: contacting a polypeptide and/or polynucleotide of the invention with a compound be screened under conditions to permit binding to or other interaction between the compound and the polypeptide and/or polynucleotide to assess the binding to or other interaction with the compound, such binding or interaction preferably being associated with a second component capable of providing a detectable signal in response to the binding or interaction of the polypeptide and/or polynucleotide with the compound; and determining whether the compound binds to or otherwise interacts with and activates or inhibits an activity or expression of the polypeptide and/or polynucleotide by detecting the presence or absence of a signal generated from the binding or interaction of the compound with the polypeptide and/or polynucleotide.
Another example of an assay for trmD agonists is a competitive assay that combines trmD and a potential agonist with trmD-binding molecules, recombinant trmD binding molecules, natural substrates or ligands, or substate or ligand mimetics, under appropriate conditions for a competitive inhibition assay. TrmD can be labeled, such as by radioactivity or a colorimetric compound, such that the number of trmD molecules bound to a binding molecule or converted to product can be determined accurately to assess the effectiveness of the potential antagonist.
It will be readily appreciated by the skilled artisan that a polypeptide and/or polynucleotide of the present invention may also be used in a method for the structure-based design of an agonist or antagonist of the polypeptide and/or polynucleotide, by: (a) determining in the first instance the three-dimensional structure of the polypeptide and/or polynucleotide, or complexes thereof; (b) deducing the three-dimensional stucture for the likely reactive site(s), binding site(s) or motif(s) of an agonist or antagonist; (c) synthesizing candidate compounds that are predicted to bind to or react with the deduced binding site(s), reactive site(s), and/or motif(s); and (d) tesing whether the candidate compounds are indeed agonists or antagonists.
It wil be further appreciated that this will normally be an iterative process, and this iterative process may be performed using automated and computer-controlled steps.
In a further a the present invention provides methods of treating abnormal conditions such as, for instance, a Disease, related to either an excess of, an under-expression of, an elevated activity of, or a decreased activity of trmD polypeptide and/or polynucleotide.
If the expression and/or activity of the polypeptide and/or polynucleotide is in excess, several approaches are available. One approach comprises administering to an individual in need thereof an inhibitor compound (antagonist) as herein described, optionally in combination with a pharmaceutically acceptable carrier, in an amount effective to inhibit the function and/or expression of the polypeptide and/or polynucleotide, such as, for example, by blocking the binding of ligands, substrates, receptors, enzymes etc., or by inhibiting a second signal, and thereby alleviating the abnormal condition. In another approach, soluble forms of the polypeptides still capable of binding the ligand, substrate, enzymes, receptors, etc. in competition with endogenous polypeptide and/or polynucleotide may be administered. Typical examples of such competitors include fragments of the trmD polypeptide and/or polypeptide.
In still another approach, expression of the gene encoding endogenous trmD polypeptide can be inhibited using expression blocking techniques. This blocking may be targeted against any step in gene expression, but is preferably targeted against transcription and/or tanslation. An examples of a known technique of this sort involve the use of antisense sequences, either internally generated or separately administered (see, for example, O'Connor, J Neurochem (1991) 56:560 in Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, Fla. (1988)). Alternatively, oligonucleotides that form triple helices with the gene can be supplied (see, for example, Lee et al., Nucleic Acids Res (1979) 6:3073; Cooney et al., Science (1988) 241:456; Dervan et al., Science (1991) 251:1360). These oligomers can be administered per se or the relevant oligomers can be expressed in vivo.
Each of the polynucleotide sequences provided herein may be used in the discovery and development of antibacterial compounds. The encoded protein, upon expression, can be used as a target for the screening of antibacterial drugs. Additionally, the polynucleotide sequences encoding the amino terminal regions of the encoded protein or Shine-Delgarno or other translation facilitating sequences of the respective mRNA can be used to construct antisense sequences to control the expression of the coding sequence of interest.
The invention also provides the use of the polypeptide, polynucleotide, agonist or antagonist of the invention to interfere with the initial physical interaction between a pathogen or pathogens and a eukaryotic, preferably mammalian, host responsible for sequelae of infection. In particular, the molecules of the invention may be used: in the prevention of adhesion of bacteria, in particular gram positive and/or grain negative bacteria, to eukaryotic, preferably mammalian, extracellular matrix proteins on in-dwelling devices or to extacellular matrix proteins in wounds; to block bacterial adhesion between eukaryotic, preferably mammalian, extracellular matrix proteins and bacterial trmD proteins that mediate tissue damage and/or; to block the normal progression of pathogenesis in infections initiated other than by the implantation of in-dwelling devices or by other surgical techniques.
In accordance with yet another aspect of the invention, there are provided trmD agonists and antagonists, preferably bacteristic or bactericidal agonists and antagonists.
The antagonist and agonists of the invention may be employed, for instance, to prevent, inhibit and/or treat diseases.
Helicobacter pylori (herein “ H. pylori ”) bacteria infect the stomachs of over one-third of the world's population causing stomach cancer, ulcers, and gastritis (International Agency for Research on Cancer (1994) Schistosomes, Liver Flukes and Helicobacter Pylori (International Agency for Research on Cancer, Lyon, France, http://www.uicc.ch/ecp/ecp2904.htm). Moreover, the International Agency for Research on Cancer recently recognized a cause-and-effect relationship between H. pylori and gastric adenocarcinoma, clasifying the bacterium as a Group I (definite) carcinogen. Preferred antimicrobial compounds of the invention (agonists and antagonists of trmD polypeptides and/or polynucleotides) found using screens provided by the invention, or known in the art, particularly narrow-spectrum antibiotics, should be useful in the treatmet of H. pylori infection. Such treatment should decrease the advent of H. pylori -induced cancers, such as gastrointestinal carcinoma. Such treatment should also prevent, inhibit and/or cure gastric ulcers and gastritis.
All publications and references, including but not limited to patents and patent applications, cited in this specification are herein incorporated by reference in their entirety as if each individual publication or reference were specifically and individually indicted to be incorporated by reference herein as being fully set forth. Any patent application to which this application claims priority is also incorporated by reference herein in its entirety in the manner described above for publications and references.
GLOSSARY
The following definitions are provided to facilitate understaning of certain terms used frequently herein.
“Bodily material(s) means any material derived from an individual or from an organism infecting, infesting or inhabiting an individual, including but not noted to, cells, tissues and waste, such as, bone, blood, serum, cerebrospinal fluid, semens, saliva, muscle, cartilage, organ tissue, skin, urine, stool or autopsy materials.
“Disease(s)” means any disease caused by or related to infection by a bacteria, including, for example, otitis media, conjuctivitis, pneumonia, bacteremia, meningitis, sinusitis, pleural empyema and endocarditis, and most particularly meningitis, such as for example infection of cerebrospinal fluid.
“Host cell(s)” is a cell that has been introduced (e.g., transformed or transfected) or is capable of introduction (e.g., transformation or transfection) by an exogenous polynucleotide sequence.
“Identity,” as known in the art, is a relationship between two or more polypeptide sequences or two or more polynucleotide sequences, as the case may be, as determined by comparing the sequences. In the art, “identity” also means the degree of sequence relatedness between polypeptide or polynucleotide sequences, as the case may be, as determined by the match between strings of such sequences. “Identity” can be readily calculated by known methods, including but not limited to those described in ( Compuational Molecular Biology , Lesk, A. M., ed., Oxford University Press, New York, 1988 ; Biocomputing: Informatics and Genome Projects , Smith, D. W., ed., Academic Press, New York, 1993 ; Computer Analysis of Sequence Data , Part I, Griffin, A. M., and Griffin, H. G., eds., Humana Press, New Jersey, 1994 ; Sequence Analysis in Molecular Biology , von Heinje, G., Academic Press, 1987; and Sequence Analysis Primer , Gribskov, M. and Devereux, J., eds., M Stockton Press, New York, 1991; and Carillo, H., and Lipman, D., SLAM J. Applied Math ., 48: 1073 (1988). Methods to determine identity are designed to give the largest match between the sequences tested. Moreover, methods to determine identity are codified in publicly available computer programs. Computer program methods to determine identity between two sequences include, but are not limited to, the GCG program package (Devereux, J., et al., Nucleic Acids Research 12(1)387 (1984)), BLASTP, BLASTN, and FASTA (Altschul, S. F. et al., J. Molec. Biol . 215: 403-410 (1990). The BLAST X program is publicly available from NCBI and other sources ( BLAST Manual , Altschul, S., et al., NCBI NLM NIH Bethesda, Md. 20894; Altschul. S., et al., J. Mol. Biol . 215: 403-410 (1990). The well known Smith Waterman algorithm may also be used to determine identity.
Parameters for polypeptide sequence comparison include the following: Algorithm: Needleman and Wunsch, J. Mol Biol. 48: 443-453 (1970) Comparison matrix: BLOSSUM62 from Hentikoff and Hentikoff, Proc. Natl. Acad. Sci. USA. 89:10915-10919 (1992)
Gap Penalty: 12
Gap Length Penalty 4
A program useful with these parameters is publicly available as the “gap” program from Genetics Computr Group, Madison Wis. The aforementioned parameters are the default parameters for peptide comparisons (along with no penalty for end gaps).
Parameters for polynucleotide comparison include the following: Algorithm: Needleman and Wunsch, J. Mol Biol. 48: 443-453 (1970)
Comparison matrix: matches=+10, mismatch=0
Gap Penalty: 50
Gap Penalty: 3
Available as: The “gap” program from Genetics Computer Group, Madison Wis. These are the default parameters for nucleic acid comparisons.
A preferred meaning for “identity” for polynucleotides and polypeptides, as the case may be, are provided in (1) and (2) below.
(1) Polynucleotide embodiments further include an isolated polynucleotide comprising a polynucleotide sequence having at least a 95, 97, 99.5 or 100% identity to the reference sequence of SEQ ID NO:1, wherein said polynucleotide sequence may be identical to the reference sequence of SEQ ID NO:1 or may include up to a certain integer number of nucleotide alterations as compared to the reference sequence, wherein said alterations are selected from the group consisting of at least one nucleotide deletion, substitution, including transition and transversion, or insertion, and wherein said alterations may occur at the 5′ or 3′ terminal positions of the reference nucleotide sequence or anywhere between those terminal positions, interspersed either individually among the nucleotides in the reference sequence or in one or more contiguous groups within the reference sequence, and wherein said number of nucleotide alterations is determined by multiplying the total number of nucleotides in SEQ ID NO:1 by the integer defining the percent identity divided by 100 and then subtracting that product from said total number of nucleotides in SEQ ID NO:1, or:
n n ≦x n −(x n •y),
wherein n n is the number of nucleotide alterations, x n is the total number of nucleotides in SEQ ID NO:1, y is 0.95 for 95%, 0.97 for 97%, 0.995 for 99.5% or 1.00 for 100%, and • is the symbol for the multiplication operator, and wherein any non-integer product of x n and y is rounded down to the nearest integer prior to subtracting it from x n . Alterations of a polynucleotide sequence encoding the polypeptide of SEQ ID NO:2 may create nonsense, missense or frameshift mutations in his coding sequence and thereby alter the polypeptide encoded by the polynucleotide following such alterations.
(2) Polypeptide embodiments further include an isolated polypeptide comprising a polypeptide having at least a 95, 97 or 100% identity to a polypeptide reference sequence of SEQ ID NO:2, wherein said polypeptide sequence may be identical to the reference sequence of SEQ ID NO:2 or may include up to a certain integer number of amino acid alterations as compared to the reference sequence, wherein said alterations are selected from the group consisting of at least one amino acid deletion, substitution, including conservative and non-conservative substitution, or insertion, and wherein said alterations may occur at tha amino- or carboxy-terminal positions of the reference polypeptide sequence or anywhere between those terminal positions, interspersed either individually among the amino acids in the reference sequence or in one or more contiguous groups within the reference sequence, and wherein said number of amino acid alterations is determined by multiplying the total number of amino acids in SEQ ID NO:2 by the integer defining the percent identity divided by 100 and then subtracting that product from said total number of amino acids in SEQ ID NO:2, or:
n a ≦x a −(x a •y),
wherein n a is the number of amino acid alterations, x a is the total number of amino acids in SEQ ID NO:2, y is 0.95 for 95%, 0.97 for 97% or 1.00 for 100%, and • is the symbol for the multiplication operator, and wherein any non-integer product of x a and y is rounded down to the nearest integer prior to subtracting it from x a .
“Individual(s)” means a multicellular eukaryote, including, but not limited to a metzoan, a mammal an ovid, a bovid, a simian, a primate, and a human.
“Isolated” means altered “by the hand of man” from its natural state, i.e., if it occurs in nature, it has been changed or removed from its original environment, or both. For example, a polynucleotide or a polypeptide naturally present in a living organism is not “isolated,” but the same polynucleotide or polypeptide separated from the coexisting materials of its natural state is “isolated”, as the term is employed herein. Moreover, a polynucleotide or polypeptide a is introduced into an organism by transformation, genetic manipulation or by any other recombinant method is “isolated” even if it is still present in said organism, which organism may be living or non-living.
“Organism(s)” mmeans a (i) pro karyote icluding but not limited to, a member of the genus Streptococcus, Staphylococcus, Bordetella, Corynebacterium, Mycobacterium, Neissera, Haemophilus, Actinomycetes, Streptomycetes, Nocardia, Enterobacter, Yersinia, Fancisella, Pasturella, Moraxella, Acinetobacter, Erysipelothrix, Branhamella, Actinobacillus, Streptobacillus, Listeria, Calymmatobacterium, Brucella, Bacillus, Clostridium, Treponema, Escherichia, Salmonella, Kleibsiella, Vibrio, Proteus, Erwinia, Borrelia, Leptospira, Spirillum, Campylobacter, Shigella, Legionella, Pseudomonas, Aeromonas, Rickettsia, Chlamydia, Borrelia and Mycoplasma, and further induding, but not limited to, a member of the species or group, Group A Streptococcus, Group B Streptococcus, Group C Streptococcus, Group D Streptococcus, Group G Streptococcus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus faecalis, Streptococcus faecium, Streptococcus durans, Neisseria gonorrheae, Neisseria meningitidis, Staphylococcus aureus, Staphylococcus epidermidis, Corynebacterium diptheriae, Gardnerella vaginalis, Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium ulcerans, Mycobacterium leprae, Actinomyctes israelii, Listeria monocytogenes, Bordetella pertusis, Bordatella parapertusis, Bordetella bronchiseptica, Escherichia coli, Shigella dysenteriae, Haemophilus influenzae, Haemophilus aegyptius, Haemophilus parainfluenzae, Haemophilus ducreyi , Bordetella, Salmonella typhi, Citrobacter freundii, Proteus mirabilis, Proteus vulgaris, Yersinia pestis, Kleibsiella pneumoniae, Serratia marcessens, Serratia liquefaciens, Vibrio cholera, Shigella dysenterii, Shigella flexneri, Pseudomonas aerusinosa, Franscisella tularensis, Brucella abortis, Bacillus anthracis, Bacillus cereus, Clostridium perfringens, Clostridium tetani, Clostridium botulinum, Treponema pallidum, Rickettsia rickettsii and Chlamydia trachomitis , (n) an archaeon, including but not limited to Archaebacter, and (iii) a unicellular or filamentous eukaryote, including but not limited to, a protozoan, a fungus, a member of the genus Saccharomyces, Kluveromyces, or Candida, and a menber of the species Saccharomyces ceriviseae, Kluveromyces lactis , or Candida albicans.
“Polynucleotide(s)” generally refers to any polyribonucleotide or polydeoxyribonucleotide, that may be unmodified RNA or DNA or modified RNA or DNA. “Polynucleotide(s)” include, without limitation, single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions or single-, double- and triple-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single and double-straned regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded, or triple-stranded regions, or a mixture of single- and double-stranded regions. In addition, “polynucleotide” as used herein refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The so in such regions may be from the same molecule or from different molecules. The regions may include all of one or more of the molecules, but more typically involve only a region of some of the molecules. One of the molecules of a triple-helical region often is an oligonucleotide. As used herein, the term “polynucleotide(s)” also includes DNAs or RNAs as described above that comprise one or more modified bases. Thus, DNAs or RNAs with backbones modified for stability or for other reasons are “polynucleotide(s)” as that term is intended herein. Moreover, DNAs or RNAs comprising unusual bases, such as inosine, or modified bases, such as tritylated bases, to name just two examples, are polynucleotides as the term is used herein. It will be appreciated that a great vatiety of modifications have been made to DNA and RNA that serve many useful purposes known to those of skilled in the art. The term “polynucleotide(s)” as it is employed herein embraces such chemically, enzymatically or metabolically modified forms of polynucleotides, as well as the chemical forms of DNA and RNA characteristic of viruses and cells, including for example, simple and complex cells. “Polynucleotide(s)” also embraces short polynucleotides often referred to as oligonucleotide(s).
“Polypeptide(s)” refers to any peptide or protein compising two or more amino acids joined to each other by peptide bonds or modified peptide bonds. “Polypeptide(s)” refers to both short chains, commonly referred to as peptides, oligopeptides and oligomers and to longer chains generally referred to as proteins. Polypeptides may comprise amimo acids other than the 20 gene encoded amino acids. “Polypeptide(s)” include those modified either by natural processes, such as processing and other post-translational modifications, but also by chemical modification techniques. Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature, and they are well known to those of skill in the art. It will be appreciated that the same type of modification may be present in the same or varying degree at several sites in a given polypeptide. Also, a given polypeptide may comprise many types of modifications. Modifications can occur anywhere in a polypeptide, including the peptide backbone, the amino acid side-chains, and the amino or carboxyl termini. Modifications include, for example, acetylation, acylation, ADP-ribosylation, amidation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links, formation of cysteine, formation of pyroglutamate, formylation, gamma-carboxylation, GPI anchor formation, hydroxylation, iodination, methlation, myristoylation, oxidation, proteolytic processing, phosphorylation, prenylation, racemization, glycosylation, lipid attachment, sulfation, gamma-carboxylation of glutamic acid residues, hydroxylation and ADP-ribosylation, selenoylation, sulfation, tansfer-RNA mediated addition of amino acids to proteins, such as arginylation, and ubiquitination. See, for instance, PROTEINS—STRUCTURE AND MOLECULAR PROPERTIES , 2nd Ed., T. E. Creighton W. H. Freeman and Company, New York (1993) and Wold, F., Posttranslational Protein Modifications: Perspectives and Prospects, pgs. 1-12 in POSTTRANSLATIONAL COVALENT MODIFICATION OF PROTEINS , B. C. Johnson, Ed., Academic Press, New York (1983); Seifter et al., Meth. Enzymol . 182:626-646 (1990) and Rattan et al., Protein Synthesis: Posttranslational Modifications and Aging , Ann. N.Y. Acad. Sci. 663: 48-62 (1992). Polypeptides may be branched or cyclic, with or without branching. Cyclic, branched and branched circular peptides may result from post-translational natural processes and may be made by entirely synthetic methods, as well.
“Recombinant expression system(s)” refers to expression systems or portions thereof or polynucleotides of the invention introduced or transformed into a host cell or host cell lysate for the production of the polynucleotides and polypeptides of the invention.
“Variant(s)” as the term is used herein, is a polynucleotide or polypeptide that differs from a reference polynucleotide or polypeptide respectively, but retains essential properties. A typical variant of a polynucleotide differs in nucleotide sequence from another, reference polynucleotide. Changes in the nucleotide sequence of the variant may or may not alter the amino acid sequence of a polypeptide encoded by the reference polynucleotide. Nucleotide changes may result in amino acid substitutions, additions, deletions, fusion proteins and truncations in the polypeptide encoded by the reference sequence, as discussed below. A typical variant of a polypeptide differs in amino acid sequence from another, reference polypeptide. Generally, differences are limited so that the sequences of the reference polypeptide and the variant are closely similar overall and, in many regions, identical. A variant and reference polypeptide may differ in amino acid sequence by one or more substitutions, additions, deletions in any combination. A substituted or inserted amino acid residue may or may not be one encoded by the genetic code. The present invention also includes include variants of each of the polypeptides of the invention, that is polypeptides that vary from the referents by conservative amino acid substuitions, whereby a residue is substituted by another with like characteristics. Typical such substitutions are among Ala, Val, Leu, and Ile; among Ser and Thr; among the acidic residues Asp and Glu; among Asn and Gln; and among the basic resides Lys and Arg; or aromatic residues Phe and Tyr. Particularly preferred are variants in which several, 5-10, 1-5, 1-3, 1-2 or 1 amino acids are substituted, deleted, or added in any combination. A variant of a polynucleotide or polypeptide may be a naturally occurring such as an allelic variant, or it may be a variant that is not known to occur naturally. Non-naturally occurring variants of polynucleotides and polypeptides may be made by mutagenesis techniques, by direct synthesis, and by other recombinant methods known to skilled artisans.
EXAMPLES
The examples below are carried out using standard techniques, that are well known and routine to those of skilled in the art, except where otherwise described in detail. The examples are illustrative, but do not limit the invention.
Example 1
Strain Selection, Library Production and Sequencing
The polynucleotide having a DNA sequence given in Table 1 [SEQ ID NO:1] was obtained from a library of clones of chromosomal DNA of Streptococcus pneumoniae in E. coli . The sequencing data from two or more clones comprising overlapping Streptococcus pneumoniae DNAs was used to construct the contiguous DNA sequence in SEQ ID NO:1. Libraries may be prepared by routine methods, for example:
Methods 1 and 2 Below.
Total cellular DNA is isolated from Streptococcus pneumoniae 0100993 according to standard procedures and size-fractionated by either of two methods.
Method 1
Total cellular DNA is mechanically sheared by passage through a needle in order to size-fractionate according to standard procedures. DNA fragments of up to 11 kbp in size are rendered blunt by treatment with exonuclease and DNA polymerase, and EcoRI linkers added. Fragments are ligated into the vector Lambda ZapII that has been cut with EcoRI, the library packaged by standard procedures and E. coli infected with the packaged library. The library is amplified by standard procedures.
Method 2
Total cellular DNA is partially hydrolyzed with a one or a combination of restriction enzymes appropriate to generate a series of fragments for cloning into library vectors (e.g., RsaI, PalI, AluI, Bshl235I), and such fragments are size-fractionated according to standard procedures. EcoRI linkers are ligated to the DNA and the fragments then ligated into the vector Lambda ZapII that have been cut with EcoRI, the library packaged by standard procedures, and E. coli infected with the packaged library. The library is amplified by standard procedures.
Example 2
TrmD Characterization
The S. pneumoniae trmD gene is expressed during infection in a respiratory tract infection model
The determination of expression during infection of a gene from Streptococcus pneumoniae Excised lungs from a 48 hour respiratory tract infection of Streptococcus pneumoniae 0100993 in the mouse is efficiently disrupted and processed in the presence of chaotropic agents and RNAase inhibitor to provide a mixture of animal and bacterial RNA. The optimal conditions for disruption and processing to give stable preparations and high yields of bacterial RNA are followod by the use of hybridisation to a radiolabelled oligonucleotide specific to Streptococcus pneumoniae 16S RNA on Northern blots. The RNAase free, DNAase free, DNA and protein free preparations of RNA obtained are suitable for Reverse Transcription PCR (RT-PCR) using unique primer pairs designed from the sequence of each gene of Streptococcus pneumoniae 0100993.
a) Isolation of tissue infected with Streptococcus pneumoniae 0100993 from a mouse animal model of infection (lungs)
Streptococcus pneumoniae 0100993 is seeded onto TSA (Tryptic Soy Agar, BBL) plates containing 5% horse blood and allowed to grow overnight at 37° C. in a CO2 incubator. Bacterial growth is scraped into 5 ml of phosphate-buffered saline (PBS) and adjusted to an A600˜0.6 (4×106/ml). Mice (male CBA/J-1 mice, approximately 20 g) were anaesthetized with isoflurane and 50 microliters of the prepared bacterial inoculum is delivered by intranasal instillation. Animals are allowed to recover and observed twice daily for signs of moribundancy. Forty-eight hours after infection the animals are euthanized by carbon dioxide overdose and their torsos swabbed with ethanol and then RNAZap. The torso is then opened, and the lungs are aseptically removed. Half of each pair of lungs is placed in a cryovial and immediately frozen in liquid nitrogen; the other half is used for bacterial enumeration after homogenization of the tissue in 1 ml of PBS.
b) Isolation of Streptococcus pneumoniae 0100993 RNA from infected tissue samples
Infected tissue samples, in 2-ml cryo-strorage tubes, are removed from −80° C. storage into a dry ice ethanol bath. In a microbiological safety cabinet the samples are disrupted up to eight at a time while the remaining samples are kept frozen in the dry ice ethanol bath. To disrupt the bacteria within the tissue sample, 50-100 mg of the tissue is transfered to a FastRNA tube containing a silica/ceramic matrix (BIO101). Immediately, 1 ml of extraction reagents (FastRNA reagents, BIO101) are added to give a sample to reagent volume ratio of approximately 1 to 20. The tubes are shaken in a reciprocating shaker (FastPrep FP120, BIO101) at 6000 rpm for 20-120 sec. The crude RNA preparation is extracted with chloroform/isoamyl alcohol, and precipitated with DEPC-treated/Isopropanol Precipitation Solution (BIO101). RNA preparations are stored in this isopropanol solution at −80° C. if necessary. The RNA is pelleted (12,000 g for 10 min.), washed with 75% ethanol (v/v in DEPC-treated water), air died for 5-10 min, and resupended in 0.1 ml of DEPC-treated water, followed by 5-10 minutes at 55° C. Finally, after at least 1 minute on ice, 200 units of Rnasin (Promega) is added.
RNA preparations are stored at −80° C. for up to one month. For longer term storage the RNA precipitate can be stored at the wash stage of the protocol in 75% ethanol for at least one year at −20° C.
Quality of the RNA isolated is assessed by running samples on 1% agarose gels. 1×TBE gels stained with ethidium bromide are used to visualise total RNA yields. To demonstrate the isolation of bacterial RNA from the infected tissue 1×MOPS, 2.2M formaldehyde gels are run and vacuum blotted to Hybond-N (Amersham). The blot is then hybridised with a 32P-labelled oligonucleotide probe, of sequence 5′ AACTGAGACTGGCTTTAAGAGATTA 3′ [SEQ ID NO:3], specific to 16S rRNA of Streptococcus pneumoniae . The size of the hybridising band is compared to that of control RNA isolated from in vitro grown Streptococcus pneumoniae 0100993 in the Northern blot. Correct sized bacterial 16S rRNA bands can be detected in total RNA samples which show degradation of the mammalian RNA when visualised on TBE Sels.
c) The removal of DNA from Streptococcus pneumoniae -derived RNA
DNA was removed from 50 microgram samples of RNA by a 30 minute treatment at 37° C. with 20 units of RNAase-free DNAaseI (GenHunter) in the buffer supplied in a final volume of 57 microliters.
The DNAase was inactivated and removed by treatment with TRIzol LS Reagent (Gibco BRL, Life Technologies) according to the manufacturers protocol.
DNAase teated RNA was resuspended in 100 microliters of DEPC treated water with the addition of Rnasin as described before.
d) The preparation of cDNA from RNA samples derived from infected tissue
3 microgram samples of DNAase treated RNA are reverse transcribed using a SuperScript Preamplification System for First Strand cDNA Synthesis kit (Gibco BRL, Life Technologies) according to the manufacturers instructions. 150 nanogram of random hexamers is used to prime each reaction. Controls without the addition of SuperScriptII reverse transcriptase are also run. Both +/−RT samples are treated with RNaseH before proceeding to the PCR reaction
e) The use of PCR to determine the presence of a bacterial cDNA species
PCR reactions are set up on ice in 0.2 ml tubes by adding the following components: 43 microliters PCR Master Mix (Advanced Biotechnologies Ltd.); 1 microliter PCR primers (optimally 18-25 basepairs in length and designed to possess similar annealing temperatures), each primer at 10 mM initial concentration; and 5 microliters cDNA.
PCR reactions are run on a Perkin Elmer GeneAmp PCR System 9600 as follows: 2 minutes at 94° C., then 50 cycles of 30 seconds each at 94° C., 50° C. and 72° C. followed by 7 minutes at 72° C. and then a hold temperature of 20° C. (the number of cycles is optimally 30-50 to determine the appearance or lack of a PCR product and optimally 8-30 cycles if an estimation of the starting quantity of cDNA from the RT reaction is to be made); 10 microliter aliquots are then run out on 1% 1×TBE gels stained with ethidium bromide, with PCR product, if present, sizes estimated by comparison to a 100 bp DNA Ladder (Gibco BRL, Life Technologies). Alternatively if the PCR products are conveniently labelled by the use of a labelled PCR primer (e.g. labelled at the 5′end with a dye) a suitable aliquot of the PCR product is run out on a polyacrylamide sequencing gel and its presence and quantiy detected using a suitable gel scanning system (e.g. ABI Prism™ 377 Sequencer using GeneScan™ software as supplied by Perkin Elmer).
RT/PCR controls may include +/− reverse transcriptase reactions, 16S rRNA primers or DNA specific primer pairs designed to produce PCR products from non-transcribed Streptococcus pneumoniae 0100993 genomic sequences.
To test the efficiency of the primer pairs they are used in DNA PCR with Streptococus pneumoniae 0100993 total DNA. PCR reactions are set up and run as described above using approx. 1 microgram of DNA in place of the cDNA.
Primer pairs which fail to give the predicted sized product in either DNA PCR or RT/PCR are PCR failures and as such are uninformative. Of those which give the correct size product with DNA PCR two classes are distinguished in RT/PCR: 1. Genes which are not transcribed in vivo reproducibly fail to give a product in RT/PCR; and 2. Genes which are transcribed in vivo reproducibly give the correct size product in RT/PCR and show a stonger signal in the +RT samples than the signal (if at all present) in −RT controls.
Example 3
The trmD gene is essential for S. pneumoniae in vitro growth.
Demonstration of gene essential to bacterial viability
An allelic replacement cassette was generated using PCR technology. The cassette consisted of a pair of 500 bp chromosomal DNA fragments flanking an erythromycin resistance gene. The chromosomal DNA sequences are the 500 bp preceding and following the DNA sequence encoding the trmD gene contained in Seq. ID NO.1.
The allelic replacement cassette was introduced into S. pneumoniae R6 by transformation. Competent cells were prepared according to published protocols. DNA was introduced into the cells by incubation of ng quantities of allelic replacement cassette with 10 6 cells at 30° C. for 30 minutes. The cells were transferred to 37° C. for 90 minutes to allow expression of the erythromycin resistance gene. Cells were plated in agar containing lug erythromycin per ml. Following incubation at 37° C. for 36 hours, colonies are picked and grown overnight in Todd-Hewitt broth supplemented with 0.5% yeast extract. Typically 1000 transformants containing the appropriate allelic replacement are obtained. If no transformants are obtained in three separate transformation experiments as was the case for this gene trmD, then the gene is considered as being essential in vitro.
3
1
720
DNA
Streptococcus pneumoniae
1
atgaagattg atattttaac cctctttcca gagatgtttt ctccactgga gcactcaatc 60
gttggaaagg ctcgagaaaa agggctcttg gatatccagt atcataattt tcgagaaaat 120
gctgaaaagg cccgtcatgt agatgatgag ccctacggag gcggtcaggg catgttgctc 180
agagcacaac ctattttcaa ttcctttgat gctattgaaa agaaaaatcc gcgcgttatt 240
ctcctcgatc ctgctggaaa gcagtttgat caggcttatg ctgaagattt ggctcaagag 300
gaagagctaa tctttatctg tgggcactat gagggttatg atgagcgcat taagaccttg 360
gtaacagatg agatttccct aggcgactat gtcctcactg gtggagaatt ggcagctatg 420
accatgattg atgctacagt tcgcctgatt ccagaagtga ttggcaagga gtctagccac 480
caagatgata gtttttcttc aggtctttta gaatatcctc agtacacacg tccctatgat 540
tatcgaggca tggtcgtgcc agatgtattg atgagtggcc accatgaaaa gattcgtcag 600
tggcgattgt acgagagttt aaagaaaacc tacgagcgca gaccagattt acttgaacat 660
tatcaactga cagtagaaga agaaaaaatg ctggcagaaa tcaaagaaaa caaagaataa 720
2
239
PRT
Streptococcus pneumoniae
2
Met Lys Ile Asp Ile Leu Thr Leu Phe Pro Glu Met Phe Ser Pro Leu
1 5 10 15
Glu His Ser Ile Val Gly Lys Ala Arg Glu Lys Gly Leu Leu Asp Ile
20 25 30
Gln Tyr His Asn Phe Arg Glu Asn Ala Glu Lys Ala Arg His Val Asp
35 40 45
Asp Glu Pro Tyr Gly Gly Gly Gln Gly Met Leu Leu Arg Ala Gln Pro
50 55 60
Ile Phe Asn Ser Phe Asp Ala Ile Glu Lys Lys Asn Pro Arg Val Ile
65 70 75 80
Leu Leu Asp Pro Ala Gly Lys Gln Phe Asp Gln Ala Tyr Ala Glu Asp
85 90 95
Leu Ala Gln Glu Glu Glu Leu Ile Phe Ile Cys Gly His Tyr Glu Gly
100 105 110
Tyr Asp Glu Arg Ile Lys Thr Leu Val Thr Asp Glu Ile Ser Leu Gly
115 120 125
Asp Tyr Val Leu Thr Gly Gly Glu Leu Ala Ala Met Thr Met Ile Asp
130 135 140
Ala Thr Val Arg Leu Ile Pro Glu Val Ile Gly Lys Glu Ser Ser His
145 150 155 160
Gln Asp Asp Ser Phe Ser Ser Gly Leu Leu Glu Tyr Pro Gln Tyr Thr
165 170 175
Arg Pro Tyr Asp Tyr Arg Gly Met Val Val Pro Asp Val Leu Met Ser
180 185 190
Gly His His Glu Lys Ile Arg Gln Trp Arg Leu Tyr Glu Ser Leu Lys
195 200 205
Lys Thr Tyr Glu Arg Arg Pro Asp Leu Leu Glu His Tyr Gln Leu Thr
210 215 220
Val Glu Glu Glu Lys Met Leu Ala Glu Ile Lys Glu Asn Lys Glu
225 230 235
3
25
DNA
Streptococcus pneumoniae
3
aactgagact ggctttaaga gatta 25 | 1a
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FIELD OF THE INVENTION
The present invention refers to improvements to latex prophylactics, which have a certain and constructive novel arrangement, wherein an increase in the resistance of the already known prophylactics is obtained. The construction of the prophylactic of the present invention increases its safety and efficiency, decreasing the risks of breakages, with the outstanding advantages of economic and practicality as noted in the details of the present specification.
BACKGROUND OF THE INVENTION
Known prophylactics or contraceptives are generally manufactured in latex or a similar elastomeric material in a form such that the prophylactics are conveniently used to cover the penis thereby avoiding the communication of the aqueous fluids in the act of sexual relations. As a consequence, the transmission of a plurality of sexually transmitted diseases that seriously risk the world population is reduced. When taking into consideration that contraceptive prophylactics are preferably manufactured in an elastomeric material of the latex type or the like, this presents the serious disadvantage of spontaneous breakage of the prophylactic, as well as, inconvenience due to its generally undesirable longitudinal stretching, so that its use becomes extremely risky due to the possibility of leakage or breakage in critical situations.
OBJECTS AND SUMMARY OF THE INVENTION
The undesirable effects of known prophylactics have been extremely surpassed and overcome with the prophylactics of the present invention. The novel features of the present invention, of which no prior antecedents are known, include the use of fabric incorporated in the manufacturing process of the contraceptive and include the incorporation of the fabric in the manufactured contraceptive. The incorporated fabric is shaped by the weaving of an inelastic weft in a longitudinal direction which is fastened to an elastic warp in a cross sectional sense, so as to allow the elasticity, adaptation and adjustment of the contraceptive in a transverse direction with respect to its central axis and an inelasticity in the longitudinal direction to the above mentioned axis so as not prejudice to its adaptability. This provides a total resistance to breakages and splits without affecting the adhesion or adaptability of the prophylactic and without requiring additional thickness in the walls of the contraceptive prophylactic, since the additional thickness may provoke irritation during use.
DESCRIPTION OF THE DRAWINGS
In order that the present invention be clearly understood and easily taken into operation, there has been submitted in one of its embodiments of a preferred form as noted in the illustrative drawings that accompany this specification in which:
FIG. 1 is a perspective view of the improved prophylactic of the present invention showing a close-up detail in elevation of the incorporated improvements of the weave of the prophylactic; its structural configuration and a warp and weft section, as shown through lines "A"--"A".
FIG. 2 is a close-up view of the incorporated fabric, showing the elastomeric filaments of the fabric and the elasticity of the fabric warp, and its elasticity in a sense direction and the rigid filaments of the weft interweaving on the above mentioned warp which are incorporated in the improvement illustrated in FIG. 1.
FIG. 3 shows an alternate embodiment for a variant of the improvement illustrated in FIG. 1, in the construction of which the elastomeric filaments of the warp, showing its expansion sense; as well as the inelastic longitudinal filaments of the waft, which are interweaved with the elastomeric filaments of the warp. The elastomeric filaments of the warp are shown in the expansion direction, as well as the inelastic longitudinal filaments that constitute the waft in the fabric of the improvement of the prophylactic of the present invention.
In said figures, the same reference figures indicate equal or similar parts.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Now, having illustrated the improvement of the present invention there is shown the construction of the prophylactic (1). As shown in the close-up window detail view of FIG. 1, the prophylactic (1) includes incorporated fabric (2). Fabric (2) is constituted by a patterned weave consisting essentially of inelastic extremely thin filaments (3), which filaments (3) constitute the weft of the weave connected to extremely thin elastomeric filaments (4) that constitute the warp of the weave of the fabric (2) incorporated into the prophylactic (1). Fabric (2) is incorporated in the following manner: a base latex layer (11) is shaped on which a second layer (12) being also of latex is arranged (12). Once both layers (11) and (12) are consolidated and superposed, such as is illustrated in detail in FIG. 1, the fabric (2) base of the present improvement to the basic body of the prophylactic (1) is interpolated in solidarity with the body of the prophylactic (1) in an integral set, through a coating of the assembly with a lasting and extremely thin latex layer (13). The prophylactic (1) is finally shaped in definitive form in a simple and effective manner since the fabric (2) shaped by the weft (3) and the warp (4) is allowed to have an elastic adjustment of the improved unit in a radial direction to the axis of prophylactic (1), following a deformation in the direction illustrated by arrows f-f' thereby avoiding the stretching in the longitudinal direction of the prophylactic (1). This construction of prophylactic (1) with woven fabric (2) removes the possibilities of producing cracks in the prophylactic (1) or the breaking of same, since woven fabric (2) eliminates the longitudinal stretching, which longitudinal stretching is precisely the cause that most frequently produces same. Optionally, further layers may constitute a plurality of layers with layers (11), (12) and (13) of prophylactic (1). FIG. 2 shows a close-up view of the embodiment of the incorporated fabric of the prophylactic, as shown in FIG. 1, showing the elastomeric filaments 4 of the fabric 2 and the elasticity of the fabric warp, and its elasticity in a sense direction and the rigid filaments 3 of the weft interweaving on the above mentioned warp, which filaments 3, 4 are incorporated in the improvement illustrated in FIG. 1.
FIG. 3 shows an alternate embodiment for a variant of the improved prophylactic illustrated in FIG. 1, in the construction of which prophylactic there is provided the elastomeric filaments 4' of the warp, showing the expansion sense of the warp; as well as the inelastic longitudinal filaments 3' of the waft, which are interweaved with the elastomeric filaments 4' of the warp. The elastomeric filaments 4' of the warp are shown in the expansion direction, as well as the inelastic longitudinal filaments 3' that constitute the waft in the fabric of the improved prophylactic of the present invention.
It is hereby clarified that although the above mentioned construction of the prophylactic of the present invention is shown arranged a simple illustrative example, of the embodiments made therein, the fabric may be incorporated among any of the latex layers with which the prophylactic is manufactured, without same affecting the scope or essence of the present invention as noted in the appended claims. | 1a
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. patent application Ser. No. 10/553,643, filed Oct. 14, 2005, which is a U.S. national stage application of International Application No. PCT/IB2004/000898, filed on Jan. 27, 2004, which claims the benefit of French Application No. 0300858, filed on Jan. 27, 2003, and of U.S. Provisional Patent Application No. 60/496,074, filed on Aug. 18, 2003.
BACKGROUND OF THE INVENTION
[0002] This invention relates in general to methods and devices for breathing assistance.
[0003] More precisely, the invention relates to a breathing assistance device comprising:
a turbine to generate a flow of pressurised respiratory gas, a duct to carry the pressurised gas to a patient, means for controlling the gas pressure capable of elaborating a pressure setting for the turbine.
[0007] And the invention also relates to a method for regulating the pressure of a respiratory gas delivered by a turbine to a patient, the method consisting of elaborating a pressure setting for the turbine.
[0008] Devices of the type mentioned above already exist.
[0009] The basic architecture of such devices is shown in a very schematic manner in FIG. 1 a , which shows a device 10 a consisting of a turbine 100 a allowing to generate a flow of pressurised respiratory gas (air or other), a means 120 a allowing a patient to receive said pressurised gas and a duct 110 a to carry the gas from the turbine 100 a to means 120 a.
[0010] Means 120 a is generally made up of a mask that can include vents to make respiratory gas leaks possible.
[0011] Note that this means can be replaced with an expiratory valve.
[0012] And the invention applies to devices with leakage masks as well as to expiratory valve devices.
[0013] Note that the term “patient” is here used broadly, and does not necessarily correspond to a person afflicted with an extensive pathology.
[0014] The devices according to the invention can thus be implemented for numerous applications, for example to provide respiratory assistance while a patient is sleeping with a view to treating sleep apnea.
[0015] However, the devices according to the invention are not in any way limited to treating sleep apnea, which is an application of the invention mentioned here by way of non-limitating example.
[0016] The invention relates to in fact as we shall see a new type of device and associated regulation, and its applications are extremely broad.
[0017] Returning to the device of the state of the art shown in FIG. 1 a , such devices are known to be implemented by controlling the pressure generated by turbine 100 a in such a way that this pressure has a fixed value.
[0018] Such devices are said to be of the continuous pressure airway pressure type (and are generally known under the acronym of CPAP- Trade Mark-in English).
[0019] These devices may however not be accepted by a portion of the patients, or be improperly adapted for treating certain pathologies.
[0020] More elaborate devices also exist, in which the means of controlling gas pressure are capable of elaborating several different pressure settings for the turbine.
BRIEF SUMMARY OF THE INVENTION
[0021] Such devices are shown (here again in a very schematic manner) in FIG. 1 b.
[0022] This figure shows a device 10 b . On this figure the elements labeled as 100 a, 110 a and 120 a are the same as those elements in FIG. 1 a.
[0023] Device 10 b farther comprises a flowmeter 130 b capable of providing to means of Calculation 132 b a measurement of flow in duct 110 a.
[0024] Means of calculation 132 b are capable of elaborating, as a function of the measured flow, a pressure setting that will be sent to the turbine for more precisely to a turbine operation regulation circuit) via a connection 131 b.
[0025] This disposition makes it possible to adapt the pressure according to the flow measured in duet 110 a, with this flow being linked to the respiratory activity of the patient.
[0026] The start of inspiration or expiration of the patient can thus in particular be detected, and the pressure setting sent to the turbine can be adapted according to the cycle (inspiration or expiration) which is in progress or which is starting.
[0027] EP 425 092 shows an example of such a device.
[0028] These devices correspond to an enhancement compared to devices of the type as shown in FIG. 1 a.
[0029] But they require a flowmeter to be integrated.
[0030] Such a flowmeter is an expensive element. It furthermore has a tendency to complicate the device and to increase breakdown risks of it as well as increase its cost.
[0031] The purpose of the invention is to further enhance the devices of the type mentioned at the beginning of this text, by avoiding the inconveniences and limitations exposed above.
[0032] In order to reach this purpose, the invention offers according to a first aspect a breathing assistance device comprising:
a turbine to generate a flow of pressurised respiratory gas, a duct to carry the pressurised gas to a patient, control means for controlling the gas pressure capable of elaborating a pressure setting for the turbine, characterised in that the turbine is associated to a speed sensor capable of acquiring a signal corresponding to the rotation speed of a rotating element of the turbine, and the control means include means of calculation connected to said speed sensor in order to elaborate from said signal a pressure setting and send said pressure setting to the turbine.
[0037] Preferable but not limited aspects of such a device are the following:
said speed sensor implements a Hall effect sensor, said speed sensor is a sensor capable of acquiring a speed signal from the turbine linked directly to the rotation speed of a rotating element of the turbine, the means of calculation elaborate the pressure setting according to variations in speed, said means of calculation are capable of detecting new inspiration or expiration cycles, and to consequently adapt the level of the pressure setting, said means of calculation are associated to a program for detecting inspiratory cycle using a comparison between:
A memorised speed value extrapolated using recent values of measured speed, and An instantaneous speed actually measured,
said means of calculation are associated to a program for detecting inspiratory cycle using a comparison between:
A memorised speed value as representative of a recent speed bearing, and An instantaneous speed actually measured,
said means of calculation are associated to a program for detecting inspiratory cycle using a comparison between:
A memorised speed value as representative of a speed at the end of an expiratory cycle, and An instantaneous speed actually measured,
said means of calculation are associated to several programs for detecting inspiratory cycle operating simultaneously, and are capable of elaborating a pressure setting corresponding to a start of inspiration as soon as one of said programs for detecting inspiratory cycle has signaled a start of inspiration, the programs (s) for detecting inspiratory cycle is (are) associated to disabling means for a determined duration following the start of a new expiratory cycle, the means of calculation are associated to a program for detecting expiratory cycle, said program for detecting expiratory cycle uses a comparison between:
A maximum speed of the turbine memorised, corresponding to a cycle of inspiration, and An instantaneous speed actually measured,
said means of calculation include a microprocessor connected to the speed sensor and an input for pressure setting of the turbine, the device also includes a pressure regulation loop comprising:
a pressure sensor on the duct, and a circuit receiving the pressure setting resulting from the means of calculation as well as the pressure measured by the pressure sensor, said circuit being capable of elaborating an instantaneous setting for turbine rotation speed, said circuit being connected to an input for speed setting of the turbine.
[0061] The invention offers according to a second aspect a method for regulating the pressure of a respiratory gas delivered by a turbine to a patient, the method comprising elaborating a pressure setting for the turbine, characterised in that said pressure setting is elaborated using a signal representative of the rotation speed of a rotating element of the turbine.
[0062] Preferable but not limited aspects of such a method are the following:
said signal corresponds to the rotation speed of the rotor of the turbine, the method is capable of detecting new inspiration or expiration cycles, and to consequently adapt the level of the pressure setting, the method implements a program for detecting inspiratory cycle using a comparison between:
A memorised speed value that was extrapolated using recent values of measured speeds, and An instantaneous speed actually measured,
the method implements a program for detecting inspiratory cycle using a comparison between:
A memorised speed value as representative of a recent speed bearing, and An instantaneous speed actually measured,
the method implements a program for detecting inspiratory cycle using a comparison between:
A memorised speed value as representative of a speed at the end of an expiratory cycle, and An instantaneous speed actually measured,
the method implements several programs for detecting inspiratory cycle operating simultaneously, and elaborates a pressure setting corresponding to a start of inspiration as soon as one of said programs for detecting inspiratory cycle has signalled a start of inspiration, the programs (s) for detecting inspiratory cycle is (are) associated to disabling means for a determined duration following the start of a new expiratory cycle, the means of calculation are associated to a program for detecting expiratory cycle, the method implements a program for detecting expiratory cycle, said program for detecting expiratory cycle uses a comparison between:
A maximum speed of the turbine memorised, corresponding to an inspiratory cycle, and) An instantaneous speed actually measured,
[0081] Other aspects, purposes and advantages of the invention will appear better in the following description of the invention, made in reference to the annexed drawings on which, in addition to FIGS. 1 a and 1 b which have already been commented in reference to the state of the art.
BRIEF DESCRIPTION OF THE DRAWINGS
[0082] FIGS. 1 a and 1 b shows a basic architecture for a device.
[0083] FIG. 2 is a schematic representation of a device according to the invention,
[0084] FIG. 3 is a graphical characteristic of a turbine implemented in a device according to the invention, showing for a given value of turbine rotation speed the relation between the pressure output of the turbine, and the flow generated by this turbine.
[0085] FIG. 4 includes three graphs showing a typical evolution of pressure, of flow, and of a parameter associated with the turbine of a device according to the invention, during an alternation of inspiratory and expiratory cycles.
[0086] FIGS. 5 to 8 illustrate four modes for detecting the start of a new inspiratory cycle,
[0087] FIG. 9 illustrates a mode for detecting the start of a new expiratory cycle.
DETAILED DESCRIPTION
[0088] With reference now to FIG. 2 , a device 20 according to the invention is shown in a schematic manner.
[0089] This device includes (as the devices of the state of the art) a turbine 100 a, means 120 a allowing a patient to receive the pressurized gas coming from the turbine, and a duct 110 a for a carrying said gas from the turbine 100 a to the means 120 a.
[0090] Here again, the means 120 a can be a mask comprising leakage means, or include an expiratory valve.
[0091] The device according to the invention includes (as the device shown in FIG. 1 b ) means for regulating the pressure.
[0092] Note however that in the case of the invention no flowmeter is associated to duct 210 .
[0093] Means for regulating the pressure indeed include means of calculation 132 b capable of receiving from the turbine a value of a signal which is characteristic of the operation of said turbine, via a connection 131 b.
[0094] Means of calculation 132 b include a microprocessor and are connected to a memory, in which different parameters are memorized.
[0095] The value characteristic of the operation of the turbine is a signal corresponding to the rotation speed of a rotating element of the turbine (e. g. its rotor).
[0096] In the remainder of this text, the signal received from the turbine will be called “measured speed”.
[0097] To provide the means of calculation 132 b with this measured speed, a speed sensor is integrated into the turbine. This speed sensor can be for example a Hall effect sensor.
[0098] Details will be provided hereafter concerning the different modes according to which the means of calculation are capable of automatically detecting the start of inspiratory and/or expiratory cycles, according to the signal received from the turbine and to different memorised parameters.
[0099] Means of calculation 132 b are also connected to a circuit 240 for regulating the rotation speed of the turbine.
[0100] This circuit 240 receives two inputs: Via a first connection 241 , it receives a pressure setting elaborated by the means of calculation 132 b, via a second connection 242 , it receives a pressure measured by a pressure sensor 250 on duct 110 a.
[0101] As a function of these two inputs, the circuit 240 is capable of elaborating a rotation speed setting that is sends to turbine 100 a via a connection 243 .
[0102] This rotation speed setting is elaborated by the circuit 240 so that the pressure measured by sensor 250 reaches the value of the pressure setting received from the means of calculation 132 b.
[0103] Note that the circuit 240 can be embodied by one or more component (s) of the turbine.
[0104] The device described above makes is possible to control the pressure of the respiratory gas carried by duct 110 a to the patient.
[0105] More precisely, a first advantage of this control is to allow the establishment of a pressure with a desired value, corresponding to a value of the pressure setting that is received from means of calculation 132 b.
[0106] In this way, when a bearing for which a constant pressure is to be maintained, circuit 240 is permanently active since it receives in real time the pressure measured by sensor 250 , and it constantly adapts the rotation speed setting sent to the turbine in order to regulate the pressure.
[0107] And beyond this regulation of turbine rotation speed in order to maintain pressure at a given value, the invention makes it possible to detect in real time modifications in the respiratory behaviour of the patient, in order to trigger new inspiratory or respiratory cycles by having a modified pressure setting sent to the regulation circuit 240 by means of calculation 132 b.
[0108] To this effect, means of calculation 132 b use the measured speed received from the turbine.
[0109] This speed is constantly measured, and acquired at regular intervals, for example every 100 milliseconds. It is also possible to provide for continuous acquisition.
[0110] Note that in order to realise such a directing of the pressure setting according to a measured speed coming from the turbine, it is necessary that the sum of the inertia of the device remains low enough to be compatible with a control of this pressure setting in real time.
[0111] It would in fact not be acceptable for the new pressure setting to arrive at circuit 240 while the respiratory event that led to this new setting has occurred for a time that is too long.
[0112] In practice, the maximum acceptable delay between the respiratory event and the elaboration of the corresponding new pressure setting is about 50 to 100 milliseconds.
[0113] The inertia of the device which are likely to introduce delays in the elaboration of this pressure setting are mainly derived from:
turbine 100 a duct 110 a pressure sensor 250 .
[0117] The inertia associated to duct 110 a and to sensor 250 are classical pneumatic inertia, which are generally totally compatible with the maximum reaction timeframe mentioned above.
[0118] The inertia associated to the turbine must, as far as it is concerned, have a reduced value.
[0119] To this effect, a turbine with very low inertia has to be implemented in the invention.
[0120] Such a turbine can comprise e.g.:
a portion bearing the blades having a diameter of about 44 mm for a weight of about 5.6 g-which corresponds to an inertia of about 90 g·cm 2 , a rotor having also an inertia of the same order (about 90 g·cm2).
[0123] Therefore, the total inertia of the turbine remains lower than a value of about 200 g·cm 2 .
[0124] Below are the general principles that are the basis for exploiting a measured speed here from the turbine in order to direct the pressure setting of the device.
[0125] Assuming that a patient who wants to breathe provides an energy E which is equal to D×P, with:
[0000] D: instantaneous flow of the patient,
P: instantaneous pressure of the patient,
[0126] The effort provided by the patient during an interval of time dt is the following:
[0000] dE/dt =( dD/dt )·( dP/dt ).
[0127] Since the device must compensate for the efforts of the patient, the turbine of the device must provide over the same time interval a work that corresponds to the effort of the patient.
[0128] The turbine of the device has a pneumatic power, which is according to the rotation speed of this turbine:
[0000] P turb =f ( n )
[0000] where P turb :pneumatic power of the turbine and f (n): function of turbine speed.
And the pneumatic energy of the turbine is therefore of the form:
[0000] E=dP turb /dt=f ( n )
[0000] where
E: pneumatic energy,
dP turb /dt: variation in pressure over interval dt,
f(n): in relation to time of the function of the turbine speed.
[0129] The following balance must therefore be obtained:
[0000] De/dt=df ′( n )/ dt=d 2 f ( n ) dt 2 =dD/dt·dP/dt.
[0130] Thus is obtained:
[0000] dE/dt=f ′( n )= dD·dP/dt 2
[0000] where dE: pneumatic effort,
F″(n): function of turbine speed resulting from f (n),
dD: variation in patient flow,
dP: variation in patient pressure.
[0131] FIG. 3 shows a graph characteristic of a turbine implemented in a device according to the invention.
[0132] This graph shows the relationship between the flow and the pressure of the turbine, for a given rotation speed.
[0133] It is thus possible to plot such a characteristic curve for each rotation speed.
[0134] It is also possible to exploit the measurements of variation in turbine rotation speed, in order to determine, from a reference curve such as that in FIG. 3 and calculated for a given rotation speed, the characteristic parameters of the turbine for a second rotation speed.
[0135] The Applicant has thus determined a law for a reference rotation speed n0 (corresponding in the case of the turbine used to 46000 rpm).
[0136] For this rotation speed, between the flow and the pressure, a relationship is obtained of the following type:
[0000] Q=A 2 ·Dp 2 +A 1 ·Dp+A 0
[0000] with
Dp=pressure from sensor 250
A2=−6.47·10 −4
A1=−3.45·10 −3
AO=−5.92
[0137] This reference equation corresponds to the graph in FIG. 3 .
[0138] For a second rotation speed n1 that is not equal to n0, the Applicant has established a law of transposition:
[0000] T=Dp·n 0 /n 1 2
[0000] and
[0000] Q =( A 2 T 2+Alt+ A 0)· n 1 /n 0,
[0000] with:
Dp=pressure from the sensor,
T=rotation speed adaptation factor,
Q=flow,
[0139] This law of transposition establishes a correspondence between the turbine rotation speed and the flow parameters of the respiratory gas generated by this turbine.
[0140] It makes it possible to determine the conditions for establishing respiratory gas flow, and to control the operation of the device, by using a measurement of turbine rotation speed.
[0141] Note that in the case of the invention, a measurement of flow is not exploited, but rather a measurement of turbine rotation speed.
[0142] This gives access in particular to the following advantages:
to be free from the presence of a flowmeter, to work in real time in relation to the operation of the operation (indeed, in known devices in which the control is performed using a flow measurement, a certain time is needed for a modification in the turbine operating conditions translate into a difference in flow at the level of the flowmeter-and this “certain time” is largely greater than the limits mentioned above, making a “real time” control impossible).
[0145] It is specified regarding this aspect that the device and process according to the invention use only a measurement of speed of the turbine.
[0146] In this respect, the invention totally differs from known devices such as the one described in patent EP 656 216.
[0147] This patent mentions turbine motor speed as a parameter which can be used in some way to control the operation of the device.
[0148] This patent further states that modifications of the airflow which are due to the respiration of the patient will alter parameters such as the turbine motor's speed and/or current.
[0149] It further explains that it proposes to use specific signals to detect the points at which the patient starts to inhale and exhale.
[0150] As exposed column 3 lines 37-39 of this patent, these specific signals can be derived:
Either from the motor speed and power measurements (first option), or From the spill valve position and power measurements (second option).
[0153] In the first option, motor speed is thus used in some way for detecting the beginning/end of respiratory cycles. But it is to be noted that motor speed is in no way used by itself, as a single control parameter. This parameter is indeed systematically used in combination with power measurements.
[0154] This is understandable, since turbines known at the priority date of EP 656 216 had quite an important inertia-in the order of 1500 g·cm2 at least.
[0155] For such turbines, a change in the airflow conditions would not change turbine speed before some inertia time (greater than the limit mentioned above).
[0156] Thus, in order to detect such airflow changes in “real time” (or at least as fast as possible, which is of course desired), the mere monitoring and exploitation of turbine speed would in any event not have been appropriate.
[0157] Therefore, such known devices have to use as a main parameter not turbine speed but motor power, in order to detect airflow changes as fast as possible.
[0158] In turbines such as the ones known at the priority date of this patent, this parameter “motor power” will indeed vary much faster than the turbine speed, which can change only after some time because of the large inertia of the turbine.
[0159] It should be further noted that the systematic exploitation of motor power in the case of EP 656 216 makes it necessary to filter the signals based on power.
[0160] This is not the case for the present invention, turbine speed in itself requires no filtering, and can be exploited per se.
[0161] The invention also strongly differs from earlier disclosures such as the one of EP 505 232, which discloses the use of a signal which is the control signal sent to the turbine itself.
[0162] The idea which is exploited in this document is the fact that when airflow conditions change, the control loop which sends said control signal to the turbine will adapt very quickly its control signal in reaction to the change in pressure detected in the inspiration duct.
[0163] Thus, this other prior art patent does not teach or even suggest using directly the turbine speed to detect new respiratory cycles and control the operation of the turbine.
[0164] Furthermore, here again, the signal used for controlling the turbine does not provide a direct indication of the airflow conditions: the signal indeed comprises electrical noise which must be filtered.
[0165] And in any event, here again at the priority date of the patent the turbines used in respiratory devices had a large inertia which made the device incompatible with a real time control of the turbine based on turbine speed measurements.
[0166] Finally, it is specified that the prior art discloses in US 2003/0015200 a respiratory devices which use a speed signal for its operation.
[0167] This document indeed mentions a use of turbine speed.
[0168] But the use disclosed by this document is very different from the use made in the present invention: this prior art document concerns a very specific device with two gas sources (a pressurized gas source, and a depressurized source).
[0169] The general architecture of the device of this document is thus completely different from the architecture of the device of the present invention, which comprises only one source for the respiratory gas.
[0170] And not surprisingly, this fundamental difference in the structure of the device is also associated with a difference in the exploitation of the turbine speed: in the case of US 2003/0015200 turbine speed is used for activating a three-way valve 211, not for controlling a turbine.
[0171] In fact, US 2003/0015200 is not concerned by the control of a turbine.
[0172] In the case of this document the control of the airflow conditions is indeed sought through this valve 211 , which selectively connects the patient to one of the two gas sources 234 , 236 .
[0173] As said above, the device according to the invention is capable of elaborating in real time (i. e. with a timeframe less than the maximum timeframe mentioned above) pressure settings corresponding to new inspiratory and/or expiratory cycles.
[0174] More precisely, means of calculation 230 are associated with several programs for detecting inspiratory cycles being able to operate simultaneously.
[0175] Each one of these programs for detecting inspiratory cycles follows in real time the changes in certain parameters of the respiratory activity of the patient, and is capable of triggering a new inspiratory cycle when conditions that are proper to the program are met.
[0176] And when the different programs operate simultaneously, as soon as the conditions corresponding to a new inspiratory cycle for one of the programs are met, the means of calculation 230 elaborate a pressure setting corresponding to a new inspiratory cycle and transmit this pressure setting to the turbine.
[0177] Below is described the different detection modes for a new inspiratory cycle, corresponding to these different programs.
[0178] Note that it is possible to implement only one of these programs, or to only implement certain ones simultaneously.
[0179] It is also possible to implement them all simultaneously as mentioned above.
[0180] Before describing in greater detail the different detection modes for a new inspiratory cycle, in reference to FIG. 4 the typical change in several parameters during a succession of inspiratory and expiratory cycles is reminded.
[0181] The two curves in the upper portion of this figure show respectively the change in the pressure in the duct carrying the respirator gas and in the corresponding gas flow.
[0182] The different cycles are marked in the lower portion of the figure (I for the inspiratory cycle, E for the expiratory cycle).
[0183] The lower curve shows the change during the same succession of cycles in the turbine speed signal.
[0184] Note that this curve varies according to the turbines used, the curve shown in FIG. 4 (and which will be used in the rest of this text) corresponding to a turbine of which the inertia corresponds to the values mentioned above.
[0185] The lower curve shows the fact that turbine rotation speed in the device is not constant.
[0186] On the contrary, this speed is higher during the inspiratory phases, and lower during the expiratory phases.
[0187] Therefore, the change in this rotation speed as a function of time contains information associated to the respiratory behaviour of the patient.
[0188] And as we shall see, the invention uses this information to detect new inspiratory or expiratory cycles, and consequently modify the pressure setting which is elaborated by means of calculation 230 , and send to the regulation circuit 240 .
[0189] It is to be noted that in all the FIGS. 5 to 8 , which show different modes for triggering inspiratory and/or expiratory cycles, the values measured in real time are represented with white points, while black points represent memorised values.
[0190] In reference now to FIG. 5 the triggering of an inspiratory cycle according to a first mode, called “fast effort detection”, is described.
[0191] As we shall see, this detection mode uses a comparison between:
an instantaneous speed actually measured by the speed sensor of the turbine (it is reminded that in this text “speed” designates the rotation speed of a rotating element of the turbine-typically its rotor), and parameters memorised in the memory mentioned which has been above and which is associated to means of calculation 230 .
[0194] More precisely, the variations in this rotation speed are used in the different modes for detecting the start of inspiratory cycles, but also in the detection of the start of expiratory cycles.
[0195] Returning to the description of this first mode for detecting the start of an inspiratory cycle, the program associated with this first mode constantly evaluates an extrapolation f the speed according to the latest measured speeds.
[0196] This extrapolation can for example be performed on the basis of the last two speeds actually measured.
[0197] The value extrapolated in this way is memorised in the memory associated to the means of calculation 230 . It is represented by a black dot on the graph in FIG. 5 .
[0198] At every given instant, an extrapolation is available that corresponds to an expected speed at the next speed measurement.
[0199] And during this next speed measurement, the program compares the extrapolated speed value with the value of speed actually measured.
[0200] If the difference between these two speed values is greater than a given threshold, the program concludes to an initiation of a new respiratory cycle.
[0201] In this case, means of calculation 230 consequently elaborate a new adapted pressure setting.
[0202] This threshold can be for example 2200 points, with “points” being a unit that is representative of the turbine rotation speed.
[0203] Note that this detection mode can-as with all the other modes for detecting the start of a new inspiratory cycle-be disabled for a given timeframe following the start of a new expiration (with expiratory cycles being initiated in the manner that will be described further on in this text).
[0204] An auto-triggering of the inspiratory cycle by error is therefore avoided in the case for example of an expiratory valve rebounding (which corresponds to a negative variation then a positive one for pressure at the start of expiration).
[0205] The timeframe for disabling this triggering of a new inspiratory cycle (i. e. the time during which the triggering is disabled) can be for example about 300 milliseconds.
[0206] FIG. 6 shows a second mode for detecting a new inspiratory cycle.
[0207] This mode is activated when operating stability in the turbine is observed for a duration that is greater than a given minimum value, said given value being memorised in the memory of the means of calculation 230 as all the operating parameters for the device.
[0208] Said given minimum value can be 300 milliseconds, for example.
[0209] Note that “stability” is defined as the operating conditions that correspond to speed variations contained within given percentages of variation (corresponding to a triggering threshold).
[0210] By way of example, for a nominal turbine rotation speed of about 40,000 to 6,0000 rpm, these given variation percentages correspond to values of about 100 to 400 rpm, depending on the pressure present in duct 210 .
[0211] Note that the lower this pressure is, the more it is possible to tolerate large variations in speed, while still considering that the state is “stable”.
[0212] Thus, in a range of low pressures, the range of speed variations corresponding to “stable” operating conditions is enlarged, and approaches a maximum range of 400 rev/min more or less.
[0213] When this mode is in this way activated, the average value of rotation speed corresponding to the range of stability is memorised in the memory associated to the means of calculation 230 .
[0214] Since turbine rotation speed is always measured in real time, a new inspiratory cycle is triggered by the means of calculation when the absolute value of the difference between the measured speed and said memorised stability value is greater than the triggering threshold.
[0215] This triggering threshold can be for example 1800 points. We have seen that its value can further depend on the pressure measured FIG. 6 thus corresponds to triggering an inspiratory cycle in a mode called “detection of substantial effort after stability”.
[0216] FIG. 7 corresponds to a similar mode, operating on the basis of different values.
[0217] In this case, the mode is called “detection of substantial effort after prolonged stability”.
[0218] In this case, the duration of stability from which the value of speed is memorised is 500 milliseconds, not 300 milliseconds. It is in any event longer than the corresponding value for the preceding mode.
[0219] And the triggering threshold is lower (typically 1500 points, instead of 1800).
[0220] FIG. 8 shows another mode for triggering an inspiratory cycle, called “cycle to cycle detection of effort”.
[0221] This mode is implemented by memorising the value of measured rotation speed at the end of the previous expiratory cycle.
[0222] This memorised value in association with means of calculation 230 will serve as a reference for triggering not the inspiratory cycle that immediately follows the acquisition of this memorised value, but of the inspiratory cycle that will follow yet.
[0223] The program corresponding to this mode triggers a new inspiratory cycle when the absolute value of the difference between the measured speed Value and this memorised value is greater than a given triggering threshold.
[0224] This triggering threshold can be for example about 2200 to 2500 points (note that the curves are not strictly to scale-in particular with regards to the triggering thresholds).
[0225] In reference now to FIG. 9 , a mode for triggering expiratory cycles is shown.
[0226] To implement this triggering, the device memorises the maximum value for turbine rotation speed (this maximum is produced during inspiratory cycles).
[0227] A new maximum can therefore be memorised at each inspiratory cycle.
[0228] It is also possible to only memorise a new maximum value only every N inspiratory cycles, N being able to be set freely.
[0229] When the speed measured in real time goes down to a value that represents a determined proportion of this maximum, means of calculation 230 provoke the triggering of a new expiratory cycle, and elaborate to this effect an adapted pressure setting.
[0230] The proportion in question can be for example 70% of the memorised maximum.
[0231] Note that this triggering of a new expiratory cycle can be disabled for a given duration (for example 200 milliseconds) after the occurrence of the maximum rotation speed in the inspiratory cycle.
[0232] It thus appears that the invention makes it possible to regulate in real time the operation of a turbine, by following the rotation speed of this turbine and the pressure of the gas carried to the patient.
[0233] And the invention also makes possible, using the monitoring of the turbine rotation speed, to trigger new inspiratory and/or expiratory cycles, by modifying a pressure setting sent to the turbine.
[0234] It is to be noted that the invention makes it possible to avoid using a flowmeter, and the limitations that are associated with such a component.
[0235] And as mentioned above, this invention also makes it possible to actually-control the device in real time, which improves patient comfort.
[0236] Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims. | 1a
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BACKGROUND OF THE DISCLOSURE
The process of drilling an oil or gas well is a dangerous process which involves the risk of fire. The risk of fire is particularly well known, but in spite of the high level of risk, fires are relatively few and far between. Nevertheless, they occasionally do happen on or at the drilling rig. The risk of fire is increased during certain drilling circumstances. Specifically, the risk of fire can be increased markedly when the well penetrates a high pressure natural gas formation. In that event, the well may experience a surge in which the high pressure natural gas flows up the well borehole during drilling. For that reason, the normal, safe operating procedures require that the well be protected by filling the well with a heavy weight drilling fluid, normally known as drilling mud. The drilling fluid is placed in the well to maintain a column of fluid acting on the formation which overcomes the gas pressure. This prevents a surge of natural gas from flowing rapidly up the borehole and escaping at the surface. In addition to that protection, there is also a blow out preventer (BOP) which is installed at the surface, typically being installed beneath the floor of the drilling rig. The blow out preventer is an emergency device which clamps off flow through the borehole.
Occasionally, problems can still arise even though the foregoing protective procedures are fully practiced. For instance, it may be necessary to use an oil base drilling fluid as opposed to a water base drilling fluid. There is another circumstance in which the risk of fire is increased. One example of this involves horizontal drilling. A good example of horizontal drilling is found in the formation which is known as the Austin Chalk which is a formation having various producing strata at about 7000-9000 feet in depth stretching from approximately Laredo, Tex. to the Northeast and extending almost to the Red River. The Austin Chalk is a tight formation which can be produced from vertical wells provided the well passes through the formation and intercepts a formation fracture. Wells of this sort can produce from the tight formation, but the well life has been somewhat shortened because of difficulties in lateral migration through the formation. In a number of occasions, vertical wells into the Austin Chalk have been produced for the useful lives and when that production has been depleted, the wells have been reworked by redrilling the last few hundred feet of the well. Typically, this involves the use of a milling tool to cut a window in the casing in the well, the window being about 100-300 feet in length, and then reentering the well at that region with the appropriate equipment to drill from or through the window in a radius of curvature until the well is then horizontal or substantially so. This requires that the deviated well form a horizontal leg which is ideally centered in the Austin Chalk and is ideally positioned at the midpoint of the formation. The horizontal leg can be several hundred feet long. Indeed, this rework procedure has proven so popular that it has now been adapted for new wells into the Austin Chalk formation.
Assume for purposes of description that the horizontal portion is to be 1000 feet in length. This forms an open hole of approximately 1000 feet in length in the Austin Chalk formation which is a producing formation with a substantial formation pressure drive. In that event, the entire drilling process through the Austin Chalk involves drilling while producing. That is, during the process of extending the horizontal leg to 1000 feet, the Austin Chalk formation will produce at all points along this horizontal leg and thereby seriously increase the risk of drilling. As the partially completed horizontal leg extends through the Austin Chalk, more and more oil or gas or both is produced and comingles with the drilling fluid. Since the drilling fluid is circulated to the well head in the annular space of the borehole, the mud handling procedures at the surface are frought with danger of fire because the oil and gas produced during this time is brought to the surface. There is a risk of fire where the annular flow comes to the surface which is immediately under the drilling rig at the BOP. There is an additional chance of fire hazard in the equipment area where the mud is also handled by the choke equipment, the shale shaker or other mud handling equipment. This equipment is normally deployed at one region at the time of rigging up. Suffice it to say, the circulation of drilling mud through the Austin Chalk brings to the surface some oil or gas, and thereby increases in the risk of fire.
SUMMARY OF THE INVENTION
The present apparatus is fire control system to be installed at a drilling rig. It is particularly adapted for use at a rig where the well to be drilled will have greater exposer to fire and other hazards of this sort. For instance, if the well is to be drilled through the Tuscalosa Sand which yields extremely high pressure natural gas, this type of equipment would be highly desirable. It is installed either at spudding in or at least in the first or three days of operation. It is installed and left at the rig until the well has been completed. The equipment utilizes spray nozzles which are mounted at selected locations to put out any fire which might occur. Indeed, the equipment is installed, switched on, and operated in a standby mode throughout the drilling interval. When drilling is finished, it can be removed to another drilling location and reused at that location. In particular, the equipment features a standby mode of operation so that it is always ready to operate by delivery a flood of water. Indeed, the delivery rate can be as high as 1200 gallons per minute for fire protection. The equipment features a portable engine and pump which are connected to strategically located nozzles. An engine control unit sets the throttle of the engine at a desired engine speed and is changed to full output in the event of a fire by suitable switches which are located at or on the rig floor. By this approach, the personnel on the rig floor are able to initiate fire protection with minimal time delay.
DESCRIPTION OF THE DRAWINGS
The drawing with the present disclosure sets forth the fire protection apparatus of this disclosure installed at a drilling rig and particularly shows how nozzles are positioned at selected locations to protect the major work areas at the rig site.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Attention is directed to FIG. 1 of the drawings where the numeral 10 identifies a drilling rig. The rig will be described first to provide the context of the present invention which will be described in detail with the understanding that it is placed on a typical drilling rig where fire protection is needed. The drilling rig 10 incorporates an upstanding derrick 12 which is assumed to have four edges which extend upwardly to the crown (not shown). Obviously, the rig can have other types of construction including the typical tilt up rig where the derrick is constructed differently. The numeral 12 identifies a rig floor which supports a drive system connected with a rotary table (not shown). The rig floor is located several feet above the ground and is supported on a support structure 14. The floor is sufficiently high above the structure 14 that there is room beneath the rig floor for the BOP equipment 16. That is normally installed below the rig floor to clamp around the drill pipe. That is, the BOP equipment 16 is installed around the drill pipe. There is a flow pathway downwardly through the drill string for drilling mud which is delivered by a mud pump where the mud circulates downwardly through the drill bit, and flows back up in the well. This return flow is in the annular space on the exterior of the drill pipe and the drilling fluid returns to the surface and is removed to the side for recycling. The drilling mud flow normally directs the mud through various recovery devices such as shale shakers or desanders. In addition, a degasser may also be connected with the mud flow. In any event, the BOP 16 is normally located beneath the rig floor and immediately adjacent to the upper end of the borehole to operate in the intended fashion.
The drilling mud is directed through the various pieces of equipment identified at 18 which includes the choke, the shaker, and other mud handling equipment. These are normally deployed in a group, and typically includes two or three mud pits. In particular, there will be a mud pump, the choke and the control equipment for the choke, degasser, desander, or shale shaker.
The present apparatus is generally identified by the numeral 20. This equipment is preferably installed somewhat remote from the rig floor 12. In the event of fire, the fire will normally occur at two or three locations and the protective equipment 20 is located remote from these locations to assure that it is clear of the fire so that it can operate to provide fire protection. Thus, the protective equipment 20 is positioned somewhat remote from the BOP 16 and is also remote from the mud handling equipment indicated generally at 18. The present apparatus is ideally portable, at least portable by means of a flatbed trailer, and to this end, it incorporates a skid 22 which supports the pump 24 and a diesel engine 26. These are commonly mounted on a single skid. A second skid is normally included to support a fuel tank 28. The fuel tank 28 provides sufficient fuel for operation for several days, e.g., 7 days. The remainder of the equipment shown in the drawing is relatively small and normally located on the skid 22 as will be detailed.
The fire protection equipment utilizes a large water tank 30. Preferably, a closed tank can be used, typically one that holds about 500 barrels of water. Such tanks are routinely available. The tank 30 is provided with an optional heater 32. In northern climates, it may be necessary to add the heater so that the water is sufficiently heated that it does not freeze. Of course, the heater can be omitted should this not be a problem. The tank 30 is connected with a large diameter hose extending to the pump 24. A typical pump provides an output of 1200 gallons per minute with a discharge pressure of about 130 psi. The preferred form of pump is relatively simple, and to this end, a centrifugal pump will suffice. To handle this kind of flow, a flow line 34 is connected from the tank to the pump 24. Typically, the flow line is perhaps a 6 inch suction line. The pump 24 is connected directly to the engine 26. In the preferred form of equipment, both units are mounted on the common skid which is equipped with eyelets at the top so that the skid mounted equipment can be lifted as a unit. A suitable engine is a 6 cylinder diesel provided by Cummings Engine Company, Inc. capable of 177 BHP. This typical engine has an idle speed of about 800 rpm. It has an adjustable throttle which permits it to be set at desired speeds, and in this particular embodiment, it is operated at a continuous speed of perhaps 1500 rpm. Maximum output with peak torque is obtained at about 2500 rpm. More will be noted regarding these throttle settings hereinafter.
The skid mounted engine 26 normally requires a specified quantity of lubricating oil in the crank case. A supplemental lube oil supply is finished at 36. In addition, the fuel for the engine 26 is provided by the large tank 28 mounted on a separate skid. The engine is normally operated at one of three speeds. Idle speed was mentioned above and that occurs when the equipment is first switched on. The speed is set to a higher level, perhaps 1200-1500 rpm, by an engine control unit 40. This accomplishes that speed simply by positioning the throttle for operation at a selected speed. The engine control unit adjusts the speed to full power at about 2500 rpm. The engine control unit is provided with a radio receiver 42. When a signal is provided by the receiver 42 to the engine control 40, the engine throttle is moved to the higher speed, namely 2500 rpm. This setting will be described as maximum power output. The engine control unit really has two operative states. One which is at the standby speed, and the other is at maximum power. The engine control unit is also connected with a siren or other alarm device. The siren 44 is included to provide a clear warning to rig personnel including those remote from the rig floor, e.g., those sleeping in temporary quarters nearby.
The skid 22 supports a running light 46. The running light is duplicated at two locations. There is one immediately on the skid. It is sufficiently large that it can be viewed even in the darkest of conditions, even when obscured with fog, etc. There is a parallel light 48 which is located on the rig floor. Both lights are operated when the engine 26 is running. This provides a positive signal to personnel that the equipment is operating. The rig floor is the location of two important pieces of equipment involved in the fire protection system 20. One is the running light. It provides the clear indication to personnel on the rig floor that the equipment is successfully operating to provide a fail safe warning. Thus, if the engine 26 stops operating for any reason, the lights 46 and 48 go out and that provides the necessary safety feedback for personnel. Assume for purposes of description that the tool pusher is the person in charge. The tool pusher will watch the running light 48 at all times. In addition to that, the tool pusher is usually adjacent to a switch 50 which connects with the engine control unit 40. That is, the switch can be wired directly to the engine control 40. The switch does not switch the engine control off; rather, it switches the equipment from the standby speed to maximum power operation. The switch 50 is connected by means of a fixed wire which is safely installed out of harms way extending from the rig floor. It is available for operation by the tool pusher at any time. A duplicate switch can be placed on the rig floor if desired so that the driller might also operate the equipment. An alternate mode of asserting control over the fire protection equipment 20 is accomplished by a hand held portable transmitter 52. It is a portable device which communicates with the receiver 42. It provides an alternate signal. The transmitter 52 can be implemented by means of a relative small hand held transmitter which fits in the pocket of a key or selected personnel around the rig. The transmitter 52 can be placed in the pocket of any roughneck anywhere on the rig even up in the derrick, for instance, up on the monkey board. First and second separately located switches can be included for different personnel to operate, e.g., one for the driller, and another for the tool pusher. Also, the alarm devices are at spaced locations.
The present equipment utilizes selected nozzles with standpipes. A standpipe 54 supports a nozzle 56 under the rig floor 12 directed at the area of the BOP 16. In similar fashion, a standpipe 58 extends well above the rig floor and supports a nozzle 60 above the rig floor, perhaps 10 feet over the floor. A third standpipe 62 supports a nozzle 64 directed at the choke and other equipment. All three of the nozzles are directed in a fixed direction. All three are provided with an outlet to provide a broad spray as opposed to a narrow stream of water. All three are constructed with the standpipes momentarily or temporarily anchored in position and of sufficient strength to resist the reaction force that arises from operation. All three are connected by means of fire hoses line extending from the three respective standpipes to the pump 24. The pump is provided with an outlet header which connects with the three fire hoses identified at 66, 68, and 70.
Deployment of the equipment is accomplished along the lines described hereinabove, namely, at an early point in the drilling routine when the derrick and drilling rig are first installed and the safety equipment of the present disclosure is installed and switched on. The tanks 28 and 36 are filled and the engine is turned on. Of course, the water tank 30 is also filled. It is characteristic of a centrifugal pump that it will not provide an output flow at an idle speed. Accordingly, the hoses 66, 68, and 70 are installed by connection with the pump outlet header and are extended to the respective nozzles deployed as illustrated. These hoses are substantially empty of water at this juncture because the pump 24 has no output flow. By contrast, when the engine 26 is raised to maximum power output, the pump 24 will speed up to provide full suction at the input and will deliver several hundred gallons per minute through the three hoses. The water flows through the hoses and is delivered through the three respective nozzles to form a sprayed fog or mist of substantial water volume directed to the suspect fire areas.
Several options can be incorporated in the present apparatus. For instance, the number of nozzles can be varied and additional nozzles can be located as desired. In another modification, a foaming agent can be added to the water either at the tank 30 or otherwise input to the pump 24 along with the flow of water. When the water flow starts, the siren 44 is triggered. This provides an alarm device to all personnel. In addition to that, an important feature is the provision of the signal, typically a visual signal, provided by the running lights 46 and 48. These two signals are useful to assure rig personnel at all times that the equipment is in a ready to operate condition. Obviously, if the fuel tank 28 is emptied and the engine switches off for lack of fuel, the absence of that light is an alarm condition suggesting to rig personnel that they ought to stop drilling and restart that equipment to assure the continued provision of safety at the rig site.
The present apparatus can provide a spray of water within about 1.5 seconds of providing the signal. Thus, the switch 50 is operated forming a signal to the engine control unit. This changes the speed of the engine 26 and initiates water pumping from the pump 24. There is only a modest time delay as water is drawn from the tank 30 into the pump 24 and then is delivered through the fire hoses 66, 68, and 70. The 1.5 second time delay is typical where the hoses are approximately equal in length and are approximately 200 feet or less in length. Preferably, the hoses have a nomimal size of 3 inches and the nozzles are compatible for this size. With three hoses and a nominal 3 inch nozzle, approximately 1200 gallons per minute through put can be provided.
While the foregoing is directed to the preferred embodiment, the scope is determined by the claims which follow. | 1a
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BACKGROUND OF THE INVENTION
[0001] Vascular occlusions (clots or thrombi and occlusional deposits, such as calcium, fatty deposits, or plaque) result in the restriction or blockage of blood flow in the vessels in which they occur. Occlusions result in oxygen deprivation (“ischemia”) of tissues supplied by these blood vessels. Prolonged ischemia results in permanent damage of tissue that can lead to myocardial infarction, stroke, or death. Targets for occlusion include coronary arteries, peripheral arteries and other blood vessels. The disruption of an occlusion or thrombolysis can be effected by pharmacological agents and/or or mechanical means.
[0002] Ultrasonic probes are devices which use ultrasonic energy to fragment body tissue (see, e.g., U.S. Pat. Nos. 5,112,300; 5,180,363; 4,989,583; 4,931,047; 4,922,902; and 3,805,787) and have been used in many surgical procedures. The use of ultrasonic energy has been proposed both to mechanically disrupt clots, and to enhance the intravascular delivery of drugs to clot formations (see, e.g., U.S. Pat. Nos. 5,725,494; 5,728,062; and 5,735,811). Ultrasonic devices used for vascular treatments typically comprise an extra-corporeal transducer coupled to a solid metal wire that is attached to a plurality of wires at the distal end, that is then threaded through the blood vessel and placed in contact with the occlusion (see, e.g., U.S. Pat. No. 5,269,297). In some cases, the transducer is delivered to the site of the clot, the transducer comprising a bendable plate (see, U.S. Pat. No. 5,931,805).
[0003] The ultrasonic energy produced by an ultrasonic probe is in the form of very intense, high frequency sound vibrations that result in powerful chemical and physical reactions in the water molecules within a body tissue or surrounding fluids in proximity to the probe. These reactions ultimately result in a process called “cavitation,” which can be thought of as a form of cold (i.e., non-thermal) boiling of the water in the body tissue, such that microscopic bubbles are rapidly created and destroyed in the water creating cavities in their wake. As surrounding water molecules rush in to fill the cavity created by collapsed bubbles, they collide with each other with great force. This process is called cavitation and results in shock waves running outward from the collapsed bubbles which can fragment or ablate material such as surrounding tissue in the vicinity of the probe. Some ultrasonic probes include a mechanism for irrigating an area where the ultrasonic treatment is being performed (e.g., a body cavity or lumen) to wash tissue debris from the area. Mechanisms used for irrigation or aspiration described in the art are generally structured such that they increase the overall cross-sectional profile of the probe, by including inner and outer concentric lumens within the probe to provide irrigation and aspiration channels for removal of particulate matter. In addition to making the probe more invasive, prior art probes also maintain a strict orientation of the aspiration and the irrigation mechanism, such that the inner and outer lumens for irrigation and aspiration remain in a fixed position relative to one another, which is generally closely adjacent the area of treatment. Thus, the irrigation lumen does not extend beyond the suction lumen (i.e., there is no movement of the lumens relative to one another) and any aspiration is limited to picking up fluid and/or tissue remnants within the defined distance between the two lumens.
[0004] Another drawback of existing ultrasonic medical probes is that they typically remove tissue relatively slowly in comparison to instruments that excise tissue by mechanical cutting. Part of the reason for this is that existing ultrasonic devices rely on a longitudinal vibration of the tip of the probe for their tissue-disrupting effects. Because the tip of the probe is vibrated in a direction in line with the longitudinal axis of the probe, a tissue-destroying effect is only generated at the tip of the probe. One solution that has been proposed is to vibrate the tip of the probe in a direction other than perpendicular to the longitudinal axis of the probe, in addition to vibrating the tip in the longitudinal direction. It is proposed that such motions will supplement the main point of tissue destruction, which is at the probe tip, since efficiency is determined by surface area of the probe tip. For example, U.S. Pat. No. 4,961,424 to Kubota, et al. discloses an ultrasonic treatment device that produces both a primary longitudinal motion, and a supplementary lateral motion of the probe tip to increase the tissue disrupting efficiency. The Kubota, et al. device, however, still relies primarily on the tip of the probe to act as a working surface. The ancillary lateral motion of the probe is intended to provide an incremental efficiency for the device operation. Thus, while destruction of tissue in proximity to the tip of the probe is more efficient, tissue destruction is still predominantly limited to the area in the immediate vicinity at the tip of the probe. The said invention is therefore limited in its ability to ablate tissue within inner surfaces of cylindrical blood vessels, for example, in vascular occlusions. U.S. Pat. No. 4,504,264 to Kelman discloses an ultrasonic treatment device containing a probe that is capable of longitudinal vibrations and lateral oscillation. The said invention is intended to improve the efficiency of ultrasonic tissue removal by providing a dual function of a fragmentation and a cutting device. Tissue fragmentation is caused primarily by oscillating the tip of the probe in addition to relying on longitudinal vibrations of the probe, while the lateral oscillations. Tissue fragmentation is caused primarily at the tip of the device, while the oscillatory motion can be employed by the surgeon to cut tissue, thereby increasing efficiency of surgical procedures. The foregoing inventions also require complex instrument design that require incorporation of a plurality of electrodes, ultrasound frequency generating elements, switches or voltage controllers.
[0005] The longitudinal probe vibration required for tissue ablation in prior art devices necessitates the probe lengths to be relatively short, since use of long probes result in a substantial loss of ultrasonic energy at the probe tip due to thermal dissipation and undesirable horizontal vibration that interferes with the required longitudinal vibration.
[0006] Although narrow probe diameters are advantages especially for negotiation through narrow blood vessels and occluded arteries, the utilization of such probes have been precluded by inability to effectively control the vibrational amplitude of thin probes, that result in potential damage to the probe and greater risk of tissue damage resulting from their use. The use of narrow-diameter probes have been disclosed in the art for providing greater maneuverability ease of insertion in narrow blood vessels. U.S. Pat. No. 4,920,954 to Allinger discloses a narrow diameter ultrasonic device wherein a rigid sleeve is used to prevent transverse vibrations U.S. Pat. No. 5,380,274 discloses a narrow diameter probe for improved longitudinal vibration having a sheath to inhibit transverse vibration U.S. Pat. No. 5,469,853 to Law discloses a thin, longitudinally vibrating ultrasonic device with a bendable sheath that facilitates directing the probe within narrow blood vessels. While the prior art has focused on the need for using sheaths on thin ultrasonic devices, their use has been entirely to prevent transverse vibrations of the device and to protect such devices from damage resulting from such vibrations.
[0007] Based on the aforementioned limitations of ultrasonic probes in the art, there is a need for ultrasonic probe functioning in a transverse mode that further obviates the shortcomings of that further overcomes limitations imposed by of narrow diameter requirements for efficient operation of such probes for rapid tissue ablation. Transversely vibrating ultrasonic probes for tissue ablation are described in the Applicant's co-pending provisional applications U.S. Ser. Nos. 60/178,901 and 60/225,060, and 20563/1010 (Attorney Docket No.) which further describe the design parameters for such a probe its use in ultrasonic devices for tissue ablation. The entirety of these applications are herein incorporated by reference.
[0008] This limitation has precluded the use of ultrasonic tissue ablation devices in surgical procedures wherein access to vascular occlusion requires traversing an anatomically lengthy or sharply curved path along tubular vessels. The self-suggesting idea of effecting ultrasonic transmission through a plurality of flexible thin wires has been found impracticable because (1) relatively high power (˜25 watts) is required to deliver sufficient energy to the probe tip, and (2) such thin wires tend to perform buckling vibrations, resulting in almost the entire ultrasonic power introduced in the probe is dissipated during its passage to the probe tip.
[0009] The relatively high-energy requirement for such devices causes probe heating that can cause fibrin to re-clot blood within the occluded vessel (thermally induced re-occlusion). Additionally, the elevation in probe temperature is not just limited to probe tip, but also occurs at points wherein the narrow diameter wire probes have to bend to conform to the shape of the blood vessel, thereby limiting causing probe damage and limiting its reuse.
[0010] A single thick wire probe on the other hand, cannot negotiate the anatomical curves of tubular arterial and venous vessels due to its inflexibility, and could cause damage to the interior wall of such vessels. Currently, such exchange procedures are not possible because ultrasonic probes used in endovascular procedures are permanently attached to the transducer energy source or a probe handle coupled to such source, such as for example, by welding, thereby precluding probe detachment. Moreover, since probe vibration in such devices in a longitudinal mode, i.e. along the probe longitudinal axis, a proximal contact with the transducer or the probe handle segment connect is essential to prevent a “hammering” effect that can result in probe damage.
SUMMARY OF THE INVENTION
[0011] The present invention relates to an ultrasonic device comprising an elongated catheter probe vibrating substantially in a direction transverse to the probe longitudinal axis and capable of emulsifying endovascular materials, particularly tissue. The diameter of the catheter probe is sufficiently small to confer flexibility on said probe so as to enable its negotiation through narrow and anatomically curved tubular vessels to the site of an occlusion that is remotely located from the point of probe insertion into the body. The catheter probe of the invention is designed to work in conjunction with standard vascular introducers and guide catheters. Another aspect of the invention is to provide a rapidly attachable and detachable or “quick attachment-detachment” means (referred to hereinafter as “QAD”) for the catheter probe to and from the ultrasonic energy source, thereby enabling manipulation and positioning of the probe within the body vessel without being limited by the relatively bulky energy generating source. The catheter probe of the invention additionally comprises a concentric tubular sheath to facilitate fluid irrigation, aspiration of ablated tissue fragments and introducing a therapeutic drug to the site of occlusion.
[0012] An ultrasonic probe vibrating in a transverse mode for removal of occlusions in blood vessels has been disclosed in applicants' co-pending application Ser. No. 09/776,015, the entireity of which is incorporated herein as reference. The said reference discloses an ultrasonic device in which a transducer is connected to a probe with a flexible tip capable of vibrating in a direction transverse to the probe longitudinal axis. With such a probe a situation may arise where it will be desirable to utilize an elongated probe resembling a catheter guide-wire probe to make possible exchange procedures often used in angioplasty.
[0013] In general, it is an object of the invention to provide an ultrasonic medical device for removing vascular occlusions comprising a detachable elongated catheter guide wire probe capable of vibrating in a transverse mode.
[0014] Another object of the invention is to provide an elongated guide wire probe of the above character of the above character that is and comparable in size to existing guide wires.
[0015] Another object of the invention is to provide an elongated guide wire probe of the above character which includes a quick attachment-detachment means to an ultrasound energy source.
[0016] Another object of the invention is to provide an elongated guide wire probe of the above characteristics which is compatible with the existing guide wire exchange systems.
[0017] Another object of the invention is to provide a probe attachment-detachment means comprising a coupling assembly.
[0018] Yet another object of the invention is to provide a guide wire of the above character which can be inserted, retracted or torqued in a detached mode to prevent interference with the probe handle and the ultrasound transducer.
[0019] A further object of the invention is to provide a guide wire assembly and system and apparatus utilizing the same of the above character, which permits intravascular ultrasonic tissue ablation.
[0020] Additional objects and features of the invention will appear from the following description in which the preferred embodiments are set forth in detail in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] In order that the invention may be more readily understood, reference is made to the accompanying figures, which illustrate diagramatically and by way of example, several embodiments thereof and in which:
[0022] [0022]FIG. 1 is a general view of the elongated flexible wire probe catheter of the invention.
[0023] [0023]FIGS. 2A and 2B show a varied diameter probe, QAD collet-horn assembly and locking nut in disassembled ( 2 A) and assembled ( 2 B) configurations.
[0024] [0024]FIG. 2C shows an assembled configuration of a uniformly small diameter wire probe.
[0025] [0025]FIG. 3 shows a cross sectional view of the probe assembled to QAD collet (Version 1) assembly.
[0026] [0026]FIGS. 4A and 4B show the locking nut viewed from the opposite cylindrical ends.
[0027] [0027]FIG. 5 shows a cross sectional view of the locking nut coupling the probe to the QAD collet-horn assembly.
[0028] [0028]FIG. 6 shows the threaded horn component of the QAD collet-horn assembly.
[0029] [0029]FIG. 7 shows scaled and cross-sectional views of a second preferred version of the QAD collet assembly.
[0030] [0030]FIGS. 8A and 8B show the QAD collet rod and housing assemblies of the second preferred version.
[0031] [0031]FIG. 9 shows scaled and cross-sectional views of a third preferred version of the QAD collet assembly.
[0032] [0032]FIGS. 10A and 10B show the QAD collet rod and housing assemblies of the third preferred version.
[0033] [0033]FIG. 11 shows scaled and cross-sectional views of a fourth preferred version of the QAD collet assembly.
[0034] [0034]FIGS. 12A, 12B and 12 C show the collet, QAD base component and compression housing of the fourth preferred version.
DETAILED DESCRIPTION OF THE INVENTION
[0035] The following terms and definitions are used herein:
[0036] “Anti-node” as used herein refers to a region of minimum energy emitted by an ultrasonic probe on or proximal to a position along the probe.
[0037] “Cavitation” as used herein refers to shock waves produced by ultrasonic vibration, wherein the vibration creates a plurality of microscopic bubbles which rapidly collapse, resulting in molecular collision by water molecules which collide with force thereby producing the shock waves.
[0038] “Fenestration” as used herein refers to an aperture, window, opening, hole, or space.
[0039] “Node” as used herein refers to a region of maximum energy emitted by an ultrasonic probe at or proximal to a specific location along the longitudinal axis probe.
[0040] “Anti-node” as used herein refers to a region of minimum energy emitted by an ultrasonic probe at or proximal to a specific location along the longitudinal axis probe.
[0041] “Probe” as used herein refers to a device capable of being adapted to an ultrasonic generator means, which is capable of propagating the energy emitted by the ultrasonic generator means along its length, resolving this energy into effective cavitational energy at a specific resonance (defined by a plurality of nodes and anti-nodes at a predetermined locations (defined as “active area” of the probe) and is capable of acoustic impedance transformation of ultrasound energy to mechanical energy.
[0042] “Sheath” as used herein refers to a device for covering, encasing, or shielding in whole or in part, a probe or portion thereof connected to an ultrasonic generation means.
[0043] “Transverse” as used herein refers to vibration of a probe at right angles to the axis of a probe. A “transverse wave” as used herein is a wave propagated along an ultrasonic probe in which the direction of the disturbance at each point of the medium is perpendicular to the wave vector.
[0044] “Tuning” as used herein refers to a process of adjusting the frequency of the ultrasonic generator means to select a frequency that establishes a standing wave along the length of the probe.
[0045] The present invention provides an ultrasonic medical device operating in a transverse mode for removing a vascular occlusion by causing fragmentation of occlusion materials such as tissue. Because the device is minimally invasive, flexible and articulable, it can be inserted into narrow, tortuous blood vessels without risking damage to those vessels. Transverse vibration of the probe in such a device generates multiple nodes of cavitation energy along the longitudinal axis of the probe, which are resolved into caviational nodes emanating radially from these nodes at a specific points along the active portion of the probe. The occlusion tissue is fragmented to debris approximately of sub-micron sizes, and the transverse vibration generates a retrograde flow of debris that carries the debris away from the probe tip.
[0046] The transverse mode of vibration of the ultrasonic probe according to the invention differs from the axial (or longitudinal) mode of vibration that is conventional in the prior art. Rather than vibrating in the axial direction, the probe vibrates exclusively in a direction transverse (perpendicular) to the axial direction. As a consequence of the transverse vibration of the probe, the tissue-destroying effects of the device are not limited to those regions of a tissue coming into contact with the tip of the probe. Rather, as the active portion of the probe is positioned in proximity to an occlusion or other blockage of a blood vessel, the tissue is removed in all areas adjacent to the multiplicity of energy nodes that are produced along the entire length of the probe, typically in a region having a radius of up to about 6 mm around the probe.
[0047] By eliminating the axial motion of the probe and allowing transverse vibrations only, fragmentation of large areas of tissue spanning the entire length of the active portion of the probe due to generation of multiple cavitational nodes along the probe length perpendicular to the probe axis. Since substantially larger affected areas within an occluded blood vessel can be denuded of the occluded tissue in a short time, actual treatment time using the transverse mode ultrasonic medical device according to the invention is greatly reduced as compared to methods using prior art probes that primarily utilize longitudinal vibration (along probe axis) for tissue ablation. An distinguishing feature of the present invention is the ability to utilize probes of extremely small diameter (about 0.025″ and smaller) compared to prior art probes without loss of efficiency, since the tissue fragmentation process in not dependent on area of the probe tip (distal end). Highly flexible probes can therefore, be designed to mimic device shapes that enable facile insertion into highly occluded or extremely narrow interstices within blood vessels. Another advantage provided by the present invention is its ability to rapidly remove occlusion tissue from large areas within cylindrical or tubular surfaces such as arteries and arterial valves or selected areas within the tubular walls, which is not possible by previously disclosed devices that rely on the longitudinal vibrating probe tip for effecting tissue fragmentation.
[0048] The number of nodes occurring along the axial length of the probe is modulated by changing the frequency of energy supplied by the ultrasonic generator. The exact frequency, however, is not critical and a ultrasonic generator run at, for example, 20 kHz is generally sufficient to create an effective number of tissue destroying nodes along the axial length of the probe. In addition, as will be appreciated by those skilled in the art, it is possible to adjust the dimensions of the probe, including diameter, length, and distance to the ultrasonic energy generator, in order to affect the number and spacing of nodes along the probe. The present invention allows the use of ultrasonic energy to be applied to tissue selectively, because the probe conducts energy across a frequency range of from about 20 kHz through about 80 kHz. The amount of ultrasonic energy to be applied to a particular treatment site is a function of the amplitude and frequency of vibration of the probe. In general, the amplitude or throw rate of the energy is in the range of 150 microns to 250 microns, and the frequency in the range of 20,000 to 80,000 Hertz (20-80 kHz). In the currently preferred embodiment, the frequency of ultrasonic energy is from 20,000 Hertz to 35,000 Hertz (20-35 kHz). Frequencies in this range are specifically destructive of hydrated (water-laden) tissues and vascular occlusive material, while substantially ineffective toward high-collagen connective tissue, or other fibrous tissues such as, for example, vascular tissues, skin or muscle tissues.
[0049] In a preferred embodiment, the ultrasonic medical device of the present invention, comprises an ultrasonic generator that is mechanically coupled to a probe having a proximal and distal end that is capable of oscillating in a direction transverse to its longitudinal axis. Alternatively, a magneto-strictive generator may be used for generation of ultrasound energy. The preferred generator is a piezoelectric transducer that is mechanically coupled to the probe to enable transfer of ultrasonic excitation energy and cause the probe to oscillate in a transverse direction relative to its longitudinal axis. The device is designed to have a small cross-sectional profile, which also allows the probe to flex along its length, thereby allowing it to be used in a minimally invasive manner. Transverse oscillation of the probe generates a plurality of cavitation nodes along the longitudinal axis of the member, thereby efficiently destroying the occlusion. A significant feature of the invention is the retrograde movement of debris, e.g., away from the tip of the probe i.e. backwards up along the shaft of the probe that results from the transversely generated energy. The amount of cavitation energy to be applied to a particular site requiring treatment is a function of the amplitude and frequency of vibration of the probe, as well as the longitudinal length of the probe tip, the proximity of the tip to a tissue, and the degree to which the probe tip is exposed to the tissues.
[0050] A distinguishing feature of the present invention is the ability to utilize probes of extremely small diameter (narrow diameter probes) compared previously disclosed devices (large diameter probes) without loss of efficiency or efficacy, since the tissue fragmentation process in not dependent on area of the probe tip (distal end). Highly flexible probes can therefore be obtained to mimic device shapes that enable facile insertion into highly occluded or extremely narrow interstices without resulting in breakage of the probe or puncture or damage of the tissue or body cavity while ensuring optimal results.
[0051] A second distinguishing feature of the small diameter probes of the invention is that the probe diameter is approximately the same over their entire length, that is,—the active tip segment (distal end) and the rear segment (proximal end) of the probes are approximately similar in diameter. In a preferred embodiment the probe diameters at the proximal and distal ends respectively are about 0.025 inch. An advantage of the shape configuration of the probes of the invention is that they are adaptable to currently used standard vascular introducers. Since the rear segment (proximal end) of the probes have no non-cylindrical shape or “bulk”, catheters and guides can be introduced over the ends of the elongated wire probes of the invention, thereby—allowing their use in standard-configuration endovascular procedures.
[0052] The ultrasonic device of the invention comprises a longitudinal resonator such as for example, a Mason (Langevin) horn that is in intimate contact with an elongated catheter wire probe through a coupling assembly. The horn assembly is in turn, connected to an ultrasound energy source. Upon device activation, ultrasonic energy from the source is transmitted to the horn assembly wherein it is amplified by the horn and in turn, transmitted to the probe thorough the coupling assembly. Transverse vibrational modes along the longitudinal axis of the probe that lie within the horn resonance are excited.
[0053] The coupling between the elongated probe and the horn is adjusted so as to present a relatively large impedance mismatch, and be located at an anti-node of the horn. Longitudinal waves impinging on the coupling interface are either reflected back into the horn or transmitted out to the probe in proportion to the degree of impedance mismatch at the said coupling interface. In a preferred embodiment, the coupling interface is configured in a manner so as to reflect most of the energy back into the horn. The horn therefore, essentially acts as an energy storage device or “reservoir”, thereby allowing a substantial increase in drive amplitude.
[0054] Since the energy coupled into the elongated probe is a small portion of the energy reflected back to the horn, changes in the transverse oscillation on the probe due to bending or damping have minimal effect on the longitudinal resonance of the horn. By decoupling the transverse probe oscillation from the longitudinal horn resonance, the electrical source of the vibrations (piezoelectric or magnetostrictive) to compensate only for shifts in the resonant frequency of the horn (due to temperature, manufacturing variations, etc.). The drive mechanism is therefore, completely independent of vibrational motions on the probe.
[0055] The transverse vibrating elongated probe of the invention does not require its terminal end be permanently affixed in intimate contact to the horn assembly, since a “hammering” action associated with longitudinal vibration is absent. The elongated probe of the invention can therefore be coupled, and not welded, to the horn via a coupling assembly that grips the probe along the cylindrical surface near its terminal end in a non-permanent way. The coupling assembly of the invention therefore, allows for quick attachment and detachment of the probe from the horn assembly and source components, thereby enabling manipulation of the elongated flexible probe into anatomically curved blood vessels without hindrance by the bulky horn and energy source components. The probe of the invention can therefore be inserted into a venal cavity, positioned near the occlusion site prior to coupling it to the horn source assembly. The device is then activated to effect tissue ablation and removal, after which the probe is decoupled from the horn and source component for its easy removal from the cavity.
[0056] In a preferred embodiment a longitudinal horn is coupled to an elongated wire catheter through a coupling assembly that is rapidly attachable and detachable. In a most preferred embodiment, the coupling assembly comprises a quick attachment-detachment (QAD) collet. The attachment of the coupling assembly to the elongated probe is located at an antinode and the dimensions are scaled (i.e. it collet head has a relatively larger diameter at the attachment point than the diameter of the probe) to produce an optimal impedance mismatch. In another embodiment of the invention, the elongated probe is permanently attached to the coupling assembly by a welded joint.
[0057] The QAD collet of the invention is housed within an externally mounted compressive clamp that is capable of exerting a compressive force on the collet after insertion of the ultrasonic probe into said collet, thereby causing a non-removable attachment of the probe to the coupling assembly. The collet therefore, applies a restraining inwardly compressive force on the probe in a manner so as to not torque or twist the probe material. As a result, the probe can be subject to a multiple attachment and detachment procedures, without causing probe destruction, thereby enabling its extended reuse in surgical procedures.
[0058] The collet of the invention comprises is at least one slit in its terminal compressible segment; alternatively it comprises of a plurality of slits. In a preferred embodiment, the collet, compressive clamp and housing assembly are all attached to the device handle by a mechanical assembly means, such as for example, a screw thread comprising a locking nut, bayonet mount, keyless chuck and cam fittings. Alternatively, the rear segment of the mechanical assembly means is a hollow cylindrical segment comprising a screw thread that allows insertion and attachment of the ultrasonic device handle containing a drive assembly containing a complementary thread arrangement to be inserted into and non-removably attached to said cylindrical segment by applying a torque. In another preferred embodiment, ultrasonic probe is mounted to the attachment means such that the collet holds the probe at a point greater than about 1 mm and less than about 30 from the probe terminal end, or is adjustable to any point in between, to optimize probe vibration based on the frequency of the ultrasound transducer in the device handle. In another preferred embodiment, the probe attachment means comprising the external compressive clamp, collet and collet housing are all attached to the operating handle of the ultrasonic device.
[0059] In another preferred embodiment the collet is retained within the confines of an outer shell that is attached to the collet housing segment of the probe attachment means that to precludes its disassembly, thereby preventing either loss or disengagement of the collet. The outer shell compresses the collet to engage contact with the probe upon its tightening to the collet housing assembly by application of torque, causing the probe to be attached to the collet in a non-removable manner. An inner bias is maintained within the rear portion of the attachment means such that a portion of the probe protruding from the proximal end of the collet maintains contact with the surface of the collet housing within the coupling assembly.
[0060] The terminal ends of the collet are tapered so as to allow the collet to maintain a true axial orientation within the coupling assembly, thereby enabling multiple insertions and retractions of the probe into and from the collet prior to and after device use, without causing the probe to kink. Additionally, the shape of the proximal end of the segment (rear segment with respect to the entering probe), so as to maximize contact area between the collet and the distal end of the transducer-sound conductor assembly (the “drive assembly”). The collet proximal end is shaped in any suitable form providing maximal contact area, including conical, frusto-conical, triangular, square, oblong, and ovoid, upon probe attachment to the collet within the housing assembly, which in turn maintains intimate contact with the drive assembly. The four component assembly that include probe, outer ring, collet and rear drive assembly, form a single assembled component in the device operational state, in terms of their combined ability to transmit sound energy from the transducer in the drive assembly to the probe without energy loss thermally or mechanically. The collets of the invention can be designed to accommodate a series of probe diameters, or for a specific probe diameter by varying the inner diameter of the cylindrical slot. The outer diameters of the collets, however remain unchanged, thereby allowing attachment of probes of differing diameters into a universal coupling and drive assembly.
[0061] The elongated probe of the invention is either a single diameter wire with a uniform cross section offering flexural stiffness along its entire length, or is tapered or stepped along its length to control the amplitude of the transverse wave along its entire longitudinal axis. Alternatively, the probe can be cross-sectionally non-cylindrical that is capable of providing both flexural stiffness and support energy conversion along its entire length. The length or the elongated probe of the invention is chosen so as to be resonant in either in an exclusively transverse mode, or be resonant in combination of transverse and longitudinal modes to provide a wider operating range. In a preferred embodiment, the elongated probe of the invention is chosen to be from about 30 cm to about 300 cm in length. In a most preferred embodiment, the elongated probe of the invention has a length of about 70 cm to about 210 cm in length. Suitable probe materials include metallic materials and metallic alloys suited for ultrasound energy transmission. In a preferred embodiment the metallic material comprising the elongated probe is titanium.
[0062] In another preferred embodiment, the elongated probe of the invention is circumferentially enclosed in a sheath that provides a conduit for irrigation fluids, aspiration of fragmented tissue, or for delivery of therapeutic drugs to the occlusion site. The said sheath can extend either partially or over the entirety of the probe, and can additionally comprise of fenestrations for directing ultrasonic energy from the probe at specific locations within venal cavities for selective ablation of tissue. An ultrasonic tissue ablation device comprising a sheath for removal of occlusions in blood vessels has been disclosed in applicants' co-pending application Ser. No. 09/776,015, the entireity of which is incorporated herein as reference.
[0063] In one embodiment, the elongated catheter probe is comprised of a proximal end and a distal end with respect to the horn assembly, and is in the form of a long small diameter wire incorporating a series of telescoping segments along its longitudinal axis, such that the largest diameter segment is proximal to the horn assembly, and either continually or segmental, sequentially decreasing diameters from the proximal to the distal end. With reference to the probe, coupling and horn assemblies as shown in the figures describing the present invention, the proximal end for each component refers to the end farthest from the probe tip, while distal end refers to the end closest to the probe tip. In another embodiment, the elongated probe is comprised of a non-segmented, uniformly narrow diameter wire, such as for example a guide wire, such as those used in insertion of catheters.
[0064] Referring now to FIG. 1, a preferred embodiment of the elongated ultrasonic probe 10 of the invention comprising a proximal end 12 and a distal end 22 , is shown. Probe 10 is coupled to a transducer and sound conductor assembly (not shown) constructed in accordance with the present invention that function as generation and transmission sources respectively, of ultrasound energy for activation of said probe. The generation source may or may not be a physical part of the device itself. The probe 10 transmits ultrasonic energy received from the sound conductor along its length, and is capable of engaging the sound conductor component at its proximal end 12 via a coupling assembly with sufficient restraint to form an acoustical mass that can propagate the ultrasonic energy provided by the source. The probe diameter decreases at defined segment intervals 14 , 18 , and 20 . Segment 22 because of its small diameter, is capable of flexing more than segments 14 and 18 , thereby enabling probe 10 to generate more cavitation energy along segment 20 distal end 22 . Energy from the generator is transmitted along the length of the probe, causing the probe to vibrate in a direction that is transverse to its longitudinal axis. Probe interval 14 has a head segment 24 for engaging the coupling assembly for attachment to the sound conductor-transducer assembly. In a preferred embodiment, the sound conductor component of the invention for providing, amplifying and transferring ultrasonic energy to elongated probe 10 is a Mason (Langevin) horn that is detachably connected to said probe through a coupling assembly.
[0065] Referring now to FIGS. 2 A-B, the unassembled and assembled views of individual components comprising the varied diameter probe and sound conductor elements, and the coupling assembly are illustrated. FIG. 2A shows the individual components comprising elongated probe 10 , horn assembly 34 comprising a proximal end 38 and a comprising a cylindrical slot 36 at the distal end, which includes the horn and coupling assembly components, elongated probe 10 and locking nut 30 . The coupling assembly components comprising threading arrangements 40 and 42 , cylindrical slot 36 , and locking nut 30 . Attachment of proximal end 12 of probe 10 is accomplished by insertion of probe head 24 into the cylindrical slot at distal end 36 of the horn assembly, followed by “threading” the probe through locking nut 30 to enable threads on the inner surface of locking nut 30 (not shown) to engage complementary threads 40 , thereby providing intimate contact between probe distal end 12 and the proximal end 36 of the horn assembly. The probe attachment is rendered to be mechanically rigid by tightening locking nut 30 . FIG. 2B shows the enlongated varied diameter probe attached to the horn assembly and held rigidly by the coupling assembly and maintaining intimate contact between the “coupled” components. FIG. 2C shows a similar assembly comprising a uniform narrow diameter wire probe of the invention.
[0066] [0066]FIG. 3 shows a cross-sectional view of the probe-horn assembly shown in a “coupled” mode. The attachment means comprising the coupling assembly of the invention utilized to “couple” the elongated probe to the horn assembly is chosen from conventional means of connecting physically separated components in a manner so as to provide a rigid joining of said components while maintaining intimate material surface contact between the components in the “coupled” state. Suitable attachment means of the present invention include a locking nut comprising a screw thread, and a bayonet or ring clamp mechanism to effect coupling between the elongated probe and the horn assembly. FIGS. 4A and 4B show opposite-end views of a preferred embodiment of the locking means, comprising a locking nut 30 consisting a screw thread arrangement 44 that is capable of engaging a complementary thread arrangement located along the outer diameter of the distal end of the horn assembly. When engaged with the horn assembly 34 with the elongated probe 10 positioned proximally to provide “coupling”, locking nut 30 provides a rigid interface between the probe and horn components and ensures intimate contact between the terminal end surfaces of the said components, which is important for efficient transmission of ultrasound energy to the probe. FIG. 5 shows a cross-sectional view of the horn assembly 34 and elongated probe 10 “coupled” by the locking nut 30 of the invention by engaging screw thread 44 with complementary threads 40 in the horn assembly.
[0067] Now referring to FIG. 6, the horn assembly 34 comprises of a distal end 38 that is capable of being coupled to the enlongated probe of the invention, and a proximal end 38 that is coupled to a transducer (not shown) functioning as an ultrasound energy source by screw threads 40 and 42 located terminally at either end. As mentioned previously, horn assembly 34 comprising the sound conductor or “horn” functions as an energy reservoir that allows only a small fraction of the energy transmitted by the source to the probe, thereby minimizing energy loss due to probe bending or damping that can occur when it is inserted into blood vessels.
[0068] [0068]FIG. 7 shows disassembled and assembled views of another preferred embodiment of the probe attachment means of the invention, including cross-sectional views in the assembled state, that includes a coupling assembly comprising a “quick attachment/detachment” (QAD) collet rod 48 and housing assembly 54 that enables efficient coupling of the elongated catheter probe to the horn assembly (not shown). As seen in the figure, collet rod 48 is configured to slideably receive and retain the proximal end of the ultrasonic probe of the invention within the interior volume of collet housing 64 , and restrained in a rigid, non-removable manner by socket screw 58 , which comprises a cylindrical head 60 with a uniformly flat end to facilitate its intimate contact with other device components, including the terminal end of the horn assembly. FIG. 7 also shows regular and expanded cross-sectional views of QAD collet rod 48 inserted into collet housing 64 that is non-removably retained within said housing by socket screw 58 . As seen in segment “C” of the cross-sectional view, the inner surface of collet housing tapers circumferentially outwardly at the distal end so as to enable partial insertion of the cylindrically slotted head of the QAD collet rod. The inner diameter of the of the circumferentially tapered section of the housing is chosen to be slightly larger then the insertable segment QAD collet rod head so as to create a “clearance” that facilitates easy 20 insertion and retraction of the said collet rod (shown in the detail cross-sectional view in FIG. 7).
[0069] As shown in FIG. 8A, QAD collet rod 48 is comprised of a hollow cylindrical segment 49 with a proximal end 50 and a head segment 51 at distal end 52 (the end farthest from the collet housing and horn assembly) with a diameter larger than that of cylindrical segment. The head segment at distal end 52 comprises a compressible slit 54 that is capable of accommodating the proximal end of the elongated probe. The proximal end 50 of the QAD collet rod comprises a hollow cylindrical opening containing a screw thread inscribed along the inner surface of said opening that is capable of receiving a retaining a socket screw 58 (shown in FIG. 7) inserted from the proximal end of the QAD collet housing, so as to render collet rod 48 with attached probe to be rigidly and non-removably restrained within said collet housing. As shown in FIG. 8B, collet housing 64 comprises a hollow cylinder with a distal end 68 capable receiving the entire cylindrical segment 49 of the probe QAD collet rod (FIG. 8A) and part of the cylindrically slotted head segment 51 when the collet rod is inserted at its proximal end 50 into collet housing 64 , and a distal end 72 comprising a screw-thread 74 along the outer surface. The proximal end 72 of collet housing further comprises a screw thread 74 on its outer surface capable of engaging the terminal end of a horn assembly in a manner so as to provide intimate contact between the horn and the flat head of socket screw 58 restraining QAD collet rod 48 attached to the elongated probe, thereby enabling transmission of ultrasound energy from the horn to the elongated probe.
[0070] The socket screw 58 of the invention is capable of being “tightened” by applying a torque by conventional methods causing it to simultaneously engage the thread assemblies if of collet rod housing 64 and the QAD collet rod 48 respectively, after insertion of the collet rod into said housing. Such a tightening action which is performed after attachment of the elongated probe to collet rod 48 by insertion of the probe into slotted head 54 at the distal end 52 of the collet rod causes retraction of the said slotted head into the collet housing. This in turn, results in elimination of the “clearance” between the collet rod and the collet housing, causing a contraction in the diameter of the slot in the head of collet rod and in turn, resulting in 1) its intimate contact with the surface of the proximal end of the inserted elongated probe, and 2) restraining the probe in a non-detachable manner to the collet rod—housing coupling assembly. The rigid and non-removable mode of probe attachment to the said coupling assembly enables transmission of ultrasound energy from a horn assembly attached to the collet rod housing coupling assembly to the elongated probe so as to cause it to vibrate in a transverse mode, and hence provide cavitation energy for tissue destruction. Conversely, the probe is detached (or “de-coupled”) from the collet rod-housing coupling assembly by loosening the socket screw 58 by application of a torque in a direction opposite to that used for the probe attachment process.
[0071] [0071]FIG. 9 shows disassembled and assembled views of another preferred embodiment of the probe attachment means of the invention, including cross-sectional views in the assembled state, consisting a QAD collet rod -housing assembly that comprises a outwardly cylindrically tapered collet housing component 80 with a proximal end 86 and a distal end 90 , further comprising a centrally located cylindrical bore with open ends extending through its longitudinal axis that is capable of slideably receiving and retaining a collet rod. As seen in segment “C” of the cross-sectional view in FIG. 9, the inner surface of collet housing tapers circumferentially outwardly at the distal end so as to enable partial insertion of the cylindrically slotted head of the QAD collet rod. The inner diameter of the of the circumferentially tapered section of the housing is chosen to be slightly larger then the insertable segment QAD collet rod head so as to create a “clearance” that facilitates easy insertion and retraction of the said collet rod (shown in the detail cross-sectional view). The cross-sectional view of the FIG. 9 shows the QAD collet rod restrained within the collet rod housing by a locking nut 88 . FIGS. 10A and 10B show the collet rod and collet housing respectively, of the embodiment. As seen in FIG. 10A, QAD collet rod comprises a solid cylindrical body 94 with a head segment 98 attached at proximal end 92 . A longitudinal slit 99 extends from head segment 98 partially into the cylindrical body 94 . The distal end 96 of cylindrical body 94 comprises a thread assembly 100 . As seen in FIG. 10B, collet housing 80 comprises a cylindrical rod with a continuously decreasing external diameter from proximal end 86 to distal end 90 , further comprising a centrally located cylindrical inner bore extending along its entire length providing openings at both ends. The diameter of the bore increases proximally to the distal end so as to circumferentially taper outwardly in a manner permitting partial insertion of head segment 98 of the collet rod The cylindrical bore of the collet housing 80 is capable of slideably receiving a collet rod 94 such that thread assembly 100 of the said collet rod extends beyond proximal end 86 of the end proximal end 92 to permit a rigid and non-removable attachment of the collet rod by engaging thread assembly 100 with locking nut 88 (shown in FIG. 9). The locking nut performs a similar function and in a manner that is substantially similar to that of the restraining screw described in a previous embodiment (FIG. 7) in enabling the elongated probe to be non-removably attached to and detached from the QCD collet rod for operation of the device as described previously. Upon rigid non-removable attachment of the elongated probe to the coupling assembly, the threading 88 of the collet housing is engaged to complementary threading of the horn assembly (not shown) of the assembly so as to render intimate contact of the sound conductor (horn) in said horn assembly with the proximal end 92 of the collet rod to enable transmission of ultrasound energy from the horn to the elongated probe attached at proximal end 96 of the collet rod.
[0072] [0072]FIG. 11 shows another preferred embodiment of probe coupling assembly of the invention, including a cross-sectional view, comprising a QAD collet 105 that is insertable into a “compression” collet housing component 115 comprising a circular bore 114 that is detachably connected to a QAD base component 120 . As seen in FIG. 12A, QAD collet 105 comprises a cylindrical segment 106 with a cylindrical slot 108 extending through its longitudinal axis that is capable of slideably receiving the proximal end of the elongated probe, and symmetrically tapered at proximal and distal ends 110 . As seen in FIG. 12B, QAD base component 120 comprises a conical slot 130 at the cylindrical distal end capable of accommodating the one of the symmetrically tapered ends 110 of the collet. QAD base component 120 further comprises a thread assembly 132 located along its outer circumference proximal to its distal end, that is capable of engaging complementary threads in the QAD compression housing component 115 . The proximal end 136 of the base component contains a thread assembly 134 along the outer circumference that is capable of engaging and attaching to the horn assembly (not shown) of the invention. As seen in FIG. 12C, QAD compression housing component 115 comprises a hollow cylindrical segment with a proximal end 117 and a circular bore 114 (shown in FIG. 11) tapered distal end 119 capable of slideably receiving the proximal end of the elongated probe. The inner diameter at the proximal end of the QCD compression housing component 115 is chosen so as to accommodate the symmetrically tapered terminal end 110 of collet 105 that is distal to the base component, and further comprises a thread assembly 118 that enables compression housing component to engage with complementary threading 132 on the distal end of QAD base component 120 . The proximal end of the elongated probe of the invention is inserted through the circular bore 114 at proximal end of compression housing component 115 and the inserted symmetrically tapered end 110 of collet 105 in a manner so as to occupy the entire length of cylindrical slot 108 in collet 105 . The other symmetric end 110 distal to the compression housing 115 is then placed inside conical pocket 130 of base component 120 , following which threads 118 of the compression housing is engaged with the complementary threads 132 in QAD base component 120 by applying a torque so as to render the collet 105 to be non-removably retained inside the coupled base-compression housing assembly, thereby restraining the inserted elongated probe rigidly and non-removably within the coupling assembly. Additionally, the mode of restraint provided by the coupling assembly of the embodiment enables the probe to maintain intimate contact with said assembly and in turn the horn assembly (not shown) of the invention attached to the coupling assembly by engaging thread 134 in QAD base component 120 with complementary threading in the horn assembly. Ultrasound energy transmitted from the horn is therefore communicated to the probe via the coupling assembly. The elongated probe is detached by disassembling the coupling assembly, thereby allowing the probe to be withdrawn from collet 105 and compression housing component 115 .
[0073] The device of the invention upon being activated causes the ultrasound generator component to transmit ultrasonic energy to the horn component. The transmitted energy is amplified by the horn component, which in turn, due to it's intimate and proximal contact with the elongated probe, transmits the amplified energy to the said probe. Transverse vibration modes on the elongated probe that fall within the horn resonance are therefore, excited. The “coupling” between the elongated probe and the horn is configured so to as to present a relatively large impedance mismatch. The coupling is located at an anti-node of the horn. Longitudinal waves impinging on the coupling will be either reflected back inside the horn, or transmitted outward to the elongated probe proportionally to the degree of the impedance mismatch at the coupling interface. In a preferred embodiment, the coupling is arranged in a manner so as to cause reflection of a substantial portion of ultrasound energy back into the horn. Under these conditions, the horn essentially functions as an energy storage device or reservoir, thereby allowing for a substantial increase in drive amplitude.
[0074] The ultrasonic device of the present invention provides several advantages for tissue ablation within narrow arteries over convention devices. The transverse energy is transmitted extremely efficiently, and therefore the required force to cause cavitation is low. The transverse probe vibration provides sufficient cavitation energy at a substantially low power (˜1 watt). Because transverse cavitation occurs over a significantly greater i.e. along the entire probe longitudinal axis that comes in contact with the tissue, the rates of endovascular materials that can be removed are both significantly greater and faster than conventional devices. The transverse vibrational mode of the elongated probe of the invention and its attachable/detachable coupling mode to the horn assembly allows for the bending of the probe without causing probe heating as heat in the probe.
[0075] Another advantage offered by the device of the invention is that the mechanism for probe attachment and detachment by means of a lateral wall compression and decompression provided by the coupling assembly. The probe can therefore, be rapidly attached to and detached from the coupling assembly without necessitating its “screwing” or “torquing” that are utilized conventional modes of attachment of ultrasonic probes to the probe handle. This feature facilitates ease of manipulation of the probe within narrow and torturous venal cavities, and its positioning at the occlusion site in a manner substantially similar to narrow lumen catheters prior to and after device use. | 1a
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present disclosure relates to the biological activity of aza-podophyllotoxin derivatives. More particularly, the use of aza-podophyllotoxin derivatives for modulation of the immune system.
[0003] 2. Discussion of the Background
[0004] The innate immune response is the first line of defense against infections. The cells of the innate immune system have the capacity to recognize generic structural patterns present in pathogens called Pathogen Associated Molecular Patterns (PAMPs), and mounts an immediate immune response against these agents. This system works as a barrier that protects mammals against many ailments including infectious diseases, activate the complement system, recruits cells of the immune system to induce the process of inflammation, identifies and remove pathogens, and one of the most important features of this system, which is to activate the adaptive immune response. The term “ailment” as used in this disclosure refers to any disease, physical disorder, or complaint, generally of a chronic, acute, or mild nature. “Mosby's Medical Dictionary”, 8th edition. (2009), Elsevier.
[0005] Defined broadly, immunomodulation encompasses all therapeutic interventions aimed at modifying the immune response. Runge, Marschall S., Patterson, Cam (Eds.) “Principles of Molecular Medicine”, Humana Press, 2nd Ed. (2006), p. 893. More particularly, immunomodulation can include adjustment of the immune response to a desired level, as in immunopotentiation, immunosuppression, or induction of immunologic tolerance. “Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health”, 7th Ed. (2003) by Saunders, an imprint of Elsevier, Inc.
[0006] Immunomodulation can be used as a therapeutic treatment against desease. Particularly, it can be used for the treatment of autoimmune disease. Greenwood, Steinman & Zamvil, “Statin therapy and autoimmune disease: from protein prenylation to immunomodulation”, Nature Reviews Immunology 6, (May 2006) p. 358-370. The art is rich with publications relating to the use of immunomodulation, including through the use of statins (Id.); probiotics (Erickson et al., “Probiotic Immunomodulation in Health and Disease”, J. Nutr. Feb. 1, (2000) vol. 130 no. 2 403S-409S), botanical polysaccharides (Schepetkin et al., “Botanical polysaccharides: Macrophage immunomodulation and therapeutic potential”, International Immunopharmacology, vol. 6, Issue 3, March 2006, Pages 317-333), fungal toxins (Bondy et al., “Immunomodulation By Fungal Toxins”, Journal of Toxicology and Environmental Health, Part B: Critical Reviews Volume 3, Issue 2, 2000), and exercise (Pederson et al., “Exercise-induced immunomodulation—possible roles of neuroendocrine and metabolic factors”, International Journal of Sports Medicine [1997, 18 Suppl 1:S2-7]).
[0007] Podophyllotoxin is a cyclolignan isolated from plants of genus Podophyllum pelatum L . and P. emodi L . It is an antimitotic agent known to bind tubulin and inhibits microtubule assembly causing cell cycle arrest in the metaphase and has been studied extensively as an antitumor agent. However, it causes severe gastrointestinal side effects, due to epimerization at C2 to cis-lactone. Derivatives of podophyllotoxin, namely etoposide and tenoposide have been developed and are currently used in clinic for the treatment of a variety of malignancies and CPH 82 is used to treat rheumatoid arthritis.
[0008] The structural complexity of podophyllotoxin has restricted most of the structural activity relationship (SAR) studied due to limitations in the derivatization of the parent natural compound. Selective transformation of—OMe groups present on ring E of the starting lignan would be a very difficult task.
[0009] Several new members of the podophyllotoxin derivatives have emerged as potentially superior chemotherapeutics, displaying improved water solubility and bioavailability, such as Nippon-Kayaku's NK-611 [2], GL-331 and Taiho's TOP-53 [3,4]. Podophyllotoxin derivatives also display anti-HIV-1 [5,6] and antibacterial [7] activities. Kumar et al., “Synthesis of novel functionalized 4-aza-2,3-didehydropodophyllotoxin derivatives with potential antitumor activity”, J. Heterocyclic Chem., 47, 1275 (2010). There have been previous reports on the synthesis of some podophyllotoxin derivatives, particularly, functionalized 4-Aza-2,3-didehydropodophyllotoxin derivatives. Id. Also previously reported is the use of N-Hydroxyethyl-4-aza-didehydropodophyllotoxin derivatives as potential antitumor agents. Kumar et al., “N-Hydroxyethyl-4-aza-didehydropodophyllotoxin derivatives as potential antitumor agents”, European Journal of Pharmaceutical Sciences 44 (2011) p. 21-26. Previous reports on the Biological Activity of N-Hydroxyethyl-4-aza-2,3-didehydropodophyllotoxin derivatives upon Colorectal Adenocarcinoma Cells have also been published. Velez et al., “Biological Activity of N-Hydroxyethyl-4-aza-2,3-didehydropodophyllotoxin Derivatives upon Colorectal Adenocarcinoma Cells”, Open Journal of Medicinal Chemistry, 2014, 4, p. 1-11. However, there are no published reports on the immunomodulatory activity of N-Hydroxyethyl-4-aza-didehydropodophyllotoxin or its derivatives.
SUMMARY OF THE INVENTION
[0010] Disclosed, for the first time, is the novel use of some Aza-podophyllotoxin derivatives (AZPs) for modulation of the immune system (immunomodulation). We conducted stimulation of mouse lymphocites and measured the release of cytokines from in vitro cultures of mouse splenocytes to determine the Immunomodulatory effects of our AZPs. Cytokines are regulatory peptides that participate in host defense and repair processes and can also participate of coordination of cellular responses. Thomson et al., “The Cytokyne Handbook” 4th Ed. (2003) Elsiever Science Ltd, p. xxv. Therefore cytokines play a key role in immune response. House et al. (Eds), “Cytokines in Human Health Methods in Pharmacology and Toxicology” (2007) pp. 1-15.
[0011] Specifically, our data shows AP102, AP103, AP104, and
[0012] AP205 (AZP compounds) to induce 2208, 2575, 2071, and 7166 pg/mL of GCSF, respectively, and the AP311, AP312, AP102, AP103, AP104, and AP205 induced 551, 810, 772, 1125, 782, and 4351 pg/mL of IL6, respectively. These data demonstrates the immuno-stimulatory ability of these AZP compounds.
[0013] The disclosure, both as to its configuration and its mode of operation will be best understood, and additional objects and advantages thereof will become apparent, by the following detailed description of several embodiments taken in conjunction with the accompanying drawings.
[0014] Further, the purpose of the accompanying abstract is to enable the U.S. Patent and Trademark Office and the public generally, and especially the scientists, engineers, and practitioners in the art who are not familiar with patent or legal terms or phraseology, to determine quickly from a cursory inspection the nature and essence of the technical disclosure of the application. The abstract is neither intended to limit the breadth of the application, which is measured by the claims, nor is it intended to be limiting as to the scope of the disclosure in any way.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] The accompanying drawings, which are incorporated herein, constitute part of the specifications and illustrate the preferred embodiments of the disclosure.
[0016] FIG. 1 Shows a graph of the concentration of IL-6 produced by the tested AZP compounds.
[0017] FIG. 2 Shows a graph of the concentration of G-CSF produced by the tested AZP compounds.
[0018] FIG. 3 Shows the profile of AP-treated mouse splenocytes. In order from left to right: naïve, AP-311, AP-312, AP-102, AP-103, AP-104, and AP-205.
[0019] FIG. 4 Shows a chart of the average concentration of the cytokines produced by the tested AZP compounds.
[0020] FIG. 5 Shows a chart of the standard error of the mean (SEM) concentration of the cytokines produced by the tested AZP compounds.
[0021] FIG. 6 shows the library of AZP compounds.
[0022] FIG. 7 shows the general structure and full name of AP102.
[0023] FIG. 8 shows the general structure and full name of AP103.
[0024] FIG. 9 shows the general structure and full name of AP104.
[0025] FIG. 10 shows the general structure and full name of AP205.
[0026] FIG. 11 shows the general structure and full name of AP311.
[0027] FIG. 12 shows the general structure and full name of AP312.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0028] Disclosed below are examples of several embodiments.
[0029] A total of 2×10 5 mouse splenocytes per well were cultured in a humidified atmosphere at 37° C. and 5% CO 2 in round-bottomed 96-well culture plates for five days with the AP compounds at 10 mM. Concanavalin A (10 mg/mL) and culture media were used as positive and negative controls, respectively. Plates were centrifuged at 1,200 RPM for five minutes, and supernatants were collected. The resulting cytokine profile produced after lymphocyte stimulation was analyzed using a fluorescently-labeled protein microarray chip as indicated by the manufacturer (RayBiotech, Norcross, Ga., USA).
[0030] The immunomodulatory effect of the AP compounds was assessed by in vitro stimulation of mouse lymphocytes for five days. Specifically, our preliminary data shows AP-102, AP-103, AP-104, and AP-205 to induce 2208, 2575, 2071, and 7166 pg/mL of G-CSF, respectively, and the AP-311, AP-312,
[0031] AP-102, AP-103, AP-104, and AP-205 induced 551, 810, 772, 1125, 782, and 4351 pg/mL of IL-6, respectively. These data demonstrate the immunostimulatory ability of our AP compounds.
EXAMPLE 1
IL-6
[0032] IL-6 is secreted by macrophages after a stimuli like PAMPs. This cytokine has an important role mediating fever and the acute phase response. The acute phase response is an early-defense system activated by the onset of infection, trauma, inflammatory processes, neoplastia, stress, and some malignant conditions. “Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health”, Seventh Edition, (2003) by Saunders, an imprint of Elsevier, Inc.; and Cray et al., “Acute Phase Response in Animals: A Review”, Comp Med. 2009 December; 59(6): pp. 517-526. It has a critical role against bacterial infections, as it is required for the resistance mechanisms against the bacteria Streptococcus pneumonia.
[0033] Our data shows that IL-6 is produced by all the compounds tested in this project. Specifically, 184, 270, 257, 375, 261, and 1445 pg/mL of IL-6 was produced by AP311, AP312, AP102, AP103, AP104, and AP205. respectively. Among the tested compounds, AP205 induced the highest release of IL-6.
EXAMPLE 2
GCSF
[0034] GCSF is a glycoprotein produced by macrophages with the role of stimulating the production of granulocytes and stem cells from the bone marrow. It also has a role in the survival, proliferation, differentiation, and function of mature neutrophils and their precursors.
[0035] The therapeutic role of this cytokine has been commercially exploited by several pharmaceutical corporations. Specifically, cancer patients are in myelosuppression conditions, therefore, they lack of sufficient levels of white cells for disease control, making them susceptible to infections and sepsis. As GCSF has the capacity to produce granulocytes, it is used for the control of neutropenia in cancer patients, enhancing their quality of life. Moreover, during the hematopoietic stem cell transplant, GCSF is administered to the transplant donor to enhance the amount of hematopoietic stem cells before collecting by leukapheresis.
[0036] In our study, we observed levels of GCSF of 736, 858, 690, and 2336 pg/mL, when stimulated with AP102, AP103, AP104, and AP205, respectively. This information is extremely important, as GCSF is currently used for the re-establishment of neutrophils and granulocytes in cancer patients under chemotherapy. Based on this information, the compounds will perform their antitumoral activity through re-establishment of neutrophil and granulocytes.
[0037] Both, IL-6 and GCSF are important for the protection against several pathogenic infections. The capacity of IL-6 to promote neutrophil survival in the lung protects against H1N1 influenza. The interrelation between IL-6 and GCSF has been well documented. IL-6 and GCSF have a crucial role protecting against candida infections. Interestingly, all of our compounds produce both IL-6 and GCSF, which support their potential use against infections.
Example 3
IL-12
[0038] IL-12 is an heterodimer coded by two genes (p35 and p40). The p70 heterodimer is the active form. IL-12 is involved in the differentiation of the naive T-cells to Th1. In this sense, this cytokine has the capacity of reducing the IFN-suppression mediated by IL-4.
[0039] During the innate immune response, the macrophages are the main responsible for the production of IL-12. It stimulates the production of IFN-gamma from T and NK cells.
[0040] One of the most important roles of IL-12 is its capacity to mediate the cytotoxic activity of both, the NK and the CD8+ T-cells. IFN-gamma has an anti-angiogenic activity, blocking the formation of new blood vessels, which supports tumor growth. As IL-12 induces the release of IFN-gamma, this cytokine has an indirect antineoplastic role.
[0041] Cultured splenocytes induced 13, 29, 21, 22, and 60 pg/mL when stimulated with AP312, AP102, AP103, AP104, and AP205.
Example 4
IL-10
[0042] L-10 is mainly produced by monocytes and Th2 cells. Also, this is an anti-inflammatory cytokine, as in produced by Treg cells. This makes IL-10 as a very important regulatory cytokine.
[0043] IL-10 is a pleiotropic cytokine with several functions. It has an important role in the downregulation of the Th1-type cytokines expression. Also, it promotes the survival and proliferation of B cells, with the concomitant production of antibodies.
[0044] The IL-10 has an important role in the regulation of the immune response in the gastrointestinal tract, with an important anti-inflammatory role. The administration of IL-10 alleviates the undesired inflammatory effects of patients in conditions like Crohn disease. Also, the fact that the mastocytes also release IL-10, suggests this cytokine to have a role in allergy control.
[0045] This cytokine inhibits the production of IFN-g, IL-2, IL-3, TNF-a, and GM-CSF produced by macrophages and Treg cells. This means that it has a strong role in the regulation of the inflammatory processes. Low levels of IL-10 have been correlated with several autoimmune diseases like Multiple Sclerosis.
[0046] Culture of splenocytes induced 14 pg/mL of IL-10 when stimulated with AP104. No other compound induced the release of IL-10.
Example 5
IL-1a
[0047] IL-1a is one of the major players in the induction of inflammation, fever, and in extreme cases, sepsis. It is mainly produced by macrophages, although neutrophils, epitelial cells, and endothelial cells also produce IL-1a. It is constitutively expressed in skin keratinocytes, presumably as part of the skin protective barrier mechanism. After stimulation, a precursor of this cytokine is produced by fibroblasts, macrophages, granulocytes, eosinophils, mastocytes, and basophils. Also, IL-1a activates TNF-alpha.
[0048] Culture of splenocytes induced 20 pg/mL of IL-1a when stimulated with AP205. No other compound induced the release of IL-1a.
Example 6
IL-1b
[0049] IL-1 beta is produced as a pro-protein by activated macrophages. In its active form, it is an important mediator of inflammation with several activities that include proliferation, differentiation, and apoptosis. It could induce undesired autoimmune effects if expressed in abnormally high amounts.
[0050] Culture of splenocytes induced 12, and 19 pg/mL of IL-10 when stimulated with AP103 and AP205, respectively.
Example 7
IL-2
[0051] IL-2 has a critical role in important events like tolerance and activation of immunity. In the thyme it plays an important role during the development of Treg cells, which has important implications in the development of tolerance. During the development of the immune response, it promotes the development of the differentiation of the naive T cells to effector cells. Moreover, IL-2 promotes the differentiation of memory cells. However, one of the most important characteristics of IL-2 is its supportive role of the cell-mediated immune response, which is important against viral diseases and other intracellular pathogens.
[0052] IL-2 is licensed as part of the treatment against certain types of cancers like myelomas, renal cell cancer, lymphomas, and leukemias. In clinical studies, it has been used in a vaccine formulation as an adjuvant against viral infections.
[0053] Culture of splenocytes induced 17 pg/mL of IL-2 when stimulated with AP102. No other compound induced the release of IL-2.
Example 8
IL-9
[0054] IL-9 is produced by Th-CD4+ T-cells. It stimulates cell proliferation, and prevents apoptosis. It has been found to inhibit melanomas in mouse models.
[0055] Culture of splenocytes induced 30 pg/mL of IL-9 when stimulated with AP205. No other compound induced the release of IL-9.
Example 9
IL-15
[0056] After viral infections, IL-15 is secreted, among other cells, from mononuclear phagocytes. It induces the proliferation of NK cells. Is produced as a mature protein from dendritic cells, monocytes, and macrophages. Its expression could be stimulated by GM-CSF and several PAMPs. Also, monocytic herpes virus, Mycobacterium tuberculosis, and Candida albicans infections stimulates its expression.
[0057] IL-15 regulates the activation and proliferation of T and NK cells. In the absence of the relevant antigen, it provides the signal for the survival and maintenance of memory T-cells. IL-15 and IL-2 share some receptor subunits. The balanced combination between those two cytokines is crucial for the preservation of a memory CD8+ T-cell population.
[0058] Culture of splenocytes induced 56 and 94 pg/mL of IL-15 when stimulated with AP311 and AP205, respectively.
Example 10
IL-17:
[0059] IL-17 is an important mediator of the delayed-type reactions, as it increases the production of chemokines in various tissues with the intend of recruit monocytes and neutrophils to the inflammation site. This cytokine is produced by Th cells, and induced by IL-23, which result in destructive tissue damage during delayed-type reactions.
[0060] The IL-17 functions as a proinflammatory cytokine that responds to the invasion of extracellular pathogens, inducing the destruction of their extracellular matrix. It acts synergistically with TNF-alpha and IL-1.
[0061] IL-17 has various regulatory functions, in which its proinflammatory activity is the most notable. This regulatory functions are associated to the response of this cytokine to allergies. It induces the production of IL-6, GCSF, GMCSF, IL1b, TNF-a, various chemokines like IL-8, GRO-alpha, y MCP-1, and prostaglandins like PGE2 from various cell types like fibroblasts, endothelial cells, epithelial cells, keratinocytes, and macrophages. The release of these cytokines cause various effects like remodeling of the airways, which is characteristic for IL-17. The function of the IL017 is essential for the function of the Th17 cells.
[0062] Culture of splenocytes induced 294 pg/mL of IL-17 when stimulated with AP102. No other compound induced the release of IL-17.
Example 11
IL-23
[0063] Similar to IL-12, IL-23 it has a proinflammatory role. Culture of splenocytes induced 27, 58, and 80 pg/mL of IL-23 when stimulated with AP311, AP104, and AP205, respectively.
Example 12
IFN-gamma
[0064] IFn-gamma is mainly produced by NK and CD8+ T-cells. It plays a critical role in the differentiation lymphocytes from naive to effector T-cells, which also produce IFN-gamma. It has a critical role in both, the innate and the adaptive immune responses against an ample spectrum of infectious agents. Besides activate macrophages, it induces the expression of MHC II. It has antiviral, immunoregulatory, and anti-tumoral properties. Among its capacities are: promote the activation of the NK cells, enhances antigen-presentation by macrophages, activates iNOs, induce the production of IgG2a and IgG3 from plasma cells, promotes the differentiation of the Th1 cells, directing the response towards a cytotoxic immune response, increases the expression of MHC I in normal cells, and MHC II in APCs, promotes the adhesion of lymphocytes that migrated to the inflammation site, induces the expression of the intrinsic defense mechanisms. Also, it has a relevant role in the induction of granulomas.
[0065] IFN-gamma is licensed for the treatment of granulomatous chronic diseases and also against osteoporosis.
[0066] AP205 was the compound with the highest capacity to induce both, the highest amount and type of cytokines. It induced the release of 2336.49, 20.29, 19.45, 1444.71, 30.45, 60.14, 94.04, and 79.96 pg/mL of GCSF, IL-1a, IL-1b, IL-6, IL-9, IL-12p70, IL-15, and IL-23, respectively. From all of these cytokines, the release of GCSF is important, as in cancer patients it is used in the re-establishment of neutrophils.
[0067] AP104 was the second compound with the highest capacity of inducing cytokine release. Specifically, this compound induced the release of 690.39, 260.85, 13.78, 21.99, 58.48, and 104.58 pg/mL og GCSF, IL-6, IL-10, IL-2p70, IL-23, and IFN-gamma, respectively. No other compound induced the release of IFN-g.
[0068] AP-311 induced 183.76 and 26.66 pg/mL of IL-6 and IL-23, respectively.
[0069] AP-312 induced 11.89, 269.89, and 27.89 pg/mL of IL-1b, IL-6, and IL-12p70, respectively.
[0070] AP-102 induced 735.83, 17.36, 257.35, and 29.09 pg/mL of GCSF, IL-2, IL-6, and IL-12p70, respectively.
[0071] AP-103 induced the release of 858.15, 3.95, 535.06, and 35.70 pg/mL of GCSF, IL-1b, IL-6, and IL-12p70, respectively.
[0072] Our data shows that AP-102 expresses the cytokine milieu with the highest TH17 cytokine biased, followed by a close TH2 biased and a smaller TH1 cytokine milieu. AP-311 and AP-312, induces a strong TH2 cytokine milieu, followed by a TH17, and a smaller TH1 cytokine profile. AP-103, AP-104, and AP-205 showed high TH2-type cytokines, but equally comparably low TH1 and TH2.
[0073] It should be apparent from consideration of the above illustrative examples that numerous exceptionally valuable products and processes are provided by the present disclosure in its many aspects. Viewed in light, therefore, the specific disclosures of illustrative examples are clearly not intended to be limiting upon the scope. Numerous modifications and variations are expected to occur to those skilled in the art. | 1a
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FIELD
[0001] The present invention relates to a portable spirometer. The portable spirometer may have a portable structure, and may correspond to a breath flow measuring device capable of measuring and analyzing lung capacity.
BACKGROUND
[0002] Measuring of lung capacity in a breath test and measuring of a heartbeat of a patient may provide useful information for diagnosing whether a patient has a breathing disorder and a cardiac disorder, for example, myocardial infarction, atrial fibrillation, and the like.
[0003] A scheme of measuring lung capacity may be classified into a type corresponding to a scheme of directly measuring a variation of a lung volume while a patient is breathing and a type corresponding to a breath flow measuring scheme of detecting and measuring a flow flowing in and out of a lung while a patient is breathing.
[0004] Conventionally, the scheme of directly measuring a variation of a lung volume has been primarily used in measuring lung capacity. However, the breath flow measuring scheme is being used more frequently.
[0005] A conventional breath flow measuring device such as a clinical spirometer may be manufactured for clinical use and thus, may be high-priced and big in size, which may prevent people with chronic respiratory problems from easily measuring a breath flow by carrying the device. Through miniaturization of an electronic spirometer to achieve portability, it may be difficult to miniaturize a sensor device for measuring a breath flow that converts a directly immeasurable living body variable into a measurable physical variable.
[0006] A conventional pneumotachograph may be difficult to be miniaturized since a fluid resistance may be inserted into a breath path (a breath tube), and a structure of the fluid resistance including a mesh screen, a capillary tube, and the like may be inappropriate to miniaturization. A tubinometer may be difficult to be miniaturized since a rotating turbine may be included on a breath path (a breath tube).
DETAILED DESCRIPTION
Technical Goals
[0007] An aspect of the present invention provides a portable spirometer that may be easily carried and is capable of easily measuring a breath flow.
[0008] Another aspect of the present invention provides a portable spirometer that may be used for a medical treatment and a telemedicine.
[0009] Still another aspect of the present invention provides a portable spirometer that may expend a relatively low amount of power and effectively perform wired and wireless communication.
[0010] Technical Solutions
[0011] According to an aspect of the present invention, there is provided a portable spirometer, including a small breathing tube for measuring a unidirectional flow, to which a breath flow of a patient is inputted, a breath signal processing unit to generate a breath signal from the breath flow, remove noise contained in the breath signal, and amplify a signal level so as to generate a target signal for analysis, a breath signal analysis unit to analyze the target signal for analysis to calculate a diagnosis parameter, and a display unit to display an analysis result of the breath signal.
[0012] The small breathing tube for measuring a unidirectional flow may include a circular tube including an entrance, formed by disposable paper or plastic, to be brought into contact with the mouth of the patient, and an outlet opposing the entrance, and a sensing path formed to be adjacent to the outlet of the circular tube and to pass through the circular tube from an upper portion to be extended to a lower portion outside of the circular tube, and formed to have a tubular shape in which the upper portion is closed and the lower portion is open.
[0013] The sensing path may have multiple sampling holes for measuring a flow separated by a predetermined interval along a lengthwise direction at an entrance side of the circular tube, on a breathing route of the circular tube.
[0014] The portable spirometer may further include a power controller to block a power supply to the breath signal processing unit and the breath signal analysis unit in response to the small breathing tube for measuring a unidirectional flow being removed.
[0015] The portable spirometer may further include a wireless communication unit to wired-exchange data with an external device, a wired communication unit to wiredly exchange data with the external device, and a communication mode selector to inactivate one of the wireless communication unit and the wired communication unit in response to the same device being connected to the wireless communication unit and the wired communication unit.
[0016] The portable spirometer may further include a connection controller to inactivate the breath signal analysis unit, and control so that the target signal for analysis does not pass through the breath signal analysis unit and is transmitted to the external device through the wireless communication unit or the wired communication unit in response to the wireless communication unit or the wired communication unit being connected to the external device.
[0017] The portable spirometer may further include a storage unit to store the analysis result of the breath signal, wherein the display unit displays data corresponding to a highest lung capacity measurement value in data stored in the storage unit in response to power being turned ON.
[0018] The diagnosis parameter may include at least one of a peak expiratory flow rate (PEF), a first second forced expiratory volume (FEV 1.0), a forced vital capacity (FVC), and FEV 1.0/FVC.
Effect of the Invention
[0019] According to embodiments of the present invention, it is possible to provide a portable spirometer that may be easily carried and is capable of easily measuring a breath flow.
[0020] According to embodiments of the present invention, it is possible to provide a portable spirometer that may be used for a medical treatment and a telemedicine.
[0021] According to embodiments of the present invention, it is possible to provide a portable spirometer that may expend a relatively low amount of power and effectively perform wired and wireless communication.
BRIEF DESCRIPTION OF DRAWINGS
[0022] FIG. 1 illustrates a configuration of a portable spirometer according to an embodiment of the present invention.
[0023] FIG. 2 illustrates a configuration of a portable spirometer according to another embodiment of the present invention.
[0024] FIG. 3 illustrates a cross-sectional view of a small breath tube, for measuring a unidirectional flow, of FIG. 1 or FIG. 2 .
EMBODIMENTS OF THE INVENTION
[0025] Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to the like elements throughout. The embodiments are described below in order to explain the present invention by referring to the figures.
[0026] FIG. 1 illustrates a configuration of a portable spirometer according to an embodiment of the present invention.
[0027] Referring to FIG. 1 , a portable spirometer 100 may include a small breathing tube for measuring a unidirectional flow 110 , a breath signal processing unit 120 , a breath signal analysis unit 130 , and a display unit 140 . The portable spirometer 100 may further include a storage unit 150 .
[0028] The small breathing tube for measuring a unidirectional flow 110 may receive an input of a breath flow of a patient. The small breathing tube for measuring a unidirectional flow 110 may be detachable, and may be formed by disposable paper or plastic. The small breathing tube for measuring a unidirectional flow 110 may further include a breath detection sensor (not shown). In this instance, the breath detection sensor may detect a temperature or a pressure of the breath flow, and generate a breath flow signal.
[0029] The breath signal processing unit 120 may generate a breath signal from the breath flow or the breath flow signal, remove noise contained in the breath signal, and amplify a signal level so as to generate a target signal for analysis. The breath signal processing unit 120 may include a filter unit 121 and a signal level amplifier 123 . The filter unit 121 may remove noise contained in the breath signal, and the signal level amplifier 123 may amplify a signal level of the breath signal from which noise is removed. The breath signal, from which noise is removed, having an amplified signal level may correspond to the target signal for analysis.
[0030] According to an embodiment, the breath signal processing unit 120 may further include a differential pressure sensor (not shown) to generate an electric signal by detecting a dynamic pressure.
[0031] The breath signal analysis unit 130 may analyze the target signal for analysis to calculate a diagnostic parameter. The breath signal analysis unit 130 may include a target signal for analysis receiver 131 and a calculator 133 . The target signal for analysis receiver 131 may receive the target signal for analysis. The calculator 133 may calculate a volume, a velocity, and the like of the breath flow. In this instance, the diagnosis parameter may include at least one of a peak expiratory flow rate (PEF), a first second forced expiratory volume (FEV 1.0), a forced vital capacity (FVC), and FEV 1.0/FVC. A general calculation scheme may be used as a calculation scheme for a volume, a velocity, and the like of the breath flow.
[0032] The display unit 140 may display an analysis result of the breath signal. The display unit 140 may display a result of analysis of the breath signal, or display high/moderate/low of the volume of the breath flow.
[0033] The storage unit 150 may store the result of analysis of the breath signal. According to an embodiment, the storage unit 150 may include a mobile storage medium.
[0034] The portable spirometer 100 may display, on the display unit 140 , data corresponding to a highest lung capacity measurement value in data stored in the storage unit 140 in response to power being turned ON. When measuring of a lung capacity is performed a several times after power is turned ON, the portable spirometer 100 may display a highest value, and may operate in a standby state after a predetermined period of time. According to an embodiment, the portable spirometer 100 may include a processor to control various operations of the portable spirometer 100 .
[0035] FIG. 2 illustrates a configuration of a portable spirometer according to another embodiment of the present invention.
[0036] A portable spirometer 200 illustrated in FIG. 2 may be suitable as a portable type, and may include components for realizing a telemedicine and expending a low amount of power. Reference numbers of FIG. 2 illustrate components performing the same function and operation as reference numbers of FIG. 1 . Thus, further descriptions of components having the same reference number as those of FIG. 1 will be omitted for conciseness and ease of description.
[0037] The portable spirometer 200 may include all components of the portable spirometer 100 , and include a small breathing tube for measuring unidirectional flow 110 , a body portion 201 , a user interface unit 203 , a display unit 140 , and an audio output unit 205 .
[0038] The body portion 201 may include a breath signal processing unit 120 , a breath signal analysis unit 130 , a power controller 260 , a communication unit 270 , and a connection controller 280 .
[0039] In response to the small breathing tube for measuring unidirectional flow 110 being detached, the power controller 260 may block a power supply to the breath signal processing unit 120 and the breath signal analysis unit 130 . In response to the small breathing tube for measuring unidirectional flow 110 being detached, the portable spirometer 200 may perform an operation other than a lung capacity measurement. Thus, to reduce power from being wastefully expended, the power controller 260 may block a power supply to the breath signal processing unit 120 and the breath signal analysis unit 130 in response to the small breathing tube for measuring unidirectional flow 110 being detached. The power controller 260 may include a mechanical switch, a transistor, a soft switch, and the like.
[0040] The communication unit 270 may exchange data with an external device. That is, the communication unit 270 may transmit data stored in a storage unit 140 to a personal computer (PC), and the like, or transmit a target signal for analysis to an external device. The communication unit 270 may include a wireless communication unit 271 , a wired communication unit 273 , and a communication mode selector 275 .
[0041] The wireless communication unit 271 may wirelessly exchange data with an external device. The wireless communication unit 271 may perform wireless communication with a mobile phone, a laptop computer, a PC, and the like using a wireless interface of short distance communication such as Bluetooth communication, infrared-ray communication, a wireless local area network (LAN), and the like.
[0042] The wired communication unit 273 may wirelessly exchange data with the external device. To achieve this communication, the wired communication unit 273 may include a connector, a cable connecting terminal, a universal serial bus (USB), and the like.
[0043] The communication mode selector 275 may inactivate one of the wireless communication unit 271 and the wired communication unit 273 in response to the same device being connected to the wireless communication unit 271 and the wired communication unit 273 . To achieve this communication, the communication mode selector 275 may include a unit to detect whether the same device is connected to the wireless communication unit 271 and the wired communication unit 273 , and a unit to connect the portable spirometer 200 and the external device via one of the wireless communication unit 271 and the wired communication unit 273 according to a predetermined scheme in response to the same device being detected to be connected to the wireless communication unit 271 and the wired communication unit 273 . In this instance, the predetermined scheme may be determined based on a selection of a user or a communication state. The communication mode selector 275 may determine whether the same device is connected to the wireless communication unit 271 and the wired communication unit 273 using identification (ID) information received from the external device. In response to determining a residual quantity of a battery (not shown) included in the portable spirometer 200 to be inadequate, the communication mode selector 275 may control the communication unit 270 to perform wired communication thus expending less power when compared to wireless communication.
[0044] The connection controller 280 may inactivate the breath signal analysis unit, and control so that the target signal for analysis does not pass through the breath signal analysis unit and is transmitted to the external device through the wireless communication unit or the wired communication unit in response to the wireless communication unit or the wired communication unit being connected to the external device. That is, in response to a communication state being set between the portable spirometer 200 and the PC, the connection controller 280 may perform a function for analyzing a breath signal through software installed in the PC, thereby reducing an amount of power expended and performing a relatively accurate measurement.
[0045] The user interface 203 may include a button or a keypad to be operated by a user.
[0046] The audio output unit 205 may inform a patient that a measurement is completed by outputting a mechanical sound in response to a breath flow being input at an amount greater than or equal to a predetermined amount.
[0047] FIG. 3 illustrates a cross-sectional view of a small breath tube for measuring a unidirectional flow of FIG. 1 or FIG. 2 .
[0048] Referring to FIG. 3 , a small breathing tube for measuring a unidirectional flow 110 may be formed by disposable paper or plastic, and may include a circular tube 310 that includes an entrance 312 to be brought into contact with the mouth of a patient, and an outlet 313 opposing the entrance 312 , and a sensing path 330 formed to be adjacent to an outlet of the circular tube 310 , and formed to have a relatively thin stick type circular tube having an internal diameter of about 1 millimeter (mm).
[0049] The sensing path 330 may be formed to be adjacent to the outlet side of the circular tube 310 , within a tolerance of about 5 mm, and be formed to have a relatively thin stick type circular tube having an internal diameter of about 1 mm that passes through the circular tube 310 from an upper portion of the circular tube 310 to be extended to a lower portion outside of the circular tube 310 . The upper portion of the sensing path 330 may be closed, and the lower portion of the sensing path 330 may be open. Multiple sampling holes 331 for measuring a flow separated by a predetermined interval along a lengthwise direction may be formed at one side of the sensing path 330 formed inside of the circular tube 310 , that is, at an entrance side of the circular tube 310 .
[0050] The circular tube 310 may have a length of about 35 mm and a diameter of about 15 mm, and a fluid resistance may be nearly absent in an inside of the circular tube 310 corresponding to a breathing route of the small breathing tube for measuring a unidirectional flow 110 since only the sensing path 330 corresponding to the relatively thin stick type circular tube having an internal diameter of about 1 mm may be present. A total of three sampling holes 331 formed at one side of the sensing path 330 (that is, the entrance side of the circular tube 310 ) may be located on a central axis of a flow and at positions apart from the central axis by ±2.5 mm.
[0051] A length of the circular tube 310 included in the small breathing tube for measuring a unidirectional flow 110 may be set to 35 mm, which may correspond to a minimum length, so that a patient may breathe easily with the circular tube 310 in a mouth, and the sensing path 330 for measuring a velocity of the flow may be inserted into the circular tube 310 . In response to the length of the circular tube 310 being set, a diameter of the circular tube 310 and a location at which the sensing path 330 is formed may be determined according to the set length. In this instance, a diameter of the small breathing tube for measuring a unidirectional flow 110 may be manufactured, so as to satisfy a standard of American Thoracic Society (ATS).
[0052] ATS advises that a maximum value of a fluid resistance of a clinical spirometer be about 1.5 cmH2O/Λ/sec, a maximum value of a fluid resistance of a spirometer for self-diagnosis be about 2.5 cmH2O/Λ/sec, and a maximum breath flow value (F) to be measured be about 14 Λ/sec.
[0053] The exemplary embodiments according to the present invention may be recorded in computer-readable media including program instructions to implement various operations embodied by a computer. The media may also include, alone or in combination with the program instructions, data files, data structures, and the like. The media and program instructions may be those specially designed and constructed for the purposes of the present invention, or they may be of the well-known variety and available to those having skill in the computer software arts. Examples of computer-readable media include magnetic media such as hard disks, floppy disks, and magnetic tape; optical media such as CD ROM discs and DVD; magneto-optical media such as optical discs; and hardware devices that are specially configured to store and perform program instructions, such as read-only memory (ROM), random access memory (RAM), flash memory, and the like. Examples of program instructions include both machine code, such as produced by a compiler, and files containing higher level code that may be executed by the computer using an interpreter. The described hardware devices may be configured to act as one or more software modules in order to perform the operations of the above-described embodiments of the present invention.
[0054] Although a few embodiments of the present invention have been shown and described, the present invention is not limited to the described embodiments. Instead, it would be appreciated by those skilled in the art that changes may be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.
[0055] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed. | 1a
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CROSS REFERENCE TO RELATED APPLICATIONS
This is a continuation-in-part of my copending application Ser. No. 502,301 filed Aug. 30, 1974, abandoned as of the filing date of this application.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates generally to space saving devices and more particularly to a novel and improved tiered spaced saver or table top consisting of a plurality of independently revolving trays, or table tops, disposed in vertically spaced apart stacked relationship.
2. Description of the Prior Art
In view of the constant clutter about the home and office individuals are constantly seeking space saving devices for maximizing available storage space. A particular problem concerns dining tables, where the number of dishes served, such as during holiday meals, may exceed the space available, particularly with more diners than normal. While it has been known in the prior art to provide many types and varieties of such space saving devices, all of such devices suffer from one or more disadvantages as to being overly expensive and complex to manufacture, require routine maintenance, are difficult to wash and maintain in a clean manner, and otherwise are nor completely satisfactory to prospective purchasers and thus have not met with widespread commercial success.
SUMMARY OF THE INVENTION
The present invention recognizes the need for space saving devices and, upon recognizing the deficiencies and disadvantages of presently available space saving devices, provides a novel solution thereto in the form of a tiered space saver or table top consisting of a plurality of various diameter trays stacked in vertical spaced apart relationship with each tray being independently rotatable to provide ease of access to the contents of any tray.
It is a feature of the present invention to provide a tiered space saver or table top of size and stability to place food dishes upon to provide more space at a dining table.
A further feature of the present invention provides a tiered space saver or table top which is relatively simple in its construction and which therefore may be readily manufactured at a relatively low cost and by simple manufacturing methods.
Still a further feature of the present invention provides a tiered space saver or table top which is possessed of few parts and which therefore is unlikely to get out of order.
Yet still a further feature of the present invention provides a tiered space saver or table top which is easy to use and reliable and efficient in operation.
Still yet a further feature of the present invention provides a tiered space saver or table top which is aesthetically pleasing and refined in appearance.
Yet still a further feature of the present invention provides a tiered space saver or table top which can be retailed at a sufficiently low price to encourage widespread use thereof.
Other features and advantages of this invention will be apparent during the course of the following description.
BRIEF DESCRIPTION OF THE DRAWINGS
In the accompanying drawings forming a part of this specification, and in which like reference characters are employed to designate like parts throughout the same:
FIG. 1 is a top perspective view of the tiered space saver or table top of the present invention;
FIG. 2 is a front elevational view of the tiered space saver or table top of FIG. 1.
FIG. 3 is a top plan view of the tiered space saver or table top of the present invention; and
FIG. 4 is an enlarged fragmentary cross-sectional view taken along line 4--4 of FIG. 3.
FIG. 5 is a perspective view of an alternate embodiment of a tiered space saver or table top mounted on a dining table.
FIG. 6 is a vertical cross-sectional view of the tiered space saver or table top of FIG. 5.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings in detail there is illustrated a preferred form of a tiered space saver or table top constructed in accordance with the principles of the present invention and which is designated generally in its entirety by the reference numeral 10 and which is comprised of a stand 11, a base 12, a plurality of trays 13, 14 and 15, and a handle 16.
The tiered space saver table top 10 may be manufactured out of metal, wood, hard rubber, plastic, or any other suitable satisfactory material providing an aesthetically pleasing and refined appearance, with the preferred embodiment being manufactured of a high density plastic material such as polyethylene, polystyrene, and the like which may be provided in a variety of colors appealing to prospective purchasers.
The stand 11 is of a hollow open topped closed bottom cylindrical configuration having a bottom 21 and depending surrounding cylindrical side walls 22 extending upwardly therefrom and defining a cylindrical recess 23 interiorly thereof.
The base 12 is of a flat circular disc shaped configuration having a top surface 31, a bottom surface 32, and an open topped cylindrical shaft 33 disposed concentric therewith and extending upwardly from the top surface thereof and terminating at an open top end 34 defining a passageway 35 interiorly thereof. The base 12 rests in recess 23 on bottom 21 concentric therewith and is rotatable therein in either direction about its central axis.
Each of the circular trays 13-15 are of an identical structure except for the dimensions thereof in that tray 15 is of a lesser diameter than tray 14 which, in turn, is of a lesser diameter than tray 13, which, in turn, is of a lesser diameter than the base 12.
Tray 13 is of a circular configuration having a flat disc shaped bottom surface 41 with depending vertically extending cylindrical side walls 42 extending upwardly from the peripheral edges thereof and defining interiorly thereof an open topped interior compartment 43. Disposed concentric with the bottom 41 and extending downwardly therefrom is a cylindrical boss 44 of a diameter less than the diameter of passageway 35 and is adapted to be received in the top end of the passageway with the top end 34 of the sleeve 33 restingly engaged against the bottom 41 about the boss 44 to rotatably support tray 13 thereon for rotation about its central axis. Mounted concentric with bottom 41 in compartment 43 and projecting axially vertically upwardly therefrom is collar member 45 of a cylindrical configuration provided with a cylindrical bore 46 centrally thereof and opening out of the top 47 thereof.
Tray 14 is of a circular configuration having flat disc shaped bottom 51 with depending vertically upwardly extending cylindrical side walls 52 defining interiorly thereof compartment 53. A cylindrical supporting shaft 54 is disposed concentric with bottom 51 and extends vertically downwardly therefrom terminating at bottom end 55, the shaft being of a diameter to be received in recess or socket 46 in a snug but rotative manner. A cylindrical collar member 56 is disposed concentric of bottom 51 in compartment 53 and extends vertically upwardly therefrom and has defined therein a cylindrical socket 57 opening out of the top end 58 thereof.
Tray 15 is of a circular configuration having flat disc shaped bottom 61, cylindrical depending upwardly extending side walls 62, a cylindrical compartment 63 defined therein, a supporting shaft 64 of a cylindrical configuration disposed concentric with the bottom 61 projecting vertically downwardly therefrom and terminating in bottom end 65 and being of a diameter to be received in socket 57 and rotatable relative thereof, and a collar member 66 formed concentric in compartment 63 and projecting vertically upwardly therefrom and having an interiorly threaded socket 67 opening out of the top end 68 thereof.
The handle 16 includes an elongated cylindrical shaft 71 threaded at its bottom end to be threadedly received in socket 67, and terminating in its upper end in a closed loop 72 of a rectangular frame configuration adapted to be readily grasped in an individual's hand.
There is thus provided a tiered space saving device wherein each of the trays are independently rotatable relative to each other, and wherein the base is independently rotatable in the stand to provide each of access to items stored thereon.
FIG. 5 shows an alternate embodiment of a tiered table top for a dining table. A conventional table 73 is shown having a pedestal or supporting structure 75 and top 77, which is circular in the preferred embodiment. The table 73 may be of any shape and size. Conventional sizes include 36, 42 and 48 inch widths. A tiered table top 79 is carried by the table 73, and the tiered table top 79 will be sized appropriately, allowing eating space peripherally around the tiered table top 79.
The tiered table top 79 has a stand 80 mounted frictionally on the top of the table. The lower surface of the stand 80 may contain a rubber or textured layer (not shown) to prevent slippage about the table. Stand 80 comprises a flat circular disc 81 having a short cylindrical side wall 83 about its perimeter. A smooth inner step 85 of lesser height than the outer portion of side wall 83 forms the inner portion of the side wall. Step 85 is in the shape of a relatively thin annular ring and serves as a smooth bearing surface for a base tray, to be described below. A nylon bushing (not shown) may be placed on the step 85 to reduce friction is desired.
A center shaft 87 rises vertically from the stand 80. The shaft 87 is rigidly fastened to the stand so that it is nonrotatable, and may be integrally formed with the stand as indicated in the drawing. The shaft 87 is ascendingly reduced in diameter at several selected points, thereby forming shoulders 89, 91, 93 and 95. The shoulders serve as a smooth bearing surface for respective trays or table tops, to be described hereinafter. Nylon bushings or other bushings (not shown) may be placed on the shoulders to further reduce friction if desired.
A base tray, or base table top, 97 rests upon the step 85 of the side wall and the lowermost shoulder 89, which are of equal heighth. The smoothness of the bearing surfaces allow the base tray to be freely rotatable about shaft 87. A center aperture 99 allows the base tray to be inserted over the shaft 87 and is slightly larger than the shaft diameter at that point. The perimeter of the base tray 97 has a curved lip 101 to prevent objects from sliding off, and the upper surface is flat for the placement of food dishes, indicated by numeral 100. The lip 101 protrudes higher than the side wall 83 so that it may be gripped, for example, to rotate the base tray.
The size of the base tray 97 may vary depending on the size of table 73. There should be sufficient space surrounding base tray 97 for the placement of plates and glasses for the diners. For example, the base tray 97 may be 20 inches in diameter for a 42 inch diameter circular table 73, thereby allowing 11 inches for the placement of plates. Diameter for the base tray 97 may range from 16 to 24 inches.
Directly above the base tray 97 at selected intervals, shown as three in the embodiment, are a plurality of upper trays, or additional table tops, 103, 105, 107, positioned respectively over shoulders 91, 93, 95. Each upper tray is similar to each other and to the base tray 97, in that each contains a lip at the perimeter and an aperture at the center. As illustrated, the trays have ascendingly monotonically decreasing diameters, peripheral and central. Expressed otherwise, each succcessively higher tray is smaller in diameter and has a smaller center aperture size than the adjacent lower tray. Each center aperture is of slightly larger diameter than the shoulder upon which the particular tray is designed to be carried to reduce friction during rotation. Each tray will fit only upon its respective shoulder. For example, upper tray 103 will fit only upon shoulder 91, being too small to pass to shoulder 89, and too large to remain on shoulders 93 or 95. The upper surfaces of the upper trays are flat for the placement of food dishes.
Each upper tray or additional table top 103, 105, 107 also contains a tubular member or boss 113 rigidly attached or formed to the tray and extending upwardly from center aperture 91. Boss 113 fits closely over shaft 79 and extends upwardly a suffficient distance to prevent tipping of the tray if eccentrically loaded. The heighth of boss 113 may be in the range from 1 to 3 inches.
The upper trays 103, 105, 107 are spaced apart from each other a distance sufficient for most food dishes to be placed thereon. which may be in the range from 5 to 8 inches, preferably 6 inches. The diameters of the upper trays may vary in diameter; tray 103 being in the range from 12 to 20 inches. preferably 16 inches. Tray 105 may be from 8 to 16 inches, preferably 12 inches, while the tray 107, the uppermost may be from 6 to 10 inches, preferably 8 inches.
A handle 109 is rigidly mounted to the top of shaft 87, as by threads 111. The handle 109 is of a configuration, shown as a circular loop, that is comfortable to grip while lifting the stand.
The tiered table top 79 is utilized by first placing the stand 80 and trays securely on the table 73. Food dishes may be placed on the trays, with the heavier dishes on the base tray.
It may be readily seen that an invention having significant advantages has been provided. Each tray is independently rotatable, and in the second embodiment, rotation of one will not affect the others. The base tray in the second embodiment is easily rotatable as well, yet will withstand heavy food dishes without tipping since the step 85 directly bears any tilting forces. Construction is simple, yet an effective surface for rotation is provided.
While a rubber or textured layer on the bottom of stand 80 has been described for preventing slippage on the table, a plurality of suction cups may be employed, if desired. Suitable furniture oil or the like can be employed to prevent marring fine furniture and the suction cups prevent any chance of tipping; even when the table top is eccentrically loaded and inadvertently hit by a guest taking or replacing a dish or the like.
It is to be understood that the two forms of this invention herewith shown and described are to be taken as preferred examples of the same, and that this invention is not to be limited to the exact arrangement of parts shown in the accompanying drawings or described in this specification as various changes in the details of construction as to shape, size, and arrangement of parts may be resorted to without departing from the spirit of the invention, the scope of the novel concepts thereof, or the scope of the sub-joined claims. | 1a
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BACKGROUND
[0001] The present disclosure relates to flexible hand grips and particularly, grips of the type employed on a handle or shaft such as may be found on shovels or sporting implements such as tennis racquets and golf clubs for example. Such hand grips are typically molded of pliable or flexible material such as rubber or elastomer and assembled onto the handle or portion of the implement to be grasped manually. Hand grips for such implements have the need to be frictionally retained on the handle portion of the implement and yet need to provide a soft pliable and flexible gripping surface for the user's hand, particularly where the implement is to be moved in an arcuate or swinging motion which would create exertion by the user, as is the case with golf clubs, tennis racquets and tools such as hammers. This has necessitated forming the thickness of the hand grip to an amount sufficient to provide a soft resilient or pliable surface for the user's hand not only for providing adequate grip retention but to prevent discomfort which would cause blisters upon repeated usage. However, where the material thickness has been provided sufficient to yield a compliant or pliable soft flexible surface for the user's hand, this has resulted in the need for a substantial amount of material to be provided in the grip and has yielded a grip that added weight to the implement, increased the amount of material required and a resultant increase in manufacturing costs.
[0002] Thus, it has been desired to provide a flexible pliable hand grip for use on an implement which is sufficiently soft to enable the user to grip and retain a hold on the implement during forceful movement and yet provide such a grip that requires a minimum use of material and one that is relatively light in weight.
BRIEF DESCRIPTION
[0003] The present disclosure describes a flexible compliant hand grip for assembly onto the handle of an implement such as, for example a hammer, shovel, golf club or tennis racquet and which has an inner tubular core formed of flexible material for receiving the implement handle with an outer tubular member formed of similar flexible compliant material disposed over the inner core with an annular space provided there between which space is filled with a spacer formed of flexible material of substantially lower or reduced bulk density relative to the core and outer member. The inner core is provided with a plurality of spaced apertures through which is injected curable material for forming a filler or spacer in the annular space between the core and the outer tubular member for maintaining the outer tubular member in its position over the core. In the present practice, it has been found satisfactory to form the spacer of injectable curable foam material and to form the core and outer tubular member of flexible elastomeric material.
BRIEF DESCRIPTION OF THE DRAWINGS
[0004] FIG. 1 is a cross-sectional view of an exemplary embodiment of the outer tubular member;
[0005] FIG. 2 is a sectional view of an exemplary embodiment of the core member;
[0006] FIG. 3 is an exploded perspective view of the tooling arrangement for punching the apertures in the core member;
[0007] FIG. 4 is a cross-sectional view of an exemplary embodiment of the assembled hand grip;
[0008] FIG. 5 is a portion of a cross-sectional view similar to FIG. 1 showing an alternate embodiment of the outer tubular member; and,
[0009] FIG. 6 is a portion of a sectional view similar to FIG. 2 showing an alternate embodiment of the core member.
DETAILED DESCRIPTION
[0010] Referring to FIGS. 1 , 2 and 4 , a hand grip is indicated generally at 10 and includes a core member 12 having a generally tubular configuration with an outwardly extending flange portion 14 formed on one end thereof with the outer face 16 optionally tapered and, if desired, the flange 14 may include an annular undercut 18 to provide radial resiliency and facilitate manufacture of the grip 10 . The core member 12 may include an annular rib 20 on the inner periphery thereof in proximity of the end remote from the flange 14 .
[0011] Referring to FIG. 1 , the outer tubular member 22 is shown as having a closed end 24 provided with a vent hole 26 extending through an inwardly extending projection 28 which may have an annular or circumferential groove 30 formed therein to be engaged by the rib 20 in the core member upon assembly. The outer tubular member 22 may also be provided with an inwardly extending annular rib 32 adjacent the end opposite the closed end 24 which rib 32 is operative to engage an annular groove 36 formed in the outer periphery of the flange 14 of core 12 as shown in the assembled condition in FIG. 4 .
[0012] Referring to FIG. 2 , the core member has a plurality of spaced apertures 38 formed through the wall thereof in a manner as will hereinafter be described in further detail.
[0013] Referring to FIGS. 5 and 6 , alternate exemplary embodiments of the ends of the core 12 and outer tubular member 22 are shown wherein the tubular member 122 has the end face 124 thereof provided with an inwardly extending projection 128 which has an annular taper 130 provided thereon. The corresponding embodiment 112 of the core member has the end thereof provided with a tapered surface 120 on the inner periphery thereof which engages the tapered surface 130 on the outer tubular member as shown in FIG. 4 .
[0014] Referring to FIG. 3 , the core member 12 is shown positioned to have a mandrel 40 with relief holes or apertures 42 formed therein which are sized and located to correspond with the apertures 38 provided on the core 12 with the mandrel inserted into the core member 12 and positioned such that the holes 42 align with the respective apertures 38 in the core member.
[0015] A plurality of punches indicated generally at 44 are positioned adjacent the core member 12 and guided by guide blocks 46 . The punches 44 are then urged into contact by the drivers 48 which may comprise any convenient mechanical, hydraulic, electrical or pneumatic device such that the punches form the apertures 38 in the core member with the material removed, or plugs, passing to the interior of the mandrel 40 through apertures 42 . The material removed by formation of the apertures 38 may then be removed from the mandrel 40 by any suitable expedient, for example, blowing through with compressed air. Upon completion of the punching operation, the mandrel 40 is then removed from the core member 12 .
[0016] It will be understood that the punching operation the apparatus illustrated in FIG. 3 is performed on the core member 12 prior to assembly with the outer tubular member.
[0017] Referring to FIG. 4 , the annular space between the outer tubular member 22 , 122 and the core 12 , 112 is filled with suitable lightweight material or material having a bulk density substantially less than that of the outer tubular member or core as denoted by reference numeral 50 . In the present practice, it has been found satisfactory to insert curable material through the apertures 38 in the core member and it has been found particularly satisfactory to inject curable foam material through the apertures 38 to form the spacer 50 in the annular space between the core and outer tubular member. Thus, the lightweight curable material, once cured, provides a resilient support for the relatively thin wall of the outer tubular member, thereby providing adequate cushioning and “feel” to the hand grip when grasped by the user's hand.
[0018] In the present practice it has been found suitable to employ ethylene-propylene-diene-monomer (EPDM) material and particularly EPDM foam material for the spacer 50 . In the present practice, it has been found satisfactory to form the spacer 50 of curable material having a specific gravity in the range of about 0.1 to 0.7 and having a durometer in the range of about 20-50 on the Shore ‘A’ scale. However, it will be understood that other suitable injectable curable lightweight materials with adequate flexibility for supporting and flexibly cushioning the outer tubular member may also be employed.
[0019] In the present practice, it has been found satisfactory to form the core member 12 , 112 and the outer tubular member 22 , 122 of flexible elastomeric or rubber material. In particular, it has been found satisfactory to form the core member of material having a specific gravity in the range of about 0.8 to 1.5, of material having a durometer in the range of about 35 to 75 on the Shore ‘A’ scale and a material having the combination of both. In the present practice, it has also been found satisfactory to form the outer tubular member of flexible material having a specific gravity in the range of about 0.8-1.5, of material having a durometer in the range of about 35 to 75 on the Shore ‘A’ scale and of material having both properties. However, it will be understood that other materials may be employed as desired for providing adequate gripping by the user and the desired flexibility and “feel” when gripped sufficiently to retain control of an implement upon which the grip is affixed during rapid or forceful movement thereof.
[0020] It will be understood that although the hand grip illustrated herein is shown having the inner diameter of the core member relatively small compared to the outer diameter of the tubular member, as would be the case for a golf club hand grip, that the proportions may be changed to accommodate larger size implements to be gripped such as would be the case for a hand grip for an implement such as a hammer, sledge hammer or shovel.
[0021] The present disclosure thus describes a flexible relatively soft hand grip for an implement which is light in weight by virtue of a resilient foam facer between the core and outer tubular portion formed in material significantly lighter than the core or outer tubular portion.
[0022] The exemplary embodiment has been described with reference to the preferred embodiments. Obviously, modifications and alterations will occur to others upon reading and understanding the preceding detailed description. It is intended that the exemplary embodiment be construed as including all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof. | 1a
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RELATED APPLICATIONS
[0001] This application is a divisional of co-pending application Ser. No. 11/199,715, filed Aug. 9, 2005, which is a divisional of application Ser. No. 10/747,547, filed 29 Dec. 2003, now U.S. Pat. No. 6,981,981, which is a divisional of application Ser. No. 10/411,573, filed Apr. 10, 2003, now abandoned, which is a divisional of application Ser. No. 10/200,674, filed Jul. 22, 2002, now U.S. Pat. No. 6,663,647, which is a divisional of 09/059,796, filed Apr. 13, 1998, now U.S. Pat. No. 6,423,083, which is a divisional of application Ser. No. 08/788,786, filed Jan. 23, 1997, now U.S. Pat. No. 6,235,043, which is a continuation of application Ser. No. 08/188,224, filed on Jan. 26, 1994 (now abandoned).
FIELD OF THE INVENTION
[0002] This invention relates to improvements in the surgical treatment of bone conditions of the human and other animal bone systems and, more particularly, to an inflatable balloon-like device for use in treating such bone conditions. Osteoporosis, avascular necrosis and bone cancer are diseases of bone that predispose the bone to fracture or collapse. There are 2 million fractures each year in the United States, of which about 1.3 million are caused by osteoporosis. Avascular necrosis and bone cancers are more rare but can cause bone problems that are currently poorly addressed.
BACKGROUND OF THE INVENTION
[0003] In U.S. Pat. Nos. 4,969,888 and 5,108,404, an apparatus and method are disclosed for the fixation of fractures or other conditions of human and other animal bone systems, both osteoporotic and non-osteoporotic. The apparatus and method are especially suitable for use in the fixation of, but not limited to, vertebral body compression fractures, Colles fractures and fractures of the proximal humerus.
[0004] The method disclosed in these two patents includes a series of steps which a surgeon or health care provider can perform to form a cavity in pathological bone (including but not limited to osteoporotic bone, osteoporotic fractured metaphyseal and epiphyseal bone, osteoporotic vertebral bodies, fractured osteoporotic vertebral bodies, fractures of vertebral bodies due to tumors especially round cell tumors, avascular necrosis of the epiphyses of long bones, especially avascular necrosis of the proximal femur, distal femur and proximal humerus and defects arising from endocrine conditions).
[0005] The method further includes an incision in the skin (usually one incision, but a second small incision may also be required if a suction egress is used) followed by the placement of a guide pin which is passed through the soft tissue down to and into the bone.
[0006] The method further includes drilling the bone to be treated to form a cavity or passage in the bone, following which an inflatable balloon-like device is inserted into the cavity or passage and inflated. The inflation of the inflatable device causes a compacting of the cancellous bone and bone marrow against the inner surface of the cortical wall of the bone to further enlarge the cavity or passage. The inflatable device is then deflated and then is completely removed from the bone. A smaller inflatable device (a starter balloon) can be used initially, if needed, to initiate the compacting of the bone marrow and to commence the formation of the cavity or passage in the cancellous bone and marrow. After this has occurred, a larger, inflatable device is inserted into the cavity or passage to further compact the bone marrow in all directions.
[0007] A flowable biocompatible filling material, such as methylmethacrylate cement or a synthetic bone substitute, is then directed into the cavity or passage and allowed to set to a hardened condition to provide structural support for the bone. Following this latter step, the insertion instruments are removed from the body and the incision in the skin is covered with a bandage.
[0008] While the apparatus and method of the above patents provide an adequate protocol for the fixation of bone, it has been found that the compacting of the bone marrow and/or the trabecular bone and/or cancellous bone against the inner surface of the cortical wall of the bone to be treated can be significantly improved with the use of inflatable devices that incorporate additional engineering features not heretofore described and not properly controlled with prior inflatable devices in such patents. A need has therefore arisen for improvements in the shape, construction and size of inflatable devices for use with the foregoing apparatus and method, and the present invention satisfies such need.
[0009] Prior Techniques for the Manufacture of Balloons for In-Patient Use
[0010] A review of the prior art relating to the manufacture of balloons shows that a fair amount of background information has been amassed in the formation of guiding catheters which are introduced into cardiovascular systems of patients through the brachial femoral arteries. However, there is a scarcity of disclosures relating to inflatable devices used in bone, and none for compacting bone marrow in vertebral bodies and long bones.
[0011] In a dilatation catheter, the catheter is advanced into a patient until a balloon is properly positioned across a lesion to be treated. The balloon is inflated with a radiopaque liquid at pressures above four atmospheres to compress the plaque of the lesion to thereby dilate the lumen of the artery. The balloon can then be deflated, then removed from the artery so that the blood flow can be restored through the dilated artery.
[0012] A discussion of such catheter usage technique is found and clearly disclosed in U.S. Pat. No. 5,163,989. Other details of angioplasty catheter procedures, and details of balloons used in such procedures can be found in U.S. Pat. Nos. 4,323,071, 4,332,254, 4,439,185, 4,168,224, 4,516,672, 4,538,622, 4,554,929, and 4,616,652.
[0013] Extrusions have also been made to form prism shaped balloons using molds which require very accurate machining of the interior surface thereof to form acceptable balloons for angioplastic catheters. However, this technique of extrusion forms parting lines in the balloon product which parting lines are limiting in the sense of providing a weak wall for the balloon itself.
[0014] U.S. Pat. No. 5,163,989 discloses a mold and technique for molding dilatation catheters in which the balloon of the catheter is free of parting lines. The technique involves inflating a plastic member of tubular shape so as to press it against the inner molding surface which is heated. Inflatable devices are molded into the desired size and shape, then cooled and deflated to remove it from the mold. The patent states that, while the balloon of the present invention is especially suitable for forming prism-like balloons, it can also be used for forming balloons of a wide variety of sizes and shapes.
[0015] A particular improvement in the catheter art with respect to this patent, namely U.S. Pat. No. 4,706,670, is the use of a coaxial catheter with inner and outer: tubing formed and reinforced by continuous helical filaments. Such filaments cross each other causing the shaft of the balloon to become shorter in length while the moving portion of the shank becomes longer in length. By suitably balancing the lengths and the angle of the weave of the balloon and moving portions of the filaments, changes in length can be made to offset each other. Thus, the position of the inner and outer tubing can be adjusted as needed to keep the balloon in a desired position in the blood vessel.
[0016] Other disclosures relating to the insertion of inflatable devices for treating the skeleton of patients include the following:
[0017] U.S. Pat. No. 4,313,434 relates to the fixation of a long bone by inserting a deflated flexible bladder into a medullary cavity, inflating the balloon bladder, sealing the interior of the long bone until healing has occurred, then removing the bladder and filling the opening through which the bladder emerges from the long bone.
[0018] U.S. Pat. No. 5,102,413 discloses the way in which an inflatable bladder is used to anchor a metal rod for the fixation of a fractured long bone.
[0019] Other references which disclose the use of balloons and cement for anchoring of a prosthesis include U.S. Pat. Nos. 5,147,366, 4,892,550, 4,697,584, 4,562,598, and 4,399,814.
[0020] A Dutch patent, NL 901858, discloses a means for fracture repair with a cement-impregnated bag which is inflated into a preformed cavity and allowed to harden.
[0021] It can be concluded from the foregoing review of the prior art that there is little or no substantive information on inflatable devices used to create cavities in bone. It does not teach the shape of the balloon which creates a cavity that best supports the bone when appropriately filled. It does not teach how to prevent balloons from being spherical when inflated, when this is desired. Current medical balloons can compress bone but are too small and generally have the wrong configuration and are generally not strong enough to accomplish adequate cavity formation in either the vertebral bodies or long bones of the body.
[0022] U.S. Pat. Nos. 4,969,888 and 5,108,404 disclose a checker-shaped balloon for compressing cancellous bone, but does not provide information on how this balloon remains in its shape when inflated.
[0023] Thus, the need continues for an improved inflatable device for use with pathological bones and the treatment thereof.
SUMMARY OF THE INVENTION
[0024] The present invention is directed to a balloon-like inflatable device or balloon for use in carrying out the apparatus and method of the above-mentioned U.S. Pat. Nos. 4,969,888 and 5,108,404. Such inflatable devices, hereinafter sometimes referred to as balloons, have shapes for compressing cancellous bone and marrow (also known as medullary bone or trabecular bone) against the inner cortex of bones whether the bones are fractured or not.
[0025] In particular, the present invention is directed to a balloon for use in treating a bone predisposed to fracture or to collapse. The balloon comprises an inflatable, non-expandable balloon body for insertion into said bone. The body has a predetermined shape and size when substantially inflated sufficient to compress at least a portion of the inner cancellous bone to create a cavity in the cancellous bone and to restore the original position of the outer cortical bone, if fractured or collapsed. The balloon body is restrained to create said predetermined shape and size so that the fully inflated balloon body is prevented from applying substantial pressure to the inner surface of the outer cortical bone if said bone is unfractured or uncollapsed.
[0026] In addition to the shape of the inflatable device itself, another aspect of importance is the construction of the wall or walls of the balloon such that proper inflation the balloon body is achieved to provide for optimum compression of all the bone marrow. The material of the balloon is also desirably chosen so as to be able to fold the balloon so that it can be inserted quickly and easily into a bone using guide pin and a cannula, yet can also withstand high pressures when inflated. The balloon can also include optional ridges or indentations which are left in the cavity after the balloon has been removed, to enhance the stability of the filler. Also, the inflatable device can be made to have an optional, built-in suction catheter. This is used to remove any fat or fluid extruded from the bone during balloon inflation in the bone. Also, the balloon body can be protected from puncture by the cortical bone or canula by being covered while inside the canula with an optional protective sleeve of suitable material, such as Kevlar or PET or other polymer or substance that can protect the balloon. The main purpose of the inflatable device, therefore, is the forming or enlarging of a cavity or passage in a bone, especially in, but not limited to, vertebral bodies.
[0027] The primary object of the present invention is to provide an improved balloon-like inflatable device for use in carrying out a surgical protocol of cavity formation in bones to enhance the efficiency of the protocol, to minimize the time prior to performing the surgery for which the protocol is designed and to improve the clinical outcome. These balloons approximate the inner shape of the bone they are inside of in order to maximally compress cancellous bone. They have additional design elements to achieve specific clinical goals. Preferably, they are made of inelastic material and kept in their defined configurations when inflated, by various restraints, including (but not limited to) use of inelastic materials in the balloon body, seams in the balloon body created by bonding or fusing separate pieces of material together, or by fusing or bonding together opposing sides of the balloon body, woven material bonded inside or outside the balloon body, strings or bands placed at selected points in the balloon body, and stacking balloons of similar or different sizes or shapes on top of each other by gluing or by heat fusing them together. Optional ridges or indentations created by the foregoing structures, or added on by bonding additional material, increases stability of the filler. Optional suction devices, preferably placed so that if at least one hole is in the lowest point of the cavity being formed, will allow the cavity to be cleaned before filling.
[0028] Among the various embodiments of the present invention are the following:
[0029] 1. A doughnut (or torus) shaped balloon with an optional built-in suction catheter to remove fat and other products extruded during balloon expansion.
[0030] 2. A balloon with a spherical outer shape surrounded by a ring-shaped balloon segment for body cavity formation.
[0031] 3. A balloon which is kidney bean shaped in configuration. Such a balloon can be constructed in a single layer, or several layers stacked on top of each other.
[0032] 4. A spherically shaped balloon approximating the size of the head of the femur (i.e. the proximal femoral epiphysis). Such a balloon can also be a hemisphere.
[0033] 5. A balloon in the shape of a humpbacked banana or a modified pyramid shape approximating the configuration of the distal end of the radius (i.e. the distal radial epiphysis and metaphysis).
[0034] 6. A balloon in the shape of a cylindrical ellipse to approximate the configuration of either the medial half or the lateral half of the proximal tibial epiphysis. Such a balloon can also be constructed to approximate the configuration of both halves of the proximal tibial epiphysis.
[0035] 7. A balloon in the shape of sphere on a base to approximate the shape of the proximal humeral epiphysis and metaphysis with a plug to compress cancellous bone into the diaphysis, sealing it off.
[0036] 8. A balloon device with optional suction device.
[0037] 9. Protective sheaths to act as puncture guard members optionally covering each balloon inside its catheter.
[0038] The present invention, therefore, provides improved, inflatable devices for creating or enlarging a cavity or passage in a bone wherein the devices are inserted into the bone. The configuration of each device is defined by the surrounding cortical bone and adjacent internal structures, and is designed to occupy about 70-90% of the volume of the inside of the bone, although balloons that are as small as about 40% and as large as about 99% are workable for fractures. In certain cases, usually avascular necrosis, the balloon size may be as small as 10% of the cancellous bone volume of the area of bone being treated, due to the localized nature of the fracture or collapse. The fully expanded size and shape of the balloon is limited by additional material in selected portions of the balloon body whose extra thickness creates a restraint as well as by either internal or external restraints formed in the device including, but not limited to, mesh work, a winding or spooling of material laminated to portions of the balloon body, continuous or non-continuous strings across the inside held in place at specific locations by glue inside or by threading them through to the outside and seams in the balloon body created by bonding two pieces of body together or by bonding opposing sides of a body through glue or heat. Spherical portions of balloons may be restrained by using inelastic materials in the construction of the balloon body, or may be additionally restrained as just described. The material of the balloon is preferably a non-elastic material, such as polyethylene tetraphthalate (PET), Kevlar or other patented medical balloon materials. It can also be made of semi-elastic materials, such as silicone or elastic material such as latex, if appropriate restraints are incorporated. The restraints can be made of a flexible, inelastic high tensile strength material including, but not limited, to those described in U.S. Pat. No. 4,706,670. The thickness of the balloon wall is typically in the range of 2/1000ths to 25/1000ths of an inch, or other thicknesses that can withstand pressures of up to 250-400 psi.
[0039] A primary goal of percutaneous vertebral body augmentation of the present invention is to provide a balloon which can create a cavity inside the vertebral body whose configuration is optimal for supporting the bone. Another important goal is to move the top of the vertebral body back into place to retain height where possible, however, both of these objectives must be achieved without fracturing the cortical wall of the vertebral body. This feature could push vertebral bone toward the spinal cord, a condition which is not to be desired.
[0040] The present invention satisfies these goals through the design of inflatable devices to be described. Inflating such a device compresses the calcium-containing soft cancellous bone into a thin shell that lines the inside of the hard cortical bone creating a large cavity.
[0041] At the same time, the biological components (red blood cells, bone progenitor cells) within the soft bone are pressed out and removed by rinsing during the procedure. The body recreates the shape of the inside of an unfractured vertebral body, but optimally stops at approximately 70 to 90% of the inner volume. The balloons of the present invention are inelastic, so maximally inflating them can only recreate the predetermined shape and size. However, conventional balloons become spherical when inflated. Spherical shapes will not allow the hardened bone cement to support the spine adequately, because they make single points of contact on each vertebral body surface (the equivalent of a circle inside a square, or a sphere inside a cylinder). The balloons of the present invention recreate the flat surfaces of the vertebral body by including restraints that keep the balloon in the desired shape. This maximizes the contacts between the vertebral body surfaces and the bone cement, which strengthens the spine. In addition, the volume of bone cement that fills these cavities creates a thick mantle of cement (4 mm or greater), which is required for appropriate compressive strength. Another useful feature, although not required, are ridges in the balloons which leave their imprint in the lining of compressed cancellous bone. The resulting bone cement “fingers” provide enhanced stability.
[0042] The balloons which optimally compress cancellous bone in vertebral bodies are the balloons listed as balloon types 1, 2 and 3 above. These balloons are configured to approximate the shape of the vertebral body. Since the balloon is chosen to occupy 70 to 90% of the inner volume, it will not exert undue pressure on the sides of the vertebral body, thus the vertebral body will not expand beyond its normal size (fractured or unfractured). However, since the balloon has the height of an unfractured vertebral body, it can move the top, which has collapsed, back to its original position.
[0043] One aspect of the invention provides a device for insertion into a vertebral body to apply a force capable of compacting cancellous bone and moving fractured cortical bone. The device includes a catheter extending along an axis and having a distal end sized and configured for insertion through a cannula into the vertebral body. The catheter carries near its distal end an inflatable body having a wall sized and configured for passage within the cannula into the vertebral body when the inflatable body is in a collapsed condition. The wall is further sized and configured to apply the in response to expansion of the inflatable body within the vertebral body. The wall includes, when inflated, opposed side surfaces extending along an elongated longitudinal axis that is substantially aligned with the axis of the catheter. The inflatable body has a height of approximately 0.5 cm to 3.5 cm, an anterior to posterior dimension of approximately 0.5 cm to 3.5 cm, and a side to side dimension of approximately 0.5 cm to 5.0 cm.
[0044] In a representative embodiment, the inflatable body comprises a balloon and the cannula is a percutaneious cannula.
[0045] In another aspect of the invention, the wall includes changes in wall thickness which restrain the opposed sided surfaces from expanding beyond a substantially flat condition.
[0046] According to another aspect of the invention, the wall includes an internal restraint which restrains the opposed side surfaces from expanding beyond a substantially flat condition. The internal restraint may include a mesh material, a string material, a woven material, a seam, or an essentially non-elastic material.
[0047] In yet another aspect of the invention, the wall includes an external restraint which restrains the opposed side surfaces from expanding beyond a substantially flat condition. The internal restraint may include a mesh material, a string material, a woven material, a seam, or an essentially non-elastic material.
[0048] A primary goal of percutaneous proximal humeral augmentation is to create a cavity inside the proximal humerus whose configuration is optimal for supporting the proximal humerus. Another important goal is to help realign the humeral head with the shaft of the humerus when they are separated by a fracture. Both of these goals must be achieved by exerting pressure primarily on the cancellous bone, and not the cortical bone. Undue pressure against the cortical bone could conceivably cause a worsening of a shoulder fracture by causing cortical bone fractures.
[0049] The present invention satisfies these goals through the design of the inflatable devices to be described. Inflating such a device compresses the cancellous bone against the cortical walls of the epiphysis and metaphysis of the proximal humerus thereby creating a cavity. In some cases, depending on the fracture location, the balloon or inflatable device may be used to extend the cavity into the proximal part of the humeral diaphysis.
[0050] Due to the design of the “sphere on a stand” balloon (described as number 7 above), the cavity made by this balloon recreates or approximates the shape of the inside cortical wall of the proximal humerus. The approximate volume of the cavity made by the “spherical on a stand balloon” is 70 to 90% that of the proximal humeral epiphysis and metaphysis, primarily, but not necessarily exclusive of, part of the diaphysis. The shape approximates the shape of the humeral head. The “base” is designed to compress the trabecular bone into a “plug” of bone in the distal metaphysis or proximal diaphysis. This plug of bone will prevent the flow of injectable material into the shaft of the humerus, improving the clinical outcome. The sphere can also be used without a base.
[0051] A primary goal of percutaneous distal radius augmentation is to create a cavity inside the distal radius whose configuration is optimal for supporting the distal radius. Another important goal is to help fine tune fracture realignment after the fracture has been partially realigned by finger traps. Both of these goals must be achieved by exerting pressure primarily on the cancellous bone and not on the cortical bone. Excessive pressure against the cortical bone could conceivably cause cortical bone fractures, thus worsening the condition.
[0052] The present invention satisfies these goals through the design of inflatable devices either already described or to be described.
[0053] The design of the “humpbacked banana”, or modified pyramid design (as described as number 5 above), approximates the shape of the distal radius and therefore, the cavity made by this balloon approximates the shape of the distal radius as well. The approximate volume of the cavity to be made by this humpbacked banana shaped balloon is 70 to 90% that of the distal radial epiphysis and metaphysis primarily of, but not necessarily exclusive of, some part of the distal radial diaphysis. Inflating such a device compresses the cancellous bone against the cortical walls of the epiphysis and metaphysis of the distal radius in order to create a cavity. In some cases, depending on the fracture location, the osseous balloon or inflatable device may be used to extend the cavity into the distal part of the radial diaphysis.
[0054] A primary goal of percutaneous femoral head (or humeral head) augmentation is to create a cavity inside the femoral head (or humeral head) whose configuration is optimal for supporting the femoral head.
[0055] Another important goal is to help compress avascular (or aseptic) necrotic bone or support avascular necrotic bone is the femoral head. This goal may include the realignment of avascular bone back into the position it previously occupied in the femoral head in order to improve the spherical shape of the femoral head. These goals must be achieved by exerting pressure primarily on the cancellous bone inside the femoral head.
[0056] The present invention satisfied these goals through the design of inflatable devices either already described or to be described.
[0057] The design of the spherical osseous balloon (described as balloon type 4 above) approximates the shape of the femoral head and therefore creates a cavity which approximates the shape of the femoral head as well. (It should be noted that the spherical shape of this inflatable device also approximates the shape of the humeral head and would, in fact, be appropriate for cavity formation in this osseous location as well.) Inflating such a device compresses the cancellous bone of the femoral head against its inner cortical walls in order to create a cavity. In some cases, depending upon the extent of the avascular necrosis, a smaller or larger cavity inside the femoral head will be formed. In some cases, if the area of avascular necrosis is small, a small balloon will be utilized which might create a cavity only 10 to 15% of the total volume of the femoral head. If larger areas of the femoral head are involved with the avascular necrosis, then a larger balloon would be utilized which might create a much larger cavity, approaching 80 to 90% of the volume of the femoral head.
[0058] The hemispherical balloon approximates the shape of the top half of the femoral (and humeral) head, and provides a means for compacting cancellous bone in an area of avascular necrosis or small fracture without disturbing the rest of the head. This makes it easier to do a future total joint replacement if required.
[0059] A primary goal of percutaneous proximal tibial augmentation is to create a cavity inside the proximal tibia whose configuration is optimal for supporting either the medial or lateral tibial plateaus. Another important goal is to help realign the fracture fragments of tibial plateau fractures, particularly those features with fragments depressed below (or inferior to) their usual location. Both of these objectives must be achieved by exerting pressure on primarily the cancellous bone and not the cortical bone. Pressure on the cortical bone could conceivably cause worsening of the tibial plateau fracture.
[0060] The present invention satisfies these goals through the design of the inflatable devices to be described. Inflating such a device compresses the cancellous bone against the cortical walls of the medial or lateral tibial plateau in order to create a cavity.
[0061] Due to the design of the “elliptical cylinder” balloon (described as balloon type 6 above) the cavity made by this balloon recreates or approximates the shape of the cortical walls of either the medial or lateral tibial plateaus. The approximate volume of the cavity to be made by the appropriate elliptical cylindrical balloon is 50 to 90% of the proximal epiphyseal bone of either the medial half or the lateral half of the tibial.
[0062] According to one aspect of the invention, a system for treating a bone having an interior volume occupied, at least in part, by cancellous bone comprises a first tool, a second tool, and a third tool. The bone may be e.g., a vertebral body. The first tool establishes a percutaneous access path to bone. The second tool is sized and configured to be introduced through the percutaneous access path to form a void that occupies less than the interior volume. The third tool places within the void through the percutaneous access path a volume of filling material.
[0063] In one embodiment, the interior volume has a maximum anterior-to-posterior dimension and the void has a dimension, measured in an anterior-to-posterior direction, that is less than the maximum anterior-to-posterior dimension of the interior volume.
[0064] In one embodiment, the interior volume has a maximum side-to-side dimension and the void has a dimension, measured in a side-to-side direction, that is less than the maximum side-to-side dimension of the interior volume.
[0065] Another aspect of the invention provides a method of treating a bone having an interior volume occupied, at least in part, by cancellous bone. The bone may be, e.g., a vertebral body. The method provides establishing a percutaneous access path to bone. A tool . . . is introduced through the percutaneous access path and manipulated to form a void that occupies less than the interior-volume. A volume of filling material is then placed within the void through the percutaneous access path.
[0066] In one embodiment, the interior volume has a maximum anterior-to-posterior dimension and the void has a dimension, measured in an anterior-to-posterior direction, that is less than the maximum anterior-to-posterior dimension of the interior volume.
[0067] In one embodiment, the interior volume has a maximum side-to-side dimension and the void has a dimension, measured in a side-to-side direction, that is less than the maximum side-to-side dimension of the interior volume.
[0068] Other objects of the present invention will become apparent as the following specification progresses, reference being had to the accompanying drawings for an illustration of the invention.
DESCRIPTION OF THE DRAWINGS
[0069] FIG. 1 is a perspective view of a first embodiment of the balloon of the present invention, the embodiment being in the shape of a stacked doughnut assembly.
[0070] FIG. 2 is a vertical section through the balloon of FIG. 1 showing the way in which the doughnut portions of the balloon of FIG. 1 , fit into a cavity of a vertebral body.
[0071] FIG. 3 is a schematic view of another embodiment of the balloon of the present invention showing three stacked balloons and string-like restraints for limiting the expansion of the balloon in directions of inflation.
[0072] FIG. 4 is a top plan view of a spherical balloon having a cylindrical ring surrounding the balloon.
[0073] FIG. 5 is a vertical section through the spherical balloon and ring of FIG. 4 .
[0074] FIG. 6 shows an oblong-shaped balloon with a catheter extending into the central portion of the balloon.
[0075] FIG. 6A is a perspective view of the way in which a catheter is arranged relative to the inner tubes for inflating the balloon of FIG. 6 .
[0076] FIG. 7 is a suction tube and a contrast injection tube for carrying out the inflation of the balloon and removal of debris caused by expansion from the balloon itself.
[0077] FIG. 8 is a vertical section through a balloon after it has been deflated and as it is being inserted into the vertebral body of a human.
[0078] FIGS. 9 and 9 A are side elevational views of a cannula showing how the protective sleeve or guard member expands when leaving the cannula.
[0079] FIG. 9B is a vertical section through a vertebral bone into which an access hole has been drilled.
[0080] FIG. 10 is a perspective view of another embodiment of the balloon of the present invention formed in the shape of a kidney bean.
[0081] FIG. 11 is a perspective view of the vertebral bone showing the kidney shaped balloon of FIG. 10 inserted in the bone and expanded.
[0082] FIG. 12 is a top view of a kidney shaped balloon formed of several compartments by a heating element or branding tool.
[0083] FIG. 13 is a cross-sectional view taken along line 13 - 13 of FIG. 12 but with two kidney shaped balloons that have been stacked.
[0084] FIG. 14 is a view similar to FIG. 11 but showing the stacked kidney shaped balloon of FIG. 13 in the vertebral bone.
[0085] FIG. 15 is a top view of a kidney balloon showing outer tufts holding inner strings in place interconnecting the top and bottom walls of the balloon.
[0086] FIG. 16 is a cross sectional view taken along lines 16 - 16 of FIG. 15 .
[0087] FIG. 17A is a dorsal view of a humpback banana balloon in a right distal radius.
[0088] FIG. 17B is a cross sectional view of FIG. 17A taken along line 17 B- 17 B of FIG. 17A .
[0089] FIG. 18 is a spherical balloon with a base in a proximal humerus viewed from the front (anterior) of the left proximal humerus.
[0090] FIG. 19A is the front (anterior) view of the proximal tibia with the elliptical cylinder balloon introduced beneath the medial tibial plateau.
[0091] FIG. 19B is a three quarter view of the balloon of FIG. 19A .
[0092] FIG. 19C is a side elevational view of the balloon of FIG. 19A .
[0093] FIG. 19D is a top plan view of the balloon of FIG. 19A .
[0094] FIG. 20 is a spherically shaped balloon for treating avascular necrosis of the head of the femur (or humerus) as seen from the front (anterior) of the left hip.
[0095] FIG. 20A is a side view of a hemispherically shaped balloon for treating avascular necrosis of the head of the femur (or humerus).
DETAILED DESCRIPTION
Balloons for Vertebral Bodies
[0096] A first embodiment of the balloon ( FIG. 1 ) of the present invention is broadly denoted by the numeral 10 and includes a balloon body 11 having a pair of hollow, inflatable, non-expandable parts 12 and 14 of flexible material, such as PET or Kevlar. Parts 12 and 14 have a suction tube 16 therebetween for drawing fats and other debris by suction into tube 16 for transfer to a remote disposal location. Catheter 16 has one or more suction holes so that suction may be applied to the open end of tube 16 from a suction source (not shown).
[0097] The parts 12 and 14 are connected together by an adhesive which can be of any suitable type. Parts 12 and 14 are doughnut-shaped as shown in FIG. 1 and have tubes 18 and 20 which communicate with and extend away from the parts 12 and 14 , respectively, to a source of inflating liquid under pressure (not shown). The liquid can be any sterile biocompatible solution. The liquid inflates the balloon 10 , particularly parts 12 and 14 thereof after the balloon has been inserted in a collapsed condition ( FIG. 8 ) into a bone to be treated, such as a vertebral bone 22 in FIG. 2 . The above-mentioned U.S. Pat. Nos. 4,969,888 and 5,108,404 disclose the use of a guide pin and cannula for inserting the balloon into bone to be treated when the balloon is deflated and has been inserted into a tube and driven by the catheter into the cortical bone where the balloon is inflated.
[0098] FIG. 8 shows a deflated balloon 10 being inserted through a cannula 26 into bone. The balloon in cannula 26 is deflated and is forced through the cannula by exerting manual force on the catheter 21 which extends into a passage 28 extending into the interior of the bone. The catheter is slightly flexible but is sufficiently rigid to allow the balloon to be forced into the interior of the bone where the balloon is then inflated by directing fluid into tube 88 whose outlet ends are coupled to respective parts 12 and 14 .
[0099] In use, balloon 10 is initially deflated and, after the bone to be filled with the balloon has been prepared to receive the balloon with drilling, the deflated balloon is forced into the bone in a collapsed condition through cannula 26 . The bone is shown in FIG. 2 . The balloon is oriented preferably in the bone such that it allows minimum pressure to be exerted on the bone marrow and/or cancellous bone if there is no fracture or collapse of the bone. Such pressure will compress the bone marrow and/or cancellous bone against the inner wall of the cortical bone, thereby compacting the bone marrow of the bone to be treated and to further enlarge the cavity in which the bone marrow is to be replaced by a biocompatible, flowable bone material.
[0100] The balloon is then inflated to compact the bone marrow and/or cancellous bone in the cavity and, after compaction of the bone marrow and/or cancellous bone, the balloon is deflated and removed from the cavity. While inflation of the balloon and compaction occurs, fats and other debris are sucked out of the space between and around parts 12 and 14 by applying a suction force to catheter tube 16 . Following this, and following the compaction of the bone marrow, the balloon is deflated and pulled out of the cavity by applying a manual pulling force to the catheter tube 21 .
[0101] The second embodiment of the inflatable device of the present invention is broadly denoted by the numeral 60 and is shown in FIGS. 4 and 5 . Balloon 60 includes a central spherical part 62 which is hollow and which receives an inflating liquid under pressure through a tube 64 . The spherical part is provided with a spherical outer surface 66 and has an outer periphery which is surrounded substantially by a ring shaped part 68 having tube segments 70 for inflation of part 68 . A pair of passages 69 interconnect parts 62 and 68 . A suction tube segment 72 draws liquid and debris from the bone cavity being formed by the balloon 60 .
[0102] Provision can be made for a balloon sleeve 71 for balloon 60 and for all balloons disclosed herein. A balloon sleeve 71 ( FIG. 9 ) is shiftably mounted in an outer tube 71 a and can be used to insert the balloon 60 when deflated into a cortical bone. The sleeve 71 has resilient fingers 71 b which bear against the interior of the entrance opening 71 c of the vertebral bone 22 ( FIG. 9A ) to prevent tearing of the balloon. Upon removal of the balloon sleeve, liquid under pressure will be directed into tube 64 which will inflate parts 62 and 68 so as to compact the bone marrow within the cortical bone. Following this, balloon 60 is deflated and removed from the bone cavity.
[0103] FIGS. 6 and 6 A show several views of a modified doughnut shape balloon 80 of the type shown in FIGS. 1 and 2 , except the doughnut shapes of balloon 80 are not stitched onto one another. In FIG. 6 , balloon 80 has a pear-shaped outer convex surface 82 which is made up of a first hollow part 84 and a second hollow part 85 . A tube 88 is provided for directing liquid into the two parts along branches 90 and 92 to inflate the parts after the parts have been inserted into the medullary cavity of a bone. A catheter tube 16 is inserted into the space 96 between two parts of the balloon 80 . An adhesive bonds the two parts 84 and 85 together at the interface thereof.
[0104] FIG. 6A shows the way in which the catheter tube 16 is inserted into the space or opening 96 between the two parts of the balloon 80 .
[0105] FIG. 7 shows tube 88 of which, after directing inflating liquid into the balloon 80 , can inject contrast material into the balloon 80 so that x-rays can be taken of the balloon with the inflating material therewithin to determine the proper placement of the balloon. Tube 16 is also shown in FIG. 6 , it being attached in some suitable manner to the outer side wall surface of tube 88 .
[0106] Still another embodiment of the invention is shown in FIG. 3 which is similar to FIG. 1 except that it is round and not a doughnut and includes an inflatable device 109 having three balloon units 110 , 112 and 114 which are inflatable and which have string-like restraints 117 which limit the expansion of the balloon units in a direction transverse to the longitudinal axes of the balloon units. The restraints are made of the same or similar material as that of the balloon so that they have some resilience but substantially no expansion capability.
[0107] A tube system 115 is provided to direct liquid under pressure into balloon units 110 , 112 and 114 so that liquid can be used to inflate the balloon units when placed inside the bone in a deflated state. Following the proper inflation and compaction of the bone marrow, the balloon can be removed by deflating it and pulling it outwardly of the bone being treated. The restraints keep the opposed sides 77 and 79 substantially flat and parallel with each other.
[0108] In FIG. 10 , another embodiment of the inflatable balloon is shown. The device is a kidney shaped balloon body 130 having a pair of opposed kidney shaped side walls 132 which are adapted to be collapsed and to cooperate with a continuous end wall 134 so that the balloon 130 can be forced into a bone 136 shown in FIG. 11 . A tube 138 is used to direct inflating liquid into the balloon to inflate the balloon and cause it to assume the dimensions and location shown vertebral body 136 in FIG. 11 . Device 130 will compress the cancellous bone if there is no fracture or collapse of the cancellous bone. The restraints for this action are due to the side and end walls of the balloon.
[0109] FIG. 12 shows a balloon 140 which is also kidney shaped and has a tube 142 for directing an inflatable liquid into the tube for inflating the balloon. The balloon is initially a single chamber bladder but the bladder can be branded along curved lines or strips 141 to form attachment lines 144 which take the shape of side-by-side compartments 146 which are kidney shaped as shown in FIG. 13 . The branding causes a welding of the two sides of the bladder to occur since the material is standard medical balloon material, which is similar to plastic and can be formed by heat.
[0110] FIG. 14 is a perspective view of a vertebral body 147 containing the balloon of FIG. 12 , showing a double stacked balloon 140 when it is inserted in vertebral bone 147 .
[0111] FIG. 15 is a view similar to FIG. 10 except that tufts 155 , which are string-like restraints, extend between and are connected to the side walls 152 of inflatable device 150 and limit the expansion of the side walls with respect to each other, thus rendering the side walls generally parallel with each other. Tube 88 is used to fill the kidney shaped balloon with an inflating liquid in the manner described above.
[0112] The dimensions for the vertebral body balloon will vary across a broad range. The heights (H, FIG. 11 ) of the vertebral body balloon for both lumbar and thoracic vertebral bodies typically range from 0.5 cm to 3.5 cm. The anterior to posterior (A, FIG. 11 ) vertebral body balloon dimensions for both lumbar and thoracic vertebral bodies range from 0.5 cm to 3.5 cm. The side to side (L, FIG. 11 ) vertebral body dimensions for thoracic vertebral bodies will range from 0.5 cm to 3.5 cm. The side to side vertebral body dimensions for lumbar vertebral bodies will range from 0.5 cm to 5.0 cm.
[0113] The eventual selection of the appropriate balloon for, for instance, a given vertebral body is based upon several factors. The anterior-posterior (A-P) balloon dimension for a given vertebral body is selected from the CT scan or plain film x-ray views of the vertebral body. The A-P dimension is measured from the internal cortical wall of the anterior cortex to the internal cortical wall of the posterior cortex of the vertebral body. In general, the appropriate A-P balloon dimension is 5 to 7 millimeters less than this measurement.
[0114] The appropriate side to side balloon dimensions for a given vertebral body is selected from the CT scan or from a plain film x-ray view of the vertebral body to be treated. The side to side distance is measured from the internal cortical walls of the side of the vertebral bone. In general, the appropriate side to side balloon dimension is 5 to 7 millimeters less than this measurement by the addition of the lumbar vertebral body tends to be much wider than side to side dimension then their A-P dimension. In thoracic vertebral bodies, the side to side dimension and their A-P dimensions are almost equal.
[0115] The height dimensions of the appropriate vertebral body balloon for a given vertebral body is chosen by the CT scan or x-ray views of the vertebral bodies above and below the vertebral body to be treated. The height of the vertebral bodies above and below the vertebral body to be treated are measured and averaged. This average is used to determine the appropriate height dimension of the chosen vertebral body balloon.
Balloons for Long Bones
[0116] Long bones which can be treated with the use of balloons of the present invention include distal radius (larger arm bone at the wrist), proximal tibial plateau (leg bone just below the knee), proximal humerus (upper end of the arm at the shoulder), and proximal femoral head (leg bone in the hip).
Distal Radius Balloon
[0117] For the distal radius, a balloon 160 is shown in the distal radius 152 and the balloon has a shape which approximates a pyramid but more closely can be considered the shape of a humpbacked banana in that it substantially fills the interior of the space of the distal radius to force cancellous bone 154 lightly against the inner surface 156 of cortical bone 158 .
[0118] The balloon 160 has a lower, conical portion 159 which extends downwardly into the hollow space of the distal radius 152 , and this conical portion 159 increases in cross section as a central distal portion 161 is approached. The cross section of the balloon 160 is shown at a central location ( FIG. 17B ) and this location is near the widest location of the balloon. The upper end of the balloon, denoted by the numeral 162 , converges to the catheter 88 for directing a liquid into the balloon for inflating the same to force the cancellous bone against the inner surface of the cortical bone. The shape of the balloon 160 is determined and restrained by tufts formed by string restraints 165 . These restraints are optional and provide additional strength to the balloon body 160 , but are not required to achieve the desired configuration. The balloon is placed into and taken out of the distal radius in the same manner as that described above with respect to the vertebral bone.
[0119] The dimensions of the distal radius balloon vary as follows:
[0120] The proximal end of the balloon (i.e. the part nearest the elbow) is cylindrical in shape and will vary from 0.5.times.0.5 cm to 1.8.times.1.8 cm.
[0121] The length of the distal radius balloon will vary from 1.0 cm to 12.0 cm.
[0122] The widest medial to lateral dimension of the distal radius balloon, which occurs at or near the distal radio-ulnar joint, will measure from 1.0 cm to 2.5 cm.
[0123] The distal anterior-posterior dimension of the distal radius balloon will vary from 0.5 to 3.0 cm.
Proximal Humerus Fracture Balloon
[0124] The selection of the appropriate balloon size to treat a given fracture of the distal radius will depend on the radiological size of the distal radius and the location of the fracture.
[0125] In the case of the proximal humerus 169 , a balloon 166 shown in FIG. 18 is spherical and has a base design. It compacts the cancellous bone 168 in a proximal humerus 169 . A mesh 170 , embedded or laminated and/or winding, may be used to form a neck 172 on the balloon 166 , and second mesh 170 a may be used to conform the bottom of the base 172 a to the shape of the inner cortical wall at the start of the shaft. These restraints provide additional strength to the balloon body, but the configuration can be achieved through molding of the balloon body. This is so that the cancellous bone will be as shown in the compacted region surrounding the balloon 166 as shown in FIG. 18 . The cortical bone 173 is relatively wide at the base 174 and is thin-walled at the upper end 175 . The balloon 166 has a feed tube 177 into which liquid under pressure is forced into the balloon to inflate it to lightly compact the cancellous bone in the proximal humerus. The balloon is inserted into and taken out of the proximal humerus in the same manner as that described above with respect to the vertebral bone.
[0126] The dimensions of the proximal humerus fracture balloon vary as follows:
[0127] The spherical end of the balloon will vary from 1.0.times.1.0 cm to 3.0.times.3.0 cm.
[0128] The neck of the proximal humeral fracture balloon will vary from 0.8.times.0.8 cm to 3.0.times.3.0 cm.
[0129] The width of the base portion or distal portion of the proximal numeral fracture balloon will vary from 0.5.times.0.5 cm to 2.5.times.2.5 cm.
[0130] The length of the balloon will vary from 4.0 cm to 14.0 cm.
[0131] The selection of the appropriate balloon to treat a given proximal humeral fracture depends on the radiologic size of the proximal humerus and the location of the fracture.
Proximal Tibial Plateau Fracture Balloon
[0132] The tibial fracture is shown in FIG. 19A in which a balloon 180 is placed in one side 182 of a tibia 183 . The balloon, when inflated, compacts the cancellous bone in the layer 184 surrounding the balloon 180 . A cross section of the balloon is shown in FIG. 19C wherein the balloon has a pair of opposed sides 185 and 187 which are interconnected by restraints 188 which can be in the form of strings or flexible members of any suitable construction. The main purpose of the restraints is to make the sides 185 and 187 substantially parallel with each other and non-spherical. A tube 190 is coupled to the balloon 180 to direct liquid into and out of the balloon. The ends of the restraints are shown in FIGS. 19B and 19D and denoted by the numeral 191 . The balloon is inserted into and taken out of the tibia in the same manner as that described above with respect to the vertebral bone. FIG. 19B shows a substantially circular configuration for the balloon; whereas, FIG. 19D shows a substantially elliptical version of the balloon.
[0133] The dimensions of the proximal tibial plateau fracture balloon vary as follows:
[0134] The thickness or height of the balloon will vary from 0.5 cm to 5.0 cm.
[0135] The anterior/posterior (front to back) dimension will vary from 1.0 cm to 6.0 cm.
[0136] The side to side (medial to lateral) dimension will vary from 1.0 cm to 6.0 cm.
[0137] The selection of the appropriate balloon to treat a given tibial plateau fracture will depend on the radiological size of the proximal tibial and the location of the fracture.
Femoral Head Balloon
[0138] In the case of the femoral head, a balloon 200 is shown as having been inserted inside the cortical bone 202 of the femoral head which is thin at the outer end 204 of the femur and which can increase in thickness at the lower end 206 of the femur. The cortical bone surrounds the cancellous bone 207 and this bone is compacted by the inflation of balloon 200 . The tube for directing liquid for inflation purposes into the balloon is denoted by the numeral 209 . It extends along the femoral neck and is directed into the femoral head which is generally spherical in configuration. FIG. 20A shows that the balloon, denoted by the numeral 200 a , can be hemispherical as well as spherical, as shown in FIG. 20 . The balloon 200 is inserted into and taken out of the femoral head in the same manner as that described with respect to the vertebral bone. The hemispherical shape is maintained in this example by bonding overlapping portions of the bottom, creating pleats 200 b as shown in FIG. 20A .
[0139] The dimensions of the femoral head balloon vary as follows:
[0140] The diameter of the femoral head balloon will vary from 1.0 cm to up to 4.5 cm. The appropriate size of the femoral head balloon to be chosen depends on the radiological or CT scan size of the head of the femur and the location and size of the avascular necrotic bone. The dimensions of the hemispherical balloon are the same as those of the spherical balloon, except that approximately one half is provided. | 1a
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CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation of U.S. application Ser. No. 10/641,757, filed Aug. 15, 2003 now U.S. Pat. No. 6,895,775, which claims the benefit of U.S. Provisional Application No. 60/404,069, filed Aug. 16, 2002.
FIELD OF THE INVENTION
The present invention relates to the slicing of ready to eat meat logs or chubs.
BACKGROUND
Ready-to-eat (“RTE”) meat logs, or chubs, are rolls of processed meat which can be, for example, of a diameter from about 3 to about 6 inches, and up to about 72 inches in length. After the meat logs are processed, i.e., prepared, they must be sliced for market. In order to slice the meat logs in a cost effective manner, especially in consideration of the amount of material that must be sliced, it is necessary to cool and preferably freeze the surface layer of the meat log for proper and effective slicing. The cylindrical shape of the meat log makes them difficult to freeze in standard chilling tunnels and, in those situations where the crust is frozen unevenly, the slicing process is less effective and the cutting device becomes clogged with the meat material.
The market for ready-to-eat (“RTE”) products offered in supermarkets is increasing, as is the need for cost-effective slicing processes.
An unfrozen meat log impacted by a slicing blade is cut less effectively and less accurately than would be the case when using a surface frozen meat log. Conventional meat log cutting apparatus, upon retraction of the blade for a subsequent cut, cause portions of the product to adhere to the blade, which portions are flung about the processing area, while some of the material is retained on the blade surface during the subsequent cut. This causes increased maintenance and repair of the blade and support for the machinery, and is a less effective processing of the meat log. In machines conducting 1000 slices a minute, this could translate into a 5-15 percent loss of product.
Typical meat log processing apparatus include the following:
1. Conveyer belts upon which the food product is conveyed to a chilling region, which chills only one side of the meat log. 2. A plurality of meat logs are loaded in bulk into a large cryogen freezer, and the cooling medium is circulated about the meat logs in order to cool them to where the meat logs are ready for slicing.
However, these known processes take from 15 minutes to 4 hours, depending upon the equipment installed and the consistency of the composition of the meat logs. These known apparatus and methods are not cost effective, are time consuming, and consume large amounts of floor space.
Other apparatus and methods of crust-freezing meat products in preparation for cutting or slicing operations are disclosed in U.S. Pat. No. 4,943,442, which is directed to a method and apparatus for forming a frozen crust on a preformed meat body by direct immersion of a pumped, meat stream in liquid nitrogen in a freezer, followed by downstream severing and patty formation; and in U.S. Pat. No. 5,352,472, which is directed to a method and apparatus for freezing the surface of loaf-shaped meat products by compressing the loaf against a refrigerated contact surface prior to slicing. These apparatus and methods involve direct contact with either a liquid or solid heat exchange medium.
It would therefore be desirable to have a high gas-flow cruster apparatus and method, which uniformly freezes the exterior surface crust of the meat log and also is adapted to conform to the shape of the meat log for effective and accurate processing thereof.
SUMMARY
An apparatus is provided for surface crust freezing of a food product comprising: a shell enclosing a freezing chamber, the freezing chamber having a cavity shaped to substantially accommodate a shape of the exterior surface of the food product; the cavity in communication with the shell; a transport substrate to carry the food product within the freezing chamber; a cryogen supply; and a gas circulation device in the shell in communication with the cryogen supply to introduce a cooling flow of gas containing cryogen into the cavity to contact the food product along its exterior surface.
In one embodiment in which the food product is cylindrical in shape, the freezing chamber comprises an impingement cylinder having openings substantially across its length for communicating the cooling flow from the gas circulation device into cooling impingement jets of cryogen directed perpendicular to the surface of the food product.
In another embodiment in which the food product is cylindrical in shape, the freezing chamber comprises a cylinder having an opening for communicating the cooling flow from the gas circulation device along the interior of the cavity parallel to the exterior and longitudinal axis of the food product.
In another embodiment, the freezing chamber includes at least one open mesh basket adapted to accommodate the shape of the food product, the basket is carried on a drive wheel through a substantially ovaloid (that is, circular or oval) impingement chamber within the shell, the impingement chamber having impingement holes about its circumference communicating with the shell exteriorly and the freezing chamber interiorly, the basket being adapted to rotate in relation to the drive wheel such that the entire exterior of the food product is exposed to the cooling flow from the gas circulation device into the cooling impingement jets of cryogen directed through the impingement holes from the exterior of the impingement chamber substantially perpendicular to the surface of the food product. The interior of the impingement chamber is in communication with the gas circulation device to recirculate gas and cryogen to the gas circulation device.
In yet another embodiment, the freezing chamber includes at least one open mesh basket adapted to accommodate the shape of the food product, the basket is carried on a drive wheel through an elongated, substantially ovaloid (that is, circular or oval) elongated shell within the shell, the elongated shell communicating with the shell exteriorly and the freezing chamber interiorly, the basket being adapted to rotate in relation to the drive wheel such that the entire exterior of the food product is exposed to the cooling flow from the gas circulation device along the interior of the elongated shell parallel to the exterior and longitudinal axis of the food product.
A method of surface crust freezing of a food product is provided comprising: transporting the food product into a freezing chamber having a cavity shaped to substantially accommodate the shape of the exterior surface of the food product; and, introducing a cooling flow of gas containing cryogen into the cavity so as to contact the food product along its exterior surface.
In one embodiment, the method includes communicating the cooling flow into cooling impingement jets of cryogen directed perpendicular to the surface of the food product.
In another embodiment, the method includes communicating the cooling flow along the interior of the cavity parallel to the exterior and longitudinal axis of the food product.
BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification. The drawings illustrate embodiments of the invention, and, together with the description, serve to explain the principles of the invention, but are not intended to limit the invention as encompassed the claims of the application.
FIG. 1 is a perspective view of an RTE meat log inside a cylinder where impingement flow is employed.
FIG. 2 is a perspective view of an RTE meat log inside a cylinder where cross flow is employed.
FIG. 3 is a cross-sectional view of one embodiment of the cruster apparatus.
FIG. 4 is a cross-sectional view along the longitudinal length of the embodiment of FIG. 3 of the cruster apparatus.
FIG. 5 is a cross-sectional view of another embodiment of the cruster apparatus.
FIG. 6 is a cross-sectional view of a further embodiment of the cruster apparatus.
FIG. 7 is a perspective view of the embodiment of FIG. 6 of the cruster apparatus.
FIG. 8 is a cross-sectional view of another embodiment of the cruster apparatus.
FIG. 9 is a cross-sectional view along the longitudinal length of the embodiment of FIG. 8 of the cruster apparatus.
FIG. 10 is a cross-sectional view of yet another embodiment of the cruster apparatus.
FIG. 11 is a cross-sectional view along the longitudinal length of the embodiment of FIG. 10 of the cruster apparatus.
DETAILED DESCRIPTION
The present apparatus and method provides for a uniform freezing (“crusting”) of the meat log to a selected depth from the meat log surface, preferably ¼ inch, which crusting is uniform throughout the surface of the meat log, in order to overcome the disadvantages of known apparatus and methods. Freezing or crusting time for apparatus and process disclosed herein is about 1½ minutes to about 2 minutes.
The apparatus provides a cylindrically shaped freezing section that crusts a meat log product uniformly and much more efficiently than known chilling tunnels. In one embodiment, an impinging-type gas flow is employed which is directed uniformly along an exterior surface of the meat log, disposed within a cylindrically shaped chamber, so that the high velocity and perpendicular impingement heat transfer is effected along the entire surface of the meat log. In an alternative embodiment, a cross-flow gas flow is used, wherein the gas moves at high velocities parallel to a surface or longitudinal axis of the meat log. This embodiment produces comparable surface heat transfer coefficients to that of the impingement heat transfer embodiment.
Each of the embodiments described provides for a very cold surface crust (approximately ¼ inch deep) to be rapidly achieved by the meat log. Upon removal from the apparatus, the meat log can be sped to a high-speed slicer, wherein the crusting process permits a uniform, neat, and cost effective slicing operation.
As an example, one embodiment of the apparatus and process utilizes impingement type gas flow of cryogen, such as carbon dioxide or nitrogen gas, in a straight pass-through configuration. The meat log is loaded into one end of the apparatus, and is removed with a full frozen crust at the opposite end. A plurality of screw-type conveyors may be used to convey the product through the freezing apparatus and process. This method is effective for freezing round, cylindrical shaped meat logs. As a result of the conveying process, the meat log is rotated while it is frozen, eliminating the need for a moving impingement cylinder. Since meat logs are produced in a number of various cross-sectional shapes, other embodiments of the apparatus and process accommodate these shapes. The “cryogen” discussed in this Specification may include solid or liquid carbon dioxide or nitrogen, provided by a cryogen supply and mixed with the respective cryogenic gas to form a cooling gas flow.
In certain embodiments, the meat log is conveyed for crusting along a passage formed between a pair of dual hemispheres or impingement plates through which a cooling flow of a cryogen, such as carbon dioxide or nitrogen gas, is circulated to crust the meat log. In an alternative embodiment, the arrangement of the dual hemisphere impingement plates may be set off to the side, as opposed to being beneath the blower which circulates the cryogen. The conveyer in these embodiments may be a screw-type system, where the meat log has a circular cross-section. However, if the cross-section of the meat log is other than round, the conveyer may comprise belts. In yet another embodiment, the apparatus is inverted to facilitate cleaning beneath the apparatus, and between the apparatus and the underlying surface.
In alternative embodiments, the blower may be opposite the slot so that gas is drawn through the cylinder. That is, the blower may be positioned at an exit of the impingement cylinder and the slot at an entrance to the impingement cylinder.
In certain embodiments, a “rotary type” meat log crusting apparatus may be employed, again utilizing impingement type gas flow. The meat logs may be loaded and discharged at one port, for example by being placed in a stainless steel mesh basket, and being conveyed between two cylinders. One complete rotation will result in all surfaces of the product being frozen. Centrifugal fans mounted to the sidewall of the freezer provide the high-pressure cryogen gas to the impingement cylinders.
Another “rotary type” apparatus embodiment utilizes cross-flow type gas movement. The meat log is conveyed along a similar path as described above. However, without using impingement cylinders, the total space required for freezing is significantly reduced. As in the above embodiment, the meat logs are conveyed in mesh baskets and centrifugal fans provide the necessary gas flows. The cryogen gas is forced along the surface of the meat log and is circulated back into the fans, as the process continues.
Food freezing apparatus and methods are disclosed in U.S. Pat. Nos. 4,803,851; 6,263,680; and 6,434,950; and in U.S. Published Patent Application No. 2001/0025495, all assigned to The BOC Group. These patents and application are incorporated by reference herein, as if fully written below.
For a more complete understanding of the apparatus and process, reference may be had to FIGS. 1 to 11 shown in connection with the description of various the embodiments.
The flow patterns of the various embodiments of the cruster apparatus are generally described in FIGS. 1 and 2 . The cylinders 12 and 16 are used for exemplary purposes to illustrate the flow patterns used to freeze the surface layers of the RTE meat logs in the various embodiments of the apparatus and process. In FIG. 1 the surface layer of an RTE meat log 13 is frozen to a specified depth with impingement flow of a cooling flow. For example, the cylinder 12 is provided with holes 14 up and down its length, and the holes 14 provide for communication between the interior cavity 37 and exterior of the cylinder 12 . Therefore, when the cooling flow is directed toward the cylinder 12 , it is focused by the holes 14 into various cooling jets 15 . Inside the cylinder 12 , the cooling jets 15 are perpendicular to the exterior of the RTE meat log 13 . As the cooling jets 15 impinge the exterior of the RTE meat log 13 , the cooling jets 15 absorb heat, and subsequently freeze the surface layer of the RTE meat log 13 . The impingement flow as described hereinabove is used in the first, second, third, and fourth embodiments described hereinafter, to freeze the surface layer of the RTE meat logs.
In FIG. 2 , the surface layer of an RTE meat log 17 is frozen to a specified depth with cross flow of a cooling flow 18 . For example, the cylinder 16 is provided with a slot 19 , and the slot 19 allows for communication between the interior cavity 37 and exterior of the cylinder 16 . Therefore, when the cooling flow 18 is directed toward the cylinder 16 , it enters the slot 19 , and moves at a high velocity parallel to the exterior of and along the longitudinal axis of the RTE meat logs 17 . As the cooling flow 18 is applied to the exterior of the RTE meat log 17 , the cooling flow 18 absorbs heat, and subsequently freezes the surface layer of the RTE meat log 17 . The cross flow as described hereinabove is used in the fifth embodiment of the apparatus and process to freeze the surface layer of the RTE meat logs.
As shown in FIGS. 3 and 4 , the first embodiment of the cruster using impingement flow is generally indicated by the numeral 20 . The impingement cruster 20 includes a refrigeration shell 21 having a ceiling 22 , a floor 23 , and side walls 24 and 25 . The refrigeration shell 21 has an entrance 26 and exit 27 , and functions as a tunnel freezer for freezing the surface layer of the RTE meat log 30 .
Extending through the ceiling 22 is a motor shaft 31 attached to a motor 32 . The motor 32 is located on the exterior surface of the ceiling 22 , and is provided with an electrical supply (not shown). The motor 32 drives a blower assembly 33 , and the blower assembly 33 includes an impeller 34 and a volute 35 . The blower assembly 33 is attached to an impingement shell 40 using a shroud 36 , and is used to circulate and re-circulate gas around the impingement shell 40 .
The impingement shell 40 is formed from hemispherical impingement plates 41 and 42 , and is supported in the interior of the refrigeration shell 21 using support legs 38 and 39 . As shown in FIG. 3 , the impingement shell 40 is cylindrically shaped to accommodate the cylindrical shape of the RTE meat log 30 . That is, the hemispherical impingement plates 41 and 42 effectively envelop the cylindrical shape of the RTE meat log 30 . However, the impingement shell 40 can be adapted to accommodate RTE meat logs having different shapes.
As shown in FIG. 4 , the impingement shell 40 extends through the longitudinal length of the refrigeration shell 21 . Furthermore, as shown in FIG. 3 , a conveyer system 44 consisting of two rotating screws 45 and 46 is provided on the interior cavity 37 of the impingement shell 40 . The rotating screws 45 and 46 support the RTE meat log 30 inside the impingement shell 40 , and are used to convey the RTE meat log 30 along the longitudinal lengths of the refrigeration shell 21 and impingement shell 40 . Furthermore, as the rotating screws 45 and 46 move the RTE meat log 30 through the impingement shell 40 , the rotating screws 45 and 46 simultaneously rotate the RTE meat log 30 .
The rotation of the RTE meat log 30 allows a cooling flow 47 supplied by the blower assembly 33 to be applied uniformly to the exterior of the RTE meat log 30 . For example, the impingement shell 40 is provided with holes (or apertures) 48 , and these holes 48 allow the cooling flow 47 to enter, and be spread throughout the interior cavity 37 of impingement shell 40 .
The cooling jet pattern 50 created by cooling flow 47 inside the impingement shell 40 is shown in FIG. 3 . Various cooling jets are formed as the cooling flow 47 passes through the holes 48 . The cooling flow 47 may comprise a cryogenic gas (CO or N 2 ), and the heat of the RTE meat log 30 is absorbed when the cooling flow 47 impinges the exterior of the RTE meat log 30 . As such, the uniform application of the cooling jet pattern 50 to the exterior of the RTE meat log 30 uniformly freezes the surface layer of the RTE meat log 30 to a selected depth. In practice, the RTE meat log 30 is loaded onto the conveyer system 44 and into the impingement shell 40 at the entrance 26 of the refrigeration shell 21 , and is subsequently removed from the exit 27 with a frozen surface layer.
After the cooling jet pattern 50 is applied to the exterior of the RTE meat log 30 , the reflected gas flow 51 is drawn by the impeller 34 into the blower assembly 33 , and is subsequently re-circulated. For example, the impeller draws the reflected gas flow 51 into the shroud 36 . The shroud 36 communicates with the interior cavity 37 of the impingement shell 40 , and encloses an opening therein. After entering the shroud 36 , the impeller 34 draws the reflected gas flow 51 through the volute 35 . The volute 35 acts as the entrance to the impeller 34 . After entering the impeller 34 , the reflected gas flow 51 is mixed with the above-discussed cryogen, and subsequently re-circulated as the cooling flow 47 .
Attached to the exterior of the impingement shell 40 are vibrators 56 and 57 . The vibrators 56 and 57 can be pneumatically or mechanically actuated, and are used to prevent snow and ice from building up inside the holes provided in the impingement shell 40 . The frequency and time intervals of the vibrations provided by the vibrators 56 and 57 are dependent on the process conditions, including the moisture content of the RTE meat log 30 , the humidity of the ambient air in and outside the refrigeration shell 21 , and the temperature on the interior of the refrigeration shell 21 .
As shown in FIG. 5 , the second embodiment of the cruster apparatus using impingement flow is generally indicated by the numeral 60 . The impingement cruster 60 includes a refrigeration shell 61 having a ceiling 62 , a floor 63 , and side walls 64 and 65 . Like refrigeration shell 21 , the refrigeration shell 61 functions as a tunnel freezer for freezing the surface layer of an RTE meat log 30 is frozen. However, unlike the refrigeration shell 21 , the motor shaft 31 extends through the floor 63 . The motor shaft 31 is attached to a motor 32 , and the motor 32 is located on the exterior surface of the floor 63 . As such, the legs 66 and 67 support the refrigeration shell 61 , and provided clearance for the motor 32 .
Like the impingement cruster 20 , the motor 32 in the impingement cruster 60 drives the blower assembly 33 , and the blower assembly 33 is used to circulate and re-circulate gas around the impingement shell 40 . However, in the impingement cruster 60 and refrigeration shell 61 , the blower assembly 33 is inverted. For example, a support plate 68 is provided inside the refrigeration shell 61 . The support plate 68 extends between the side walls 64 and 65 , and carries the support legs (not shown) supporting the impingement shell 40 . Consequently, the volute 35 is provided below the support plate 68 , the shroud 36 is provided above the support plate 68 , and a opening (not shown) in the support plate allows the volute 35 and shroud 36 to communicate.
Other than the different configuration, the impingement cruster 60 operates like the impingement cruster 20 . That is, as the RTE meat log 30 is conveyed and rotated by the conveyer system, the cooling flow supplied by the blower assembly 33 enters the impingement shell 40 , and a cooling jet pattern is applied uniformly to the exterior of the RTE meat log 30 . The uniform application of the cooling jet pattern to the exterior of the RTE meat log 30 uniformly freezes the surface layer of the RTE meat log 30 to a selected depth. After the cooling jet pattern impinges the exterior of the RTE meat log 30 , the reflected gas flow is drawn by the impeller 34 through the shroud 36 into the volute 25 , and is subsequently re-circulated by the blower assembly 33 .
As shown in FIGS. 6 and 7 , the third embodiment of the cruster apparatus using impingement flow is generally indicated by the numeral 70 . The impingement cruster 70 includes a refrigeration shell 71 having a ceiling 72 , a floor 73 , and side walls 74 and 75 . Like refrigeration shells 21 and 61 , the refrigeration shell 71 functions as a tunnel freezer for freezing the surface layer of an RTE meat log 30 . Furthermore, like the refrigeration shell 21 , but unlike the refrigeration shell 61 , the motor shaft 31 extends through the ceiling 72 . The motor shaft 31 is attached to a motor 32 , and the motor 32 is located on the exterior surface of the ceiling 72 .
Like the impingement crusters 20 and 60 , the motor 32 in the impingement cruster 70 drives the blower assembly 33 , and the blower assembly 33 is used to circulate and re-circulate gas around the impingement shell 40 . However, in the impingement cruster 70 and refrigeration shell 71 , a low pressure plenum 76 and shroud 77 are used. For example, the impingement shell 40 is attached to the low pressure plenum 76 using brackets 78 . The shroud 77 provides for communication between the interior cavity 37 of the impingement shell 40 and the low pressure plenum 76 .
When operating, the cooling flow supplied by the blower assembly 33 enters the impingement shell 40 through holes 48 to create cooling jet pattern 50 . The uniform application of the cooling jet pattern 50 the exterior of the RTE meat log 30 uniformly freezes the surface layer of the RTE meat log 30 to a selected depth. Furthermore, after the cooling jet pattern 50 is applied to the exterior of the RTE meat log 30 , the reflected gas flow is drawn by the impeller 34 into the lower pressure plenum 76 through the shroud 77 , and is subsequently re-circulated by the blower assembly 33 .
As shown in FIGS. 8 and 9 , the fourth embodiment of the cruster apparatus using impingement flow is generally indicated by the numeral 100 . The impingement cruster 100 includes a cube-shaped refrigeration shell 101 having a ceiling 102 , a floor 103 and side walls 104 , 105 , 106 and 107 . The impingement cruster 100 is supported by pedestals 108 and 109 attached to the exterior surface of the floor 103 .
Extending through the side wall 107 are motor shafts 112 and 113 attached to motors 114 and 115 . The motors 114 and 115 are located on the exterior surface of the side wall 107 , and are provided with an electrical supply (not shown). The motors 114 and 115 are used to rotate blowers 116 and 117 attached to the motor shafts 112 and 113 . As will be discussed hereinbelow, the blowers 116 and 117 are used to circulate and re-circulate gas around the interior of the refrigeration shell 101 .
Supported on the interior of the refrigeration shell 101 is a cup-shaped impinger 118 . The cup-shaped impinger 118 is partially formed from concentric impingement cylinders 120 and 121 . As shown in FIG. 9 , the impingement cylinder 120 has a larger diameter than impingement cylinder 121 . Furthermore, the impingement cylinder 120 also has a longer length than the impingement cylinder 121 .
To form the cup shape of the cup-shaped impinger 118 , the space between the impingement cylinders 120 and 121 is enclosed using a ring-shaped plate 124 , and circular-shaped plates 125 and 126 . For example, the ring-shaped plate 124 is joined to the diameters of the impingement cylinders 120 and 121 , and encloses one end of the cup-shaped impinger 118 . Furthermore, to enclose the other end of the cup-impinger 118 , the circular-shaped plate 125 is joined around the circumference of the impingement cylinder 120 and the circular-shaped plate 126 is joined around the circumference of the impingement cylinder 121 . As such, the impingement cylinders 120 and 121 , along with the ring-shaped plate 124 and the circular plates 125 and 126 form the cup-shaped impinger 118 . Like the above-referenced impingement shell 40 , the cup-shaped impinger 118 is provided with holes 128 . The holes 128 extend through the impingement cylinders 120 and 121 , and allow for communication between the interior of the refrigeration shell 101 and the interior of the impinger 118 .
Supported on the interior of the cup-shaped impinger 118 is a drive wheel 131 . The drive wheel 131 supports a plurality of conveying baskets 132 at various positions around the circumference of the cup-shaped impinger 118 . The conveying baskets 132 are hinged to the drive wheel 131 , and, like the baskets of a ferris wheel, the orientation of the conveying baskets 132 adjusts with respect to the drive wheel 131 as the drive wheel 131 rotates. The conveying baskets 132 are composed of wire mesh, and, as shown in FIG. 9 , extend through the interior of the cup-shaped impinger 118 .
Carried by each of the conveying baskets 132 are RTE meat logs 133 . The individual conveying baskets 132 are adapted to accommodate the shape of the RTE meat logs 133 . Consequently, as the drive wheel 131 rotates, the conveying baskets 132 and RTE meat logs 133 are rotated within the interior of the cup-shaped impinger 131 . As will be discussed hereinbelow, the rotation of the drive wheel allows the surface layer of the RTE meat logs 133 to be frozen.
As the drive wheel rotates inside the cup-shaped impinger 118 , cooling flows 134 and 135 are provided by the blowers 116 and 117 . The cooling flows 134 and 135 circulate around the interior of the refrigeration shell 101 and the exterior of the cup-shaped impinger 118 , and ultimately enter the interior of the cup-shaped impinger 118 through holes 128 . As the cooling flows 134 and 135 enter the holes 128 various cooling jets (not shown) are formed. The cooling jets ultimately impinge the exterior of the RTE meat log 133 . The cooling flows 134 and 135 consist of a cryogenic gas (CO or N 2 ), and the heat from the RTE meat logs 133 is absorbed when cooling jets formed from the cooling flows 134 and 135 are applied to the exterior of the RTE meat logs 133 .
An inlet 136 and an outlet (not shown) are provided near the bottom of the refrigeration shell 101 , and a conveyer system 138 extends therethrough. The inlet 136 allows RTE meat logs 133 to be loaded and the outlet allows RTE meat logs 133 to be unloaded via the conveyer system 138 into the conveying baskets 132 . As such, the conveying system effectively allows the individual RTE meat logs 133 to be loaded and subsequently unloaded from the conveying baskets 132 as the drive wheel 131 rotates between various positions.
In practice, each of the RTE meat logs 133 is loaded into the conveyor baskets 132 via the conveyor system 138 at the inlet 136 . The rotation of the drive wheel 131 , enables each of the RTE meat logs 133 to complete at least one rotation around the interior of the cup-shaped impinger 118 . During the rotation of the RTE logs 133 around the interior of the cup-shaped impinger 118 , the uniform application of the cooling flows 134 and 135 to the exterior of the RTE meat logs 133 uniformly freezes the surface layer of the RTE meat logs 133 to a selected depth. After at least one rotation around the interior of the cup-shaped impinger 118 , each of the RTE meat logs 133 is unloaded from the conveying baskets 132 at the outlet.
As described hereinabove, the cooling jets formed from the cooling flows 134 and 135 freeze the surface layer of the RTE meat logs 133 . However, after the cooling jets impinge the exterior of the RTE meat logs 133 , the reflected gas flows 140 and 141 are drawn from the interior of the cup-shaped impinger 118 through the holes 142 and 143 and into the blowers 116 and 117 . The holes 142 and 143 are provided in the circular-shaped plate 125 , and allow the reflected gas flows 140 and 141 to enter the blowers 116 and 117 to be re-circulated as cooling flows 134 and 135 .
As shown in FIGS. 10 and 11 , the fifth embodiment of the cruster apparatus using cross flow is generally indicated by the numeral 200 . The cruster 200 includes a box-shaped refrigeration shell 201 having a ceiling 202 , a floor 203 and side walls 204 , 205 , 206 and 207 . The cruster 200 is supported by pedestals 208 and 209 attached to exterior surface of the floor 203 .
Extending through the side wall 207 are motor shafts 212 , 213 , and 214 attached to motors 216 , 217 , and 218 . The motors 216 , 217 , and 218 are located on the exterior surface of the side wall 207 , and are provided with an electrical supply (not shown). The motors 216 , 217 , and 218 are used to rotate blowers 220 , 221 , and 222 attached to the motor shafts 212 , 213 , and 214 . As will be discussed hereinbelow, the blowers 220 , 221 , and 222 are used to circulate and re-circulate gas around the interior of the refrigeration shell 101 .
Supported on the interior of the refrigeration shell 201 is an oval-shaped plate 225 with holes 226 , 227 , and 228 . Extending from the perimeter of the oval-shaped plate 225 is an elongated shell 230 having an oval cross-section. Furthermore, provided adjacent the blowers 220 , 221 , and 222 is an oval-shaped baffle 231 .
Supported on the interior of the refrigeration shell 201 is a drive wheel 241 . The drive wheel 241 supports a plurality of conveying baskets 242 at various positions. The conveying baskets 242 are hinged to the drive wheel 241 , and, like the baskets of a ferris wheel, the orientation of the conveying baskets 242 adjusts with respect to the drive wheel 241 as the drive wheel 241 rotates. The conveying baskets 242 are composed of wire mesh, and, as shown in FIGS. 10 and 11 , are encapsulated inside the elongated shell 230 along with the drive wheel 241 .
Carried by each of the conveying baskets 242 are RTE meat logs 243 . The individual conveying baskets 242 are adapted to accommodate the shape of the RTE meat logs 243 . Like the conveying baskets 132 , the conveying baskets 242 are composed of wire mesh. As will be discussed hereinbelow, as the drive wheel 241 rotates, the conveying baskets 132 and RTE meat logs 243 are rotated within the interior of the elongated shell 230 , and the rotation of the drive wheel 241 allows the surface layer of the RTE meat logs 243 to be frozen.
As the drive wheel rotates inside the elongated shell 230 , a cooling flow 244 is provided by the blowers 220 , 221 , and 222 . The cooling flow 244 circulates around the inside of the elongated shell 230 . For example, the oval-shaped baffle 231 causes the cooling flow 244 to be directed outwardly from the blowers 220 , 221 , and 222 toward the conveying baskets 242 and RTE meat logs 243 . However, the elongated shell 230 captures the cooling flow 244 , and ensures that the cooling flow is adequately applied to the RTE meat logs 243 . The cooling flow 244 is a cross flow which moves at a high velocity parallel to the exterior along the longitudinal axis of the RTE meat logs 243 . As shown in FIG. 10 , parts of the cooling flow 244 are disposed adjacent the conveying baskets 242 and RTE meat logs 243 . The cooling flow 244 consists of a cryogenic gas (CO or N 2 ), and the heat from the RTE meat logs 243 is absorbed when the cooling flow 244 is applied to the exterior of the RTE meat logs 243 . Overall, the heat transfer coefficients of the cooling flow 244 is comparable to the heat transfer coefficients of the cooling jets formed from the cooling flows 134 and 135 when using impingement flow.
An inlet 246 and an outlet (not shown) are provided near the bottom of the refrigeration shell 201 , and a conveyer system 248 extends therethrough. The inlet 246 allows RTE meat logs 243 to be loaded and the outlet allows RTE meat logs 243 to be unloaded via the conveyer system 248 into the conveying baskets 242 . As such, the conveying system effectively allows the individual RTE meat logs 243 to be loaded and subsequently unloaded from the conveying baskets 242 as the drive wheel rotates between various positions.
In practice, each of the RTE meat logs 243 are loaded into the conveyor baskets 242 via the conveyor system 248 at the inlet 246 . The rotation of the drive wheel 241 , enables each of the RTE meat logs 243 complete at least one rotation around the inside of the elongated shell 230 . During the rotation of the RTE logs 243 around the inside of the elongated shell 230 , the uniform application of the cooling flow 244 to the exterior of the RTE meat logs 243 uniformly freezes the surface layer of the RTE meat logs 243 to a selected depth. After at least one rotation around the inside of the elongated shell 230 , each of the RTE meat logs 243 are unloaded from the conveying baskets 242 at the outlet.
As described hereinabove, the cooling flow 244 freezes the surface layer of the RTE meat logs 243 . However, after the cooling flow 244 is applied to the exterior of the RTE meat logs 243 , the remaining gas flows 250 and 251 flow around the outside of the elongated shell 230 and into the blowers 220 , 221 , and 222 . The holes 226 , 227 , and 228 allow the remaining gas flows 250 and 251 to pass into the blowers 220 , 221 , and 222 , and be re-circulated as cooling flow 244 .
Each of the embodiments of the cruster apparatus act to rapidly freeze the surface layer of the RTE meat logs to approximately 0.25 inch deep. Upon removal from the various embodiments, the RTE meat logs can be transferred to a cutting blade to be sliced. The frozen surface layer of the RTE meat logs allows for a uniform, neat, and cost-effective slicing operation as described hereinabove.
All dimensions and parameters discussed with respect to all the embodiments are by way of example and not limitation. It will be appreciated that other sizes and shapes of the apparatus and its component parts may be employed. Although the invention has been described in detail through the above detailed description and the preceding examples, these examples are for the purpose of illustration only and it is understood that variations and modifications can be made by one skilled in the art without departing from the spirit and the scope of the invention. It should be understood that the embodiments described above are not only in the alternative, but can be combined. | 1a
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FIELD OF THE INVENTION
This application is a 35 U.S.C. 371 application of PCT/FI96/00015 filed on Jan. 18, 1993.
The present invention relates to a surgical instrument for installation of a surgical implant in a living tissue, particularly in connection with a surgical operation. The installation instrument comprises a frame with an installation channel, in which the implant is inserted in the beginning of installation. The instrument further comprises an installation part arranged to be inserted in the installation channel and to convey an external force needed for the installation of the implant to the implant. The frame is placed in connection with the tissue in a manner that the implant is inserted in the tissue when it exits the installation channel at the installation end of the frame.
In the context of the present invention, living tissue refers particularly to bone, ligament, connective tissue, synovial or joint tissue, muscular tissue, as well as others. Further, important fields of applying the invention include corrective surgery of meniscal rupture as well as bone surgery as treatment of bone fractures. The installation instrument of the invention is suitable for use in arthroscopic surgery. In this invention, implant refers to a usually elongated macroscopic piece that is suitable to be surgically installed with a force effective thereon. The force moves the implant essentially in the direction of its largest dimension into the tissue.
BACKGROUND OF THE INVENTION
Implants of this kind typically include rod-shaped and arrow-shaped implants. As to arrow-shaped implants, reference is made to U.S. Pat. No. 4,873,976. This patent discloses an arrow-shaped implant and a method for its installation. The implant and method are to be used particularly in the repairing surgery of meniscal rupture. The implant is typically manufactured of at least martially bioabsorbable polymer material.
In surgery, it is generally known to use installation instruments, typically manufactured of metal, for installing macroscopic implants, such as rods, hooks, pins, bolts and the like. Such implants are used in living tissues to connect operated or damaged tissues with each other or with other tissues. In such surgical installation instruments, the implant is typically placed at the initial stage either in part or wholly inside an installation channel in the installation instrument. The implant is forced from the installation instrument into the tissue by tapping manually with a hammer. A special, typically piston-like, installation part conveys the force generated with the hammer to the implant and, thus, forces the implant to penetrate into the tissue. It is also known to use an application whereby the implant is forced into the tissue by one powerful, quick stroke effected on the implant. The stroke maybe produce mechanically, pneumatically, hydraulically or electromagnetically, for example.
However, the surgical installation instruments of prior art used for installation macroscopic implants into a tissue nave certain disadvantages. If the surgeon uses a manual installation instrument, he/she needs both of his/her hands for controlling the instrument. With one hand, the surgeon must support the frame of the surgical implant, wherein the surgical implant is inserted, at least partly, in the beginning of the installation operation. With the other hand, the surgeon must tap the hammer or a corresponding tool, thus directing the force required for the transmission of the implant and conveyed by an installation part into the implant. Consequently, the surgeon cannot use his/her own hands to keep in position that part or parts of the tissue that he/she will attach to each other with the implant. Thus, the surgeon must usually have an assistant who keeps the parts of the tissue in position. As a result, the direct feel of the surgeon to the reactions of the tissue is essentially diminished as the operation proceeds. If the surgeon alternatively uses an installation instrument which forces the implant by one stroke into the tissue, his/her control over the installation procedure is also very poor. The lack of control results in an inability to change the direction or position of the implant as the installation operation proceeds. Additionally the installation operation cannot be stopped after the implant has been triggered.
SUMMARY OF THE INVENTION
It is an object of this invention to present a new kind of surgical installation instrument for use in the installation of macroscopic implants. The present invention overcomes disadvantages of installation instruments of prior art as well as factors delimiting the safety of patients. For achieving this aim, the installation instrument according to the invention is primarily characterized in that the installation part comprises means for connecting the installation part to a power transmission part arranged to perform a reciprocating movement. The reciprocating movement is arranged to be transmitted as a periodical movement of the implant from the installation channel through the installation end of the frame into the tissue.
Application of the surgical installation instrument in the manner described above provides several advantages over the instruments of prior art.
Using an installation instrument of the invention, the surgeon can install an implant into a tissue by one hand. This permits the surgeon to maintain his other hand in position those parts of the tissue through which the surgeon intends to force the implant. The surgeon can, thus, control the installation operation better than with present methods. Improved control over the installation permits the surgeon to correct the position of the tissues during the installation operation, when necessary. Also, the penetration of the implant effected by successive, quick strokes enables the surgeon to control the installation operation better than before, because he/she can, for example, change the direction of the installation instrument and/or the implant during the installation operation or interrupt the operation, if necessary. This may be required, for example, in a case when the tissues to be attached to each other are displaced for any reason during the operation.
The advantages of the installation instrument exerting quick reciprocating or vibrational movement can have the following theoretical basis: According to the viscoelastic theory, the modulus of viscoelastic material increases with an increase in the velocity of dynamic stress. In practice, this means that when an arrow-shaped implant is slowly penetrated into a viscoelastic connective tissue such as meniscal tissue, the meniscal tissue reacts as a soft material, yielding and tending to bend away from the implant penetrating into it. On the other hand, when the implant is vibrated step-by-step into the tissue utilizing a reciprocating movement by quick strokes of the installation instrument, the meniscal tissue will not react fast enough to the movement of the arrow-shaped implant in the manner of a soft material. Rather, the meniscal tissue will react as a hard material, not yielding with the forward movement of the implant anywhere near the extent as in manual penetration or stroke. The implant thus penetrates the meniscal tissue, or a preliminary hole made in it, easily without causing extensive transformation of the surrounding tissue.
In a particularly advantageous embodiment, the frame of the installation instrument further comprises at lease one arresting means that is in the operational position of the frame. According to this embodiment, the installation part is inserted inside the installation channel, in contact with the tissue, in order to arrest the installation end of the frame in position in relation to the tissue during installation of the implant. As the frame can be locked in the installation end by the arresting means into the tissue for the time of the operation, the surgeon can secure the correct position of the installation channel before the actual phase of installing the implant.
Further, according to a preferred embodiment of the invention, at least one arresting means in the surgical installation instrument is arranged to be movable and lockable in relation to the frame. According to this embodiment the said arresting means in the non-operational position is placed inside the installation end of the frame. In the operational position, the arresting means from the installation end of the frame. In this application, it is possible to place the arresting means inside a tissue, particularly a soft tissue, in a way required by the surgical operation and the dimensions of the tissue in question. The arresting means can be advantageously, locked at different penetration depths in relation to the frame in its operational position. For this purpose, the frame can be equipped with several locking means cooperating with a transfer and locking means placed in the arresting means and preferably controlled manually. The locking means can be locked in position for locking the arresting means in a desired operational penetration depth.
Further, according to another preferred embodiment of the invention, the installation instrument further comprises at least one needle-like element. The needle-like element has a cross-section at least partly formed in a manner such that the needle-like element can be placed, via the installation channel or a part thereof, to bypass the installation end of the frame in order to make a preliminary hole or a like in the tissue before the installation of the implant. The installation end of the frame is placed in the installation position of the implant and arrested by at least one arresting means. This application provides the advantage of a smaller force required for the series of strokes by the installation part on the implant. As a natural consequence, the risk of an implant to be directed into an incorrect position and damaged is substantially reduced, because the forces effective upon it during installation are reasonable. This embodiment is particularly advantageous in connection with operations on tough fibrous tissues, such as meniscus, in which the margin of error is very small.
Further, according to still another advantageous embodiment, the frame of the installation instrument is at least partially formed of a transparent material.
Installation instruments of prior art are manufactured of metal material, particularly stainless steel. For this reason, these installation instruments have the disadvantage of not enabling the surgeon to evaluate visually the progress of the installation of the instrument and the condition of the implant. In particular, lack of visual contact with at least that part of the installation instrument where the implant is situated, that is the installation end of the installation frame of the instrument, complicates arthroscopic operations. Arthroscupic operations are performed inside a joint by introducing a installation instrument into the arthral chamber through a small inclision. The stages of the operation are controlled by means of a special arthroscopic instrument that is introduced into the arthral chamber either through the same or another small incision. Consequently, the surgical installation instrument of the present invention can also be used to avoid this adverse factor present in installation instruments of prior art. Thus, the present invention can further increase reliability and safety of the installation to the patient.
Some advantageous embodiments of the surgical installation instrument of the invention are further presented below.
BRIEF DESCRIPTION OF THE DRAWINGS
In the following description, the surgical installation instrument of the invention will be illustrated further with reference to the embodiments shown in the appended drawings. In the drawings,
FIG. 1 shows a schematic perspective view of a first embodiment of the surgical installation instrument;
FIG. 2 illustrates the cross-section of the embodiment of the frame of the installation instrument shown in FIG. 1 in a longitudinal direction;
FIG. 3 shows a perspective view of a second embodiment of the surgical installation instrument, where the installation part is fixed in connection with a power transmission element;
FIG. 4 illustrates the cross-section of the embodiment the frame of the installation instrument shown in FIG. 3 in a longitudinal direction; and
FIGS. 5a-d schematically illustrate the phases of installation of an implant, particularly an arrow-shaped implant, into the meniscus; and
DETAILED DESCRIPTION OF THE INVENTION
With reference to FIG. 1, the installation instrument of the invention comprises as main parts a frame 1 and an installation part 2. FIG. 1 also illustrates two needle-like elements 3a, 3b of the surgical installation instrument.
The frame 1 comprises a combination of an elongated installation frame 4 and an operational frame 5. The frame 1 is penetrated by an installation channel 6. The cross-sectional form of the installation channel corresponds to the shape of the outer surface of the implant I as seen in the direction of the longitudinal axis of the implant. In the embodiment in FIG. 1, the installation frame 4 has a flat cross-sectional form. For example, the installation frame 4 may have a rectangular or oval form. The installation channel 6 is centrally situated in the direction of the greater dimension of the installation frame such that arresting means 7a, 7b are located on both sides thereof in the same direction. The arresting means 7a, 7b can be fixedly mounted or attached or they are placed in corresponding arresting channels 8a, 8b in the frame. The arresting channels 8a, 8b extend in the direction of the installation channel. In the non-operational position, the arresting means 7a, 7b, which are rod-like elements with a sharpened head and a circular cross-sectional form, are inside the installation end 9 or the frame 1. At the point of the arresting means, there is a longitudinal groove 10a, 10b on both sides of the operational frame 5. Protruding transfer and locking means 11a, 11b are connected with the arresting means.
In the embodiment shown above, a transverse grooving 12a, 12b has been formed in the grooves 10a, 10b. Transversely grooving 12a, 12b is perpendicular to the longitudinal direction of the grooves 10a, 10b. The transfer and locking means 11a, 11b can be placed in the transfer grooving 12a, 12b when the arresting means is moved into the operational position in the longitudinal direction of the arresting channel 8a, 8b and, thus, to protrude from the installation end 9 of the frame 1. The arresting means are 7a7b locked by moving the transfer and locking means 11a, 11b around the longitudinal axis of the arresting means into a desired groove of the transverse grooving 12a, 12b.
As mentioned above, the other end of the installation channel 6 is placed at the supply end 13 of the operational frame in a manner such that the installation part 2 can, fixed with the power transmission part 14 shown in FIG. 3 be inserted in the installation channel.
The operational frame is further equipped with a handle 15.
In the application shown in FIG. 1, the operational frame 5 further comprises a cassette or box 16 that can be changed in connection with the operational frame. A suitable number of implants I can be placed within the box 16 in advance. In FIG. 1, one implant is illustrated inside the box 16 with broken lines. In the embodiment shown, the implant I is an arrow-shaped element having a head and a stem at opposite ends of a body. The head comprises a scutellate or corresponding arresting structure. The radial dimension of the stem is formed to exceed that of the body. In connection with a surgical operation on, for example, a meniscal rupture, as illustrated particularly in FIG. 5d, the head penetrates the meniscus at least particularly. In this procedure the stem remains outside the meniscus to prevent an unintentional movement of the implant in the direction of installation. On the other hand, the scutellate or corresponding structure of the head cooperates with the stem, exerting a compressing force on the meniscus, particularly the rupture. This contributes to the healing of the meniscus. In this connection, it should be pointed out that although the invention is illustrated with an example that is applicable particularly in surgical operations of the meniscus, it is clear that the surgical instrument of the present invention can be equally well applied in bone surgery, particularly in surgical operations on bone fractures, in connective tissue surgery and other surgery of the tissues of the musculosceletal system. Further, with reference to FIG. 1, the box 16 can comprise a spring-loaded plunger 17. Plunger 17 can keep the implants I in such an order in the box 16 that upon pulling a loading device 18 between the box 16 and the operational frame 5, for example, in the direction of arrow 19, the next implant I is moved from the box 16 into the installation channel 6 within the operational frame, as shown schematically in FIG. 2. From this position, the implant I can, for example, by using the installation part 2, be transferred to the installation end 9 of the installation channel.
In an advantageous manner, the surgical installation instrument of the invention is made to be at least partly transparent. In the embodiment shown in FIG. 1, the part at the installation end 9 of the installation frame 4 is made transparent. This transparent part 4a of the installation frame 4 can be advantageously manufactured as a disposable part that can be attached with snap-in fixing means to the stationary part 4b of the installation frame mounted on the operational frame 5. The snap-in fixing means are shown by the reference numeral 20 in FIG. 2. The transparent part 4a can be manufactured of a transparent polymer, copolymer or a polymeric mixture. Also ceramic materials are feasible materials to form the transparent part. The transparent part 4a naturally comprises a part corresponding to the cross-sectional form of the Installation channel as well as parts corresponding to the arresting channel, thereby making it functionally fully compatible with the frame 1.
FIG. 1 further illustrates the installation part 2 pertaining to the surgical instrument of the invention. Part 2 is an elongated rod-like formed piece with a cross-sectional form. The part 2 is perpendicular to the longitudinal direction of the installation frame. Preferably, the part 2 has a cross-section corresponding to the cross-sectional form and size of the installation channel 6 of the frame 1. The length of the installation part is selected so that, connected with a power transmission part 14, it can act on the implant in the installation channel, particularly the stem, for the entire length of the installation channel. The other end part of the installation part 2 is equipped with a means 21 for attaching the installation part to the power transmission part 14, shown in FIG. 3. The reciprocating movement of the power transmission part 14 is arranged in a way that the installation part 2 moves backward and forward in its longitudinal direction, as indicated by the arrow L in FIG. 3).
FIG. 3 illustrates an embodiment of the frame 1 where the implant is fed into the installation channel through an opening in the supply end 13 in the installation channel. Using the installation part 2 coupled with the power transmission part 14, the implant is entered into the installation end 9 of the frame 1 in the installation channel. The power transmission part 14 can be operated on a pneumatic, hydraulic and/or electromagnetic principle. The power transmission part 14 shown in FIG. 3 is arranged to work pneumatically. It has a connecting means 14a for conveying compressed air into a piston arrangement inside the frame 14b of the power transmission part 14. Power transmission parts of this kind are available in different commercial applications, for example, as reciprocating surgical bone saws. These power transmission parts can be applied minor technical modifications for use in combination with a surgical installation instrument of this invention. An example of such power transmission parts are products marketed under the trademark HALL R . Power transmission parts of this kind, as well as their socket structures, in which the attaching means 21 of the installation part 2, shown in FIG. 1 is attached, are obvious to an artisan in the field and consequently not described more closely in this context.
FIG. 4 shows an alternative application for combining the installation frame 4, which is preferably transparent, and the operational frame 5. In this embodiment, the installation frame 4 is entirely formed of a transparent material, and its end is equipped with a flange 16. The installation frame 4 is attached to the end of the operational frame 5 as indicated by the broken lines in FIG. 4. The installation frame may be attached to the operation frame with a screw, for example. An advantage of this arrangement is that installation frames 4 of different shapes can be used in connection with the same operational frame 5. It is a generally known fact that curved or bent forms of the installation frame 4 may be required in certain surgical operations in order to get at the tissue to be operated on. Consequently, a solution of this kind can broaden the field of use of the surgical installation instrument. Naturally in these cases flexibility is required of the material of the arresting means so that they can adjust to the shape of the installation frame 4.
FIGS. 5a-5d illustrate schematically the phases of a surgical operation performed using a frame shown in FIGS. 3 and 4. The operation shown in FIG. 5a-5b is a surgical repairing operation of a rupture R of the meniscus NK. This is performed preferably by arthroscopy. In the first phase shown in FIG. 5a, the arresting means 7a, 7b are pushed into the operational position by rising the transfer and locking means 11a, 11b, whereby the arresting means can extend over the rupture. In this manner, the installation end 9 of the frame 1 is locked position and at the same time the rupture R is immobilized and, thus controlled. In the next phase according to FIG. 5b, a needle-like element 3a is introduced via the installation channel 6 into the meniscus in order to make a preliminary hole. FIG. 5b illustrates the use of a needle-like element 3a. However in the embodiment shown in FIG. 5c, a needle-like element (not shown) of FIG. 1 can also be used. The needle-like element 3b comprises two needle-like elements, one inside the other. The outer element 3b' has a larger diameter. Inside the outer element it is a relatively thin needle-like element 3b". The preliminary hole is lengthened by the element 3b" after the outer needle-like element 3b' has substantially reached the center of the meniscus and passed the rupture, all the way through the meniscus. Thus, a preliminary hole ER is formed as shown in FIG. 5c. The preliminary hole ER comprises a part ER1 with a wider diameter and a part ER2 with a smaller diameter. The diameter of the needle-like element can correspond to the diameter of the body of the implant I, whereby the needle-like element can be moved in the installation channel along the wider middle section of the installation channel. This wider middle section is shown by the reference numeral 6a in FIG. 4. Particularly for the wider wing structure of the stem of the implant I, the installation channel 6 is provided with widenings shown by the reference numeral 6b in FIG. 4. Further, FIG. 5c illustrates the placement of the implant in the installation channel 6 all the way to the installation end 9 of the installation frame 4 using the installation part 2, which is coupled with the power transmission part 14. The implant I is pressed via the preliminary hole ER through the meniscus into a position shown in FIG. 5d. In this phase, the advantages of the surgical installation instrument of the present invention are obvious. The arresting means 7a, 7b ensure that the frame 1 is kept in position. The preliminary hole ER facilitates the installation of the implant. The transparent installation frame 4 provides immediate visual control of the position of the implant in the installation frame also during arthroscopy. Further, the most important operational advantage in this phase is the fact that the surgeon, while maintaining the stem of the implant I in contact with the head of the installation part 2, can observe the implant as it proceeds into the preliminary hole and stop the installation of the implant if necessary. Thus, the implant can be installed into the tissue in stages by utilizing the reciprocating movement of the installation part and the simultaneous movement in the installation channel feeding the installation part.
It is obvious that the advantages presented above apply also to many surgical operations than other meniscal operations.
The installation instrument of the invention can be modified even to a high degree. One particular alternative for a frame, especially a transparent installation frame, is to fix the arresting means in connection with the transparent frame in a manner that they protrude from the installation end 9. Thus the arresting means 11a and 11b, which can be moved and locked in relation to the frame 1, can be eliminated from the frame 1. It is also obvious that there can be one, or more than two of the arresting means 7a, 7b placed in the same frame 1 to be moved and locked in relation to the frame 1 or to the transparent installation frame protruding from the installation end 9 of the installation frame.
Obviously, the dimensions and shape of the surgical installation instrument can even vary considerably; only a few applicable alternatives are shown in the appended drawings. In the embodiment shown in the drawings, the following dimensions can be brought up within the basic dimensions. The total length of the installation frame 4 can vary between 20 and 200 mm. The width and thickness of the flat cross-section of the installation frame 4 can be typically 3 to 6 mm and and 1 to 3 mm, respectively. The length of the operational frame 5 can be 20 to 120 mm, whereby the total length of the frame 1 varies between 40 and 320 mm. The penetration depth of the arresting means can be chosen by the transverse grooving to be 5-10 mm, for example. The arrow-shaped implant used, for example, in meniscal surgery has a length of about 14 mm. The diameter of the body is about 1.5 mm. The maximum radial dimension of the stem is 3 mm. The dimension of the stem length of the wing in the axial direction being is about 1.5 mm.
One very important detail, is that according to practical measurements, good penetration of the implant into the meniscal tissue is achieved when the maximum rate of a single stroke of the vibrating movement is at least 300 meter per minute (m/min) and the frequency of the strokes is higher than 1000/min or about 17/s and, preferably about 10000-20000/min or about 170-340/s. If the stroke rate is in the order of 50 to 150 m/min, which is a typical stroke rate when slow vibration is performed manually by hitting a cylindrical piston with a suitable hammer, the piston conveying the stroke to the implant, the rate of the stroke is thus so low that the meniscal tissue reacts in a manner of a soft material, yielding and bending, whereby the implant does not properly penetrate into the tissue.
Co-pending application "Surgical implant" of the same applicant, to which reference is hereby made describes in detail the implant described above. | 1a
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[0001] This application is the national phase under 35 U.S.C. §371 of PCT International Application No. PCT/CN01/00922 which has an International filing date of June 8, 2001, which designated the United States of America.
FIELD OF THE INVENTION
[0002] The present invention relates to the pharmaceutical use, especially about using N-desulfated heparins, which have significantly reduced anticoagulant activities and preserve anti-inflammation activity, for prevention and treatment of inflammation. The invention further relates to methods and means for testing heparin and heparin derivatives with significantly reduced anticoagulant activities for therapeutic purposes.
DESCRIPTION OF BACKGROUND AND RELATED ART
[0003] Heparin is a highly sulfated natural polysaccharide that is first described by McLean in 1916 and has been used clinically as an anticoagulant for more than 50 years [McLean, Circulation 19, 75-78 (1959)]. It is synthesized in the endoplasmic reticulum as proteoglycans attached to the protein serglycine [Toledo and Dietrich, Biochim. Biophys. Acta 498, 114-122 (1977)]. Heparin is an intracellular product found in the secretary granules of mast cells often in complexation with basic proteins. In response to certain external signal, it is released exclusively from mast cells of the lung, intestine and liver during their degranulation. The released soluble heparin carries negative charges and is know to bind to more than one hundred proteins including many growth factors and chemokines. Heparin can be isolated, in a relative inexpensive way, from highly vasculaturized tissues, such as porcine or bovine intestinal mucosa, or less commonly, from bovine lung tissue [Conrad, Heparin - Binding Proteins , Academic Press, San Diego (1998)].
[0004] Heparin is a mixture of polydisperse, structurally similar, unbranched polymers made up of repeating units of alternating disaccharides containing hexuronate (either β-D-glucuronic acid or α-L-iduronic acid) and α-D-glucosamine (either N-sulfated or N-acetylated). They are joined by (1,4) glycosidic linkages. The major sites where sulfation may be present are at the 2-O position of the iduronic acid residues as well as the 2-N position and 6-O position of the glucosamine residues. In addition, it is occasionally sulfated on either the 2-O position of glucuronic acid residues or the 3-O position of the disulfated glucosamine residues [Tyrrell et al., Adv. Pharmacol. 46, 151-208 (1999)]. The linear glycosaminoglycan chains are covalently bound to serine residues of core proteins. The heparin polymer may contain 20-100 monosaccharide units per polysaccharide chain, and due to the long repeats of (ser-gly) n in the protein sequence, a high density of heparin chains can be attached to the serglycine core [Ruoslahti, J. Biol. Chem. 264, 13369-13372 (1989)]. However, the number and position of GAG chains vary with the protein core.
[0005] Besides heparin, there has another sulfated polysaccharide, heparan sulfate, which is structurally similar to heparin and contains all of the structural motifs found in heparin. In contrast to heparin, it is normally secreted from cells. It is distributed ubiquitously on the surface of most animal cells and as a major component of the basement membranes in extracellular matrix. Heparin and heparan sulfate are members of a family of polysaccharides termed “Glycosaminoglycans,” or GAGs [Hook et al., Annu. Rev. Biochem. 53, 847-869 (1984)]. In addition to heparin and heparan sulfate, this family includes chondroitin-sulfate, dermatan sulfate and hyaluronic acid.
[0006] Heparin and heparan sulfate have the most heterogeneous structures in the GAG family. Heparan sulfate typically has a low level of N- and O-sulfation and retains more of the original N-acetylglucosamine and glucuronate residues. Compared to heparin, heparan sulfate generally has fewer and shorter GAG chains which can be attached to a variety of core proteins, often in conjunction to chondroitin sulfate chains [Kjellen and Lindahl, Ann. Rev. Biochem. 60, 443-475 (1991)]. It can also be attached directly to the cell surface (via either a transmembrane domain of the core protein or a phosphatidyl-inositol likage) or they may be bound by specific receptors at the cell surface [Gallagher, Curr. Opin. Cell Biol. 1, 1201-1218 (1989)]. It has reported that different cells can have distinct subtypes of heparan sulfate chain, suggesting a possibility that they may play roles in mediating cellular interactions [Kim et al., Mol. Biol. Cell 5, 797-805 (1994); Engelmann et al., Biochim. Biophys . Acta Mol. Cell Res. 1267, 6-14 (1995); Archer et al., J. Anat. 189, 23-35 (1996)].
[0007] Compared to heparan sulfate, heparin is more highly sulfated and contains a greater percentage of iduronate residues which have been epimerized from glucuronate. Due to the differences in composition and the extent of sulfation, heparin is more highly charged than heparan sulfate. The higher percentage of iduronate residues in heparin also increases the relative flexibility of the polymer. This flexibility coupled with an increase in the presence of additional electrostatic interactions is presumed to provide a greater biological activity associated with iduronate-containing GAGs as compared to glucuronate containing counterparts [Casu et al., Trends Biochem. Sci. 13, 221-225 (1988)].
[0008] The most widely accepted and commercially exploited functions of heparin are as an anticoagulant. This action of heparin resides in its ability to regulate the activity of an endogenous coagulation cofactor, antithrombin-III (AT-III), which inhibits many serine proteases involved in the coagulation cascade [Bourin and Lindahl, Biochem. J. 289, 313-330 (1993)]. Heparin can interact with AT-III, via a specific high-affinity pentasaccharide sequence that represents only a minor portion of any heparin chain, to form a complex that inhibits thrombin and Factor Xa much more effectively than AT-III alone. Heparin can also interact with another serine protease inhibitor, heparin cofactor II (HC-II), to further potentate the inhibition of thrombin.
[0009] Beyond its well-recognized anticoagulant activity, heparin and heparan sulfate have various non-anticoagulant actions. Among them are anti-inflammatory roles which include prevention of leukocyte adhesion [Tangelder and Arfors, Blood 77, 1565-1571 (1991); Ley et al., Am. J. Physiol. 260, H1667-H1673 (1991); Arfors and Ley, J. Lab. Clin. Med., 121, 201-202 (1993); Teixeira and Hellewell, Br. J. Pharmacol. 110, 1496-1500 (1993); Nelson et al., Blood. 82, 3253-3258 (1993); Seeds et al., J. Lipid Mediators 7, 269-278 (1995); Kitamura et al., Eur. Surg. Res. 28, 428-435 (1996); Weber et al., J. Cereb. Blood Flow Metab. 17, 1221-1229 (1997); Giuffre et al., J. Cell Biol. 136, 945-956 (1993)] and activation [Pasini et al., Thromb. Res. 35, 527-537 (1984); Bazzoni et al., J. Lab. Clin. Med. 121, 268-275 (1993); Riesenberg et al., Br. Heart J. 73, 14-19 (1995); Ahmed et al., Am. J. Respir. Crit. Care Med. 155, 1848-1855 (1997)], inhibition of complement activation [Weiler et al., J. Immunol. 148, 3210-3215 (1992); Teixeira et al., J. Leukocyte Biol. 59, 389-396 (1996)], maintenance of endothelial wall competence and integrity and protection of vascular endothelial cells from a number of damaging substances, such as chemokines, histamine, bradykinin, bacterial endotoxin, lysosomal cationic proteins and oxygen free radicals [Engelberg, Semin. Thromb. Hemost. 11, 48-55 (1985); Hiebert and Liu, Semin. Thromb. Hemost. 17(suppl 1), 42-46 (1991); Tanaka et al., Nature 361, 79-82 (1993); Webb et al., Proc. Natl. Acad. Sci. USA 90, 7158-7160 (1993)].
[0010] For example, heparin and heparan sulfate are known to bind to cell adhesion molecules P-selectin, L-selectin and Mac-1 (CD11b/CD18) and to inhibit leukocyte adhesion mediated by these molecules [Skinner et al., Biochem. Biophys. Res. Commun. 164, 1373-1379 (1989); Skinner et al., J. Biol. Chem. 266, 5371-5374 (1991); Nelson et al., Blood. 82, 3253-3258 (1993); Norgard-Sumnicht et al., Science. 261, 480-483 (1993); Diamond et al., J. Cell Biol. 130, 1473-1482 (1995); Giuffre et al., J. Cell Biol. 136, 945-956 (1997); Koenig et al., J. Clin. Invest. 101, 877-889 (1998)]. Heparan sulfate, synthesized by endothelial cells [Castillo et al., Biochem. J. 247, 687-693 (1987); Kinsella and Wight, Biochemistry 27, 2136-2144 (1988)], can bind to various chemokines and therefore optimally localize these chemotactic cytokines [Tanaka et al., Nature 254, 79-82 (1993); Furie and Randolph, Am. J. Pathol. 146, 1287-1301 (1995)]. Heparin and heparan sulfate can bind to many biochemical constituents on endothelial cells and thus restore the negative charge of the endothelial cell surface made positive following tissue injury [Engelberg, Semin. Thromb. Hemost. 11, 48-55 (1985); Hiebert and Liu, Semin. Thromb. Hemost. 17(suppl 1), 42-46 (1991)].
[0011] In literature, heparin can by modified chemically in many ways. These modified ones have been proved to be invaluable for the structural and functional studies. They include periodate oxidation, N-desulfation, N-deacetylation, modifications of N-unsubstituted heparinoids, 2-O-desulfation, 6-O-desulfation, carboxyl reduction and derivatization, epimerization, sulfate migration, and oversulfation [Conrad, Heparin-Binding Proteins, Academic Press, San Diego (1998)].
[0012] Tiozzo and his colleagues have reported the effect of desulfation of heparin on its anticoagulant. N-desulfated heparin derivatives, compared with starting heparin, have significantly reduced anticoagulant activity, but the anticoagulant activity of heparin and its derivatives has no absolute linear relationship with the N-sulfate content of heparin chains. [Tiozzo et al., Thromb. Res. 70: 99-106 (1993)].
[0013] Using chemical modifications, it has been shown that the non-anticoagulant heparins could inhibit rat arterial smooth muscle cell proliferation in vivo [Guyton et al., Circ. Res. 46, 625-634 (1980)]. The 2-O-desulfated and 3-O-desulfated heparins had reduced anticoagulant activities, but preserved their heparanase-inhibitory, angiostatic, anti-tumor and anti-metastatic properties. (Masayuki et al., U.S. Pat. No. 5,795, 875 (1997); Lapierre et al., Glycobiology 6, 355-366 (1996)].
[0014] In addition, Ahmed and his colleagues have reported that they could generate non-anticoagulant heparin by collection of the low affinity fraction of the intact, non-chemical modified heparin from affinity resins conjugated with antithrombin III. The non-anticoagulant heparin thus prepared could inhibit antigen-induced acute bronchconstriction, airway hyperresponsiveness, and mass cell degranulation [Ahmed et al., Am. J. Respir. Crit. Care Med. 155:848-1855 (1997)].
[0015] Heparin and low molecular heparin can be used to treat inflammatory diseases, but have danger side effect of hemorrhage in the tissue due to the potent anticoagulant activity, which limits their extensively clinical use on inflammatory patients. Many chemical modification methods was patented to reduced their anticoagulant activity while preserve other biological properties. An example of O-desulfated heparin derivatives is described in U.S. Pat. No. 5,795,875. It shows this O-desulfated heparin derivatives, are useful for treating various diseases including inflammation, consists of substantially unfragmented 6-O desulfated heparin, or 6-O desulfated heparin fragments, but still retains 5-30% anticoagulant activity of the starting heparin. Another example of O-desulfated heparin, preferably 2-O, 3-O desulfated heparin is described by Holme et al. U.S. Pat. No. 5,296,471, retains 5.5-23% anticoagulant activity of the starting heparin. But these O-desulfated heparins still have potent anticoagulant activity.
[0016] It has been known that N-desulfated heparin has significant reduced anticoagulant activity, but there are few reports of the effect of removing N-sulfate of heparin chain on its anti-inflammation activity, so it is deserved to research the anti-inflammation activity of N-desulfated heparin, particularly in prevention and treatment of the inflammation diseases.
PURPOSE OF THIS INVENTION
[0017] Therefore, the purpose of this invention is to provide a pharmaceutical use of N-desulfated heparin in prevention and treatment of inflammation, the anti-inflammation activity of N-desulfted heparin is better than or equal to LMH, and has a significant reduced anticoagulant activity. The present invention provides a good possibility to use N-desulfated heparin for prevention and treatment of inflammation better.
[0018] Furthermore, present invention, prevention and treatment of inflammation by N-desulfated heaprin, is based on the chemical modification method to remove the N-sulfate of heparin chain and get eight heparin derivatives, then screening the best anti-inflammation and lowest anticoagulant activity sample through the acute peritonitis mouse model and the bleeding time assay. The results indicate the effect of desulfation on its anti-inflammation and anti-coagulant activity, N-desulfated heparins have better anti-inflammation activity than LMH, while have even lower anti-anticoagulant activity.
[0019] Starting heparin was chemically modified to remove the N-sulfate, referred to the publications [Nagasawa et al., Carbohydr. Res. 36,265-271,1976; Inoue and Nagasawa, Carbohydr. Res. 46,87-95(1976)], getting N-desulfated heparin with different mount of N-sulfate. The anticoagulant activity of heparin, LMH and all N-desulfated derivatives was determined. Table 1 shows the results of absolute, relative content of N-sulfate and the aPTT time.
TABLE 1 Heparin and its Absolute N-sulfate Relative N-sulfate 2aPTT derivatives content (%) content (%) (μg/ml) UFH 3.25 100 0.56 LMH 3.54 109.1 3.3 {circle over (1)} 0.62 19.0 20.5 {circle over (2)} 0.55 17.0 34.8 {circle over (3)} 1.50 46.2 9.0 {circle over (4)} 0.36 11.0 115 {circle over (5)} 1.99 61.2 2.3 2.31 71.0 6.5 2.80 86.2 1.7 2.08 64.0 6.4
[0020] The result of Table 1 shows that: all N-desulfated heparin derivatives have significant reduced anticoagulant activity compared with starting heparin. The relative N-sulfate content of No. 3, 5, 6, 7, 8 samples is 46.2%, 61.2% 71.0%, 86.2%, 64.0% and the anticoagulant activity is {fraction (1/16)}, ¼, {fraction (1/12)}, ⅓, {fraction (1/11)} of heparin respectively. The relative N-sulfate content of No.1, 2, 4 samples is 19.0%, 7.0%, 11.0% and the anticoagulant activity is {fraction (1/37)}, {fraction (1/62)}, {fraction (1/205)} of starting heparin respectively. It should be noted that the anticoagulant activity of No.4 sample is decreased to 1/205 of starting heparin, this heparin derivative is non-anticoagulant.
[0021] Table 2 illustrated the contents of other of Chemical Moieties, including uronic acids, hexosamines, free amino groups, reducing powers and average molecular weights for heparin and the No. 4 sample (N-desulfated heparin) and their corresponding ratios.
TABLE 2 Measurements of chemical moieties of the sample No. 4. Uronic TNP- Reducing Com- acid Hexosamine NH 2 Power pound (%) (%) (Abs 348) (Abs 450) MW UFH 26.7 23.6 0.109 0.154 19,500 No.4 33.0 24.9 0.838 0.179 16,100 No.4/UFH 1.24 1.06 7.7 1.16 0.826
[0022] The result of table 2 shows that: The content of uronic acid and hexosamine in heparin chain increases 24% and 6% respectively after the N-desulfated chemical modification. As a result of the N-desulfation, more mounts of free amino acid generates, the No.4 sample contains 7.7-fold free amino acid content compared with heparin. Furthermore, chemical modification makes the chain of the No.4 sample shortened 17.4%, and the average molecular weight decreased from 19500 daltons to 16100 daltons, while the reducing power increased 16%.
[0023] In the peritonitis mouse model induced by the intraperitoneal injection of thioglycollate, intravenously administrate LMH and all N-desulfated heparin derivatives to test the inhibition effect of peritoneal infiltration of the inflammation cell including Lymphocytes, monocytes and neutrophils. FIG. 1 shows the result: the anti-inflammation of all the N-desulfated heparin derivatives is better than or equal to the LMH, then this N-desulfated heparin derivatives with 0.1-99.9% N-sulfate of the starting heparin can be used to prevention and treatment of inflammation diseases. Furthermore, intravenously administrate LMH and all N-desulfated heparin derivatives (7.5 mg/kg) to test their effect on the bleeding time. FIG. 2 shows the result, the anticoagulant activity in vivo of No. 1, 2, 4 samples is lower than LMH, while the anticoagulant activity of others is equal to or a little higher than LMH.
[0024] Another dose course of bleeding time is carried on to compare the anticoagulant activity of No.4 sample with the LMH intensively, the result is referred to FIG. 3. It demonstrates that intravenously injection of 0.75 mg/kg, 2.5 mg/kg, 7.5 mg/kg, 22.5 mg/kg respectively, the bleeding time of LMH group increases sharply with the adding dose, while the No.4 group has no apparent bleeding time prolonging. Therefore, it can be concluded that No.4 sample has non-anticoagulant activity; the result of the APTT in vivo confirmed this conclusion. As shown in FIG. 4A, intravenous injection of 2.5 mg/kg of heparin, LMWH and the sample No. 4 could trigger 17-fold, 1.6-fold (**, P<0.01 compared with heparin) and 1.1-fold (**, P<0.01 compared with heparin) prolongation of APTT respectively. Following intravenous injections, 7.5 mg/kg LMWH caused 10.7-fold prolongation of APTT while the same amount of the sample No. 4 only induced 2.4-fold (**, P<0.01 compared with LMH) prolongation of APTT (FIG. 4B).
[0025] We further compared the anti-inflammatory activities of LMWH and the sample No. 4 (N-desulfated heparin) in the mouse model of acute peritonitis using a lower dosage and a dose course. FIG. 5A shows that intravenous administration of 10 mg/kg LMWH and the sample No. 4 could significantly reduce the peritoneal deposition of neutrophils with the inhibition of 44.9%. The sample No. 4 appeared to be more potent than LMH (15.7% inhibition). This conclusion was further confirmed by the dose courses of LMWH and the sample No. 4 (FIG. 5B). The sample No. 4 was at least 10-fold more potent than LMWH for prevention of neutrophil infiltration in this in vivo model.
[0026] We investigated whether the sample No. 4 (N-desulfated heparin) could reduce ischemia and reperfusion injury using a rabbit ear model. FIG. 6A shows that compared to normal ears, complete blockade of blood flow for 6 h followed by spontaneous reperfusion caused significant tissue edema (5.4-fold increase in the ear volume) when they were measured 4 days after the operations. Intravenous injection of 10 mg/kg of the sample No. 4 markedly reduced tissue edema (3.4-fold increase in the ear volume; p<0.05). In contrast, intravenous injections of 3 mg/kg of the sample No. 4 (4.8-fold increase in the ear volumes; p>0.05) and 1 mg/kg of heparin (4.7-fold increase in the ear volumes; p>0.05) had no statistically significant effects on tissue edema. FIG. 6B illustrated the time courses of tissue edema in the operation groups treated with saline and the sample No. 4 (10 mg/kg).
[0027] Histological examination and cytologic detection further proved that blocking leukocytes flushing into inflammation sites was one of the anti-inflammation mechanisms for the No.4 sample. Using histological examinations, we found that compared to the tissues from the operation group treated with saline (FIG. 7A), 10 mg/kg the sample No. 4 (FIG. 7B) significantly decreased the deposition of leukocytes within the injured tissues. We also measured the activities of MPO, an enzyme known to be existed exclusively in neutrophils, to represent the amounts of neutrophils in the injured tissues in each group of animals. FIG. 7C shows that compared to the normal tissues, complete blockade of blood flow for 6 h followed by spontaneous reperfusion triggered a substantial amount of neutrophils deposited in the injured tissues. The sample No. 4 (10 mg/kg) significantly inhibited the neutrophil depositions (p<0.05). However, 1 mg/kg heparin (p>0.05) and 3 mg/kg the sample No. 4 (p>0.05) had no statistically significant effects on the neutrophil depositions in the injured tissues after the operations.
[0028] [0028]FIG. 8 shows that the incidence of tissue necrosis was markedly reduced by treatment with 10 mg/kg the sample No. 4 and less markedly reduced by treatment with 3 mg/kg the sample No. 4. In contrast, the incidence of tissue necrosis was only very moderately reduced after treatment with intravenous administration of heparin (1 mg/kg).
[0029] We also investigated the effect of the No.4 sample on acute lung injury using a piglet model. FIG. 9 shows the result of the pathomorphism. Histological examination of normal group indicates homogeneous dilation of alveolus, no apparent edema, hemorrhage, congestion, infiltration of inflammation cell and pathological change coursed by injury of epithelium in small air passage (FIG. 9A). While model group shows extensive edema, petechial hemorrhage, congestion, and collapse of partial lung tissue through macroscopy; through optical microscope we observed apparently congestion of, edema, hemorrhage and infiltration of inflammation cell, heterogeneous dilation, excessive inflation and collapse of alveolus; the desmohemoblast among alveolus broadened (FIG. 9B), as well as mild injury of epithelium in small air passage. In treatment group with the No.4 sample, hemorrhage, congestion, infiltration of inflammation cell was attenuated, exudation in alveolus was decreased, desmohemoblast among alveolus narrowed, homogeneous dilation of alveolus but still mild injury of epithelium in small air passage (FIG. 9C).
[0030] A mouse delayed-type hypersensitivity (DTH) model induced by picryl chloride (PCl) was used to detect the effect of the No.4 sample. Table 3 shows the results: The ALT level of the positive control group is markedly increased compared with that of normal group. Treatment with 10 mg/kg and 20 mg/kg No.4 sample markedly deduced the ALT level compared with positive control, the inhibition rate was 93% and 87% respectively, while treatment with 10 mg/ml cyclophosphamide also deduced the ALT level (87% inhibition).
[0031] In addition, two model systems in vitro were used to investigate the cellular mechanisms for the anti-inflammatory activity of the No. 4 sample. Our data clearly demonstrate that the No. 4 sample can inhibit adhesion and transendothelial migration of leukocytes, both of which are essential in inflammatory responses. FIG. 10 shows that under a physiological shear stress (2.0 dyne/cm 2 ), adhesion of HL-60 cells to stimulated HUVECs was significantly inhibited by 1 mg/ml the sample No. 4, and the inhibition rate was 78.5% (**, P<0.01). But the same concentration of LMWH only mildly neutralized the adhesion of HL-60 cells under flow (17.4%, *, P<0.05). We then tested whether these compounds could interfere with the transmigration of human neutrophils through the monolayers of HUVECs following TNF-α stimulation. FIG. 11 shows that compared to the unstimulated HUVECs (designated as neutrophils migrated more avidly through the monolayers of TNF-α stimulated HUVECs (designated as +). This increased transmigration of neutrophils could be attenuated by 1 mg/ml of both LMWH and the sample No. 4. The inhibition rate of the No.4 sample was 90.6% (**, P<0.01) while that of LMH was 70% (*, P<0.05). Above data clearly demonstrate that the No. 4 sample can inhibit adhesion and transendothelial migration of leukocytes more potent than LMN, thus the No. 4 sample has a better anti-inflammation effect.
SUMMARY OF THE INVENTION
[0032] In one embodiment, the present invention comprises the preparation of a chemically modified heparin. This chemically modified heparin is defined as an N-desulfated heparin, which results in ˜89% reduction of the N-sulfate content. This compound has significantly reduced anticoagulant activity (more than 99% reduction); it will be referred to as the N-desulfated heparin thereafter.
[0033] In a further embodiment, the invention comprises the use of the N-desulfated heparin for prevention and treatment of various acute, subacute and chronic inflammation, conditions characterized by leukocyte infiltration and deposition in the site of tissue injury leading to further damage of the tissues and organs as well as their consequently functional deterioration.
BRIEF DESCRIPTION OF THE DRAWING
[0034] Table 1 illustrates the relative and absolute amounts of N-sulfate and measurements of activated partial thromboplastin time in heparin, Low molecular weight heparin and the chemically modified heparin derivatives.
[0035] [0035]FIG. 1 shows the effects of intravenous injection of small molecular weight heparin and the chemically modified heparin derivatives on the peritoneal infiltration of total leukocytes, lymphocytes, monocytes and neutrophils in a mouse model of acute peritonitis induced by intraperitoneal injection of thioglycollate.
[0036] −: Sterile pyrogen-free saline group
[0037] +: Positive control group
[0038] LMH represents the low molecular weight heparin therapeutic group 1, 2, 3, 4, 5, 6, 7, 8 represent the N-desulfated heparin groups which contain 19.0%,17.0%,46.2%,11.0%,61.2%,71.0%,86.2%,64.0% N-sulfate respectively.
[0039] [0039]FIG. 2 shows the effects of the chemically modified heparin derivatives on the bleeding times following intravenous injection of mice.
[0040] Saline: Sterile pyrogen-free saline group
[0041] LMH: low molecular heparin therapeutic group
[0042] 1, 2, 3, 4, 5, 6, 7, 8 represent the N-desulfated heparin groups which contain 19.0%,17.0%,46.2%,11.0%,61.2%,71.0%,86.2%,64.0% N-sulfate respectively.
[0043] [0043]FIG. 3 shows the dose course of the effects of small molecular weight heparin and the N-desulfated heparin (sample No. 4) on the bleeding times following intravenous injection of mice.
[0044] [0044]FIG. 4 shows the results of aPTT in vivo of heparin, LMWH and sample No. 4 (N-desulfated heparin).
[0045] −: Sterile pyrogen-free saline group
[0046] Heparin: heparin group
[0047] LHM: low molecular group
[0048] No.4: the No.4 sample group
[0049] [0049]FIG. 5 shows the results of the dose course of the No.4 sample and the low molecular heparin in mice peritonitis model (FIG. 5B) and the anti-inflammation activity at the dose of 10 mg/kg (FIG. 5A).
[0050] −: Sterile pyrogen-free saline group
[0051] +: Positive control group
[0052] LHM: low molecular group
[0053] No.4: the No.4 sample group
[0054] [0054]FIG. 6 shows the effect of the No.4 sample in rabbit ear ischemia and reperfusion injury model.
[0055] [0055]FIG. 6A shows the effect on the day 4 after the operation:
[0056] −: Normal group
[0057] +: Positive control group
[0058] Heparin: heparin treatment group at dose of 1 mg/kg
[0059] No.4(3): the No.4 sample group at dose of 3 mg/kg
[0060] No.4(10): the No.4 sample group at dose of 10 mg/kg
[0061] [0061]FIG. 6B shows the time curve of the effect of the No.4 sample:
[0062] Saline: Sterile pyrogen-free saline group
[0063] No.4: the No.4 sample group
[0064] [0064]FIG. 7 shows the histological examinations of the effect of the No.4 sample in rabbit ear ischemia and reperfusion injury model.
[0065] [0065]FIG. 7A shows the result of leukocytes staining within the injured tissues:
[0066] Saline: Sterile pyrogen-free saline group
[0067] No.4: the No.4 sample group
[0068] [0068]FIG. 7B shows the result of detecting the amounts of neutrophils in the injured tissues:
[0069] −: Normal control group
[0070] +: Positive control group
[0071] Heparin: heparin treatment group at dose of 1 mg/kg
[0072] No.4(3): the No.4 sample group at dose of 3 mg/kg
[0073] No.4(10): the No.4 sample group at dose of 10 mg/kg
[0074] [0074]FIG. 8 shows the result of that the sample No. 4 markedly reduced the incidence of tissue necrosis.
[0075] +: Positive control group
[0076] Heparin: heparin treatment group at dose of 1 mg/kg
[0077] No.4(3): the No.4 sample group at dose of 3 mg/kg
[0078] No.4(10): the No.4 sample group at dose of 10 mg/kg
[0079] [0079]FIG. 9 shows the effect of the No.4 sample in the
[0080] A: Normal control group
[0081] B: Model control group
[0082] C: treatment group of the No.4 sample
[0083] [0083]FIG. 10 shows that the No.4 sample could inhibit adhesion of leukocytes to endothelial cells:
[0084] −: Sterile pyrogen-free saline group
[0085] +: Positive control group
[0086] EDTA: a chelator for divalent cations
[0087] LHM: low molecular group
[0088] No.4: the No.4 sample group
[0089] [0089]FIG. 11 shows the result of the No. 4 sample inhibiting the transendothelial migration of leukocytes.
[0090] −: Sterile pyrogen-free saline group
[0091] +: Positive control group
[0092] LHM: low molecular group
[0093] No.4: the No.4 sample group
DETAILED DESCRIPTION OF THE INVENTION
[0094] In accordance with the present invention, a method for treatment of inflammation is provided, which comprises administration of a therapeutically effective amount of the N-desulfated heparin. In the method of the present invention, the term “therapeutically effective amount” means the total amount of the N-desulfated heparin that is sufficient to show a meaningful patient benefit, that is, healing of pathological conditions characterized by leukocyte infiltration and deposition or increase in rate of healing of such conditions, whether administered in combination, serially or simultaneously.
[0095] In practicing the method of treatment of this invention, a therapeutically effective amount of the N-desulfated heparin is administered to a mammal having a disease state. Such disease states include inflammatory disorders such as various kinds of arthritis, asthma, dermatitis and psoriasis, acute respiratory distress syndrome, ulcerative colitis, various types of hepatitis, ischemia/reperfusion injury (including myocardial, renal, skeletal muscular, intestinal, cerebral and pulmonary ischemia/reperfusion injury), shock, severe trauma and transplant rejection.
[0096] In practicing the method of the present invention, the N-desulfated heparin may be administrated alone or in combination with other therapies. For example, the non-anticoagulant heparin may optionally be used in combination with certain cytokines, lymphokines, or other hematopoietic factors such as M-CSF, GM-CSF, NKSF, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, G-CSF, Meg-CSF, and erythropoitin to treat inflammatory states. It is contemplated that the method of treatment will allow the non-anticoagulant heparin to synergize with the cytokine, lymphokine, or other hematopoietic factor, thereby augmenting the anti-inflammatory response. Alternatively, the method of treatment will allow the N-desulfated heparin to minimize the potential side effects caused by the cytokine, lymphokine, or other hematopoietic factor.
[0097] Pharmaceutical compositions used to practice the method of the present invention may contain, in addition to the N-desulfated heparin, pharmaceutically acceptable carries, diluents, fillers, salts, buffers, stabilizers, and/or other materials well known in the art. The term “pharmaceutically acceptable” means a non-toxic material that does not interfere with the effectiveness of the biological activity of the active ingredient(s). The characteristics of the carrier or other material will depend on the route of administration.
[0098] Administration of the N-desulfated heparin used to practice the method of the present invention can be carried out in a variety of conventional ways, such as oral ingestion, or cutaneous, subcutaneous, or intravenous injection. Intravenous administration to the patient is preferred.
[0099] When a therapeutically effective amount of the N-desulfated heparin is administered orally, the non-anticoagulant heparin will be in the form of a tablet, capsule, powder, solution or elixir. When administrated in tablet form, the pharmaceutical composition of the invention may additionally contain a solid carrier such as a gelatin or an adjuvant. The tablet, capsule, and powder contain from about 5 to 95 % the N-desulfated heparin, and preferably from about 25 to 90% the N-desulfated heparin. When administered in liquid form, a liquid carrier such as water, petroleum, oils and animal or plant origin such as peanut oil, mineral oil, soybean oil, or sesame oil, or synthetic oils may be added. The liquid form of the pharmaceutical composition may further contain physiological saline solution, dextrose or other saccharide solution, or glycols such as ethylene glycol, propylene glycol or polyethylene glycol. When administered in liquid form, the pharmaceutical composition contains from about 0.5 to 90% by weight of the N-desulfated heparin, and preferably from about 1 to 50% the N-desulfated heparin.
[0100] When a therapeutically effective amount of the N-desulfated heparin is administered by intravenous, cutaneous or subcutaneous injection, the N-desulfated heparin will be in the form of a pyrogen-free, parentally acceptable protein solutions, having due regard to pH, isotonicity, stability, and the like, is within the skill in the art. A preferred pharmaceutical composition for intravenous, cutaneous, or subcutaneous injection should contain, in addition to the N-desulfated heparin, an isotonic vehicle such as Sodium Chloride Injection, Ringer Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, Lactated Ringer Injection, other vehicle as known in the art. The pharmaceutical composition used to practice the method of the present invention may also contain stabilizers, preservatives, buffers, antioxidants, or other additive known to those of skill in the art.
[0101] The amount of the N-desulfated heparin in the pharmaceutical composition used to practice the method of the present invention will depend upon the nature and severity of the condition being treated, and on the nature of prior treatments which the patient has undergone. Ultimately, the attending physician will decide the amount of the N-desulfated heparin with which to treat each individual patient. It is contemplated that the various pharmaceutical composition should contain about 0.1 μg to about 100 mg of the N-desulfated heparin per kg body weight.
[0102] The duration of intravenous therapy using the pharmaceutical composition used to practice the method of the present invention will vary, depending on the severity of the disease being treated and the condition and potential idiosyncratic response of each individual patient. It is contemplated that the duration of each application of the N-desulfated heparin will be in the range of 12 to 24 hours of continuous intravenous administration. Ultimately the attending physician will decide on the appropriate duration of intravenous therapy using the pharmaceutical composition of the present invention.
[0103] The pharmacokinetics and the toxicity experiments of the N-desulfated heparin are being carried now.
EXAMPLE 1
Chemical Modification of Heparin
[0104] Preparation of Pyridine Salt of Heparin
[0105] The sodium salt of heparin (Sigma) was passed through a column of Dowex (Strongly Acidic Cation Exchanger 50×4-100; Sigma) and the effluent was neutralized with pyridine. It was then lyophilized to give a white powder [Inoue and Nagasawa, Carbohydr. Res. 46, 87-95 (1976)].
[0106] Preparation of N- and O-Desulfated Heparins
[0107] The pyridine salt of heparin (100 mg dissolved in 0.25 ml of double destined and deionized H 2 O) was mixed with 4.75 ml of dimethylsulfoxide (DMSO; Sigma) at 50° C. for 2 hour (sample No. 4), 1 hour (sample No. 1), or 20° C. for 3 hours (sample No. 3). The sample was diluted with an equal volume of H 2 O and the reaction was terminated by adjusting pH to 7.0 with 0.1 NNaOH [Nagasawa and Inoue, Carbohydr. Res. 36, 265-271 (1976); Inoue and Nagasawa, Carbohydr. Res. 46, 87-95 (1976); Tiozzo et al., Thromb. Res. 70, 99-106 (1993)].
[0108] The sample No.1 heparin was further dissolved in 1 NNaOH (4% heparin concentration) at 60° C. for 4 hours followed by neutralization to pH 7.0 with 1 N HCl (sample No. 2). The pyridine salt of heparin was dissolved in 1 NNaOH (4% heparin concentration) followed by treatment at 40° C. (sample No. 5) or at 60° C. (sample No. 6) for 4 hours. Further, the sodium salt of heparin was dissolved in 1 N NaOH (4% heparin concentration) followed by treatment at 40° C. (sample No. 7) or at 60° C. (sample No. 8) for 4 hours. Sample was then neutralized to pH 7.0 with 1 N HCl [Tiozzo et al., Thromb. Res. 70, 99-106 (1993); Lloyd et al., Biochem. Pharmacol. 20, 637-648 (1971)].
[0109] Preparation of Final Heparin Derivatives
[0110] After chemical modification, these heparin derivatives were individually passed through a column of Amberlite IRA-400 (Strongly Basic Anion Exchanger; Sigma) to remove the free sulfate ions. The effluent was neutralized to pH 7.0 with 1 N NaOH. It was then desalted by passing through a column of Bio-Gel P-2 (Bio-Rad). Heparins were monitored at the optical densities of 214 nm and 230 nm.
EXAMPLE 2
Measurements of Activated Partial Thromboplastin Time
[0111] Activated partial thromboplastin time (APTT) was measured using fresh human blood from healthy volunteers. The known amounts of heparin, Low molecular weight heparin and the chemically modified heparin derivatives were added prior to the determination of APTT using Silimat™ (bioMeieux sa) as activator. Six assays were performed for each compound and the anticoagulant activity was expressed as the concentration (ug/ml) that doubles the aPTT time (2-aPTT). The higher concentration is parallel to the lower anticoagulant activity (Table 1). The same assay was carried to determine the aPTT time of the mice in vivo (FIG. 4.).
EXAMPLE 3
Measurement of N-Sulfate Amounts
[0112] Solution and reagents: 5% sodium nitrite, 33% acetic acid, 3.8% trichloroacetic acid, barium chloride-gelatin reagent (prepared by dissolving 1 g of gelatin in 100 ml of water, incubated at 60° C. to make a complete dissolution, then put it at 4° C. overnight. The mixture was filtered after adding 0.5 g of barium chloride and was ready to use after standing for 4 hours at room temperature. This reagent was stored at 4° C. and could be used for about one week.)
[0113] N-sulfates in heparin and various chemically modified heparin derivatives were determined by nitrous acid treatment as described [Inoue and Nagasawa, Anal. Biochem. 71, 46-52 (1976)]. Briefly, 0.5 ml of a sample solution was mixed with 0.5 ml of 5% sodium nitrite and 0.5 ml of 33% acetic acid. After shaking, the mixture was incubated at room temperature for 30 min and 4.5 ml of 3.8% trichloroacetic acid was then added. After shaking again, 1.5 ml of the barium chloride-gelatin reagent was added. Following shaking again immediately, the sample was left standing for 20 min and the turbidity of the sample was measured at 500 nm. The absolute N-sulfate mounts of all N-desulfated heparin sample were calculated with K 2 SO 4 as control, while the relative N-sulfate mounts of all N-desulfated heparin were calculated using the starting heparin as 100%.
[0114] The contents of uronic acid of the No.4 sample and heparin were determined according to the method of Bitter and Muir (Anal. Biochem. 4:330-334,1962). The hexosamine contents were determined according to the method of Elson and Morgan (Biochem. J. 27:1824-1828, 1993). The contents of free amino group, at a 2 mg/ml concentration, were determined as before (Yoshizawa et al., Biochim. Biophys. Acta., 141:358-365,1967). Reducing power, at a 2 mg/ml concentration, was measured using the 3, 6-dinitrophthalic acid method (Momose et al., Talanta, 4:33-37,1960). The average molecular weights were determined using the end group analysis (Hopwood and Robinson, Biochem. J. 135:631-637,1973).
EXAMPLE 4
Anti-Inflammatory Heparin Screening Assay in vivo
[0115] Balb/c mice (males, 5 weeks old, 20±1 g body weight) were purchased from Shanghai Animal Center of Chinese Academy of Sciences. Negative control group contained 8 mice, they were intraperitoneally injected with 1 ml of sterile pyrogen-free saline. Fifteen minutes later, mice were intravenously injected with 0.2 ml sterile pyrogen-free saline alone. The positive control group (12 mice) was intraperitoneally injected with 1 ml of 3% thioglycollate broth. Fifteen minutes later, mice were intravenously injected with 0.2 ml saline. The mice of the anti-inflammation group (7-11) were intraperitoneally injected with 1 ml of 3% thioglycollate broth. Fifteen minutes later, mice were intravenously injected with saline containing 1.5 mg of low molecular weight heparin or any of the chemically modified heparin derivatives. Mice were sacrificed at 2 hours. The peritoneal cavities were lavaged with 8 ml of ice-cold PBS containing 10 U/ml of heparin to prevent clotting. Centrifuged at 1500 rpm for 5 mins. The total peritoneal leukocytes and their differentiation (lymphocyte, monocyte and granulocyte) were measured using Cell-Dyn1700 (Abbot Laboratories, USA).
SUMMARY
[0116] The mice of heparin therapeutic groups appear more active than the positive control group during the experiments time.
[0117] Shortly after the injection of the samples, few mounts of blood was bleeding from the pinpricks of the mice administrating the No.4 sample, concomitantly the coagulant time was shorter than those groups administrating other heparin samples. Furthermore, when collecting the total peritoneal infiltrated leukocytes, the group administrating No.4 sample showed no inner bleeding phenomena, but other groups has little or more bleeding. The experiments watching above reflected the No.4 sample has significant reduced anticoagulant activity while remaining the anti-inflammation effect.
[0118] [0118]FIG. 1 shows the result of the anti-inflammation screening assay in vivo, at the same time table 2 represents the inhibition percent of the peritoneal infiltrated inflammation leukocytes.
TABLE 2 The inhibition percent of inflammation cell infiltration in the mice peritonitis model. LMH(%) 1(%) 2(%) 3(%) 4(%) 5(%) 6(%) 7(%) 8(%) WBC 54.4 52.8 52.1 68.8 70.9 60.6 69.1 68.0 66.9 Lymphocyte 54.9 49.5 62.0 72.1 72.1 59 65.9 68.0 64 Monocyte 56.2 64.7 47.6 71.2 76.3 81.7 82 79.9 80.3 Granulocyte 40.3 16.1 11.2 36.9 40.9 4.6 33.4 19.3 10.6
[0119] The inhibition percent is got through this calculating formula:
1 - ( Cell number of all heparin derivatives - Cell number of negative control ) ( Cell number of positive control - Cell number of negative control )
[0120] All N-desulfated heparin has different anti-inflammation activity, the result showed that the total white blood cell inhibition percent is about 52.1-70.9%, total Lymphocyte inhibition percent is about 49.5-72.1%, monocyte inhibition percent is about 47.6-82%, granucyte inhibition is about 10.6-40.9%, all N-desulfated heparin has better anti-inflammation activity than LMH which is commonly used in the art, besides, N0.4 sample is the best.
EXAMPLE 5
Anticoagulant Activity Screening Assay in vivo
[0121] Swiss mice (five weeks old, weigh 16 g) were purchased from Shanghai Animal Center of Chinese Academy of Sciences. Each group contained 9-11 mice. All the experiments were carried on under 25±1° C., because the bleeding time was varied according to environment temperature. Bleeding times of mice were measured exactly as described previously (Dejana et al., 1982). Low molecular weight heparin and the chemically modified heparin derivatives (all at 0.12 mg/mouse; 7.5 μg/gram of body weight) were injected into each Swiss mouse 15 min prior to the tail cutting (2 mm from the tail tip) with a razor blade. For determination of bleeding time, the amputated tail was sunk longitudinally in phosphate buffered saline, pH 7.4, at 25° C. Complete clotting was recorded after stopping the bleeding for 30 sec. And if the bleeding time was longer than 15 min, it was counted as 15 min. FIG. 2 shows the result: at the condition of injection of 120 ug sample per mouse, No.1, No.2, No.4 samples have significant shorter bleeding time than LMH, little longer that the saline group.
EXAMPLE 6
Dose Course Assay of the Anticoagulant Activity of the No.4 Sample
[0122] The assay and the experiment condition were according to that of example 5. The No.4 sample and LMH were injected into the Swiss mice with the mounts of 0.75 mg/kg, 2.5 mg/kg, 7.5 mg/kg and 22.5 mg/kg respectively to test the bleeding time. FIG. 3 shows the result, with the administration mounts of LMH increasing, the bleeding time prolongs sharply, while the No.4 group has no apparent prolonging. Therefore, we can say: No.4 sample has non-anticoagulant activity.
EXAMPLE 7
Effect of the No.4 Sample in the Rabbit Ischemia and Reperfusion Injury Model
[0123] Ischemia and reperfusion injury assay. New Zealand albino rabbits were purchased from Shanghai Animal Center of Chinese Academy of Sciences. Each group contains 6 rabbits. General anesthesia was induced and maintained by peritoneal injection of pentobarbital sodium (45 mg/kg). After subcutaneous injections of lidocaine at the bases of rabbit ears to block the supplemental local nerves, both ears were carefully amputated at their bases in sterile conditions under a surgical microscope. Only the central artery, the central vein, and a small non-vascular cartilage bridge were left intact. The ear's sensory nerves were transacted to render the ears in a permanently anesthetic condition and the ears were approximated to their bases with suture. A non-traumatic microvascular clip was then placed on the central artery of each ear to stop the blood flow for complete ischemia. After 6 h, the clip was removed and the ear was allowed to spontaneous reperfusion (Mihelcic et al., 1994;Lee et al., 1995; Han et al., 1995). For the therapeutic intervention, one bolus of intravenous administration of saline alone, saline with heparin or the No. 4 sample was given at the beginning time of reperfusion (removal of the microvascular clip).
[0124] Measurements of tissue edema and necrosis. Ear volume (as a reflection of tissue edema) was measured daily for seven continuous days following removal of the microvascular clip. Ear volume was quantified by determination of the volume displacement after inserting the amputated portion of the ear (to the level of the suture line) into a fluid-filled vessel. Tissue necrosis was assessed, in a double-blind manner, by the presence or absence of tissue necrosis (defined as >5% skin sloughing of the total ear surface) on day 7 (Han et al., 1995).
[0125] Mycloperoxidase (MPO) assay. MPO activities were measured as previously described (Geng et al., 1990; Schierwagen et al., 1990; Mihelcic et al., 1994). The ear tissues (no skins) were surgically taken 24 h after reperfusion. They were weighed and placed (0.5 g/ml) in 50 mM potassium phosphate buffer, pH 6.0, supplemented with 0.5% hexadecyltrimethyl-ammonium bromide (Sigma). They were subsequently homogenized by freeze-thaw three times and sonication twice. The mixtures were then centrifuged at 10,000 g for 10 min. The supernatants were heated at 60° C. for 2 h to inactivate potential inhibitors of MPO. For generation of standard curves, fresh blood was taken from healthy rabbits and rabbit neutrophils were isolated using Ficoll-Paque Plus (Amersham Pharmacia Biotech) according to the manufacturer's instructions. These isolated neutrophils were more than 95% pure based on differential staining of leukocytes.
[0126] Tissue histology. Tissues were taken by the 3-mm punch biopsy from the anesthetic ears 24 h after the operation. Samples were fixed by immersion in Bouin's fixation solution (75% picric acid, 24% formaldehyde, 1% acetic acid) for 24 h at 24° C. followed by paraffin embedding. Tissue sections (5-μm thick) were subsequently dewaxed and stained with hematoxylin and eosin. They were photographed at ×280.
EXAMPLE 8
The Effects of No.4 Sample on Acute Lung Injury
[0127] 17 male piglets (6.0-7.4 kg body weight, average 6.7 kg) were purchased from Shanghai Pasturage Institute, Shanghai Academy of Agricultural Sciences (SAAS). The piglets were abrosiaed for 12 hours. Before the operation the piglets were intramuscularly injected with prazosin (0.02 mg/kg) and sedated with Ketamine Hydrochloride (7 mg/kg, made by Shanghai Middle West Pharmaceutical Co. Ltd). Fifteen minutes later the piglets and the scarf skin for operation and intubation were cleaned. After the vein bypass established the piglets were given intravenous injection of with 2.5 mg/kg propofol (Fresenius, Germany) to induce anesthesia. The piglets were put on the infrared constant temperature table (YQT-2, made by Shanghai) on their back. Then 0.15 mg/kg Vecuronium Bromide (made by China Xianju Pharmaceutical company, Ltd.) was given (i.v.) to relax the muscle. A ballonet catheter was inserted through the mouth and it was linked to a respiration machine (Siemens, 900C). After conventional sterilization and laying sheets the right arteriae femoralis was separated. And 24G cannulas were left for artery blood sample collection. The femoral were linked to hemodynamics equipments, which could monitor the artery blood pressure and rhythm of heart. Thirty minutes later all items indicating the basic condition were detected. The piglets were divided into three groups and were operated according to the method. After the operation anesthesia were stopped and the piglets came round naturally. The trachea cannulas were withdrawn when they could breath independently, PaO 2 (partial pressure of oxygen) was lower than 40 mmHg, SaO 2 (oxygen saturation) was higher than 95 percent and could react to pain stimulation. Then the piglets were put in incubator where the temperature was maintained 21 centigrade. The piglets were intramuscularly injected with Bucinnazine Hydrochloride to ease pain and were given (i.v.) glucose-lactate cycle solution (10%, 5 ml/kg/h). Twenty-four hours later the piglets were induced anesthesia by intravenous injection and intubated into trachea again. The speed of injection was adjusted to 10-15 ml/kg/h according to heart rate, CVP (central venous pressure) and SAP (systemic arterial pressure). After sterilization an incision was made in left femoral and a 24G cannula was inoculated for blood sample collection and hemodynamics monitoring. An incision was made in left venae jugulalis extema and an 18G catheter was left for CVP monitoring and venous blood sample collection. When the condition of the piglets was stable the right-down part on the abdomen was sterilized and laid sheet again. After different operations depending on different group the piglet belong the incision was closed. The piglets were given intravenous injection of gentamicin (20,000 units) to prevent inflammation. When ALI appeared the piglets were treated according to requirements of each group. Sputum was suctioned every 2 hours during the experiment. 1 mg/kg propofol and 0.05 mg/kg Vecuronium Bromide were once injected discontinuously to maintain the breath frequency at 40-50 times per minute and V E at 0.3L/min/kg. The piglets were treated with 5% NaHCO 3 solution in case acidosis emerged. When SAP was lower than 60 mmHg, the piglets were given (i.v.) dopamine to maintain the blood pressure. At the end of the experiment the piglets were sacrificed with 10 ml 10% KCl solution (i.v.).
[0128] The piglets were divided into three groups at random before the experiment.
[0129] Group A (Control Group, n=5): The piglets were made an incision at the right-lower abdomen (3 cm) and the intestine were agitated before the incision was closed. Twenty-four hours later the incision was opened again and the intestine was agitated again. The incision was closed after the peritoneal cavity was washed with 200 ml saline (37C). The animals were observed for 12 hours.
[0130] Group B (Model Group, n=6): An incision at the right-lower abdomen (3 cm) was made followed by a 2-cm perforation in the distal cecum (5 cm from the end). It was sewed and 0.5 cm mucosa was evaginated in order to form an ostium with a diameter of 2 cm. The incision was then closured surgically. Twenty-four hours later, the incision was opened again and the ostium was sewn up. The incision was eventually closured after washing the peritoneal cavity with 200 ml saline.(37° C.). The piglets were treated with machinery gassing after ALI emergence.
[0131] Group C (Therapy Group, n=6): All procedures were exactly identical to Group B except that 12 mg/kg No.4 sample was intravenously administered in early phase of acute lung injury.
[0132] Criterion for Determination of ALI:
[0133] A. PaO 2 /FiO 2 <300 mmHg (PaO 2 : Partial pressure of oxygen; FiO 2 : Fraction inspired oxygen concentration)
[0134] B. Pulmonary dynamics compliance (Cdyn) is lower than that in basic condition by 30%.
[0135] Pathology Observation:
[0136] Perfusion fixation of lung: Piglets were heparinized, the thorax was opened and the left and right main bronchia were separated. The left lung was inflated with air pressure of 30 cmH 2 O. One minute later some air was let out to keep the pressure at about 10 cmH 2 O. Meanwhile the right ventricle and the left atria were opened and perfused with 4% formalin at pressure of 65 cmH 2 O for 30 minutes.
[0137] The left lung was kept in 4% formalin. Three days later lung tissue was taken at 0, 2, 6 and 9 point respectively in order to minimize the effect of gravity on the pathological change. Tissue samples were subsequently dehydrated, embedded with paraffin, sliced up and stained with hematoxylin and eosin (HE).
[0138] Tissue sections were observed with optical microscope and were classified into 5 grades according to edema, bleeding, infiltration of inflammation cell, pathological change coursed by epithelium injury of small air passage: 0 grade means normal; 1 grade means that the pathological change is light and area limited; 2 grade means that the pathological change is middling and limited; 3 grade that the pathological change is middling but extensive or remarkable at some part; 4 grade means that the pathological change is remarkable and extensive.
EXAMPLE 9
The Effects of No.4 Sample on the Mouse Model of Acute Liver Injury
[0139] Hypersensitivity on Swiss mice (18-22 g body weight) were induced by smearing 1% (w/v) PCl in absolute ethanol solution on abdomen after the ventral hair razed for 5 consecutive days. After another five days, 0.5% PCl olive oil solution (Sigma Chemical Co. St. Louis, Mo.) was intrahepatically injected. Blood samples were collected 18 hours for the measurements of alanine aminotransferase (ALT). Mice were intraperitoneal administered twice either saline, No. 4 sample (10 or 20 mg/kg) or cyclophospamide (10 mg/kg) at 0 and 5 hours after PCl intrahepatically injection. Table 3 shows the results: The ALT level of the positive control group is markedly increased compared with that of normal group. Treatment with No.4 (both dosages) or cyclophosphamide markedly deduced the ALT level compared with positive control.
TABLE 3 The effects of No. 4 sample on acute liver injury in the PCl-DTH mice Dosage Number ALT Group (mg/kg) of mice (Karmen unit) Normal — 5 21.9 ± 12.7 Positive control — 8 172.6 ± 78.2** No.4 sample 10 10 32 ± 15.9 ## No.4 sample 20 9 40.3 ± 36.2 ## Cyclophosphamide 10 8 40.4 ± 9.4 ##
EXAMPLE 10
Laminar Flow Assay of the No.4 Sample Inhibiting Adhesion of Leukocytes to Endothelial Cells
[0140] Human umbilical vein endothelial cells (HUVECs; less than three passages) were cultured on one-well chamber slide (Nalge Nunc, Naperville, Ill.) pre-coated with 1% gelatin as previously described (Geng et al., 1990; Asa et al., 1995). For cytokine stimulation, monolayers of HUVECs were incubated with 300 units/ml of tumor necrosis factor-α (TNF-α; Promega, Madison, Wis.) for 12 h. Slides were mounted in a flow chamber as before (Ma and Geng, 2000).
[0141] Human promyeloid HL-60 cells (CCL 240) were purchased from American Tissue Culture Collection (Rockville, Md.). They were cultured in RPMI 1640 medium supplemented with 10% heat inactivated newborn bovine calf serum (BCS), 4 mmol/L L-glutamine, 100 units/ml penicillin and 100 μg/ml streptomycin at 37° C. in the presence of 5% CO 2 .
[0142] After washing once with PBS, HL-60 cells were resuspended at 0.5×10 6 /ml in PBS supplemented with 10 mmol/L HEPES, pH 7.4, and 2 mmol/L CaCl 2 in the presence of heparin, LMWH and the sample No. 4 at 22° C. for 15 min. They were then precisely injected through the flow chamber at 22° C. using a syringe pump. The wall shear stress used was 2.0 dyne/cm 2 . The numbers of bound cells were quantified from videotape recordings of 10-20 fields of view obtained (3-4 min after flowing cells through the chamber).
EXAMPLE 11
Effect of the No.4 Sample on Preventing the Transmigration of Human Neutrophils Through the Monolayers of the Stimulated HUVECs
[0143] HUVECs (5×10 4 cells/well) were seeded in the upper chambers of 24-well Transwell® plates (Costar, Cambridge, Mass.) pre-coated with 1% gelatin. For cytokine stimulation, monolayers of HUVECs were incubated with 300 units/ml of TNF-α for 12 h (Geng et al., 1997). Fresh human blood was obtained from healthy volunteers according to the regulations of Chinese Academy of Sciences. Human neutrophils were isolated using Ficoll-Paque Plus (Amersham Pharmacia Biotech, Shanghai, China) according to the manufacturer's instructions. The isolated neutrophils were more than 95% pure based on differential staining of leukocytes. After washing the upper chambers twice, human neutrophils (2.5×10 6 cells/ml; more than 95% purity) were resuspended in serum-free M199 medium, in the presence of heparin, LMWH and the sample No. 4, and added to the upper chambers of the Transwell plates for 1 h. The upper wells were then removed and the cells sticking on the lower surface of the filters were released by repeated pipetting. Cells in the lower chambers were counted using a hemocytometer. | 1a
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RELATED APPLICATION
[0001] This application claims the benefit from U.S. Provisional application serial No. 60/347,152 filed Jan. 9, 2002 which is incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
[0002] Troponin I (TnI) is a 181 amino acid, 21 kDa protein, one of the three polypeptide components (along with Troponin C and Troponin T) which comprise the muscle troponin complex. Heterotrimeric troponin binds actin thin filaments in muscle and is intimately involved with Ca ++ -dependent muscle contraction. Analysis of the troponin complex reveals several distinct functional motifs for the TnI subunit: amino acids 1-47 of TnI are involved with binding to Troponin C, amino acids 96-116 comprise the “active site” involved with actomyosin ATPase activity, and the C-terminal amino acids 166-182 are involved with binding TnI to the actin filaments. Troponin is a therapeutically effective anti-angiogenic composition.
[0003] Angiogenesis, the process of new blood vessel development and formation. Pathological angiogenesis characterizes solid tumor growth which sustains progression cancer is a subject.
SUMMARY OF THE INVENTION
[0004] In particular embodiments this invention comprises an anti-metastatic therapeutic and method of its use. Troponin is therapeutically effective in suppression of malignant metastases. Particular reference is made to suppression of cancerous lung metastases. In some embodiments suppression is greater than about 90%. Melanoma metastases are significantly inhibited by constant infusion of low dose Troponin I. In some embodiments, Troponin I is administered to maintain a therapeutically effective blood level for extended periods with reference to about 1 day or longer, about 10 days or longer, and about 30 days and including chronic administration indefinitely. In certain applications, Troponin I, is administered by constant infusion in low doses. This therapeutic regimen dramatically suppressed growth of melanoma metastases in the lung. These results, illuminate a dosage protocol applicable to human therapeutic uses of Troponin. Troponin has efficacy as a clinically effective anti-angiogenic therapeutic for the prevention of tumor metastases in humans, with specific reference to high-risk cancer patients.
DETAILED DESCRIPTION OF THE INVENTION
[0005] This invention will be better understood with reference to the following definitions:
[0006] A. Troponin I (TnI) shall mean a 181 amino acid, 21 kDa protein, best known as one of the three polypeptide components (along with Troponin C and Troponin T) which comprise the muscle troponin complex. Heterotrimeric troponin binds actin thin filaments in muscle and is intimately involved with Ca ++ -dependent muscle contraction. Without being bound by specific structural aspects, it is believed troponin complex exhibits several distinct functional motifs for the TnI subunit. These motifs include: amino acids 1-47 of TnI apparently involved with binding to Troponin C, amino acids 96-116 apparently comprising the “active site” involved with actomyosin ATPase activity, and the C-terminal amino acids 166-182 apparently involved with binding TnI to the actin filaments. This is also termed Cardiac troponin I (cTnI).
[0007] The Troponin C subunit of troponin is believed to be the Ca2+ binding subunit of troponin. It is further believed to contain two homologous domains and four divalent cation binding sites. Two structural sites in the C-terminal domain of troponin C bind either Ca2+ or Mg2+, and two regulatory sites in the N-terminal domain are specific for Ca2+.
[0008] Therapeutically effective analogs of troponin subunits C, I, or T and analogs of their fragments are also contemplated within the practice of this invention. Troponin subunit fragments can be made by altering troponin sequences by substitutions, additions or deletions that provide for functionally equivalent molecules. These include, but are not limited to, troponin subunits, fragments, or analogs containing, as a primary amino acid sequence, all or part of the amino acid sequence of a troponin subunit including altered sequences in which functionally equivalent amino acid residues are substituted for residues within the sequence resulting in a silent change. For example, one or more amino acid residues within the sequence can be substituted by another amino acid of a similar polarity which acts as a functional equivalent, resulting in a silent alteration. Substitutes for an amino acid within the sequence may be selected from other members of the class to which the amino acid belongs. For example, the nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan and methionine. The polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine. The positively charged (basic) amino acids include arginine, lysine and histidine. The negatively charged (acidic) amino acids include aspartic acid and glutamic acid.
[0009] B. Low dose shall be understood to mean about 5%, and particular less than about 2% and more particularly about 1% or less of the quantity of Troponin currently being used in human clinical studies as compared with other anti-angiogenic proteins. In the practice of this invention, low doses provided a therapeutically effective dose. In humans, a dosage of about 1 to about 5 mg/kg/day is a low dose.
[0010] Therapeutically effective amount as to a drug dosage, shall be broadly understood to mean that dosage that provides the specific pharmacological response for which the drug is administered in a significant number of subjects in need of such treatment. Reference to “specific pharmacological response for which the drug is administered in a significant number of subjects in need of such treatment” is a recognition that a “therapeutically effective amount,” administered to a particular subject in a particular instance will reduce the number of metastases as anticipated based on a statistical determination. Therapeutically effective in such context offers a reduction of metastases, which while not in itself specifically curative, is palliative and useful in prolonging a subject's life and/or prolonging the stage at which a subject is treatable with an expectation of clinical improvement or survival.
[0011] Reference is made to “Tumstatin, an endothelial cell-specific inhibitor of protein synthesis,” Maeshima et al., Science Jan. 4, 2002;295(5552):140-3; “Endostatin reduces vascularization, blood flow, and growth in a rat gliosarcoma,” Sorensen, Neuro - oncol 2002 January;4(1):1-8; “Thrombospondin-1-mediated metastasis suppression by the primary tumor in human melanoma xenografts,” Rofstad, J Invest Dermatol 2001 November; 117(5):1042-9; “Experience with anti-angiogenic therapy of giant cell granuloma of the facial bones.” Collins A. Ann R Australas Coll Dent Surg 2000 October;15:170-5; “Potent anti-metastatic activity of combretastatin-A4,” Griggs, Int. J Oncol 2001 October;19(4):821-5; and “Improved survival in tumor-bearing SCID mice treated with interferon-gamma-inducible protein 10 (IP-10/CXCL10),” Arenberg, Cancer Immunol Immunother 2001 December;50(10):533-8, the teachings of which are incorporated herein by reference.
[0012] C. Metastases shall be broadly understood to include both cancer that started from cancer cells from another part of the body, the “primary site” (for example: cancer that starts in the breast can spread to the lymph nodes and then be spread throughout the body), as well as cancer starting at one site in a particular part of the body appearing at a separate site in the same part of the body (for example: a second lung tumor of a given type appearing after a first lung tumor of that type begins).
[0013] D. Suppression or inhibition of metastases by the method of this invention shall mean Troponin I or TnI subunits, analogs, derivatives, fragments or homologs is therapeutically effective in suppression of malignant metastases. Reduction of the number of metastases is calculated in comparison to the number predicted based on a statistical determination of published or clinically established results of populations with similar cancers at similar stages. Particular reference is made to suppression of cancerous lung metastases. In some embodiments suppression is greater than about 90%. Melanoma metastases are significantly inhibited by constant infusion of low dose Troponin I. In some embodiments, Troponin or analogs or fragments thereof is administered to maintain a therapeutically effective blood level for extended periods with reference to about 1 day or longer. Particular reference is made to a therapeutically effective dosage level is chronically maintained for at least about 5 days, at least about 10 days, at least about 20 days, and at least about 30 days or longer with particular reference to indefinite continuation, i.e. for the life of the subject.
[0014] In certain applications, Troponin, was administered by constant infusion in low doses to mice. This therapeutic regimen dramatically suppressed growth of melanoma metastases in the lung. These results, illuminate a dosage protocol applicable to human therapeutic uses of Troponin. Troponin has efficacy as a clinically effective anti-angiogenic therapeutic for the prevention of tumor metastases in humans, with specific reference to high-risk cancer patients.
TABLE 1 MALIGNANCIES AND RELATED DISORDERS Solid tumors sarcomas and carcinomas breast cancer Wilms' tumor fibrosarcoma ovarian cancer cervical cancer myxosarcoma prostate cancer testicular tumor liposarcoma squamous cell lung carcinoma carcinoma chondrosarcoma basal cell carcinoma small cell lung carcinoma osteogenic sarcoma adenocarcinoma bladder carcinoma chordoma sweat gland carcinoma glioma astrocytoma angiosarcoma sebaceous gland medulloblastoma carcinoma endotheliosarcoma papillary carcinoma craniopharyngioma lymphangiosarcoma papillary ependymoma adenocarcinomas llymphangioendothelios cystadenocarcinoma Kaposi's sarcoma arcoma medullary carcinoma pinealoma synovioma bronchogenic hemangioblastoma Carcinoma mesothelioma renal cell carcinoma acoustic neuroma Ewing's tumor hepatoma oligodendroglioma Leiomyosarcoma bile duct carcinoma menagioma melanoma rhabdommyosarcoma choriocarcinoma neuroblastoma colon carcinoma seminoma retinoblastoma pancreatic cancer embryonal carcinoma
[0015] Without being bound by any particular theory, it is believed that Troponin, Troponin subunits, analogs, derivatives, fragments or homologs inhibit metastases in a variety of cancers.
[0016] Publications: The following publications, all of which are incorporated herein by reference are presented by number. The numbering is offered as a matter of convenience.
[0017] 1. Farah, C. S. and Reinach, F. C. (1995). The troponin complex and regulation of muscle contraction. FASEB J. 9, 755-767.
[0018] 2. Coudrey, L. (1998). The troponins. Archives of Int. Med. 158(11), 1173-1180.
[0019] 3. Filatov, V. L., Katrukha, A. G., Bulargina, T. V., and Gusev, N. B. (1999). Troponin: structure, properties, and mechanism of functioning. Biochemistry (Mosc.) 64, 969-985.
[0020] 4. Greaser, M. L. and Gergely, J. (1971). Reconstitution of troponin activity from three protein components. J Biol Chem. 246, 4220-4233.
[0021] 5. Yates, L. D. and Greaser, M. L. (1983). Troponin subunit stoichiometry and content in rabbit skeletal muscle and myofibrils. J Biol Chem. 258, 5770-5774.
[0022] 6. Farah, C. S., Miyamoto, C. A., Ramos, C. H. I., Silva, A. C. R., Quaggio, R. B., Fujimori, K., Smillie, L. B., and Reinach, F. C. (1994). Structural and regulatory functions of the NH 2 - and COOH-terminal regions of skeletal muscle troponin I. J Biol Chem. 269, 5230-5240.
[0023] 7. Ramos, C. H. (1999). Mapping subdomains in the C-terminal region of troponin I involved in its binding to troponin C and to thin filament. J Biol Chem. 274, 18189-18195.
[0024] 8. Tao, T., Gong, B. J., Grabarek, Z., and Gergely, J. (1999). Conformational changes induced in troponin I by interaction with troponin T and actin/tropomyosin. Biochim Biophys Acta. 1450, 423-433.
[0025] 9. Hernandez, G., Blumenthal, D. K., Kennedy, M. A., Unkefer, C. J., and Trewhella, J. (1999). Troponin I inhibitory peptide (96-115) has an extended conformation when bound to skeletal muscle troponin C. Biochemistry. 38, 6911-6917.
[0026] 10. Moses, M. A., Wiederschain, D., Wu, I., Fernandez, C. A., Ghazizadeh, V., Lane, W. S., Flynn, E., Sytkowski, A., Tao, T., and Langer, R. (1999). Troponin I is present in human cartilage and inhibits angiogenesis. Proc. Natl. Acad. Sci. USA. 96, 2645-2650.
[0027] 11. Zhu, L., Perez-Alvarado, G., and Wade, R. (1994). Sequencing of a cDNA encoding the human fast-twitch skeletal muscle isoform of troponin I. Biochim Biophys Acta. 1217, 338-340.
[0028] 12. Connolly, D. T., Knight, M. B., Harakas, N. K., Wittwer, A. J., Feder, J. (1986). Determination of the number of endothelial cells in culture using an acid phosphatase assay. Anal. Biochem. 152, 136-140.
[0029] 13. Hansen, M. B., Nielsen, S. E., and Berg, K. (1989). Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol. Meth. 119,203-210.
[0030] 14. Feldman, L., Cohen, C. M., Riordan, M. A., and Dainiak, N. (1987). Purification of a membrane-derived erythroid growth factor. Proc. Natl. Acad. Sci. USA. 84, 6775-6779.
[0031] 15. Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J Biol. Chem. 193, 265-275.
[0032] 16. Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriaphage T4 . Nature. 227, 680-685.
[0033] 17. Towbin, H. Staehlin, T., and Gordon, J. (1979). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedures and applications. Proc. Natl. Acad. Sci. USA 76:4350-4354.
[0034] 18. Wiederschain D G et al., Patent Number: WO0054770, Publication date: Sep. 21, 2000.
[0035] 19. U.S. Pat. No. 5,837,680 Moses et al., Pharmaceutical compositions comprising troponin subunits, fragments and analogs thereof and methods of their use to inhibit angiogenesis.
[0036] This invention will be further understood with reference to the following examples.
EXAMPLE 1
[0037] Troponin I was administered to mice beginning 24 hours after intravenous introduction of B16 melanoma cells into the animals. These melanoma cells localize in the lung within several hours after injection of the melanoma cells. Without being bound by any particular theory, it is believed that these melanoma cells require the establishment of a vascular blood supply in order to grow to a size that is visible to the naked eye. After melanoma introduction, the mice were treated with a constant intravenous infusion of Troponin at a cumulative dose of either 1 or 5 mg/kg/day. Animals were sacrificed after 24 days of treatment. Animals receiving 1 mg/kg/day of Troponin had an approximate 65% decrease in the number of lung metastases compared to control, and animals receiving 5 mg/kg/day had a greater than 90% decrease in the number of metastases compared to control. Maintained intravenous infusion of Troponin at very low doses results in a dramatic reduction in metastatic tumor growth.
EXAMPLE 2
[0038] A 56 year old human male presents with malignant melanoma localized in the lung. This patient is treated with a constant intravenous infusion of Troponin at a cumulative dose of 1 mg/kg/day every other day for 90 days. Less than about 35% of the anticipated number of lung metastases are detected as compared with a statistical evaluation of published results of patients at a similar stage of melanoma.
EXAMPLE 3
[0039] A 60 year old human female presents with malignant melanoma localized in the lung. This patient is treated with a constant intravenous infusion of Troponin at a cumulative dose of 3 mg/kg/day every day for 25 days. At 25 days after first dose, less than about 50% of the anticipated number of lung metastases are detected as compared with a statistical evaluation of published results of patients at a similar stage of melanoma.
EXAMPLE 4
[0040] A 44 year old human male presents with malignant melanoma localized in the lung. This patient is treated with a constant intravenous infusion of Troponin at a cumulative dose of 5 mg/kg/day. Every day for 90 days. At 90 days after first dose, less than about 80% of the anticipated number of lung metastases are detected as compared with a statistical evaluation of published results of patients at a similar stage of melanoma.
[0041] The compositions and methods of this invention possess valuable pharmacological properties. They restrict cell proliferation and reduce the establishment and/or occurrence of cancer metastases with particular reference to malignant melanoma, a further reference to malignant melanoma of the lung.
[0042] Thus, these compositions can be used in the therapeutic treatment of a number of forms of cancers, with particular reference to those noted in Table I. Administration is contemplated to include chronic, acute or intermittent regimens.
[0043] The compositions of this invention are generally administered to animals, including but not limited to mammals including livestock, household pets, humans, cattle, cats, dogs, poultry, etc. Particular reference to the methods and compositions is made for the treatment of human subjects in need of such treatment such as those suffering from cancer or other cell proliferative conditions.
[0044] The pharmacologically active compositions of this invention can be processed in accordance with conventional methods of Galenic pharmacy to produce medicinal agents for administration to patients, e.g., mammals including humans.
[0045] The compositions of this invention can be employed in admixture with conventional excipients, i.e., pharmaceutically acceptable organic or inorganic carrier substances suitable for parenteral, enteral (e.g., oral or inhalation) or topical application which do not deleteriously react with the active compositions. Inhalation is particularly useful in treating or dosing lung tissue, including free Troponin or liposomal Troponin in aerosol form. Reference is made to U.S. Pat. No. 5,049,388 (Knight) regarding liposomal aerosol, the teachings of which are incorporated by reference. Suitable pharmaceutically acceptable carriers include but are not limited to water, salt solutions, alcohols, gum arabic, vegetable oils, benzyl alcohols, polyethylene glycols, gelatine, carbohydrates such as lactose, amylose or starch, magnesium stearate, talc, silicic acid, viscous paraffin, perfume oil, fatty acid esters, hydroxy methylcellulose, polyvinyl pyrrolidone, etc. The pharmaceutical preparations can be sterilized and if desired mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, flavoring and/or aromatic substances and the like which do not deleteriously react with the active compositions. They can also be combined where desired with other active agents, e.g., vitamins.
[0046] In some embodiments of the present invention, dosage forms include instructions for the use of such compositions. In some embodiments administration is in conjunction with other antineoplastic drugs and or in conjunction with radiation therapy.
[0047] For parenteral application, particularly suitable are injectable, sterile solutions, preferably oily or aqueous solutions, as well as suspensions, emulsions, or implants, including suppositories. Ampules are convenient unit dosages.
[0048] Also for parenteral application, particularly suitable are tablets, dragees, liquids, drops, suppositories, or capsules. A syrup, elixir, or the like can be used wherein a sweetened vehicle is employed.
[0049] Sustained or directed release compositions can be formulated, e.g., liposomes or those wherein the active component is protected with differentially degradable coatings, e.g., by microencapsulation, multiple coatings, etc. It is also possible to freeze-dry the new compositions and use the lyophilizates obtained, for example, for the preparation of products for injection.
[0050] Generally, the compositions of this invention are dispensed in unit dosage form comprising 0.1 to 500 mg or more in a pharmaceutically acceptable carrier per unit dosage.
[0051] It will be appreciated that the actual preferred amounts of active compositions in a specific case will vary according to the specific compositions being utilized, the particular compositions formulated, the mode of application, and the particular situs and organism being treated. Dosages for a given host can be determined using conventional considerations, e.g., by customary comparison of the differential activities of the subject compositions and of a known agent, e.g., by means of an appropriate, conventional pharmacological protocol. | 1a
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CROSS-REFERENCE TO RELATED APPLICATION
This application claims priority to and the benefit of Korean Patent Application No. 20-2012-0002124 filed in the Korean Intellectual Property Office on Mar. 16, 2012, the entire contents of which are incorporated herein by reference.
BACKGROUND
(a) Field
An exemplary embodiment of the present invention relates to a running machine.
(b) Description of the Related Art
In general, a running machine is a device for enabling exercise in the form of walking or running in an in-door environment, and is designed for a user to walk or run on a belt that rotates due to a force provided by a motor.
Such a running machine requires that the speed of the belt be controlled in a manner corresponding to the physical condition and/or a desired exercise amount of the user. When the speed of the machine is manually controlled, the user manually controls the speed by running and controlling the speed at which the user runs. However, when the speed of the machine is automatically controlled/driven, a keypad is provided on a control panel of the machine to control the speed of the motor, thereby controlling the speed of the belt, and hence, the running speed.
However, aerobic exercise such as walking or running using a conventional running machine is performed by walking or running in place in an indoor space, and thus, the user may experience boredom before achieving an effective aerobic exercise, and accordingly, the user may be prone to prematurely quitting the exercise.
The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention, and therefore may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.
SUMMARY
An exemplary embodiment of the present invention provides a running machine that can improve an exercise experience.
According to an exemplary embodiment of the present invention, there is provided a running machine including a hollow cylinder-shaped rotator having a diameter and including a wall having a constant thickness, a hollow cylinder-shaped display unit having a diameter greater than that of the rotator and encircling the rotator, and a support for supporting the rotator and the display unit in an upright state and for enabling rotation of the rotator about an axis of the rotator.
The rotator and the display unit may be integrally formed.
The rotator may include a transparent material, and the display unit and the rotator may be separated from each other.
The running machine may further include a pair of support rings respectively coupled to edges of a wall of the display unit to support the display unit, and the support rings may be configured to rotatably support the rotator.
The display unit may be configured to display an image on an interior of the display unit.
The display unit may include an organic light emitting element.
The support may be configured to rotate the rotator.
The rotator may include a transparent material, and the display unit and the rotator may be separated from each other.
The support may be at sides of the rotator while the rotator is in the upright state.
The support may include two triangularly-shaped sides and three rectangularly-shaped sides coupling the two triangularly-shaped sides to each other, one of the triangularly-shaped sides may contact the rotator, and one of the rectangularly-shaped sides may function as a base.
The running machine may further include at least one of an information display unit and a control panel at one of the rectangularly-shaped sides other than the base.
The control panel may be configured to control a rotation speed of the rotator or may be configured to control images displayed on the interior of the display unit.
The rotator may include a transparent material, and the display unit and the rotator may be separated from each other.
According to the exemplary embodiment of the present invention, the running machine can improve the exercise experience of the user.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a running machine according to an exemplary embodiment of the present invention.
FIG. 2 is a top plan view of the running machine of the embodiment shown in FIG. 1 .
FIG. 3 is a partial cross-sectional view of the running machine of the embodiment shown in FIG. 1 .
FIG. 4 is a side view of the running machine of the embodiment shown in FIG. 1 and legs of a user operating the running machine.
DETAILED DESCRIPTION
Embodiments of the present invention will be described more fully hereinafter with reference to the accompanying drawings, in which exemplary embodiments of the invention are shown. As those skilled in the art would realize, the described embodiments may be modified in various different ways, all without departing from the spirit or scope of the present invention.
It shall be noted that the drawings are schematic and do not necessarily depict exact dimensions. The relative proportions and ratios of elements in the drawings may be exaggerated or diminished in size for the sake of clarity and/or convenience, and such arbitrary proportions are intended only to be illustrative, and are not intended to be limiting in any way. Like reference numerals are used for like structures, elements, or parts shown in two or more drawings to show similar characteristics. When one part is said to be “over” or “on” another part, the one part may be directly over the other part or may be accompanied by one or more other parts interposed therebetween.
The drawings specifically show exemplary embodiments of the present invention. As a result, various modifications of the drawings in accordance with the present invention are anticipated. Accordingly, exemplary embodiments are not limited to certain forms of the regions illustrated, but may include forms that are modified due to manufacturing, for example.
Hereinafter, a running machine 101 according to an exemplary embodiment of the present invention will be described with reference to FIG. 1 to FIG. 4 .
As shown in FIG. 1 and FIG. 2 , the running machine 101 according to the present exemplary embodiment includes a rotator 200 , a display unit 100 , and a support 500 , which may include two or more individual supports.
The rotator 200 is in the shape of a hollow cylinder, which is set on the side of the cylinder when the rotator 200 is upright, and has a diameter that is greater than the height of an intended user, and also has a constant thickness (e.g., a width, or a geometric height of the cylinder). A user may walk or run on the running machine 101 by stepping on an interior of the rotator 200 with his foot (e.g., at a point higher than the lowest point of the rotator 200 ).
The rotator 200 of the present embodiment is formed of a transparent material. For example, the rotator 200 may be formed of glass or plastic.
The display unit 100 is formed in the shape of a hollow cylinder corresponding to the shape of the rotator 200 (e.g., the display unit 100 may have a slightly larger inner diameter than an outer diameter of the rotator 200 ). In addition, the display unit 100 is arranged to overlap (e.g., encircle) the rotator 200 and to be positioned on an exterior of the rotator 200 . That is, the interior circumference of the display unit 100 is located outside of the external circumference of the rotator 200 . In addition, as shown in FIG. 3 , the display unit 100 and the rotator 200 are spaced from each other.
The display unit 100 displays an image in a direction toward an interior of the cylinder that is the display unit 100 . Further, the display unit 100 includes an organic light emitting element (e.g., a plurality of organic light emitting elements). That is, the display unit 100 may be a flexible organic light emitting diode display formed in the shape of a cylinder. The flexible organic light emitting diode display forming the display unit 100 may employ various known organic light emitting diode displays.
In addition, the running machine 101 may further include a pair of support rings 300 located at both edges of the rotator 200 and the display unit 100 to support the rotator 200 and the display unit 100 . In the present embodiment, the pair of support rings 300 supports the rotator 200 to be rotatable (e.g., the rotator 200 is able to move with respect to the rings 300 ). In addition, the display unit 100 may be fixed by the pair of support rings 300 (e.g., fixed with respect to the support 500 , in a non-rotatable state) rather than rotating along, or along with, the rotator 200 .
Thus, the rotator 200 rotates according to motion (i.e., walking or running) of the user, and the display unit 100 may provide an image and/or image information to the user walking or running along the interior of the rotator 200 . Furthermore, the rotator 200 functions as a surface for supporting the user, and also functions as a protection window to protect the display unit 100 .
In further detail, the display unit 100 of the present embodiment can provide exercise information of the user such as, for example, walking or running speed, calories burned, distance traveled, etc. In addition, the display unit 100 can provide an image of a user-desired environment. That is, the display unit 100 may provide images selected by the user such as, for example, a forest park, an exotic street landscape, and/or other scenes found in nature, such that exercise experience of the user can be improved.
In FIG. 3 , the running machine 101 of the present embodiment has a structure in which the rotator 200 and the display unit 100 are separated from each other, but the exemplary embodiment of the present invention is not limited thereto. Thus, the rotator 200 and the display unit 100 may be integrally formed. In this case, the display unit 100 rotates together with the rotator 200 . In addition, the display unit 100 is driven to display an image in consideration of a rotation speed (e.g., the images displayed on the display unit 100 may be adjusted to produce an image that appears to be steady or stable with respect to the user despite the rotation of the display unit 100 ).
For rotation of the rotator 200 , the support 500 supports the rotator 200 and the display unit 100 while putting them in an erected (e.g., upright) state. The support 500 may be at opposite sides of the rotator 200 , and may be offset in a thickness or width direction of the rotator 200 , or may be aligned on opposite sides of the rotator 200 in a rotation direction of the rotator 200 . In addition, the support 500 may rotatably drive the rotator 200 , and may do so using various devices and/or methods known to a person skilled in the art. For example, the support 500 can rotate the rotator with a motor roller.
The support 500 of the present embodiment is provided at both sides of the rotator 200 while the rotator 200 is in the erected (e.g., upright) state. The support 500 may be formed in the shape of a triangle or a triangular pyramid including two triangle-shaped sides and three square-shaped, or rectangularly-shaped, sides coupling the two triangle-shaped sides. In this case, one of the two triangular-shaped sides contacts the rotator 200 , and one of the three squared-shaped sides may be a bottom side, or a base.
In addition, at least one of an information display unit and a control panel may be provided at another side of the third square-shaped sides in the support 500 . The user may control a rotation speed of the rotator 200 through the control panel 550 of the support 500 , and/or may select the type of image displayed in the display unit 100 .
With such a configuration, the running machine 101 according to the exemplary embodiment of the present invention can improve the exercise experience of the user.
Hereinafter, operation of the running machine 101 provided on a table according to the exemplary embodiment of the present invention will be described with reference to FIG. 4 .
As shown in FIG. 4 , the user stamps on, or steps on, the interior of the rotator 200 to walk or run. In this case, the user controls a rotation speed of the rotator 200 through the control panel 550 located in or on the support 500 , and selects an image displayed in the display unit 100 .
The display unit 100 provides images such as, for example, a forest park, an exotic street landscape, and/or other scenes in nature in accordance with a rotation speed of the rotator 200 to provide the user walking or running on the rotator 200 with a visual effect of walking or running outside. Accordingly, the user can expect an improved exercise experience.
While embodiments of the present invention has been described in connection with what is presently considered to be practical exemplary embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims, and their equivalents.
Description of Some of the Reference Characters
100: display unit
101: running machine
200: rotator
300: support ring
500: support
550: control panel | 1a
|
[0001] This application is a continuation-in-part of U.S. Ser. No. 10/882,291 filed Jul. 2, 2004 now U.S. Pat. No. 7,625,411 the entire contents of which are incorporated by reference herewith.
FIELD OF THE INVENTION
[0002] The invention pertains to insecticidally treated fabric and methods for its preparation, wherein the method by which, and materials with which the fabric is treated yields a textile of improved wash durability and, consequently, the useful items made from such fabrics demonstrate prolonged and improved insecticidal efficacy.
BACKGROUND OF THE INVENTION
[0003] Permethrin, a broad-spectrum insecticide useful against a variety of pests on nut, fruit, vegetable, cotton, ornamental, mushroom, potato, and cereal crops. Permethrin is a synthetic pyrethroid which exhibits repellent as well as knockdown and kill activity against insects. Pyrethroids, including both the naturally-occurring compounds and their synthetically prepared analogs effectively control a variety of pests, such as ticks, cockroaches, houseflies, mosquitoes, black flies, fleas, and other flying or crawling insects. Pyrethroids are not harmful to plants, food, animals or humans, and leave no harmful residues. Permethrin has also been applied on fabric to help combat mosqitoes, tickes, fleas, bedbugs, chiggers, and flies.
[0004] Fabrics coated with active agents, and in particular insecticidal agents, are known in the patent literature, as well as compositions and methods for preparing such treated textiles. These fabrics have beneficial utility when sewn into an article of manufacture such as a tent, tarpaulins, sleeping bag, and protective outerwear garments for both civilian and military applications. For example, U.S. Pat. Nos. 3,859,121 (Yeadon et al), 4,765,982 (Ronning et al), 5,089,298 (McNally et al), 5,198,287 (Samson et al), 5,252,387 (Samson et al), 5,503,918 (Samson et al), 5,631,072 (Samson et al), 6,015,570 (Tucci et al), 6,030,697 (Samson et al), and 6,440,438 (Platts) all pertain to textile fabrics that have been treated with an insect repellent.
[0005] A major concern of using permethrin as an insect repellent in treated fabrics resides in the wash durability of the insecticide. That is, the retention of permethrin in garments made from treated fabric through repeated wash cycles during machine laundering. It is to this aspect of insecticidally-treated textiles that the present invention pertains.
[0006] For example, U.S. Pat. No. 5,089,298 discloses a synergism between an amylopectin (a water soluble form of starch)-permethrin combination on textile fabrics to afford greater retention of permethrin in clothing through repeated wash cycles as compared to garments treated only with permethrin. Another example is disclosed in U.S. Pat. No. 5,503,918 wherein the addition of polyvinyl acetate as a binder for the permethrin dispersion preserves the effectiveness of the permethrin through more washings of the fabric than does the amylopectin used in the '298 patent. U.S. Pat. No. 5,631,072 discloses wash durable permethrin-treated garments prepared from a fabric that is either impregnated or single-side surface-coated with a dispersion of permethrin. In the case of impregnation, a dispersion of permethrin, a polymeric binder such as acrylic copolymer or polyvinylacetate, and optionally a cross-linking agent (e.g., methylated melamine resin), are used. In the single-side surface coating embodiment, the fabric is treated with the insecticide and a thickener (e.g., carboxymethylcellulose), and optionally a polymeric binder that is optionally cross-linked.
[0007] Additional patents focusing on one or both of incorporation and retention of either permethrin or a pyrethroid on fabric are as follows:
[0008] U.S. Pat. No. 3,859,121 teaches methods for retarding insect repellent contamination of foodstuffs stored in contact with cellulosic textile that has been treated with such repellent, by incorporating into the impregnation composition an antimigrating agent. An insecticidal combination of pyrethrin and piperonyl butoxide are impregnated in association with an emulsifing polyoxyethylene sorbitol ester of a mixed C 12 fatty acid, a hydroxyalkyl cellulose thickener, and an antimigrating agent such as water soluble polyalkylene glycol, polypropylene triol or pentol of specified average molecular weight, corn oil, tung oil, linseed oil, linoleic acid dimer or trimer, and others.
[0009] U.S. Pat. No. 4,765,982 discloses controlled release insect control devices (e.g., webs, tapes, sheets, pads) based on microencapsulated pyrethroid insecticide that self-adheres to rough-surfaced fibers comprised of graft polymers of cellulose and an ethylenically unsaturated material copolymerizable therewith.
[0010] U.S. Pat. No. 6,030,697 discloses a method for impregnating BDU's (battle dress uniforms), made from conventional (e.g., untreated twill) fabric with permethrin by adding an aqueous solution (approximately 1%) of permethrin to the wash cycle of an industrial washing machine, and returning all extracted and spin waters containing permethrin to a holding tank for subsequent reuse.
[0011] U.S. Pat. No. 5,198,287 discloses a tent fabric with a water repellent and flame retardant coating that includes the insecticide permethrin. The patent focuses on the oxygen- and light-sensitivity of permethrin. According to the '287 invention, permethrin is incorporated in the coating on the inner surface of the tent fabric to shield the permethrin from oxygen and ultraviolet light, thereby providing an effective life of more than six months for the permethrin. Similarly, U.S. Pat. No. 5,252,387 also deals with the oxygen- and light-sensitivity of permethrin in insect repellent fabric and discloses that permethrin can be preserved in the fabric by placing a barrier layer over the permethrin to protect the permethrin from degradation by ultraviolet light and oxygen.
[0012] The use of binders in coating “actives” on textiles is widely known in the literature and practiced in the textile industry. More specifically, polymer binders are utilized to aid in improving adhesion and abrasion resistance of the “active” (e.g., a flame retardant, a water repellant, an insect repellant.) U.S. Pat. Nos. 4,594,286 and 4,833,006 are examples of flame resistant, water repellant woven fabrics using blocked polyester/polyether urethane prepolymer or polyfunctional (unblocked) isocyanate, respectively, as binders to aid in the retention of coated “active”.
[0013] U.S. Pat. Nos. 5,300,192, 5,447,977, 5,571,618, 5,609,727, and 5,611,885 are all commonly assigned to Weyerhaeuser Co. and pertain to the use of reactivatable binders for binding particles to fibers, particularly wet laid or high bulk fibers for web or sheet production, either cellulosic (wood pulp) or synthetic in nature. These patents disclose both polymeric and non-polymeric organic binders having multiple functionalities which, via a combination of hydrogen bonding and coordinate covalent bonding, bind to both the fiber substrate and the particulate to be adhered. Both the fiber and the particulate are functionally reactive with the binder. Examples of polymeric binders include PEG, PPG, polyacrylic acid, polyamides, polyamines, polyaldehydes, and poly(caprolactone) diol. Examples of non-polymeric binders include glycerin, ascorbic acid, urea, glycine, pentaerythritol, a monosaccharide, a disaccharide, citric acid, tartaric acid, dipropylene glycol, and DMDHEU. The binders of the Weyerhaeuser patents have reactivatable funtionality, allowing, e.g., the binder to be adhered to the fiber at one point in production and at a later point in time the functionality for binding the particulate is activated to bind the particulate. While the preferred particles for adhering to the fibrous products or high bulk fibers of most of these patents are superabsorbent particles and/or antimicrobials (e.g., to produce a diaper or other absorbent hygeine product), these patents disclose a long and diverse laundry list of particulates that can be bound to the fibrous products, including, e.g., certain insecticides. (Table I). Permethrin, however, is not recited. Additionally, while the nature of the bonding (i.e., either H-bond or coordinate covalent bond) of the particles to the binder affords the particles to stay in contact with the fibers and resist dislodgement therefrom by mechanical forces applied to the endproduct (a fibrous mat) during manufacture, storage or use, the fibrous products to which these patents pertain are not intended to be laundered, either once or repeatedly. Hence the Weyerhaeuser disclosures do not appreciate the challenges posed by improving the wash durability of garments made from permethrin-treated woven textiles.
SUMMARY OF THE INVENTION
[0014] The invention is directed to a method of enhancing the wash durability of insecticidally-treated fabric and consequently and additionally to increasing the efficacy of the same to repel insects before and after repeated machine launderings.
[0015] The invention pertains more specifically to a method of impregnating a fabric with a dispersion of an insecticide and a retention additive that is either a binder polymer, a cross-linking agent, or a dye fixative agent, to produce an effective and improved insect repelling fabric.
[0016] The invention pertains further to a method of enhancing the wash durability of permethrin-treated fabric and consequently and additionally to increasing the efficacy of such permethrin-treated fabric to repel insects before and after repeated machine launderings by impregnating the fabric with a dispersion of an insecticide and a retention additive that is either a binder polymer, a cross-linking agent, or a dye fixative agent.
[0017] The invention provides for permethrin-treated fabrics that are intended for use in garment manufacture wherein the garments made from such fabrics demonstrate the improved wash durability and improved insect repelling efficacy of permethrin contained in the fabric over repeated machine launderings.
[0018] The invention pertains further to any finished good, whether a garment or tent or other fabric structure that comes into shielding contact with a subject to be protected from insects, prepared from the improved insect-repelling fabric.
[0019] The invention further provides fabrics and fibers having a retention of insecticide from >20% to >90% after 50 launderings.
[0020] These and other embodiments of the invention will become more evident from the detailed description of the invention that follows.
DETAILED DESCRIPTION OF THE INVENTION
[0021] The fabric or textile substrate to be treated in accordance with the invention is not limited as to type. Thus cotton, rayon, linen, polyester, natural and synthetic polyamides (“nylons”), acrylic, cellulose acetate, polyaramide, polypropylene fabric, blends of these, for example, cotton and polyester, cotton and nylon, are suitable fabrics in the context of the invention. Leather, both natural and man-made, are also contemplated as a garment material suitable for insecticidal impregnation according to the invention. In a preferred embodiment of the invention the fabric is a polyester fabric. In another preferred embodiment the fabric is a nylon or a nylon blend. In a further preferred embodiment, the fabrics are based on polyaramides such as poly meta-aramid and poly para-aramid.
[0022] Other fibers and fabrics of interest include FR rayon (such as Lenzing FR) and PBI (polybenzimidazole).
[0023] According to federal government guidelines, the target add-on for permethrin on the fabric is 1.25 grams/meter 2 , having been determined by the National Research Council that at this level, a soldier wearing permethrin-impregnated BDU for upwards of 18 hours a day, seven days week for several (10) years was unlikely to experience adverse health effects, and that the risk to garment workers handling fabric impregnated at this rate was even less. Before a given fabric can be treated in accordance with the present invention, it is necessary to calculate the proper concentration of insecticide, e.g., permethrin, present in an aqueous impregnating bath such as a pad mix. That calculation is dependent on the following parameters:
[0000] A) fabric weight (in grams/M 2 );
B) target permethrin (in grams/M 2 )(set at 1.25 g/M 2 );
C) percent wet pick-up of fabric; and
D) percent available permethrin in the commercial formulation being used (set by the manufacturer of the insecticide).
Parameters 1, 2, and 4 are rather straight forward to determine; the information for determining their respective values is either provided (e.g., by the manufacturer) or is easily ascertained by weighing and measuring the fabric to be treated. For parameter A, the “fabric weight” is typically expressed in the US textile market/industry as “ounces/linear yard”; therefore it will be necessary to convert those units to grams/M 2 using standard conversion factors in order to plug the values into the permethrin calculation below. The percent wet pick-up of a given fabric (variable “C”) to be insecticidally treated is defined according to the following formula:
[0000]
Wet
Weight
-
Dry
Weight
Dry
Weight
×
100
=
%
Wet
Pick
-
up
of
the
Fabric
,
[0000] wherein the dry weight is obtained by weighing a piece of the fabric to be treated and recording its weight, and the wet weight is obtained by soaking the same piece of fabric in water until thoroughly wet, running the soaked fabric through a pad squeeze roll which duplicates production squeeze pressures, reweighing and recording that weight.
[0024] The calculation for the quantity of permethrin (expressed as a percentage of the aqueous pad mix) is as follows:
[0000]
[
(
B
/
A
)
×
(
100
/
C
)
]
(
D
/
100
)
×
100
=
%
Permethrin
present
in
the
aqueous
pad
mix
,
[0000] wherein A, B, C, and D are defined above. The “% permethrin” is of the active only, to clarify from, for example, the commercial preparation (Evercide® Permethrin 40% Manufacturing Concentrate 2778—manufactured by McLaughlin Gormley King Co. in Minneapolis Minn.) which is 40% permethrin in composition. It is a routine calculation to ascertain how much of a commercial insecticidal preparation to add to the aqueous pad mix once the % active is determined from the above formula. Thus for any given type of fabric to be treated in accordance with the method of the invention, the textile worker is able to determine precisely and without undue experimentation, the desired fabric add-on.
[0025] For the sake of example only, the following ranges serve as a rough guide for the values of permethrin to be added to the pad bath. The ranges however were determined using the above calculations and based on the following assumptions about the particular fabric to be treated, namely, 1) treating a 60 inch width fabric having 2) 100% wet pick=up. Thus, a fabric with a fabric yield (or weight) of from 1 to 4 ounces per square yard (1-4 oz/yd 2 ) and further characterized by assumptions 1) and 2), would require a pad bath that is from 2 to 9% permethrin based on the weight of the bath size. In another scenario, a fabric with a fabric yield (or weight) of from 5 to 10 ounces per square yard (5-10 oz/yd 2 ) and further characterized by assumptions 1) and 2), would require a pad bath that is from 1 to 2% permethrin based on the weight of the bath size. In another scenario, a fabric with a fabric weight of from 5 to 10 ounces per square yard (5-10 oz/yd 2 ) and further characterized by assumptions 1) and 2), would require a pad bath that is from 1 to 2% permethrin based on the weight of the bath size. For fabrics weighing 11 oz./yd 2 or heavier, under the stated assumptions, one would add less than 1% permethrin based on the weight of the bath size. Once again, to satisfy the enablement requirement of the present disclosure, the amount of insecticide to be added to the bath to achieve the desired fabric add-on, is determined based on the properties (weight, width, % wet pick-up) of the fabric, the % available insecticide in the insecticidal formulation, using the stated calculation. The ranges set forth above are merely shown to provide a general idea of how much permethrin formulation (e.g., Evercide®) on a weight percentage basis needs to be added to a pad bath for fabrics of various weights and specified width and pick-up.
[0026] The method of incorporating the insecticide into the fabric is by impregnation or by exhaust methods. Thus application by conventional impregnation methods such as dipping, padding or spray processes are within the scope of the invention, as are conventional exhaust processes using one or more of long or short liquor ratios (e.g. liquor-to-goods ratios of from 100:1 to 0.5:1), optimizing (i.e., raising) the temperature of the aqueous bath, and mildly acidifying the bath conditions. In a preferred embodiment of the invention permethrin is impregnated into the fabric substrate by padding, using a pad bath at ambient temperature.
[0027] The wash durability of the insecticide impregnated in the fabric is improved by adding a retention additive or polymer binder to the pad mix or bath that also contains the insecticide. The term “retention additive” is used to designate a compound that is not a known polymer binder, but rather a compound with a different function but that in the context of the invention, is effective to improve the wash durability of the insecticide. Depending upon the type of fabric to be insecticidally treated, the type of additive or binder varies in accordance with the invention. As previously stated, fabrics such as cotton, rayon, linen, polyester, natural and synthetic polyamides (“nylons”), acrylic, cellulose acetate, polyaramide, polypropylene fabric, and blends of these (e.g., cotton and polyester, cotton and nylon) are suitable for treatment in accordance with the invention. Particularly preferred fabrics are polyester and woven nylons.
[0028] In the case of nylon fabrics, the additive that improves the wash durability of the permethrin is either a water-soluble nylon-based polymer, a polyurethane binder or a dye fixative agent. Water-soluble, nylon-based polymers suitable in the practice of the invention are typically referred to as polyetheramide polymers. These polymers arose as an improvement to traditional nylon polymers, e.g., by replacing the alkylene diamine reactant (typically reacted with a dicarboxylic acid such as adipic acid as in the formation of nylon 6,6) with an alkylene glycol diamine. In general, polyetheramide polymers can be formed by reacting polycarboxylic acids with polyetheramines. Alternatively, these polymers can be formed by copolymerizing caprolactam with, e.g., polyethyleneoxy diamines and a dibasic acid such as terephthalic acid. Polyetheramide polymers and block polymers and methods for their preparation are known in the art. See, for example, U.S. Pat. Nos. 3,454,534, 4,919,997, 5,166,309 (block polyetheramides), and 5,342,918 (carboxyl-terminated polyetheramides); French Patent Publication Nos. 2,273,021, 2,384,810, and 2,401,947; German publication DE 3,428,405 discloses polyetheramides prepared from a stoichiometric mixture of oligoamidediacid and of oligoetherdiol, and from 3-30% relative to the mixture of diol of low molecular weight; Japanese publications J63-048,332, J63-227,238, J63-280,736, J63-105,032, and J63-182,343 describe block polyetheramides and processes for their preparation. More particularly, suitable polyetheramide polymers in the practice of the invention include copolymers of a polyalkyleneglycol and a poly(C 3 -C 12 )alkyllactam. In a more preferred embodiment of the invention, copolymers of PEG/polycaprolactam polymer and PEG/polylauryllactam polymer are employed to bring about the improved wash durability of the insecticidally treated fabric.
[0029] The polyurethane binder of the invention is typically a polyurethane dispersion. The term polyurethane dispersion as used herein describes stable mixtures of polyurethane polymers in water. Methods of preparing polyurethane dispersions are well known in the art and many of polyurethane dispersions are commercially available. Polyurethane polymers are generally characterized by their monomer content and most commonly involve the reaction of a diisocyanate with a polyol and chain extender. While the present inventors believe the polyurethane dispersion can be a stable aqueous mixture of any known polyurethane, typically the polyurethanes suitable for the use in the aqueous polyurethane dispersions are the reaction products (a) an isocyanate compound having at least two isocyanate (—NCO) functionalities per molecule; (b) a polyol having at least two hydroxy functionalities per molecule and a molecular weight ranging from 250 to 10,000 g/mole. The polyol may be selected from those commonly found in polyurethane manufacturing such as hydroxy-containing or terminated polyethers, polyesters, polycarbonates, polycaprolactones, polythioethers, polyetheresters, polyolefins, and polydienes. Suitable polyether polyols for the preparation of polyether polyurethanes and their dispersions include the polymerization products of cyclic oxides such as ethylene oxide, propylene oxide, tetrahydrofuran, or mixtures thereof. Polyether polyols commonly found include polyoxyethylene (PEO) polyols, plyoxypropylene (PPO) polyols, polyoxytetramethylene (PTMO) polyols, and polyols derived from the mixture of cyclic oxides such as poly(oxyethylene-co-polypropylene) polyols. Typical molecular weight of polyether polyols can range from 250 to 10,000 g/mole. Suitable polyester polyols for the preparation of polyester polyurethanes and their aqueous dispersions include; hydroxy-terminated or containing reaction products of ethylene glycol, propylene glycol, diethylene glycol, neopentyl glycol, 1-4, butanediol, furan dimethanol, polyether diols, or mixtures thereof, with dicarboxylic acids or their ester-forming derivatives.
[0030] Modified polyether polyurethanes such as polyetherester polyurethanes and polyethercarbonate polyurethanes may also be suitable polyurethanes for the preparation of aqueous polyurethane dispersions. These modified polyether polyurethanes can be derived by incorporating additional polyester polyols or polycarbonate polyols into polyether polyols during the polyurethane manufacturing.
[0031] Typically the polyurethane polymer useful to prepare the polyurethane dispersion as component in the compositions of the present invention is selected from polyether polyurethanes, polyester polyurethanes, polycarbonate polyurethanes, polyetherester polyurethanes, polyethercarbonate polyurethanes, polycaprolactone polyurethanes, hydrocarbon polyurethanes, aliphatic polyurethanes, aromatic polyurethanes, and combinations thereof.
[0032] Polyurethane dispersion as used herein encompasses both conventional emulsions of polyurethane polymers, for example where a preformed polyurethane polymer is emulsified into an aqueous medium with the addition of surfactants and application of shear, and also includes stable mixtures of self-dispersing polyurethane polymers. Polyurethane dispersions of self-dispersing polyurethane polymers are well known in the art and many are commercially available. These polyurethane dispersions are generally free of external surfactants because chemical moieties having surfactant like characteristics have been incorporated into the polyurethane polymer and therefore are “self emulsifying” or “self dispersing”. Representative examples of internal emulsifier moieties that can be incorporated into the polyurethane dispersions useful in the present invention include; ionic groups such as sulfontates, carboxylates, and quaternary amines; as well as nonionic emulsifier groups such as polyethers. Such polyurethane dispersions are well known in the art, and are typically prepared by either a one stage or two-stage process. Typically, a isocyanate-terminated polyurethane prepolymer is made from isocyanates, polyols, optional chain extender, and at least one monomer containing a hydrophilic group to render the prepolymer water dispersible. The polyurethane dispersion can then be prepared by dispersing the isocyanate-terminated polyurethane prepolymer in water with other polyisocyanates. Further chain extension can be affected by the addition of chain extenders to the aqueous dispersion. Depending on the choice of the hydrophilic group used to render the polyurethane polymer water dispersible, an additional reaction step may be needed to convert the hydrophilic group to an ionic species, for example converting a carboxyl group to an ionic salt or an amine to an amine salt or cationic quaternary group.
[0033] Representative, non-limiting examples of polyurethane dispersions that are suitable for use as the binder component in the compositions of the present invention, as well as general descriptions of techniques useful to prepare polyurethane dispersions can be found in U.S. Pat. Nos. 4,829,122, 4,921,842, 5,025,064, 5,055,516, 5,308,914, 5,334,690, 5,342,915, 5,717,024 5,733,967, 6,017,998, 6,077,611, 6,147,155, and 6,239,213.
[0034] Representative, non-limiting examples of commercially available polyurethane dispersions that are suitable for use as component (B) in the compositions of the present invention include: WITCOBOND W 290H, W-290H, W-296, and W213 (Uniroyal Chemical Division, Crompton Corporation, Middlebury, Conn.); DISPERCOLL U42, BAYHYDROL 121, and Bayhydrol 123 polycarbonate polyurethane dispersions (100 Bayer Road, Pittsburgh, Pa. 15025); SANCURE 2710 and 2715 aliphatic polyether polyurethane dispersions (Noveon, Inc. Cleveland, Ohio); NEOREZ R-966, R-967, R-9603 aliphatic polyurethane dispersions (NeoResins Division, Avecia, Wilmington, Mass.).
[0035] Alternatively, for nylon fabrics the additive may also be a dye fixative agent. Without being bound by any one particular theory of the mechanism of interaction and the improved results obtained from using a dye fixative agent in association with permethrin, it is thought that permethrin will “bond” with the fixative into the fabric and make it more durable to home laundering. The dye fixing agent can be any of a variety of fixing agents known for application to polyamide fiber to improve dye washfastness. These agents are typically compounds or low molecular weight polymers with anionic groups which can associate with the nitrogen-containing groups of the polyamide polymer and form a surface layer that reduces diffusion of the dye out of the treated fiber. “Syntan” is usually used to describe the class of synthetic fixing agent including condensation products of aromatic sulfonic acids and formaldehyde that are in common usage in the industry for acid dye fixation on nylon. Syntans and their derivatives include sulfonated napthol-formaldehyde condensation products; sulfonated phenol-formaldehyde condensation products; polymers of methylacrylic acid or its alkali metal salt, and up to 70 weight percent of one or more monomers having ethylenic unsaturation and containing 2 to 20 atoms; a polymer of maleic acid or fumaric acid, or alkali metal salts thereof, and up to 70 weight percent of an ethylenically unsaturated aromatic comonomer containing 2 to 20 atoms; polymers of alpha-substituted acrylic acids or esters polymerized in the presence of a sulfonated aromatic formaldehyde condensation polymer; and polymers of a sulfonated hydroxyaromatic ester of an alpha-substituted acrylic acid or acrylic acid. Syntans are commercially available and are sold, for example, under the trademarks ERIONAL® (Ciba-Geigy Corp, Greensboro, N.C.), INTRATEX® (Crompton & Knowles Corp., Stamford, Conn.), MESITOL® (Mobay Corp. Pittsburgh, Pa.), and NYLOFIXAN® (Sandoz Chemical Corp., Charlotte, N.C.). The preferred dye fixing agents in the practice of the invention are sulfonated naphthalene formaldehyde condensates, sulfonated phenol formaldehyde condensates, dihydroxy diphenyl sulfone formaldehyde condensates, and mixtures thereof.
[0036] In the case of insecticidally treating a polyester fabric, the retention additive is a polymeric binder. More particularly, the polymeric binder is a polyester polymer or resin. The use of polyester (co)polymers for treating fibers, including polyester fibers and fabrics, is known in the art. The following patent disclosures exemplify such polymers and uses: U.S. Pat. Nos. 3,712,873, 3,893,929, 3,959,230, 3,962,152, 4,027,346, 4,125,370, and 4,370,143. In one or more embodiments of the invention, the polyester polymer is preferably comprised of a reaction product of a polyalkyleneglycol, an aromatic dicarboxylic acid, and a glycol. The polyalkylene glycol component of the polyester may be those normally having an average molecular weight in the range of 600-12,000, preferably in the range of 1,000-5,000, and may include polyethylene glycol, polyethylene glycol-polypropylene glycol copolymer, polyethylene glycol-polytetramethylene glycol copolymer, polypropylene glycol and polyhydric alcohol-ethylene oxide adduct etc. Other examples of usable alkylene glycols are monophenylethers, monoethylethers and monomethylethers of polyethylene glycol and polypropylene glycol.
[0037] The dicarboxylic acid component has the following general formula HOOC-A-COOH, wherein A is a bivalent organic radical selected from the group consisting of alkylene, arylene, aralkylene, alkarylene and cycloalkylene radicals having from 3 to about 14 carbon atoms. Preferably, the dibasic carboxylic acid is an aromatic dicarboxylic acid.
[0038] The glycol component is a compound having the following general formula HO—X—OH, wherein X is a bivalent organic radical selected from the group consisting of alkylene and cycloalkylene radicals having from 2 to about 4 carbon atoms. When X is alkylene, examples of suitable radicals are ethylene, propylene and butylene, and when X is a cycloalkylene radical, examples of suitable radicals are cyclopropylene and cyclobutylene.
[0039] Representative polyesters suitable in the practice of the invention include terephthalic acid-alkylene glycol-polyalkylene glycol, terephthalic acid-isophthalic acid-alkylene glycol-polyalkylene glycol, terephthalic acid-alkylene glycol-polyalkylene glycol monoether, terephthalic acid-isophthalic acid-alkylene glycol-polyalkylene glycol monoether. More preferably, the polyester polymer comprises a poly(C 2 -C 4 )alkyleneterephthalate (e.g., polyethyleneterephthalate or polytetramethylene-terephthalate) or mixtures thereof. An example of suitable polyester polymer is a proprietary material available under the tradename Pomoco253 (a product of Piedmont Chemical Industries I, LLC in High Point, N.C.) which is a polyester derived from terephthalic acid and glycols. Another suitable polyester polymer is the next generation of Pomoco 253, named Pomoco 253-P and also available from Piedmont Chemical Industries I, LLC in High Point, N.C.
[0040] For fabric blends of polyester and cotton, or even fabrics that are entirely cellulosic, the present inventors have found that an effective polymeric binder system for the permethrin may also be crosslinking agent. Crosslinking agents are widely used in the textile industry in the dyeing of certain fabric types (e.g., cellulosics) or to impart desirable properties to the textile (e.g., wrinkle recovery or crease resistance, tensile strength, and fabric smoothness). For example, the disclosures of U.S. Pat. Nos. 4,629,470 and 5,298,584 pertain to cellulosic substrates intended for eventual dyeing and which are pre-treated with finishes in order to render the fabric surface more receptive to dyes and to improve color strength of the dyed product. Such finishes comprise as major components a crosslinking agent, a catalyst and other reactive additives such as glycols or choline chloride that graft to the crosslinking agent. U.S. Pat. No. 4,396,391 provides a crosslinking agent for use as a crease-resistant finish for cellulose-containing textiles, which crosslinking agent is a reaction product of dimethylol dihyroxyethylene urea (DMDHEU) or an alkylated DMDHEU with a polyol. Crosslinking agents useful in the present invention are those which preferably possess multiple reactive sites. These include, for example, dimethylol urea, partially methylolated urea, dimethylol ethyleneurea, dimethylol propyleneurea, dimethylol dihydroxyethyleneurea (DMDHEU), alkylated DMDHEU, trimethylol acetylenediureine (3ACD), tetramethylol acetylenediureine (4ACD), and methylol melamine (TMM), dimethylol propyl carbamate, and forms of these that have been modified by grafting, e.g., with polyalkylene glycols of suitable molecular weight. In a preferred embodiment of the invention, a DMDHEU/PEG modified crosslinking agent is effective in enhancing the wash durability of permethrin-treated cotton and cotton/polyester blend fabrics.
[0041] Depending on the fabric being insecticidally treated, the polymer binder, crosslinking agent or dye fixing agent, is added to the same bath to which the permethrin (or other insecticide) is also added. The binder, crosslinker or dye fixative is present in the pad bath in an amount that varies widely from 0.01 to 20% by weight of the bath size; the wide range specified is reflective of the fact that the amount of binder, crosslinking agent or dye fixative necessary will be dependent upon the wet pick-up of the fabric. Generally a fabric with a higher wet pick-up value will require a smaller amount of binder, crosslinker or dye fixative in the pad bath, and a fabric with a lower wet pick-up value will require a larger amount. Thus, the amount of “the additive” needed depends on the type of fabric being treated (e.g., nylon, polyester, cotton, acrylic) and the relevant textile properties thereof (i.e., at least the wet pick-up of the fabric). More preferably the binder, crosslinker or dye fixative is present from about 0.5 to 10% by weight of the bath size, and in a preferred embodiment “the additive” is present from about 1 to 3% by weight of the bath size. What is essential about the amount of additive used is that it be the least amount necessary to achieve the enhanced durability of the insecticide without being detrimental to the desired hand, or feel, of the fabric.
[0042] In a less preferred and alternate embodiment, the fabric can be treated sequentially, rather than the preferred method of padding the fabric in a single pad bath that contains both the retention additive and the permethrin. Thus, for example, the fabric can be treated or padded with the polymeric binder, crosslinking agent or dye fixative agent at one point in time at one location, and then be padded with insecticide at a later point in time, and possibly at a different location, provided that the interim time and conditions to which the fabric is exposed (between the first pad and the second pad) do not have a significant adverse affect on the binding of insecticide to the fabric and the level of enhanced wash durability achieved herein.
[0043] Following impregnation, the fabric is typically subjected to at least one after-treatment conventional in textile processing. For example, the insecticidally treated fabric can be subjected to drying or curing following the padding or exhaust application. Additionally the fabric may be after-treated with customary finishes to improve, e.g., the hand, water repellancy, wrinkle resistance, brightness, antibacterial nature of the textile, provided that none of these additional agents interfere with either the extended wash durability or the insecticidal efficacy.
[0044] Additional finishes could be combined with permethrin as above with the dye fixative agent. These additional finishes include
[0045] A. UV absorbing chemistry such as Sunlife KLP from Nicca or Tinofast CEL (UV Sun CEL) from Huntsman that are used to make the fabric/garment protect the weared from the harmful UV rays of the sun.
[0046] B. Moisture control treatments that make fabrics hydrophilic such as Milease T from Clariant or Feran ICE from Rudolph Chemie.
[0047] C. Water and oil repellent chemistries such Zonyl 7040 from Dupont/Huntsman or Nuva N2114 from Clariant.
[0048] The fabrics and fibers of the invention exhibit a retention of insecticide in the range of from about >20% to about >90% after 50 launderings.
Example
[0049] The following examples are provided solely to illustrate the invention, and not to limit the scope of the invention to the particular fabrics, polymeric binders and/or dye fixative agents used therein.
[0050] A polyester warp fleece weighing approximately 7.6 oz. per linear yard was used in this trial. Based on the weight of the fabric, calculating the percent wet pick-up the of fabric using production squeeze pressures in the pad application, and the amount of permethrin target (1.25 g/m 2 ), the quantity of permethrin to be added to the pad bath was calculated using the above equation to be 1.68%. Also added to the pad bath was a polyester-based binder system (Pomoco 253P) at 2.50% based on the weight of the bath. The fabric was padded and dried at a normal drying temperature for polyester (330 to 350° F.).
[0051] After the application of permethrin to the fabric, samples of the treated fabric were extracted with toluene according to the procedure outlined below in order to determine the amount of permethrin loaded onto the fabric. A swatch of fabric measuring approximately two feet by two feet is cut from the treated roll of fabric. From that swatch, 3 smaller pieces measuring 10 cm by 10 cm, were cut and used for extraction of permethrin. Each 10 by 10 swatch was placed in a 250 ml flat-bottomed flask, and from 50-75 ml of an extraction solvent (e.g., 1,1,1-trichloroethane) was added thereto. The flask was then equipped with a reflux condenser and placed on a hot plate and allowed to reflux for 0.5-0.75 hr. Once the samples have finished refluxing and have cooled, 0.05 mg/ml of dioctylphthalate (“DOP”) is added to the liquid fraction as an internal standard for gas chromatography (“gc”). Known standard solutions of permethrin and DOP are prepared for comparison to what has been extracted from the swatches. The calculation used in conducting the gc analysis is as follows:
[0000]
Area
of
cis
and
trans
permethrin
Area
of
dioctylphthalate
×
Weight
ratio
of
internal
standard
Area
ratio
of
internal
standard
×
5.006
(
.955
)
/
10
=
permethrin
,
in
grams
/
m
2
.
[0052] Next, 10×10 inch swatches of the treated fabric were subjected to one or more machine launderings in a laundrometer using the accelerated laundering test (Test Method 61-1996) specified by the AATCC, in order to determine how well the permethrin remained impregnated in the fabric after the washings. After each of the designated washing cycles each swatch of fabric was extracted following the procedure described above in order to determine the amount of permethrin remaining therein. The results are shown in the following table:
[0000]
Amount of Permethrin in Fabric
Laundering Conditions
(g/m 2 )/% Remaining
permethrin-treated polyester fabric
1.11
using a binder according to the
invention, pre-laundering
after 1 machine laundering
1.03
93%
after 3 machine launderings
1.08
97%
after 10 machine launderings
1.02
92%
[0053] The results clearly show that initial load of permethrin is impressively retained (92-97%) in the fabric in the presence of the binder according to the invention, even after 10 machine washings. Without incorporation of the binder system of the invention, permethrin washes out of the fabric at nearly 60-80% of the initial amount loaded just after the first wash (e.g., 0.20-0.30 g/m 2 or less of permethrin remaining); not surprisingly, the amount remaining diminishes rapidly with successive launderings.
[0054] In another test run on a polyester fabric treated with Pomoco 253-P, impregnated with permethrin, and subjected to repeated launderings and extractions using procedure similar to that described in the above Example, permethrin was retained at 90% of the initial load after 50 launderings.
[0055] Additional durability Testing (For testing purposes only) (Type of fabric: Polyester) were done and the results are as follows:
[0056] (TEST 1)
[0000]
Initial Permethrin amount:
1.48 g/m2 (Testing purposes only)
After 25 washings:
1.35 g/m2
After 50 washings:
1.27 g/m2
[0057] (TEST 2)
[0000]
Initial Permethrin amount:
1.38 g/m2 (Testing purposes only)
After 25 washings:
1.20 g/m2
After 50 washings:
1.15 g/m2
[0058] (TEST 3)
[0000]
Initial Permethrin amount:
.54 g/m2 (Testing purposes only)
After 50 washings:
.50 g/m2
[0059] The fabrics of the invention were also tested against deer ticks and mosquitoes and the efficacy is in no way hindered by the binder in the permethrin applications. These tests were conducted on both nylon and polyester fabric.
[0060] Nylon fabrics were also evaluated using a poyurethane binder known as (Polyester Polyol Aliphatic Isocyanate Urethane Dispersion) Two products were used from Crompton Corp., Witcobond Dispersions Group in Tarrytown, N.Y. (Witcobond W-296 Latex and Witcobond W-290HSC).
[0061] The polyurethane binders of the invention also provide for highly effective permethrin retention.
[0062] A nylon cordura fabric was treated with the permethrin and polyurethane binder using the procedures described above for the polyester fabrics and the following results were obtained:
[0000]
Original Permethrin Values:
One Wash
After 50 washings
1.0 grams/m2 (Witcobond W-290HSC)
1.0 g/m2
.90 g/m2 (Began
from original fabric)
.94 grams/m2 (Witcobond W-296
.87 g/m2
.95 g/m2 (Began
Latex)
from original fabric)
[0063] A 100% cotton fabric utilizing Pomoco BZ 1 binder system was treated and the following results were obtained prior and after washing:
[0000] Original application: 0.453% Permethrin
After 10 washings: 0.299%
After 25 washings: 0.286%
After 50 washings: 0.227% Permethrin
[0064] Numerous other fabrics have been treated with the method of the invention and the results of those treatments and the % retention of insecticide are summarized in the Tables below.
Wash Durability on Three Different Polyester/Nylon Fabrics.
[0065]
[0000]
TABLE 1
Data Allocation (Weight of Permethrin on style
19485 and Percent Retention)
Permethrin
Fabric Style
Home Washing
(WOF)
% retention
19485 Poly Nylon
Before wash
0.53%
19485 Poly Nylon
25 Home washings
0.47%
89%
19485 Poly Nylon
50 Home Launderings
0.48%
90%
19485 Poly Nylon
75 Home Launderings
0.45%
85%
19485 Poly Nylon
95 Home Launderings
0.44%
83%
19485 Poly Nylon
110 Home launderings
0.47%
89%
[0000]
TABLE 2
Data Allocation (Weight of Permethrin on style
15899 and Percent Retention)
Permethrin
Fabric Style
Home Washing
(WOF)
% retention
15899 Poly Nylon
Before wash
0.54%
—
15899 Poly Nylon
25 Home washings
0.51%
89%
15899 Poly Nylon
50 Home Launderings
0.46%
85%
15899 Poly Nylon
75 Home Launderings
0.45%
83%
15899 Poly Nylon
95 Home Launderings
0.43%
80%
15899 Poly Nylon
110 Home launderings
0.47%
87%
[0000]
TABLE 3
Data Allocation (Weight of Permethrin on style
54023 and Percent Retention)
Permethrin
Fabric Style
Home Washing
(WOF)
% retention
54023 Poly Nylon
Before wash
0.52%
54023 Poly Nylon
25 Home washings
0.51%
98%
54023 Poly Nylon
50 Home Launderings
0.49%
94%
54023 Poly Nylon
75 Home Launderings
0.49%
94%
54023 Poly Nylon
95 Home Launderings
0.48%
92%
54023 Poly Nylon
110 Home launderings
0.35%
67%
[0000]
TABLE 4
Wash durability on flame retardant rayon/para-aramid/nylon fabrics.
LI # NFZ 38
NFZ Lab Strike
Style
Blend
FR rayon/Para-aramid/nylon
FR rayon/Para-aramid/nylon
FR rayon/Para-aramid/nylon
Pre-treatment
Without Resin
Without Resin
With Resin finished
Date of Trial
May 22, 2008
Jun. 4, 2008
May 22, 2008
Date of Test
Jun. 2, 2008
Jun. 10, 2008
Jun. 2, 2008
Finish
NFZ-Resin
NFZ/Resin
NFZ
How many passes
One pass
Two passes*
One pass
Where Tested
BFP
BFP
BFP
Permethrin (%)
Initial
0.45%
0.40%
0.50%
5X HL
0.31% (69% retention)
0.34% (86% retention)
0.41% (82% retention)
25X HL
0.25% (56% retention)
0.31% (78% retention)
0.38% (76% retention)
[0000]
TABLE 5
Wash durability on 100% polyester fabric.
PERMETHRIN
%
FABRIC TYPE
WASHINGS
(OWF)
RETENTION
100% Polyester
Original
0.46%
—
100% Polyester
25 Home Launderings
0.43%
93%
100% Polyester
50 Home Launderings
0.40%
87%
[0000]
TABLE 6
Wash durability on nylon/cotton fabric.
PERMETHRIN
FABRIC TYPE
WASHINGS
(OWF)
% RETENTION
50/50 Ny/Co
Original
0.46%
—
ACU
50/50 Ny/Co
25 Home
0.39%
85%
ACU
Launderings
50/50 Ny/Co
50 Home
0.24%
52%
ACU
Launderings
50/50 Ny/Co
75 Home
0.19%
41%
ACU
Launderings
[0000]
TABLE 7
Wash durability on 100% cotton and Nomex/FR rayon fabrics.
Permethrin
Sample Identifier
Lab Strike
Style
D6376
450
Color
Blend
100% cotton
65/35 Nomex/FR Rayon
Date of Trial
Aug. 16, 2006
Date of Test
Nov. 6, 2006
Nov. 6, 2006
Finish
NFZ
NFZ
Initial
Permethrin % w/w
0.31%
0.36%
5X
Permethrin % w/w
0.37%
Retention
100%
20X
Permethrin % w/w
0.31%
Retention
86%
25X
Permethrin % w/w
0.20%
Retention
65%
50X
Permethrin % w/w
0.18%
Retention
58%
[0000]
TABLE 8
Wash durability on Kevlar/Nomex/PBI blended fabric.
LI # NFZ 18
SCI-NFZ Lab Strike
Style
W5420-855
W5420-463
W5421-463
Product
Urban Search & Rescue
Blend
60Kevlar/20Nomex/20PBI
60Kevlar/20Nomex/20PBI
60Kevlar/20Nomex/
20PBI
Date of Trial
Jan. 16, 2007
Jan. 16, 2007
Jan. 16, 2007
Date of Test
Jan. 24, 2007
Jan. 24, 2007
Jan. 24, 2007
Finish
DWR
NFZ/DWR
NFZ/DWR
Permethrin (%)
Initial
0.29
0.32
5X HL
0.23
0.25
% Retention
79%
78%
[0000]
TABLE 9
Wash durability on 100% nylon and 100% polyester fabrics.
Sample Identifier
Style
FS 00927
GS 32724
Ack
S3245
S3438
Color
AF Blue
Blend
Poly
100% Nylon
Date of Trial
Nov. 14, 2006
Nov. 30, 2006
Date of Test
Nov. 22, 2006
Jan. 03, 2007
Company/Plant
Hurt
Hurt
Finish
NFZ
NFZ
Formula
Evercide
2.35%
8.00%
W69
2.00%
2.00%
Wetaid
0.10%
0.10%
Softener
Frame
#20
#20
Actual WPU
93%
56%
Curing
360 F/0.5 min
310 F/0.5 min
Where
Piedmont
Piedmont
Tested
Initial
Permethrin % w/w
0.52%
1.24%
25X HL
Permethrin % w/w
0.44%
0.49%
Retention
85%
40%
50X HL
Permethrin % w/w
0.37%
0.30%
Retention
71%
24%
[0000]
TABLE 10
Wash durability from plant trials on three different Nomex/flame retardant
Rayon/Nylon/Kevlar fabrics
Permethrin (%)
Construction
Finish style
Color Name
Original
25X
meta aramid/FR rayon/nylon/para aramid
05520 0NZ
MPAT WOODLAND
0.36
0.291
meta aramid/FR rayon/nylon/para aramid
05520 0NZ
MPAT DESERT
0.41
0.271
meta aramid/FR rayon/nylon/para aramid
05521 0NZ
MPAT WOODLAND
0.47
0.332
meta aramid/FR rayon/nylon/para aramid
05521 0NZ
MPAT DESERT
0.4
0.331
meta aramid/FR rayon/nylon/para aramid
05522 0NZ
MPAT WOODLAND
0.56
0.353
meta aramid/FR rayon/nylon/para aramid
05522 0NZ
MPAT DESERT
0.46
0.311
[0066] While the invention has been specifically illustrated and described in connection with numerous embodiments and further defined in the appended claims, modifications to the various embodiments are within the spirit and scope of the present invention and will be readily apparent to those of skill in the art. | 1a
|
FIELD OF THE INVENTION
[0001] This invention relates to mops, and more particularly to a mop that has a mop head adapted for spin drying within a motorized bucket assembly.
DISCUSSION OF RELATED ART
[0002] Conventional mops used in retail and commercial locations such as restaurants, shopping malls, and the like are typically of the type having an elongated handle and a string cloth mop head. A wheeled bucket is usually included that contains either one compartment for a clean water solution, or two compartments for holding the clean water solution and fouled water. A wringer may be included to wring-out the mop into the fouled water compartment.
[0003] In use, the mop is wrung-out and submerged into the clean water solution so as to absorb a quantity thereof. Such clean water may also include a cleaning agent such as bleach, or the like. The mop is then applied to the floor where it deposits a layer of the clean water solution and, simultaneously, picks-up dirt, grease and other water-fouling material. The mop, now contaminated, is then wrung-out, and the mop is once again submerged into the clean water solution. However, at this point not all of the contaminants have been removed from the mop in the wringing process, and a significant amount of water fouling material is deposited into the clean water compartment. As a result, it is not long before there is little distinction between the two compartments, both containing fouled water.
[0004] In prior art mop buckets with only a single bucket compartment, the problem is compounded by the fact that dirt that is removed from the mop and wrung-out into the water compartment can be immediately picked-up again by the mop and re-applied to the floor surface that is being mopped. Mopping with such prior art buckets quickly becomes an exercise in futility, as applying contaminated water to a contaminated floor does little to clean the floor. Further, often the employees who are charged with mopping the floor are indifferent as to whether or not the process actually cleans the floor, the result being poor sanitary conditions throughout the establishment.
[0005] Moreover, to make conditions worse, in practice many mop buckets are not emptied for days, the same fouled water sitting stagnant, a perfect media for bacteria and other biologically active organisms to thrive and multiply. Instead of cleaning the floors in a retail establishment, mopping with such a universal mopping bucket can often do more to contaminate the floors with dangerous biological agents than not mopping at all.
[0006] Several improved wringing devices have been invented that attempt to overcome the aforementioned drawbacks with the prior art. Such devices strive to more thoroughly clean the mop during the wringing process. For example, U.S. Pat. Nos. 4,464,809 and 4,344,201, issued on Aug. 14, 1984 and Aug. 17, 1982, both to Trisolini, disclose a mop with a rotating head that cooperates with a rotating mop wringer that is spun by a motorized bucket. The mop wringer takes the form of a perforated basket, and strands of the mop are thrown against the side walls thereof, whereby water and dirt are extracted from the mop. However, the perforated basket of such a device applies not only centrifugal force to the strands of the mop, but also centripetal force, which serves to keep particles of dirt and debris in the mop head. The force of the strands against the perforations of the basket can actually block water and dirt flow out of the mop strands. Thus, while such a device is better at removing dirt and water from the mop, it is by no means optimal at such. A further drawback to the Trisolini devices is that they are somewhat tall in their profile, and are therefore more difficult to store and maneuver. Further, such prior art mop assemblies are heavy due to the hollow cleaning fluid chamber therein, and as such a person mopping with such a device can quickly become exhausted.
[0007] Another prior art device, also to Trisolini, is described in U.S. Pat. No. 4,561,141 issued on Dec. 31, 1985. This device incorporates a motor and a wringing basket into the mop assembly, for providing a self-wringing mop. The main drawback with such a device is, again, the mop of such a device is heavy and quickly becomes exhausting to use. The motor of such a device, as well as the batteries to power it, are extra weight that the user is forced to propel around the floor while mopping.
[0008] Several improvements have been devised for sterilizing germs that may be present in the mop bucket or on the mop itself. For example, U.S. Pat. No. 4,135,269 to Marston on Jan. 23, 1979, teaches a mop bucket that includes an ultraviolet light sterilizing system. Japanese Patent Application JP11206666A2 to Akihiro on Aug. 3, 1999 teaches a bucket including an ozone generator for bubbling ozone up through the liquid contained in the mop bucket. Both such prior art inventions may accomplish their goals, but neither patent is directed towards a device for cleaning both the fouled water contained in the bucket and the mop head simultaneously. Further, such prior art devices do not include intelligent controlling means for shutting-off the sterilizing device if the bucket is empty or is not being used. Thus, one can easily inadvertently leave such a device activated, both wasting energy and possibly over-exposing the mop and surrounding areas to UV light and ozone.
[0009] Therefore, there is a need for an improved mopping system that allows for convenient, quick and thorough cleaning and drying of a mop head. Such a needed device would allow clean water or a cleaning solution to be applied to the mop head easily, and would not allow cross-contamination between the clean water solution and the fouled-water container. Moreover, such a needed device would provide for easy sterilization of the mop head and the fouled water to prevent biological growth therein, and would facilitate emptying of the fouled water. The needed device would be self-contained and easily portable from location to location as needed. Further, such a needed device would greatly improve the sanitary conditions of mopped floors, substantially eliminating re-contamination thereof by a fouled mop head. The present invention accomplishes these objectives.
SUMMARY OF THE INVENTION
[0010] The present device is a mopping system comprising a mop assembly and a bucket assembly. In the preferred embodiment, the mop assembly includes a mop head that is detachably fixed to a lower end of an elongated handle. The mop head is adapted to be spun around a generally vertical rotational axis thereof when the mop head is fixed within a mop head spinning means of the bucket assembly. As such, when the mop head is spun at a relatively high rate of rotational speed, water retained in the mop is forcefully dispelled from the mop by centrifugal force. The fouled water leaves the mop and is retained within the spin chamber, where it collects at the bottom thereof. A drain plunger is preferably included to allow the collected fouled water to be drained from the spin chamber into either a floor drain or a drain water container included with the invention. An ozone generator may be included for introducing ozone gas into the collected fouled water in the spin chamber, thus sterilizing any biologically active organisms contained therein.
[0011] A clean water tank with a pump and spraying means is preferably included to allow introduction of clean water to the moping surface of the mop head. Such a clean water tank is preferably mounted within the spin chamber just below the mop head when the mop head is engaged with the mop head spinning means. The clean water tank is sealed so that fouled water dispensed from the mop head during rotation does not contaminate the clean water or other cleaning fluid contained in the clean water tank.
[0012] The mop assembly may include a lever means for selectively detaching the mop head from the handle. As such, the user does not have to bend down to engage the mop head with the mop head spinning means of the bucket assembly. Alternately, the mop head may be rotationally fixed to the elongated handle such that it can only spin around its rotational axis when engaged with the mop head spinning means.
[0013] The present invention is an improved mopping system that allows for convenient, quick and thorough cleaning and drying of a mop head. The present device allows clean water or a cleaning solution to be applied to a mop head easily, and prevents contamination between a clean water solution and a fouled-water container. Moreover, the present invention provides for easy sterilization of the mop head and the fouled water to prevent biological growth therein, and allows for easy, hands-free emptying of the fouled water. The invention is self-contained, easily portable from location to location as needed, and greatly improve the sanitary conditions of floors mopped therewith, substantially eliminating re-contamination thereof by a fouled mop head. Other features and advantages of the present invention will become apparent from the following more detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the invention.
DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 is a cut-away left-side elevational view of the invention, illustrating a mop assembly of the present invention in a position to engage a mop head thereof with a bucket assembly of the present invention;
[0015] FIG. 2 is a cut-away left-side elevational view of the invention, illustrating the mop head as engaged with a mop head engagement means of the bucket assembly;
[0016] FIG. 3 is a cut-away left-side elevational view of the invention, illustrating a spinning mop head rotated by a mop head spinning means of the invention, and further illustrating dirty water being flung away from the mop head while clean water is sprayed to an underside of the mop head;
[0017] FIG. 4 is a cut-away left-side elevational view of the invention, illustrating a drain plunger being actuated to drain a spin chamber of the invention of dirty water;
[0018] FIG. 5 is a top plan view of the invention, showing a mop head as engaged with a non-circular shaft of the mop head spinning means;
[0019] FIG. 6 is a bottom plan view of the mop head of the invention, illustrating a lower surface thereof and a plurality of water absorbing strands;
[0020] FIG. 7 is a cross-sectional view of the invention, taken generally along lines 7 - 7 of FIG. 6 , illustrating a handle attachment means of the mop head and a mop head attachment means of an elongated mop handle;
[0021] FIG. 8 is a cross-sectional view of the invention, taken generally along lines 8 - 8 of FIG. 6 , illustrating in more detail the handle attachment means of the mop head and the mop head attachment means of the elongated mop handle; and
[0022] FIG. 9 is a cross-sectional view of the invention, taken generally along lines 8 - 8 of FIG. 6 , illustrating the mop head being detached from the elongated handle.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0023] FIG. 1 illustrates a mopping system 10 of the present invention. In its simplest form, the mopping system 10 comprises a mop assembly 20 and a bucket assembly 90 . The mop assembly includes a mop head 30 preferably pivotally attached to an elongated handle 40 . The mop head 30 includes a floor-engageable lower surface 50 ( FIG. 8 ) and an opposing upper surface 60 . The mop head 30 includes a handle attachment means 70 , preferably on the upper surface 60 , for attaching the mop head 30 to a lower end 80 of the handle 40 ( FIGS. 7-9 ). The handle attachment means 70 could also be provided on a peripheral edge of the mop head 30 (not shown).
[0024] The mop head 30 is preferably detachable from the elongated handle 40 so that the mop head 30 may be easily spun in the bucket assembly 90 without the need to also spin the handle 40 . However, such an arrangement is not necessarily required in an embodiment of the invention that allows for spinning the entire mop assembly 20 by aligning the longitudinal axis of the handle with the rotational axis 140 of the mop head.
[0025] Such an embodiment notwithstanding, the preferred embodiment of the invention includes a biased lever means 220 at an upper end 230 of the handle 40 mechanically coupled to a mop head attachment means 240 fixed to the lower end 80 of the handle 40 . The mope head attachment means 240 of the handle 40 and the handle attachment means 70 of the mop head 30 cooperate to retain the mop head 30 in a pivotable fashion on the lower end 80 of the handle 40 when the lever means is in a normal position 250 ( FIG. 8 ). When the lever means 220 is placed in an actuated position 260 ( FIG. 9 ), the mop head attachment means 240 of the handle 40 and the handle attachment means 70 of the mop head 30 cooperate to mechanically disconnect the mop head 30 from the lower end 80 of the handle 40 . The lever means 220 is preferably a lever as illustrated in FIGS. 8 and 9 , however, a biased spring button or knob may also be used, as could a variety of different mechanical couplings. Linkages between the upper end 230 and lower end 80 of an elongated handle 40 are known in the prior art, and the preferred embodiment herein described is just one such known method. The important feature of this embodiment is that the mop head 30 may be easily detached from the handle 40 , preferably without the operating having to bend down.
[0026] The mop head 30 preferably includes a plurality of water absorbing strands 520 attached to the lower side 50 thereof. Such strands 520 may be made from cotton, felt, or other water absorbing material. Such strands 520 , however, are made from a material that will release water when subjected to a strong centrifugal force. The mop head 30 is preferably rectangular in plan view ( FIG. 6 ), but could also be either circular or square or any other suitable shape, provided that the mop head 30 has a center of gravity proximate its longitudinal axis 140 so as to remain balanced when spinning, as described below.
[0027] The bucket assembly 90 preferably includes a spin chamber 100 complete contained therewithin, and a mop head spinning means 110 . The mop head spinning means 110 is engageable with the mop head 30 to rotationally support the mop head 30 within the spin chamber 110 , away from an inner wall 115 thereof ( FIG. 3 ). As such, when spun around the rotational axis 140 , the distance to the edge of the mop head 30 and the centrifugally extended strands 520 must be less than the distance between the shaft 180 and the inner wall 115 of the spin chamber 110 . As such, water in a strand 520 is not constrained by the inner wall 115 and is free to exit the strand 520 .
[0028] It will be appreciated by those skilled in the art that the mop head spinning means 110 can take various forms. Preferably, as illustrated in FIGS. 1-5 , the mop head spinning means includes a mop head engagement means 120 such as a shaft 180 having a non-circular cross-section. The non-circular shaft 180 is vertically and rotationally supported within the spin chamber 100 by a pair of bearings 280 each centrally supported by the spin chamber 100 . A rotational driving means 130 , such as an electric motor 150 with a rotating shaft 190 , is connected to the mop head spinning means 110 through a mechanical linkage 195 therebetween ( FIG. 1 ), such as a cog belt 195 with pulleys on the shafts 180 , 190 . In this manner the motor 150 may be isolated in a dry chamber 105 ( FIG. 2 ) of the bucket assembly 90 , away from any moisture or standing liquid 315 . Further, the rotational speed of the shaft 180 may be differed as desired from that of the motor 150 through use of varying-sized pulleys.
[0029] In the preferred embodiment of the invention, the spin chamber 100 is generally a toroid-shaped enclosure open at its top end and having an inverted frustoconical inner wall 270 centrally located therewithin. The bearings 280 are fixed to the lower outer surface of the inner wall 270 and are co-aligned to allow the shaft 180 to be supported co-axially and substantially vertically therewithin. A seal is included on the shaft 180 where the shaft 180 penetrates the inner wall 270 and protrudes into the spin chamber 100 .
[0030] It would be obvious to one skilled in the art to directly couple a motor 150 to the shaft 180 such that the motor is within the inner wall 270 , directly under the mop head 30 when the mop head 30 is engaged to the mop head engagement means 120 . The inner wall 270 would, in such an embodiment, constitute the dry chamber 105 . Other arrangements could be used for the mop head spinning means 110 , as well, as known in the prior art. What is vital to the design, however, is that water is prevented from entering the motor 150 or any other electronic components, as discussed further below.
[0031] Located just below the mop head 30 when the mop head 30 is engaged to the shaft 180 is a generally toroid-shaped clean water tank 290 having an inverted frustoconical aperture 300 formed therein ( FIGS. 1-5 ). The clean water tank 290 rests on the inner wall 270 of the spin chamber 100 , its longitudinal axis coinciding with that of the shaft 180 . The clean water tank 290 includes a pump and spraying means 310 for pumping clean water 320 from the clean water tank 290 and spraying the clean water 320 onto the lower surface 50 of the mop head 30 . The pump and spraying means 310 is preferably an electric pump fixed proximate to the lower inside surface of the clean water tank 290 that pumps clean water 320 up to an inverted spray nozzle fixed to the top outside surface of the tank 290 ( FIG. 3 ). The clean water 320 may obviously be a cleaning liquid as opposed to clean water, per se, but the clean water 320 is isolated from any fouled water 315 leaving the mop head 30 due to the clean water tank 290 being generally sealed. A water inlet port 500 may be included, the water inlet port 500 being in fluid communication with, such as with a hollow pipe, the clean water tank 290 ( FIGS. 1-5 ). The water inlet port 500 preferably exits the bucket assembly 90 at a top side 440 thereof. As such, clean water 320 or other cleaning fluids may be introduced into the water inlet port 500 in order to refill the clean water tank 290 without having to remove the clean water tank 290 from the spin chamber 100 .
[0032] A drain plunger 330 protrudes from one end 340 of the bucket assembly 90 and extends down through the bucket assembly 90 to a rubber seal 350 . The rubber seal 350 seals a drain aperture 360 in the lower-most section 370 of the spin chamber 100 . The drain plunger 330 is biased upward such that the rubber seal 350 engages and seals the drain aperture 360 in a normal position 380 thereof ( FIGS. 1-3 ). When the drain plunger 330 is placed in an actuated position 390 , against a biasing element such as a spring 395 , the drain plunger 330 causes the rubber seal 350 to disengage the drain aperture 360 of the spin chamber 100 , resulting in the draining of any fouled liquid 320 from the bucket assembly 90 ( FIG. 4 ).
[0033] Preferably a drain water container 510 is also included, open on its top side and adapted to fit under the drain aperture 360 between the bucket assembly 90 and a floor surface 420 . The bottom inside surface of the spin chamber 100 is slightly tilted towards the drain aperture 360 so that fouled water 320 within may be completely drained by gravity when the drain plunger 330 is actuated. A plurality of wheels 400 on the bottom surface 410 of the bucket assembly 90 maintain the bucket assembly 90 above the floor surface 420 . Preferably at least two of the plurality of wheels 400 are lockable, such that when the motor 150 is actuated the bucket assembly 90 does not oscillate or otherwise move along the floor surface 420 . The bucket assembly 90 may be conveniently moved about the floor surface 420 by the operator pushing or pulling the elongated handle 40 when same is engaged with the mop head 30 and the mop head 30 is mounted on the shaft 180 .
[0034] The electric motor 150 is electrically connected to a power source 170 , such as a DC battery. An AC/DC adapter 178 ( FIG. 2 ) may be used to recharge the battery, ensuring for safety that only low voltage is proximate to the bucket assembly 90 . However, an AC power cord 175 for plugging into a power outlet (not shown) could also be used ( FIG. 1 ). In either case, the power source 170 is preferably enclosed in the dry chamber 105 .
[0035] The bucket assembly 90 preferably further includes a top cover 430 slidably engaged with the top surface 440 thereof for covering the mop head 30 when the mop head 30 is engaged with the mop head engagement means 120 . As such, fouled water 315 cannot escape the bucket assembly 90 when the cover 430 is closed and the motor 150 is activated. Alternately, the mop head 30 may be both rotationally and pivotally attached to the elongated handle 40 , such that the mop head 30 may spin with respect to the handle 40 while still attached thereto (not shown). In such an embodiment, the mop head 30 remains attached to the elongated handle 40 yet may spin freely in a rotational plane when the mop head 30 is engaged to the rotating shaft 180 . The cover 430 in such an embodiment is either not included, or is provided with a handle slot (not shown) for covering most of the spin chamber 100 while allowing just the handle 40 to protrude therefrom.
[0036] Moreover, in such an embodiment the lever means 220 is not for disengaging the mop head 30 from the handle 40 , but rather rotationally unlocking the mop head 30 from spinning with respect to the handle 40 . With such an arrangement the lever means 220 is actuated only when the mop head 30 is engaged to the shaft 180 and the operator desires the mop head spinning means 110 to be activated. Indeed, such actuation of the lever means 220 may cause the button 490 to become actuated (not shown), thereby starting the washing and drying cycle of the control circuit 480 . In using such an embodiment, a user places the mop head 30 onto the shaft 180 by lifting the mop head 30 with the handle 40 . Once engaged with the shaft 180 the lever means 220 is actuated, and the mop head 30 becomes rotationally unlocked from the handle 40 and the mop head spinning means 110 is activated. Alternately, the act of engaging the mop head 30 onto the shaft 180 may rotationally free the mop head 30 from the handle 40 and actuate the head spinning means 110 , thereby eliminating the need for the lever means 220 completely. A mechanical engineer or others skilled in the art would be able to effect such alternate arrangements of the mop assembly 20 to enable the mop head 30 to rotate only when desired by the operator.
[0037] The bucket assembly 90 preferably further includes an ozone generator 450 fluidly connected to the lower-most portion 370 of the spin chamber 100 through a tube 455 . As such, when the ozone generator 450 is activated, ozone gas 460 is caused to bubble up through any fouled liquid 315 contained within the spin chamber 100 . Further, ozone gas 460 , upon reaching the surface of the fouled liquid 315 , fills the open space of the spin chamber 100 and helps to sterilize any bacteria and germs located therein, such as on the mop head 30 . Ozone gas 460 is preferred, but alternate sterilizing fluids or gases could be introduced to the fouled liquid 315 without departing from the spirit and scope of the present invention.
[0038] The dry chamber 105 includes a control circuit 480 that electrically connects the power source 170 to the motor 150 , the ozone generator 450 , and the pump and spraying means 310 as needed. Such a control circuit preferably includes a button 490 for activating a washing and drying cycle of the mopping system 10 , wherein the motor 150 is activated to spin the mop head 30 at a relatively low speed, such as between 40 and 60 RPM, while the pump and spraying means 310 sprays the clean water solutions 320 onto the lower side 50 of the mop head 30 to clean the mop head 30 . The ozone generator 450 is also activated. The control circuit then, after a predetermined period of time such as 15 to 30 seconds, deactivates the pump and spraying means 310 and increases the speed of the motor 150 to preferably between 400 and 600 RPM, to force effective centrifugal drying of the mop head 30 and the water absorbing strands 520 . As the strands 520 do not touch the inner wall 115 of the spin chamber 100 , any water 315 therein is quickly expunged therefrom. After a second predetermined period of time, such as 30 to 60 seconds, the motor 150 is deactivated, and then, after a third predetermined period of time, such as five minutes, the ozone generator 450 is deactivated so as not to overly expose the surrounding areas to ozone gas.
[0039] The button 490 may be located through the top surface 440 of the bucket assembly 90 , under the top cover 430 when the top cover 430 is in an open position ( FIGS. 1 and 2 ). As such, the button 490 may not be depressed unless the top cover 430 is closed ( FIGS. 3 and 4 ), ensuring that the motor 150 does not spin when the cover 430 is open for safety.
[0040] Alternatively, a second button 495 , in series with the button 490 , may be included to sense if a mop head 30 has been engaged with the mop head engagement means 120 . If not, the second button 495 remains open, thereby preventing the motor 150 from spinning unless both the mop head 30 is in place on the shaft 180 and the cover 430 is closed. The second button 495 may be mounted proximate the shaft 180 to detect the weight of the mop head 30 thereon, or using some other commonly known button mounting arrangement. Clearly, the second button 495 may be included without button 490 , such that merely engaging the mop head 30 on the shaft 180 starts the washing and drying cycle. In such an embodiment, a delay of several seconds may be introduced to give the operator time to withdraw the handle 40 completely from the mop head 30 . However, preferably, the button 490 is included to ensure that the cover 430 is closed prior to starting the washing and drying cycle.
[0041] In operation, a number of methods of use are preferred. The simplest method is to minimally provide the mop head 30 and a simplified bucket assembly 90 , engage the mop head 30 to the mop head spinning means 110 of the bucket assembly 90 , and activate the spinning means 110 to dry the mop head 30 . The mop head spinning means 110 in such a case is switchably connected to the power source 170 in a conventional manner, such as directly through a switch or button 490 , or by plugging a power cord into a wall outlet (not shown), and the motor 150 of the mop head spinning means 110 rotates the shaft 180 to spin the mop head 30 . When the button 490 is released, or the power cord is pulled from the wall outlet, the motor 150 is deactivated. Such a simplified embodiment, however, requires the operator to judge when the mop head 30 is dry, and such a judgment may or may not be accurate.
[0042] In such an embodiment, the mop head spinning means 110 may be used over an existing sink (not shown), the sink acting as the spin chamber 100 . Such an embodiment requires that the motor 150 is mounted in some fashion, such as in a dry chamber 105 enclosure resting on a countertop proximate the sink with the shaft 180 provided on a cantilevered arm extending out over the sink (not shown), or the like. Alternatively, the motor 150 may be mounted in an inverted cone dry chamber 105 with the shaft 180 emanating from the top thereof (not shown), the inside of the cone being sealed from the water dripping down from the mop head 30 . While such embodiments are the simplest configurations for the present invention, the safety risk of such embodiments are significantly higher, and the ease of use is considerably less than that of the preferred embodiments, as water spinning off of the mop head 30 is not fully contained and can spray out of the sink in such embodiments. Therefore, while these embodiments fall within the scope of the present invention, these embodiments are not preferred.
[0043] Additional steps of spraying clean water 320 onto the lower surface 50 of the mop head 30 may be included in the method of use of the present invention. Such spraying of clean water 320 may occur either before or after the main drying cycle (wherein the mop head 30 is spun at a relatively high rotational speed to effect centrifugal drying) and such spraying may be termed a wash cycle. Thus, various cycles, such as dry only, wash only, wash-dry, dry-wash, wash-dry-wash, or dry-wash-dry cycles, may be easily incorporated into the invention by altering the programming of the control circuit 480 . Moreover, a plurality of buttons 490 may be included (not shown), each button 490 having a dedicated cycle type, such that the operator may select the desired cycle type based on the requirements of a particular floor cleaning situation.
[0044] While a particular form of the invention has been illustrated and described, it will be apparent that various modifications can be made without departing from the spirit and scope of the invention. For example, the relative configurations of the spin and dry chambers 100 , 105 may be altered, as may aspects of the mop assembly 20 and how the mop head 30 is attached to the handle 40 . Such modifications do not affect the scope of the invention and do not substantially alter the method of its use. Accordingly, it is not intended that the invention be limited, except as by the appended claims. | 1a
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BACKGROUND OF THE INVENTION
[0001] Dogs and cats suffer from numerous disorders of the lower urinary tract. Among these are idiopathic urinary tract disease, crystalluria, bacterial cystitis, urolithiasis, idiopathic obstruction, urethal plugs, and the like. Lower Urinary Tract Disease (LUTD) is a disorder common to cats. Urolithiasis, i.e., stone formation in the urinary tract, is a condition commonly found in both dogs and cats. Although the etiology of these disorders are not completely clear, at least some of the factors associated with these disorders appear to be concentrated urine (i.e., high urine specific gravity) or high mineral supersaturation of urine. Lowering mineral concentrations in the urine by increasing urine production through increased water consumption can reduce the risk of urinary crystal or stone formation, assist in dissolving certain types of formed urinary tract stones, as well as reduce the occurrence of feline LUTD. In addition, increased urine volume initiates more frequent voiding. Frequent voiding further reduces risk of urinary tract infection, crystalluria and urolithiasis.
[0002] We have found that a high moisture palatable gel can significantly increase total water intake and urine production in a companion pet such as a dog or cat. Thus, it can be used to prevent and/or treat lower urinary tract disorder(s) including: crystalluria, urolithiasis, cystitis, idiopathic obstruction, urethal plugs, and feline LUTD in a companion pet such as a dog or cat. In addition, it can be an aide to increasing total water intake and improving hydration in conditions such as diabetes, renal disease, pregnancy, lactation, etc.
SUMMARY OF THE INVENTION
[0003] In accordance with the invention there is a gel suitable for ingestion by a dog or cat which comprises,
[0004] a. an effective amount of a gelling agent,
[0005] b. an effective amount of a dog or cat palatability enhancing agent, and
[0006] c. at least about 85 wt. % water.
[0007] A further aspect of the invention is wherein the gel is provided to the cat or dog in conjunction with a diet meeting the nutritional needs of the dog or cat.
[0008] A still further aspect of the invention is providing the gel to a dog or cat for the purpose of at least assisting in preventing lower urinary tract disorder(s) including crystalluria, urolithiasis, cystitis, LUTD, idiopathic obstruction, urethal plugs, and the like, in said dog or cat. This is particularly useful in dogs or cats at risk for lower urinary tract disorder(s); that is, seem to have a tendency to develop those diseases.
[0009] Another aspect of the invention is a method of treating a dog or cat with lower urinary tract disorder which comprises providing a gel of the invention to a dog or cat having such disorders.
DETAILED DESCRIPTION OF THE INVENTION
[0010] The usage of the gelled water brings about a much higher total water intake for dogs and cats, lower urinary specific gravity, and a correspondingly higher urine output for them compared to without the gel. Not only is the gelled water very effective in increasing total water intake and urine output but it results in more sightly surroundings since there is no water bowl and splatter, if desired. Additionally, it provides an efficient way of providing water to the pet while traveling or away from its usual settled surroundings. Furthermore, it provides pet owners with a treat of very low energy content. This is particularly useful for pet such as cats and dogs with problems of overweight or obese or other overweight-concerning conditions such as arthritis, diabetes, hypertension, and cardiovascular diseases. In addition, a highly palatable water treat will help improve water balance in animals having higher protein diets and/or having increased water needs, such as diabetes, lactation, exercise, and growth.
[0011] The gelling agent employed is any gelling agent that provides a gel with at least 85 wt % water and is acceptable to a dog or cat when orally delivered. Examples of gelling agents that can be employed include gelatin, carrageenan, agar, alginates, pectins, xanthans, guars, gum arabic, gum karaya, gum tragacanth, tara gum, gellan gum, pullulan, curdlan, microcrystalline cellulose (MCC), carboxymethylcellulose (CMC), methylcellulose (MC), hydroxypropyl methylcellulose (HPMC), chitosan, gum ghatti, locust bean, konjac flour, starch and the like.
[0012] Generally, a palatability enhancer (flavorant) is employed as well in order to overall enhance the palatability and overcome any negative flavor effects the gelling agent may have to the cat or dog. There are numerous such materials available include animal digest, animal hydrolysates, animal internal organs (such as liver, lungs, and heart), meats (such as beef, lamb, pork, chicken, and turkey), sea foods (such as fish, crab, shrimp), dairy products (such as milk and cheese), yeast, peptides, amino acids, nucleotides, fat, oil, artificial meat and/or sea food flavors, maillard reactants, sugars, plant extracts, and other aromas nature and/or artificial that are attractive to cats or dogs.
[0013] The quantity of gelling agent employed is the amount sufficient to bring about a gel that maintains its shape so as to provide an object which is readily eaten by a cat or dog. By maintaining its shape, means an integral structure that can wobble such as “jello” but still maintains its integrity and does not become liquid or flow. Generally, from about 0.05 to about 2 wt. % of the gelling agent as wt. % of the gel, desirably about 0.2 to about 1.5 wt. % can be employed.
[0014] The amount of the palatability enhancer is sufficient to bring about a palatability enhancement. This is generally between about 0.1 and 3 wt. % desirably a minimum wt. % of about 0.3 or 0.5 wt. % of the gel.
[0015] The amount of water in the gel is generally at least about 85 wt. %, desirably at least about 90 or 95 wt. % or higher.
[0016] Other components can be in the gel as well, for example nutrients such as vitamins and minerals used as supplements, preservatives, colorant(s), as well as active agents including antibacterial agent(s), anti-inflammatory agent(s), antiparasitic(s), antioxidant(s), herbal and/or botanical extracts and the like, all in effective quantities. Thus, the gel can function as a delivery system for supplements as well as active ingredients.
[0017] The gels of the invention are readily prepared by standard methods. For example, mixing all the components into a container and stirring under conventional or elevated temperatures whenever appropriate, then filling a final shaped container (gel shape) and letting the gel set. More specifically, the following components are used.
TABLE 1 Component % Water 95.48 Kappa carrageenan 1.5 Chicken hydrolysate 2.0 Brewer yeast 0.5 Salt 0.3 Potassium sorbate 0.2 FD&C Red No. 40 0.02 Total 100.00
[0018] Processing Steps
[0019] 1. Mix the ingredients in a heating container
[0020] 2. Heat the mixture to 160° F. while stirring
[0021] 3. Keep the mixture at 160° F. for 15 minutes
[0022] 4. Fill desired shaped mold with the mixture
[0023] 5. Let the gel cool and set about 2 hours
[0024] Below are examples of the invention.
[0025] Overall, dogs and cats can experience significant increases in total water intake and urine production as well as a significant decrease in urine specific gravity when utilizing the gel of this invention with a diet meeting nutritional requirements. Utilizing a canned diet, the dog or cat can experience a total water intake increase of at least about 20, desirably at least about 70 or 80%, and a urine production increase of at least about 20, desirably at least about 90 or 100 wt. %. Urine specific gravity can decrease by at least about 20, 30 or desirably at least about 40%. Utilizing a dry diet, the cat or dog can experience a total water intake increase of at least about 15, 20 desirably at least about 25% and a urine production increase of at least about 20, or desirably at least about 30 or 40 wt. %. Urine specific is gravity can decrease by at least about 10, 15 or desirably at least about 20%.
EXAMPLE 1
[0026] A crossover study design was used and the study period was eight weeks. Eight adult cats were given deionized water ad libitum and either a canned or dry cat food that was complete and balanced in nutrition. In addition to the food, the gel was provided to the cats in the test group while cats in control group received no gel. At the completion of the study, all cats received all diet and gel combinations. The treatment assignments are described below.
[0027] Eight cats were divided into four groups of two each. For the first week, two groups of cats were given canned food and two groups of cats were given dry food. In the second week, the same diets were maintained for each group. However, gel provided to one group of two cats having canned food and one group of two cats having dry food (test group). This was provided for one hour twice a day (08:30a.m.-09:30a.m. and 01:00p.m.-02:00p.m.). The other groups did not receive the gel (control). In the third week, the same diet was maintained but with no gel. In the fourth week, the control group and test groups were reversed. The control group from week two was now given the gel while the test group from week two was not given the gel. In the fifth week, no gel was given but the two groups of cats that had been on dry diet were now given canned and the two groups that had been on canned were now given dry food. In the sixth week, one group in each diet was given the gel while the other was not. In the seventh week, no gel was provided. In the eighth week, the group that did not have the gel in the sixth week was provided with the gel and the gel was withheld from the group which received the gel in the sixth week.
[0028] In this manner, each group of two cats had received the dry diet and the canned diet as well as receiving the gel or not receiving the gel.
[0029] During this study period, the intake of water from all sources (gel, water and food), output of urine, and urine specific gravity were measured for each cat. Other parameters measured in the study include weekly body weight, daily food intake, urine pH, and stool quality.
[0030] With respect to cats having the canned diet, the average total water intake increased by 70%; urine production increased by 89 wt. %; and urine specific gravity decreased by 35% when the gel was available compared to not having the gel available. All these changes are statistically significant (p<0.01).
[0031] With respect to cats having the dry diet, the total water intake increased by 20%; urine production increased by 32 wt. %; and urine specific gravity decreased by 16% for cats receiving the gel. All these changes are statistically significant (p<0.01).
[0032] The other parameters measured, i.e., body weight, food intake, urine pH, and stool quality, were not affected by the gel. | 1a
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention generally relates to a bypass type prefilled syringe in which a bypass for establishing communication between front and rear compartments for preliminarily storing two components, for example, powdery medicament and pharmaceutical liquid, respectively is formed on a tubular body, and more particularly to a gasket for dividing interior space of the tubular body of the bypass type prefilled syringe into the front and rear compartments.
2. Description of the Prior Art
FIGS. 6 and 7 show a sealing state and a communication state between a front compartment 6 and a rear compartment 7 of an elongated hollow tubular body 1 of a conventional bypass type prefilled syringe, respectively. A front assembly 15 includes an injection needle 10 and a cap 11 for covering the injection needle 10 so as to protect the injection needle 10 and is mounted on an outer periphery of a front end portion of the tubular body 1 . In FIG. 6, the conventional bypass type prefilled syringe includes a first sealing member 3 which is mounted in the front end portion of the tubular body 1 , a second sealing member 4 which is attached to a front end of a plunger rod 2 and is disposed at a rear end portion of the tubular body 1 and a gasket 5 which is slidably inserted between the first and second sealing members 3 and 4 in the tubular body 1 and divides interior space of the tubular body 1 into the front and rear compartments 6 and 7 . Powdery medicament P and pharmaceutical liquid L are preliminarily, respectively, stored in the front and rear compartments 6 and 7 so as to interpose the gasket 5 therebetween.
A bypass 1 a is formed by bulging a peripheral wall of the front compartment 6 of the tubular body 1 radially outwardly. On the other hand, a finger grip 12 is mounted on an outer periphery of the rear end portion of the tubular body 1 . By forwardly depressing the plunger rod 2 in the direction of the arrow a in FIG. 7 from the state of FIG. 6 to the state of FIG. 7, the gasket 5 is advanced by the second sealing member 4 by way of the pharmaceutical liquid L so as to be disposed between a front end portion and a rear end portion of the bypass 1 a . At this time, a gap for directly linking the front and rear compartments 6 and 7 is defined between the gasket 5 and the bypass 1 a , so that the front and rear compartments 6 and 7 are communicated with each other by the bypass 1 a and thus, the pharmaceutical liquid L is introduced from the rear compartment 7 into the powdery medicament P in the front compartment 6 along a flow path indicated by the arrow b in FIG. 7 . Then, when the powdery medicament P is sufficiently dissolved or dispersed in the pharmaceutical liquid L by shaking the tubular body 1 , injection liquid is formed.
At the time of communication between the front and rear compartments 6 and 7 through the bypass 1 a in this conventional bypass type prefilled syringe, the pharmaceutical liquid L is fed under pressure into the front compartment 6 in a state where the injection needle 10 is mounted on the tubular body 1 . At this time, the gasket 5 is disposed between the front end portion and the rear end portion of the bypass 1 a and the gap for directly linking the front and rear compartments 6 and 7 is defined between the gasket 5 and the bypass 1 a as described above. Thus, in case a user forcibly depresses the plunger rod 2 from the state of FIG. 6 to the state of FIG. 7, a so-called squirt phenomenon in which the pharmaceutical liquid L spouts from the bypass 1 a vigorously may happen, thereby resulting in such an inconvenience that the pharmaceutical liquid L impinges on the first sealing member 3 and then, leaks out of the injection needle 10 .
Meanwhile, FIG. 8 shows a sealing state between the front and rear compartments 6 and 7 of the tubular body 1 of a known bypass type prefilled syringe disclosed in U.S. Pat. No. 4,599,082. In this known bypass type prefilled syringe, a gasket 20 is employed. As shown in FIG. 9, the gasket 20 has a front end face 20 a and a rear end face 20 b and includes ribs 24 , 26 and 27 . Meanwhile, an annular recess 25 is provided between the ribs 24 and 26 and a plurality of grooves 28 extending obliquely relative to an axis of the gasket 20 are formed on the rib 24 so as to open to the front end face 20 a . In order to improve agitation and mixing of the pharmaceutical liquid L and the powdery medicament P at the time of communication between the front and rear compartments 6 and 7 via the bypass 1 a , the pharmaceutical liquid L is introduced from the grooves 28 into the powdery medicament P obliquely relative to the axis of the gasket 20 .
However, in contrast with the conventional construction shown in FIGS. 6 and 7 in which the injection needle 10 is mounted on the front end portion of the tubular body 1 , this known bypass type prefilled syringe has a construction in which a distal end cap 35 is mounted on a distal end 34 of the tubular body 1 . Thus, as described at column 8, lines 3 to 9 of the above mentioned U.S. Patent, mixing operation of the pharmaceutical liquid L and the powdery medicament P is performed by depressing a plunger rod in a state where the distal end 34 of the tubular body 1 is directed upwardly after the distal end cap 35 has been removed from the distal end 34 of the tubular body 1 . Therefore, the gasket 20 merely serves to improve agitation and mixing of the pharmaceutical liquid L and the powdery medicament P and thus does not serve to prevent leakage of the pharmaceutical liquid L from an injection needle due to the squirt phenomenon.
SUMMARY OF THE INVENTION
Accordingly, an essential object of the present invention is to provide, with a view to eliminating the above mentioned drawbacks of prior art, a gasket for a bypass type prefilled syringe which prevents a squirt phenomenon of pharmaceutical liquid at the time of communication between front and rear compartments of a tubular body by way of a bypass such that powdery medicament can be sufficiently dissolved or dispersed in the pharmaceutical liquid.
In order to accomplish this object of the present invention, a gasket for a bypass type prefilled syringe having a tubular body formed with a bypass for establishing communication between front and rear compartments for preliminarily storing medicament and pharmaceutical liquid, respectively, according to the present invention divides interior space of the tubular body into the front and rear compartments and includes a plurality of circumferential ribs which include at least first, second and third circumferential ribs disposed sequentially further away from the front compartment. A plurality of annular recesses are each formed between neighboring ones of the circumferential ribs and include at least a first annular recess formed between the first and second circumferential ribs and a second annular recess formed between the second and third circumferential ribs. A first axial slot extends through the first circumferential rib and the first annular recess, while a second axial slot is formed at a circumferential position of the second circumferential rib deviating from the first axial slot so as to bring the first and second annular recesses into communication with each other. At the time of communication between the front and rear compartments via the bypass, a bent outflow path for delivering the pharmaceutical liquid into the front compartment in a state where the tubular body at a front end side of the bypass is closed by a front end portion of the gasket is sequentially formed by the second annular recess, the second axial slot, the first annular recess and the first axial slot.
BRIEF DESCRIPTION OF THE DRAWINGS
This object and features of the present invention will become apparent from the following description taken in conjunction with the preferred embodiment thereof with reference to the accompanying drawings in which:
FIG. 1 is an enlarged schematic fragmentary sectional view showing a sealing state between front and rear compartments of a bypass type prefilled syringe including a gasket according to one embodiment of the present invention;
FIG. 2 is an enlarged schematic fragmentary sectional view showing a communication state between the front and rear compartments of the bypass type prefilled syringe of FIG. 1;
FIGS. 3A, 3 B and 3 C are, respectively, a left side elevational view, a front elevational view and a right side elevational view of a front gasket segment employed in the gasket of FIG. 1;
FIGS. 4A, 4 B and 4 C are sectional views taken along the lines IVA—IVA, IVB—IVB and IVC—IVC in FIG. 3B, respectively;
FIG. 5 is a front elevational view of a rear gasket segment employed in the gasket of FIG. 1;
FIG. 6 is a schematic sectional view showing a sealing state between front and rear compartments of a prior art bypass type prefilled syringe;
FIG. 7 is a schematic sectional view showing a communication state between the front and rear compartments of the prior art bypass type prefilled syringe of FIG. 6;
FIG. 8 is a schematic fragmentary sectional view showing a sealing state between front and rear compartments of a further prior art bypass type prefilled syringe; and
FIG. 9 is a front elevational view of a gasket employed in the further prior art bypass type prefilled syringe of FIG. 8 .
Before the description of the present invention proceeds, it is to be noted that like parts are designated by like reference numerals throughout several views of the accompanying drawings.
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, one embodiment of the present invention is described with reference to the drawings. FIGS. 1 to 5 show a gasket 50 for a bypass type prefilled syringe according to the one embodiment of the present invention. In this bypass type prefilled syringe, powdery medicament P and pharmaceutical liquid L are, respectively, stored in a front compartment 6 and a rear compartment 7 of a tubular body 1 beforehand so as to interpose the gasket 50 therebetween, while a marked line 1 b indicative of a position for temporarily stopping a front end of the gasket 50 at the time of communication between the front and rear compartments 6 and 7 via a bypass 1 a is drawn forwardly of the bypass 1 a as shown in FIG. 1 . Since other constructions of the bypass type prefilled syringe are similar to those of a prior art bypass type prefilled syringe shown in FIGS. 6 and 7 in which a first sealing member 3 and a second sealing member 4 are provided and an injection needle 10 is mounted on a front end portion of the tubular body 1 , the description is abbreviated for the sake of brevity. FIGS. 1 and 2 show a sealing state and a communication state between the front and rear compartments 6 and 7 of the tubular body 1 , respectively.
As shown in FIGS. 1 and 2, the gasket 50 is constituted by a front gasket segment 51 and a rear gasket segment 52 which are disposed so as to abut on each other. However, the gasket 50 is not required to be constituted by the two components but may also be formed by the single front gasket segment 51 only. In this case, the bypass 1 a should be set at a small dimension in conformity with the front gasket segment 51 . The gasket 50 is made of elastomer such as synthetic rubber.
FIGS. 3A, 3 B and 3 C are a left side elevational view, a front elevational view and a right side elevational view of the front gasket segment 51 , respectively, while FIGS. 4A, 4 B and 4 C are sectional views taken along the lines IVA—IVA, IVB—IVB and IVC—IVC in FIG. 3B, respectively. The front gasket segment 51 has a front end face 51 a and a rear end face 51 b each having four projections 72 and includes circumferential ribs 54 , 55 , 56 , 57 and 58 arranged sequentially from the front end face 51 a towards the rear end face 51 b . The front gasket segment 51 further has an annular recess 59 formed between the circumferential ribs 54 and 55 , an annular recess 60 formed between the circumferential ribs 55 and 56 , an annular recess 61 formed between the circumferential ribs 56 and 57 and an annular recess 62 formed between the circumferential ribs 57 and 58 .
Meanwhile, an axial rib 63 is provided at each of four circumferential positions of the annular recess 60 . Likewise, an axial rib 64 is provided at each of four circumferential positions of the annular recess 61 and an axial rib 65 is provided at each of four circumferential positions of the annular recess 62 . At the time of communication between the front and rear compartments 6 and 7 , the axial ribs 63 , 64 and 65 intercept the pharmaceutical liquid L flowing in the annular recesses 60 , 61 and 62 so as to prevent the pharmaceutical liquid L from flowing through the annular recesses 60 , 61 and 62 , respectively such that the pharmaceutical liquid L in the annular recesses 60 , 61 and 62 is carried forwardly.
Furthermore, two semicircular axial slots 70 are, respectively, formed at diametrically opposite ends of the circumferential rib 54 and extend through the circumferential rib 54 and the annular recess 59 so as to open to the front end face 51 a . On the other hand, four axial slots 71 are, respectively, formed at circumferential positions of the circumferential rib 55 deviating from the axial slots 70 so as to bring the annular recesses 59 and 60 into communication with each other. As will been seen from FIGS. 3A and 4A, a cross-sectional area of a flow path of the axial slot 70 is set to be larger than that of the axial slot 71 .
By setting an outside diameter D 1 of the circumferential ribs 54 and 55 adjacent to the front end face 51 a to be equal to or larger than an inside diameter of the tubular body 1 but smaller than an outside diameter D 2 of the circumferential ribs 56 , 57 and 58 , the gasket 50 can be advanced smoothly while a sealing state between the tubular body 1 and the gasket 50 is being secured. Meanwhile, an outside diameter of the annular recesses 59 and 60 is also set to be smaller than that of the annular recesses 61 and 62 .
FIG. 5 shows the rear gasket segment 52 . The rear gasket segment 52 has a front end face 52 a and a rear end face 52 b each having four projections 88 in the same manner as the front gasket segment 51 and includes circumferential ribs 81 , 82 and 83 which are arranged sequentially from the front end face 52 a towards the rear end face 52 b . The rear gasket segment 52 further has an annular recess 84 formed between the circumferential ribs 81 and 82 and an annular recess 85 formed between the circumferential ribs 82 and 83 . Meanwhile, in the same manner as the front gasket segment 51 , an axial rib 86 is provided at each of four circumferential positions of the annular recess 84 and an axial rib 87 is provided at each of four circumferential positions of the annular recess 85 . At the time of communication between the front and rear compartments 6 and 7 , the axial ribs 86 and 87 intercept the pharmaceutical liquid L flowing in the annular recesses 84 and 85 so as to prevent the pharmaceutical liquid L from flowing through the annular recesses 84 and 85 .
At the time of communication between the front and rear compartments 6 and 7 by way of the bypass 1 a , the gasket 50 is advanced by a plunger rod (not shown) until the front end face 51 a of the front gasket segment 51 reaches the marked line 1 b of FIG. 1 . At this time, as shown in FIG. 2, a gap is defined between a rear end portion of the rear gasket segment 52 and a rear end portion of the bypass 1 a , while a front end portion of the front gasket segment 51 is disposed forwardly of a front end portion of the bypass 1 a such that the tubular body 1 at a front end side of the bypass 1 a is closed by the front end portion of the front gasket segment 51 .
Thus, the pharmaceutical liquid L fed under pressure into the gap between the bypass 1 a and the gasket 50 as shown by the arrow b in FIG. 2 is initially introduced into the annular recesses 84 and 85 of the rear gasket segment 52 and the annular recesses 60 to 62 of the front gasket segment 51 but is intercepted by the axial ribs 86 and 87 of the rear gasket segment 52 and the axial ribs 63 to 65 of the front gasket segment 51 so as to be delivered forwardly. Then, as shown by the arrow c, the pharmaceutical liquid L is carried into the powdery medicament P along a U-shaped outflow path proceeding from the annular recess 60 to the axial slots 70 through the axial slots 71 and the annular recess 59 . This outflow path of the pharmaceutical liquid L is not restricted to the U-shaped configuration but may have an arbitrary bent shape, for example, a V-shaped configuration or an S-shaped configuration.
Meanwhile, in the above described embodiment, the gasket 50 is applied to the bypass type prefilled syringe of a construction having an injection needle mounted on the front end portion of the tubular body 1 but is not restricted to the bypass type prefilled syringe of this construction. The gasket 50 may also be applied to a bypass type prefilled syringe of other constructions, e.g., a construction in which a distal end cap is mounted on a distal end of the tubular body 1 as shown in FIG. 8 .
Furthermore, in the above described embodiment, the powdery medicament P and the pharmaceutical liquid L are, respectively, preliminarily stored in the front and rear compartments 6 and 7 . However, in the two components stored in the front and rear compartments 6 and 7 , respectively, at least the component stored in the rear compartment 7 should be liquid and thus, the two components may be liquid. Meanwhile, in case only one of the two components is liquid, it is desirable that the other component is of simply dissoluble or dispersible dosage forms such as powder and solid medicine obtained by freeze-drying. The dosage forms include sustained release drug.
For example, microsphere or the like may be recited as the sustained release drug. The microsphere includes microcapsule, microparticle, etc. More specifically, the microspheres or the microcapsules described in Japanese Patent Laid-Open Publication Nos. 60-100516 (1985), 62-201816 (1987), 02-124814 (1990), 04-321622 (1992), 05-112468 (1993), 05-194200 (1993), 06-293636 (1994), 06-145046 (1994), 06-192068 (1994), 08-169818 (1996), 09-132524 (1997), 09-221417 (1997) and 09-221418 (1997) are employed.
As injections composed of the above two components, which can be administered by the two-compartment type prefilled syringe, i.e., biologically active substances, it is possible to specify, for example, biologically active peptide, antineoplastic agent, antibiotic, antipyretic, analgesic, antiphologistic, antitussive expectorant, sedative, muscle relaxant, antiepileptic, antiulcer agent, antidepressant, antiallergic agent, cardiotonic, antiarrhythmic drug, vasodilator, hypotensive diuretic, diabetic drug, antilipemic agent, anticoagulant, hemostatic, antituberculosis drug, hormone drug, narcotic antagonist, bone resorption inhibitor, osteoplasty accelerator, angiogenesis inhibitor, etc. However, it is needless to say that the injections are not restricted to these substances.
Biologically active peptides are desirable as the biologically active substances. For example, biologically active peptide having a molecular weight of about 300 to 40,000, desirably about 400 to 30,000 and more desirably about 500 to 20,000 may be employed. Such biologically active peptide desirably has a basic group capable of forming a salt with, for example, weak acid having a pKa of not less than 4.0 including carbonic acid, acidic bicarbonate, boric acid and lower alkane monocarboxylic acid having 1 to 3 carbon atoms. Meanwhile, in place of the basic group, the biologically active peptide may also have a free acidic group or an acidic group forming a salt.
Hormonal action can be recited as a typical activity of the biologically active peptides. Meanwhile, the biologically active peptides may be any one of a natural product, a synthetic, a semisynthetic product and a product of genetic engineering, or an analogue and/or a derivative thereof. Action of these biologically active peptides may be either agonistic or antagonistic.
The biologically active peptides may include luteinizing hormone releasing agent (LH-RH) referred also to as “gonadotropin releasing agent (Gn-RH)”, insulin, somatostatin, somatostatin derivative such as Sandostatin in U.S. Pat. Nos. 4,087,390, 4,093,574, 4,100,117 and 4,253,998, growth hormone (GH) in Japanese Patent Laid-Open Publication Nos. 7-1018778 (1995) and 10-265404 (1998), growth hormone releasing hormone (GH-RH), prolactin, erythropoietin (EPO), adrenocorticotropic hormone (ACTH), ACTH derivative such as ebiratide, melanocyte-stimulating hormone (MSH), thyrotropin releasing hormone ((pyr)Glu-His-ProNh2; TRH), a salt and a derivative thereof in Japanese Patent Laid-Open Publication Nos. 50-121273 (1975) and 52-116465 (1977), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), vasopressin, vasopressin derivative such as desmopressin, oxytocin, calcitonin, glucagon, gastrin, secretin, pancreozymin, cholecystokinin, angiotensin, human placental lactogen, human chorionic gonadotropin (HCG), enkephalin, enkephalin derivative in U.S. Pat. No. 4,277,394 and EP-31567-A, endorphin, kyotorphin, interferons such as interferon-α, interferon-β and interferon-γ, interleukins such as interleukins 1 to 12, taftsin, thymopoietin, thymosin, thymostimulin, thymic humoral factor (THF), scrum thymic factor (FTS) and its derivative in U.S. Pat. No. 4,229,438, tumor necrosis factor (TNF), colony stimulating factor (CSF, GCSF, GMCSF and MCSF), motilin, dinorphin, bombesin, neurotensin, cerulein, bradykinin, atrial natriuretic factor, nerve growth factor (NGF), cell growth factors such as EGF, TGF-β, PDGF, acidic FGF and basic FGF, neurotrophic factors such as NT-3, NT4, CNTF, GDNF and BDNF, peptide having endothelin antagonism and its analogue (derivative) in EP-436189-A, EP-457195-A, EP-496452-A and Japanese Patent Laid-Open Publication Nos. 3-94692 (1991) and 3-130299 (1991), insulin receptor, insulin-like growth factor (IGF)-1 receptor, IGF-2 receptor, transferrin receptor, epidermal growth factor, low density lipoprotein (LDL) receptor, macrophage scavenger receptor, GLUT-4 transporter, growth hormone receptor, peptide derived from α1 domain of major histocompatibility class I antigen complex (MHC-I) having activity for hampering endogeny of leptin receptor (“Proceedings of the National Academy of Sciences of the United States of America”, Vol. 91, p.p. 9086-9090 (1994) and Vol. 94, p.p. 11692-11697 (1997)) and its analogue (derivative), and a fragment or a fragment derivative thereof.
In case the biologically active peptide is a salt, a pharmacologically acceptable salt or the like may be used. For example, in case the biologically active peptide has a basic group such as an amino group in its molecule, salts formed by the basic group and inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid and boric acid or organic acids such as carbonic acid, acidic bicarbonate, succinic acid, acetic acid, propionic acid and trifluoroacetic acid may be used. Meanwhile, in case the biologically active peptide has an acidic group such as a carboxyl group in its molecule, salts formed by the acidic group and inorganic bases including alkaline metals such as sodium and potassium and alkaline earth metals such as calcium and magnesium or organic bases including organic amines such as triethylamine and basic amino acids such as arginine may be used. Furthermore, the biologically active peptide may form metal complex compounds such as a copper complex and a zinc complex.
As concrete examples of the biologically active peptides desirable for use, it is possible to recite an LH-RH analogue and its salt effective for contraception and diseases dependent on either LH-RH of prostatic cancer, prostatic hypertrophy, endometriosis, myoma of the uterus, fibroma of the uterus, precocious puberty and breast cancer or a hormone derived from the LH-RH as well as a somatostatin derivative and its salt effective for diseases dependent on growth hormone and a hormone derived from the growth hormone and diseases of the digestive system such as peptic ulcer.
Concrete examples of the LH-RH analogue and its salt may include peptides described in “Treatment with GnRH analogs: Controversies and perspectives” published in 1966 by The Parthenon Publishing Group Ltd., Japanese Patent National Publication No. 3-503165 (1991) and Japanese Patent Laid-Open Publication Nos. 3-101695 (1991), 7-97334 (1995) and 8-259460 (1996).
As a concrete example of a biologically active peptide having LH-RH antagonism, i.e., an LH-RH antagonist, a biologically active peptide expressed by the following general formula [Ia] or its salt may be recited.
X-D2Na1-D4C1Phe-D3Pa1-Ser-A-B-Leu-C-Pro-DA1aNH 2 [Ia]
In the formula, “X” denotes N(4H 2 -furoy1)G1y or NAc, “A” denotes a residual group selected from NMeTyr, Tyr, Aph(Atz) and NMeAph(Atz), “B” denotes a residual group selected from DLys(Nic), DCit, DLys(AzaglyNic), DLys(AzaglyFur), DhArg(Et 2 ), DAph(Atz) and DhCi and “C” denotes Lys(Nisp), Arg or hArg(Et 2 ).
More specifically, the biologically active peptide having LH-RH antagonism, i.e., LH-RH antagonist may be NAcD2Na1-D4C1Phe-D3Pa1-Ser -NMeTyr-DLys(Nic)-Leu-Lys(Nisp)-Pro-DA1aNH 2 , N(4H 2 -furoy1)G1y-D2Na1-D4C1Phe-D3Pa1-Ser-NMeTyr-DLys(Nic)-Leu-Lys(Nisp)-Pro-DA1aNH 2 , cetrorelix, ganirelix, antarelix, detirelix, azaline, antide, ramorelix and abarelix. These peptides can be produced by the methods described in the above prior art documents or similar methods.
As a concrete example of a biologically active peptide having LH-RH agonistic action, i.e., an LH-RH agonist, a biologically active peptide expressed by the following general formula [Ib] or its salt may be recited.
5-oxo-Pro-His-Trp-Ser-Tyr-Y-Leu-Arg-Pro-Z [Ib]
In the formula, “Y” denotes a residual group selected from DLeu, DA1a, DTrp, DSer(tBu), D2Na1 and DHis(ImBz1) and “Z” denotes NH—C 2 H 5 or G1y-NH 2 . Especially, a peptide in which “Y” is Dleu and “Z” is NH—C 2 H 5 or its salt is suitable. These peptides can be produced by the methods described in the above prior art documents or similar methods.
A concrete example of the somatostatin derivative or its salt is described in, for example, “Proceedings of the National Academy of Sciences of the United States of America”, Vol. 93, p.p. 12513-12518 (1996) or the documents cited therein.
Furthermore, as a concrete example of a somatostatin derivative selectively effective for tumor in somatostatin analogues, a biologically active peptide described in U.S. Pat. No. 5,480,870 or EP-505680-A and having the following formula may be recited.
Meanwhile, Sandostatin in U.S. Pat. Nos. 4,087,390, 4,093,574, 4,100,117 and 4,253,998 may be suitable.
In the above described biologically active peptides, 5-oxo-Pro-His-Trp-Ser-Tyr-DLeu-Leu-Arg-Pro-NH—C 2 H 5 (leuprorelin) or its salt, especially, acetate is preferable.
As the above biologically active substances, non-peptide drugs, etc. may be used. More specifically, compounds described in, for example, Japanese Patent No. 2946298 and Japanese Patent Laid-Open Publication Nos. 3-232880 (1991) and 4-364179 (1992) may be recited as the drugs.
As is clear from the foregoing description of the gasket 50 for the bypass type prefilled syringe, according to the present invention, at the time of communication between the front and rear compartments 6 and 7 via the bypass 1 a , since the tubular body 1 at the front end side of the bypass 1 a is closed by the front end portion of the front gasket segment 51 and the pharmaceutical liquid L is introduced into the powdery medicament P along the U-shaped outflow path proceeding from the annular recess 60 to the axial slots 70 by way of the axial slots 71 and the annular recess 59 , a squirt phenomenon of the pharmaceutical liquid L is prevented positively. As a result, since the powdery medicament P is sufficiently dissolved or dispersed in the pharmaceutical liquid L, satisfactory injection liquid can be prepared at all times.
Meanwhile, in the gasket 50 for the bypass type prefilled syringe, according to the present invention, at the time of communication between the front and rear compartments 6 and 7 via the bypass 1 a , since the pharmaceutical liquid L carried into the annular recesses 84 and 85 of the rear gasket segment 52 and the annular recesses 60 to 62 of the front gasket segment 51 is intercepted by the axial ribs 86 and 87 and the axial ribs 63 to 65 , respectively so as to be delivered forwardly, the pharmaceutical liquid L is efficiently introduced into the powdery medicament P without incurring such a loss that the pharmaceutical liquid L remains in the annular recesses 84 and 85 of the rear gasket segment 52 and the annular recesses 60 to 62 of the front gasket segment 51 for a long time.
Furthermore, in the gasket 50 for the bypass type prefilled syringe, according to the present invention, since the cross-sectional area of the flow path of the axial slot 70 opening to the front end face 51 a of the front gasket segment 51 is set to be larger than that of the axial slot 71 formed on the circumferential rib 55 , delivery speed of the pharmaceutical liquid L in the axial slots 70 drops below that of the pharmaceutical liquid L in the axial slots 71 in the U-shaped outflow path at the time of communication between the front and rear compartments 6 and 7 via the bypass 1 a , so that the squirt phenomenon of the pharmaceutical liquid is prevented more positively.
In addition, in the gasket for the bypass type prefilled syringe, according to the present invention, since the outside diameter D 1 of the circumferential ribs 54 and 55 is set to be equal to or larger than the inside diameter of the tubular body 1 but smaller than the outside diameter D 2 of the circumferential ribs 56 to 58 , the small-diameter circumferential ribs 54 and 55 are lightly fitted into the tubular body 1 forwardly of the bypass 1 a at the time of communication between the front and rear compartments 6 and 7 via the bypass 1 a , so that an operation of advancing the front end of the gasket 50 to the marked line 1 b can be performed smoothly. | 1a
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BACKGROUND
1. Field
The present disclosure relates generally to tools and their use, and, in particular, to an apparatus and method for holding tools securely with a glove.
2. Background
The construction industry has seen the arrival of many electrical and other specialty tools. These tools offer the ability to perform construction tasks, such as cutting or nailing using more power. In addition, the power tools provide quicker and more precise operations. Nail guns give the contractor the ability to install more nails in a given period of time than could be placed by hand with a hammer. Greater uniformity of pressure and correct placement are facilitated with a nail gun. Similarly, an electric saw is much faster than a hand saw. When used correctly these tools can significantly speed up many common construction tasks.
The benefit of these tools is not without cost, however. Because the tools often incorporate electric motors or pneumatic apparatus, these tools are heavier. Often the user must be aware of a power cord and must maneuver the cord to perform operations. For ease of operation, many tools are designed to be held and operated with just one hand. No matter how well designed the power tool; in general, power tools are much heavier than their traditional counterparts.
The heavier weight of power tools may lead to fatigue in the user's hands. Given the increase in weight, it is possible that a user may lose his or her grip on a tool, which may result in poor workmanship, or an accident. The weight of power tools also requires that a user maintain a clear focus while holding, using, and manipulating the tools. Even if fatigue is not a problem, a distracted user could easily lose control of a power tool and injure himself or others nearby.
The injuries caused by power tools may range from simple bruises from a dropped tool, up to severe cuts and lacerations from grip loss on a power saw. There is a need in the art for a glove to assist a user in retaining and controlling a power tool.
SUMMARY
A glove for securely holding or grasping a tool is provided by embodiments of the invention. The glove has a flap attached to the wrist area of the palm side of the glove. This flap has a piece of adhesive fabric attached to the flap, which faces up when the user's hand is palm upward. A piece of adhesive fabric is also attached to the area of the glove over the pad of the user's thumb. Similar pieces of adhesive fabric are attached to the back side of the glove, directly over the user's fingernails.
A method of holding a tool is provided. The method comprises: wearing a glove having a flap and adhesive fabric pieces, the flap attached to a wrist area of the glove and having an adhesive fabric piece attached, the adhesive fabric pieces attached to a pad of a thumb and backs of fingers. The user then grasps the tool normally, and secures the flap and adhesive fabric pieces around the tool and secures the flap and adhesive fabric pieces around the tool.
An apparatus for holding a tool is provided. The apparatus is comprised of means for covering a user's palm and fingers with a glove; means for fabric adhesion fixed to a flap attached to a wrist area of the glove; means for fabric adhesion fixed to a pad of a thumb; and means for fabric adhesion fixed to backs of fingers. Various aspects and embodiments of the invention are described in further detail below.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an illustration of the palm side of a tool holding glove, in accordance with various embodiments of the present invention.
FIG. 2 is an illustration of the back of the hand side of a tool holding glove, in accordance with one or more embodiments the present invention.
FIG. 3 is an illustration of a tool holding glove in use, according to one or more embodiments of the present invention.
FIG. 4 is an illustration of a tool holding glove incorporating a flap holder, in use, in accordance with a further embodiment of the invention
DETAILED DESCRIPTION
Various embodiments are now described with reference to the drawings, wherein like reference numerals are used to refer to like elements throughout. In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of one or more embodiments. It may be evident, however, that such embodiments) may be practiced without these specific details. In other instances, well-known structures and devices are shown in block diagram form in order to facilitate describing one or more embodiments.
In the following paragraphs, the present invention will be described in detail by way of example with reference to the attached drawings. Throughout this description, the preferred embodiment and examples shown should be considered as exemplars, rather than as limitations on the present invention. As used herein, the “present invention” refers to any one of the embodiments of the invention described herein, and any equivalents. Furthermore, reference to various feature(s) of the “present invention” throughout this document does not mean that all claimed embodiments or methods must include the referenced feature(s).
Referring to FIG. 1 , a tool holding glove 100 , according to one embodiment is illustrated. FIG. 1 shows the palm side of the tool holding glove 100 . The glove portion 102 is similar to workman's gloves, typically worn by craft workers while performing tasks. The glove portion 102 may be made from leather or other sturdy and protective material. The glove portion extends beyond the wearer's wrist and partially up the wearer's forearm. A flap 104 is attached in the wrist area, according to an embodiment of the invention. This flap 104 has attached adhesive fabric piece 106 . Adhesive fabric piece 106 may be one part of a hook and loop adhesive fabric, that when mated lock together. Alternatively, fabric piece 106 may be any other adhesive fabric capable of repeated joining and separating without requiring replacement. A thumb pad piece 108 A is made of the same adhesive fabric as fabric piece 106 .
FIG. 2 illustrates the reverse side, or back of the wearer's hand side of the tool holding glove. The glove portion 102 is shown looking down on the back of the wearer's hand with four fingers visible. The portions of the glove on the back of the wearer's fingers, above the wearer's fingernails, are covered with adhesive fabric pieces 108 B-E. These fabric pieces 108 B-E are also made of a hook and loop adhesive fabric, and are of a type opposite that of the fabric piece 106 attached to flap 104 , in order to provide adhesion when mated together.
FIG. 3 illustrates use of the tool holding glove. The user puts on the glove as he or she would a typical glove. The wearer then picks up the tool 302 to be retained by the tool holding glove. The thumb and index finger encircle the tool and thumb pad piece 108 A is pressed against adhesive fabric piece 108 E, which covers the wearer's index finger. Pressing the thumb pad piece 108 A against adhesive fabric piece 108 E forms a secure grip around the tool, 302 . In a similar manner, the adhesive fabric piece 106 , attached to flap 104 is pressed against fabric pieces 108 B-D to complete the grip on the tool 302 .
Once the grip on the tool 302 has been formed the wearer has a secure hold on the tool 302 . The wearer may even relax the grip of his or her muscles and the tool holding glove will retain the tool 302 within the tool holding glove 100 .
The wearer may break the grip established by the tool holding glove by grasping the flap 104 and separating adhesive fabric piece 106 from adhesive fabric pieces 108 B-D. In a similar fashion, the thumb piece 108 A is separated from adhesive fabric piece 108 E, over the wearer's index finger.
A further embodiment of the tool holding glove varies the location of flap 104 . Specifically, flap 104 may be located further away from the wearer's wrist, up the forearm. This embodiment prevents flap 104 from being tangled in the grip of the wearer's hand. In a further embodiment, fabric piece 108 E may also be located closer to the base of the wearer's thumb. This embodiment facilitates a tighter grasp of tools with a small gripping diameter.
Yet another embodiment facilitates opening the flap 104 to release the grip. Flap 104 may be shaped with an “ear” on the top of flap 104 , parallel with the wearer's wrist. This “ear” provides easier opening with which to initiate separation of the adhesive fabric pieces 106 and 108 B-D.
A still further embodiment facilitates opening the grip with the wearer's other hand. Flap 104 may have “ears” or rounded portions on the sides. These “ears” allow a wearer to grasp flap 104 with the fingers of the other hand and then separate adhesive fabric piece 106 and adhesive fabric pieces 108 B-D.
Yet a further embodiment provides for holding the flap 104 when the tool holding feature is not in use. FIG. 4 provides a tool holding glove, 400 , incorporating flap 104 , positioned as described above. Adhesive fabric pieces 402 A and 402 B are affixed to flap 104 as shown. Specifically, the wrist of the glove 400 has adhesive fabric piece 402 A affixed above the attachment point for flap 104 . Flap 104 has adhesive fabric piece 402 B affixed to the outer side of flap 104 , facing away from the palm of the user. When the flap 104 is not in use, adhesive fabric pieces 402 A and 402 B are used to hold flap 104 against the wrist of the user and prevent flap 104 from tangling in the user's hand.
While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of example only, and not of limitation. Likewise, the various diagrams may depict an example architectural or other configuration for the invention, which is done to aid in understanding the features and functionality that may be included in the invention. The invention is not restricted to the illustrated example architectures or configurations, but the desired features may be implemented using a variety of alternative architectures and configurations. Indeed, it will be apparent to one of skill in the art how alternative functional, logical or physical partitioning and configurations may be implemented to implement the desired features of the present invention. Also, a multitude of different constituent module names other than those depicted herein may be applied to the various partitions. Additionally, with regard to flow diagrams, operational descriptions and method claims, the order in which the steps are presented herein shall not mandate that various embodiments be implemented to perform the recited functionality in the same order unless the context dictates otherwise.
Although the invention is described above in terms of various exemplary embodiments and implementations, it should be understood that the various features, aspects and functionality described in one or more of the individual embodiments are not limited in their applicability to the particular embodiment with which they are described, but instead may be applied, alone or in various combinations, to one or more of the other embodiments of the invention, whether or not such embodiments are described and whether or not such features are presented as being a part of a described embodiment. Thus the breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments.
Terms and phrases used in this document, and variations thereof, unless otherwise expressly stated, should be construed as open ended as opposed to limiting. As examples of the foregoing: the term “including” should be read as meaning “including, without limitation” or the like; the term “example” is used to provide exemplary instances of the item in discussion, not an exhaustive or limiting list thereof; the terms “a” or “an” should be read as meaning “at least one,” “one or more” or the like; and adjectives such as “conventional,” “traditional,” “normal,” “standard,” “known” and terms of similar meaning should not be construed as limiting the item described to a given time period or to an item available as of a given time, but instead should be read to encompass conventional, traditional, normal, or standard technologies that may be available or known now or at any time in the future. Likewise, where this document refers to technologies that would be apparent or known to one of ordinary skill in the art, such technologies encompass those apparent or known to the skilled artisan now or at any time in the future.
A group of items linked with the conjunction “and” should not be read as requiring that each and every one of those items be present in the grouping, but rather should be read as “and/or” unless expressly stated otherwise. Similarly, a group of items linked with the conjunction “or” should not be read as requiring mutual exclusivity among that group, but rather should also be read as “and/or” unless expressly stated otherwise. Furthermore, although items, elements or components of the invention may be described or claimed in the singular, the plural is contemplated to be within the scope thereof unless limitation to the singular is explicitly stated.
The presence of broadening words and phrases such as “one or more,” “at least,” “but not limited to” or other like phrases in some instances shall not be read to mean that the narrower case is intended or required in instances where such broadening phrases may be absent. The use of the term “module” does not imply that the components or functionality described or claimed as part of the module are all configured in a common package. Indeed, any or all of the various components of a module, whether control logic or other components, may be combined in a single package or separately maintained and may further be distributed across multiple locations.
Additionally, the various embodiments set forth herein are described in terms of exemplary block diagrams, flow charts and other illustrations. As will become apparent to one of ordinary skill in the art after reading this document, the illustrated embodiments and their various alternatives may be implemented without confinement to the illustrated examples. For example, block diagrams and their accompanying description should not be construed as mandating a particular architecture or configuration.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein. | 1a
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TECHNICAL FIELD
The present invention relates to biomaterials, and more particularly to biomaterials having tunable bulk and surface properties, and even more particularly to biomaterials that may be fabricated to be biocompatible, anti-microbial and bio-erodible.
BACKGROUND OF THE INVENTION
Polymeric materials are used as catheters in many clinical situations every day. Typical materials such as medical grade silicone elicit a lower immunogenic response than previously used materials (polyurethanes or polyethylenes). Even with this development, silicone catheters have significant complications during acute and chronic use. These include biofilm formation, encrustation and bacterial infection.
In 2009, roughly 40% of infections acquired in U.S. hospitals were caused by urinary catheters, costing the healthcare system over $1 billion. Central venous catheters are estimated to cause roughly 80,000 bloodstream infections, resulting in 28,000 deaths and costing up to $2.3 billion annually. The most common pathogens to induce an infection include gram-positive staphylococcus aureus and staphylococcus epidermidis , as well as gram-negative Escherichia coli and pseudomonas aeruginosa . Bacteria can come from a variety of sources, including the operating room atmosphere, surgical equipment, clothing from medical staff, and even bacteria on the patient's skin and already in their body. Therefore, even under sterilized conditions, it can be difficult to prevent infections. In addition to infections, long term urinary catheterization increases the likelihood of encrustation, which is the buildup of minerals on the catheter and can potentially lead to urinary blockage.
The mechanism for bacterial adhesion onto a catheter occurs via a three step process: 1-2 hours after implantation, non-specific and reversible bonding occurs through gravitational, van der Waals, electrostatic, hydrogen bond, dipole-dipole, ionic bond, and hydrophobic interactions; roughly 2-3 hours later, stronger adhesion occurs via specific chemical interactions between the bacteria and substrate surface, forming irreversible bonds; and finally, if sufficient nutrients are supplied, a biofilm can form on the implant surface. Once a biofilm forms, roughly 1,000 times the antibiotic dose is required to treat the infection compared to killing the bacteria in suspension. In addition to infections, long term catheterization increases the likelihood of encrustation, which is the buildup of minerals on the catheter and can potentially lead to urinary blockage. For these reasons, there is a high interest in developing catheter materials that prevent bacterial and mineral adhesion.
The Foley catheter, which is the most commonly used device for urinary catheterization, is often made of silicone materials due to its low immunological response. A lubricious coating is often added in order to reduce urethral irritation. To address the issues of infections, some catheters are being coated with antimicrobial agents such as silver alloys or nitrofurazone. While antimicrobial coatings may cost up to twice as much as an uncoated catheter, their higher costs are becoming justified due to their ability to reduce infection rates, which can cost between $3,700 and $56,000 per patient. Despite the antimicrobial coatings' ability to reduce medical costs and infection rates compared to uncoated catheters, they are still not completely effective against preventing infections. One drawback is that most antimicrobial agents are not effective against all pathogens, especially antibiotic-resistant bacteria. In addition, antimicrobial coatings are not always effective against preventing biofilm formation for long-term catheterization. Even though antimicrobial coatings may kill the initial bacteria they interact with, the dead bacteria will still stick to the catheter, providing a perfect layer for new bacterial attachment and biofilm formation. Finally, in areas where the coating has been delaminated and the underlying catheter is exposed, bacteria can adhere very quickly since current catheter materials do not have an innate ability to prevent bacterial adhesion. For all these reasons, the likelihood of a catheter induced infection is directly correlated to the duration of catheterization, with the chances of infection increasing 3-10% daily.
To mitigate these problems, many patients have turned to intermittent catheters, which are disposable catheters and are used each time the bladder is emptied. Revenues for intermittent catheters were $143 million in 2009. While the chance for infection is greatly reduced, patients must be highly trained to use intermittent catheters since they can potentially cause urethra problems due to irritation. They are also expensive since they need to be replaced often.
SUMMARY OF THE INVENTION
The present invention addresses the above needs by providing a material having a chemical structure that exhibits surface properties which result in a discontinuous surface and a self-adjusting (smart) polymer configuration. This material may exhibit bio-erosion which removes any adhered materials and/or may also prevent biofilm formation that leads to a foreign body response. Since the material has a self-adjusting/heterogeneous surface, immunological response components do not recognize the biomaterial surface. Hydrophilic micro-domains in the biomaterial also contribute to the adjusting surface properties of the biomaterial depending on the surrounding environment.
The surface properties of the material of the present invention result from both the surface and bulk polymeric structure which is formed during the manufacturing process. These systems are based on those used in the manufacture of rigid contact lenses and flexible intra-ocular lenses which have proven to be biocompatible and possess properties which inhibit protein deposition and other adverse contaminations. The polymer material of the present invention generally comprises a base polymer which may be modified to incorporate a surface active agent or a grafted polymer moiety. The material may further include the addition of one or more interfacial agent polymer components and/or therapeutic agents.
In accordance with an aspect of the present invention, the base polymer layer consists of biocompatible synthetic polymer systems which have a hydrophilic/hydrophobic profile to facilitate surface dynamics, including a balanced hydrophilic/hydrophobic profile to facilitate drug retention/delivery. The base polymer further has thermoplastic properties amenable to extrusion processing into tubing or coatings. The base polymer is tunable to specific system requirements and may include derivatization of the polymer to include amino acids, proteins, anti-bacterial and bio-erodible agents, as well as other desired chemical properties. The base polymer is generally comprised of a polyurethane produced through the reaction of a diisocyanate with chemical moieties such as siloxane diols and organic polyols, and preferably organic diols. In accordance with a further aspect of the present invention, the organic diols may be modified through a pre-polymer reaction to produce grafted polymers with mixed-phases. These grafted pre-polymer building blocks have the desired diol terminal groups while also possessing one or more additional reaction sites within the polymer chain. These reactive pre-polymers can then be modified to include additional functional moieties, such as anti-adhesive compounds, anti-microbial agents and/or therapeutic compounds before being incorporated within the polyurethane-based biomaterial.
In an embodiment of the present invention, a method of preparing a polyurethane-based mixed-phase thermoplastic biomaterial comprises contacting and reacting a diol selected from the group consisting of siloxane diols, polyether diols, polyester diols and polycarbonate diols with a graft pre-polymer and an organic diisocyanate compound, wherein the graft pre-polymer comprises a diol and at least one covalently bonded unsaturated monomer selected from the group consisting of a fluorinated monomer, a siloxane monomer, a zwitterionic monomer such as but not limited to an amino acid, phosphorycholine and the like, an aliphatic ester of methacrylic acid, a cyclic ester of methacrylic acid, a charged monomer, a sulfonium salt, a vinyl monomer with phenol or benzoic acid, N-vinyl pyrrolidone, an aminoglucoside, and a therapeutic agent. The reaction is conducted within an aprotic solvent and for a period of time and at a temperature sufficient to produce the mixed-phase thermoplastic biomaterial.
In a further embodiment of the present invention, the method further includes contacting and reacting an interfacial agent. The interfacial agent comprises a) a solvatable constituent which is solvatable within the aprotic solvent but not compatible with the diol and b) a non-solvatable constituent which is compatible with the diol but is not solvatable within the aprotic solvent.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic cross-section of an embodiment of a catheter comprised of a biomaterial in accordance with an embodiment of the present invention;
FIG. 2 is an overlay of multiple FTIR spectra showing reduction of the isocyanate peak as the polyurethane reaction progresses;
FIG. 3 is a schematic structural view of a polymeric biomaterial in accordance with the present invention;
FIG. 4 is an exemplary schematic of a graft polymer suitable for use within a polymeric biomaterial in accordance with the present invention;
FIG. 5 are XPS spectra of an exemplary mixed-phase polymer before and after heating for 3 hours at 80° C.;
FIGS. 6A and 6B are comparative DSC thermograms of A) an exemplary mixed-phase polymer and B) an ungrafted polymer;
FIG. 7 is a plot of a bacterial count on a commercial catheter and a catheter coated with an exemplary mixed-phase polymer showing reduced bacterial adhesion on the coated catheter; and
FIG. 8 is a DSC thermogram of an exemplary mixed phase biomaterial.
DETAILED DESCRIPTION
The manufacturing process used to develop the biomaterials in accordance with the present invention is based upon reverse phase polymerization. An exemplary process is described within U.S. Pat. No. 4,000,218 to Critchfield et al. issued Dec. 28, 1976. Reversed phase polymerization has been shown to produce polymers in particulate form and in high purity as required for use in medical devices. As part of the process, it is necessary to use and/or synthesize interfacial agents specifically suited for the system. The interfacial agent generally includes a diol terminated polymer chain having at least one reactive site within the chain. In accordance with a further aspect of the invention, the interfacial agent may be modified to incorporate a zwitterionic moiety such as an amino acid or phosporylcholine and derivatives thereof. An aliphatic species, preferably a saturated hydrocarbon, is chemically bonded to the reactive site. In this manner, the interfacial agent possesses a hydrophilic domain which may be incorporated within the bulk polyurethane base polymer while also having a hydrophobic tail extending outwardly from the base polymer. As a result, when the reaction materials (i.e. the polyurethane precursors, such as methylene diphenyl diisocyanate and an organic diol, and the interfacial agent) are placed within an aprotic solvent such as hexane, benzene or toluene, reverse micelles are formed. As a result, these interfacial agents serve a dual purpose: a) to suspend particles in process in the aprotic solvent and b) to modify the surface characteristics of the resultant polyurethane material.
For example, as shown in FIG. 1 , medical device 10 (such as a urinary catheter) is generally comprised of a base polymer 20 . In accordance with an aspect of the present invention, base polymer 20 is a polyurethane composed of polymerized diisocyanate/diol. The diisocyanate has a general formula O═C═N—R—N═C═O, where R is either an aliphatic chain, such as hexamethylene diisocyanate (HDI), or is aromatic such as toluene diisocyanate (TDI) or methylene diphenyl diisocyanate (MDI). The diol may be a siloxane diol or an organic diol, such as but not limited to polyethylene glycol (PEG), tetraethylene glycol, 1,4-butane diol, a lactone diol such as poly(caprolactone) diol or a polycarbonate diol. To monitor the progression of the polyurethane reaction, Fourier transform infrared (FTIR) spectroscopy may be used to interrogate isocyanate consumption. Consumption of the isocyanate groups indicates extension of the polymer backbone and the attachment of graft pre-polymers (discussed below). The isocyanate may also be monitored since specific amounts of unreacted isocyanate groups may be desired to remain on the polymer in order to improve adhesion between the substrate (i.e. medical device 10 ) and a coating later of the biomaterial of the present invention. Alternatively, unreacted isocyanate groups may also be further derivatized following the polyurethane formation reaction by quenching the reaction with a solution containing one or more zwitter ions such as amino acids or amino acid analogs. In this manner, the polyurethane backbone may be modified to increase its biocompatibility and/or increase its functionality via the additional reaction site on the zwitter ion. An overlay of exemplary FTIR spectra tracking polyurethane reaction progression is shown in FIG. 2 .
In accordance with an aspect of the present invention, partially embedded within base polymer 20 are one or more surface active agents 30 (see also FIG. 3 ). Surface active agents 30 may be covalently bonded to the diol backbone of the polyurethane base polymer 20 . Alternatively and/or additionally, surface active agents 30 may also be incorporated within the base polymer 20 via a graft pre-polymer 32 (see also FIG. 4 ) which will be discussed in greater detail below. In one aspect of the invention, surface active agents 30 are tailored to provide surface properties required for long term implants, such as catheters or other devices where long-term biocompatibility is desired.
Base polymer 20 exhibits the microstructure (hard-soft segments 26 - 28 , FIG. 3 ) well known in polyurethanes. This microstructure is arranged in such a way so as to induce a synergistic effect with the surface active agent 30 . The micro-domains present within the base polymer 20 play a role in both the mechanical and surface properties of the final devices. These domains are dictated by the feed composition in the polymer synthesis and manipulated by the thermal history and ultimate manufacturing technique employed when fabricating the polyurethane polymer.
Surface active agents 30 may be incorporated within the polyurethane base polymer 20 during polymerization of the polyurethane or may be later reactively added through suitable chemical reactions to functional groups located on the base polymer 20 . For example, U.S. Pat. No. 3,383,351 to Stamberger issued May 14, 1968, discloses a pre-polymer grafting polymerization pre-processing step before the polyurethane polymerization reaction. That is, in accordance with an aspect of the present invention, the diol grafted pre-polymer 32 employed within the polyurethane polymerization has been pre-processed so as to become derivatized to either include the surface active agent 30 or to include a reactive site for later functionalization of the polyurethane base polymer 20 (see FIG. 4 ). The grafted pre-polymer 32 also allows for compositional control of the polyurethane base polymer which further modifies both the base polymer 20 and the surface properties of the surface active agents 30 .
With continued reference to FIG. 3 , surface active agents 30 A- 30 C may be unsaturated monomers covalently integrated within backbone 34 of pre-polymer 32 . Examples of such surface active agents may include charged monomers such as methacrylic acid 30 A and vinyl sulfonic acid 30 C, and an anti-adhesive fluorinated monomer 30 B such as 2,2,2-trifluoroethyl methacrylate. Additional surface active agents may include, without limitation, aliphatic methacrylates, fluoromethacrylates, sulfonium salts, vinyl monomers with phenol or benzoic acid, N-vinyl pyrrolidone, a zwitterionic monomer such as but not limited to an amino acid, phosphorycholine and the like, and functionalized aminoglucosides.
The grafted pre-polymer creates a mixed-phase polymeric structure enabling the fine tuning of the surface properties of medical device 10 . In one aspect of the present invention wherein medical device 10 is fabricated directly from the mixed-phase biomaterial, the bulk properties of medical device 10 are dictated by the polyurethane structure of base polymer 20 and include both rheological properties and micro-domains within the polymer. Tuning of the polyurethane reaction materials and synthesis produces bulk polymers suitable for melt processing into tubing and other shapes, as well as for the application of coatings from appropriate solvents. In a further aspect of the present invention, the mixed-phase biomaterial may be surface coated onto a pre-fabricated medical device, such as already commercially available urinary catheters. In either case, the local surface characteristics of the medical device may be modified according to the proposed end-use of the medical device and may include anti-adhesive and/or anti-microbial properties, or may include covalently bonded therapeutic agents for site specific and/or time released application. Derivatization of the surface may be through complimentary functional groups on the polyurethane polymer main chain or through the grafted pre-polymers.
For instance, antimicrobial polymers may be produced by attaching or inserting an active microbial agent onto either the polyurethane or a graft pre-polymer backbone via an alkyl or acetyl linker. In accordance with one aspect of the present invention, graft pre-polymer 32 is specifically chosen for its enhanced antimicrobial properties. Examples of such antimicrobial moieties include, but are not limited to vinyl monomers with phenol or benzoic acid, functionalized aminoglucosides, charged monomers such as methacrylic acid, vinyl sulfonic acid, and sulfonium salts, and fluorinated monomers.
In accordance with a further aspect of the present invention, the mixed-phase biomaterial may reduce bacterial adhesion due to the biomaterial's non-uniform and self-adjusting surface which is non-conducive for bacterial attachment since bacteria prefer unchanging and predictable surfaces when forming biofilms. The polymers synthesized using an embodiment of the manufacturing process of the present invention have non-uniform and dynamic surface chemistries due to variation of the material's surface composition from the graft pre-polymers 32 . Graft pre-polymers 32 also create hydrophillic/hydrophobic and positively/negatively charged microdomains within the resultant biomaterial. The material's composition and micro-domains are dictated by the feed composition, solvent, reaction conditions, and post-treatment procedures such as thermal annealing and washing. By way of example, X-ray photoelectron spectroscopy (XPS), such as the results shown in FIG. 5 for a mixed-phase material including graft pre-polymers having silicon and fluorine substituted methacrylates, may verify that heat treatment at 80° C. for three hours can alter the surface chemistry so that the fluorine and silicon groups of the representative material no longer appear on the surface.
The self-adjusting nature of the biomaterial surface may also be demonstrated by its ability to be dissolved in both hydrocarbon and aprotic polar solvents. Limited solubility of the biomaterial is seen in alcohols and the biomaterial is not soluble in water, although slight surface hydration is seen because of the dynamic nature of the surface. Information on miscibility and polymer-to-polymer interactions can be revealed through the use of differential scanning calorimetry (DSC). As seen in FIG. 6A , a representative biomaterial consists of multiple phases due to graft pre-polymer (side-chain) composition. The graft pre-polymer influences the biomaterial's final properties. As can be seen in FIG. 6A , the representative biomaterial includes one or more components (such as graft pre-polymers and/or surface active agents) which are thermo-responsive and lead to multiple phase transitions. It can be seen that one phase transition is at or near body temperature (37° C.), which decreases the surface modulus and contributes to the biomaterial's self-adjusting surface properties at a biologically relevant temperature. As a comparison, FIG. 6B shows an ungrafted polymer, which contains only a single phase transition.
An example of the improved bacterial anti-adhesion properties of the biomaterials of the present invention over commercial catheters is shown in FIG. 7 . Commercial catheters, with and without biomaterial coatings, were placed into a suspension of Staphylococcus aureus bacteria for 24 hours. After staining and removing the bacteria on the catheters, the bacteria were quantified using ultra-violet spectroscopy. The number of bacteria counted was averaged over 5 samples of each catheter type (whether with or without a biomaterial coating). FIG. 7 shows that an exemplary biomaterial coating produced in accordance with the present invention exhibits a 33% reduction in bacterial adhesion compared to an uncoated commercially available catheter.
The following examples are illustrative of the present invention and not to be regarded as limitative thereto.
Example 1
Preparation of Methacrylate End-Capped Poly(Caprolactone) Diol
In a reaction vessel, hydroxyethyl methacrylate, 1.0 g, caprolactone, 60 g, and 0.1 g stannous octoate were added and mixed until homogeneous. The solution was heated to 82° C. overnight (16-24 hours). This resulted in a waxy solid.
Example 2
Preparation of Poly(Caprolactone) Diol
In a reaction vessel, tetraethylene glycol, 1.0 g, caprolactone, 60 g and 0.1 g stannous octoate were added and mixed until homogeneous. The solution was heated to 82° C. overnight (16-24 hours). This resulted in a waxy solid.
Example 3
Preparation of Graft Polymer a
In a reaction vessel, the following were added:
Component Amount (g) PEG-1000 150 N-vinyl pyrrolidone 1.0 Methyl methacrylate 10 Lauryl methacrylate 7.9 Tris 2.1 Benzoyl peroxide 0.12
where Tris is 3-[Tris(trimethylsiloxy)silyl]propyl methacrylate.
The solution was heated from 70° C. to 100° C. while mixing with an overhead mechanical agitator. After 3 hours the solution was cooled and 20 g of dimethyl acetamide was added to decrease viscosity of the polymer solution.
Example 4
Preparation of Graft Polymer B
In a reaction vessel, the following were added:
Component Amount (g) PEG-1000 90 N-vinyl pyrrolidone 2.8 Methyl methacrylate 4.0 Methacrylic acid 1.0 Lauryl methacrylate 2.0 Tris 3.1 Benzoyl peroxide 0.04
where Tris is 3-[Tris(trimethylsiloxy)silyl]propyl methacrylate.
The solution was heated at 70° C. for 48 hours. A viscous solution was recovered.
Example 5
Preparation of Graft Polymer C
In a pressure bottle, the following were added:
Component Amount (g) PEG-1000 90 N-vinyl pyrrolidone 1.0 Methyl methacrylate 2.0 Tetrafluoroethyl methacrylate 1.65 Lauryl methacrylate 2.0 Tris 5.0 AIBN 0.024
where Tris is 3-[Tris(trimethylsiloxy)silyl]propyl methacrylate.
The solution was heated at 70° C. for 48 hours in a mechanical convection oven. A viscous solution was recovered which formed into a waxy solid at room temperature.
Example 6
Preparation of Graft Polymer D
In a reaction vessel, the following were added:
Component Amount (g) PEG-1000 90 N-vinyl pyrrolidone 2.8 Methyl methacrylate 1.0 Isobornyl methacrylate 3.0 Methacrylic Acid 1.0 Lauryl methacrylate 2.0 Tris 3.1 Benzoyl peroxide 0.04
where Tris is 3-[Tris(trimethylsiloxy)silyl]propyl methacrylate.
The solution was heated at 70° C. for 48 hours in a mechanical convection oven. A viscous solution was recovered which formed into a waxy solid at room temperature.
Example 7
Preparation of Interfacial Agent a
In a pressure bottle, the following were added:
Component
Amount (g)
Polycaprolactone of Example 1
98
Lauryl methacrylate
15.0
Toluene
30
AIBN
0.03
The solution was heated at 70° C. for 48 hours in a mechanical convection oven. A viscous solution was recovered. Interfacial agent is used in polyurethane reactions where polycaprolactone diols are used in aprotic hydrocarbon solvent systems.
Example 8
Preparation of Interfacial Agent B
In a pressure bottle, the following were added:
Component
Amount (g)
Polycaprolactone of Example 1
98
Styrene
15.0
Toluene
30
AIBN
0.03
The solution was heated at 70° C. for 48 hours in a mechanical convection oven. A viscous solution was recovered. Interfacial agent is used in polyurethane reactions where polycaprolactone diols are used in aprotic hydrocarbon solvent systems.
Example 9
Preparation of Mixed-Phase Biomaterial a
Toluene, 200 g was added to a jacketed reaction vessel equipped with overhead mechanical agitator. Brij S100 strearyl 10 g was added and mixed thoroughly. Once solubilized 26.2 g tetraethylene glycol, 3.3 g butane diol and 131.1 g of polymer graft from Example 3 were added. Methyl diphenyl diisocyanate (MDI) was melted and added to 30 g of toluene. The MDI solution was added to the reactor at room temperature under agitation and mixed until exotherm was exhausted. The solution was then heated to 80° C. for 2 hours until the viscosity reached 25 cps @ 50° C. as measured by a cone & plate Brookfield viscometer. The material was recovered by precipitation into hexane. As shown in FIG. 8 , the material exhibited multiple phase transitions as measured by differential scanning calorimetry.
Example 10
Preparation of Mixed-Phase Biomaterial B
Toluene, 130 g was added to a jacketed reaction vessel equipped with overhead mechanical agitator. Brij S100 strearyl 7.2 g was added and mixed thoroughly. Once solubilized, 2.4 g butane diol and 90 g of polymer graft from Example 5 were added. Methyl diphenyl diisocyanate (MDI) 30 g was melted and was added to the reactor at room temperature under agitation. It was mixed until exotherm was exhausted. The solution was then heated to 90° C. for 2 hours until the viscosity reached 45 cps @ 50° C. as measured by a cone & plate Brookfield viscometer. The material was recovered by precipitation into hexane.
Example 11
Preparation of Methacrylate End-Capped Polycarbonate Diol
In a reaction vessel, hydroxyethyl methacrylate, 1.0 g, dimethyl carbonate, 10 g tetraethylene glycol (TEG), 10 g and 0.1 g potassium carbonate were added and mixed until homogeneous. The solution was heated to 85° C. overnight (16-24 hours) followed by 3-4 hours at 140° C. at which point the polymer was recovered. The preferred molecular weight of the methacrylate end-capped polycarbonate polymer was in the range of 1000 to 5000. Alternately a PEG of 1000 MW may be used instead of TEG to obtain higher MW functionalized diols.
Example 12
Preparation of Polycarbonate Diol
In a reaction vessel, dimethyl carbonate, 10 g tetraethylene glycol (TEG), 10 g and 0.1 g potassium carbonate were added and mixed until homogeneous. The solution was heated to 85° C. overnight (16-24 hours) followed by 3-4 hours at 140° C. at which point the polymeric diol was recovered. The preferred molecular weight of the diol was in the range of 1000 to 5000. Alternately a PEG of 1000 MW may be used instead of TEG to obtain higher MW diols.
Example 13
Polycarbonate/Polyurethane Biomaterial
Toluene, 130 g was added to a jacketed reaction vessel equipped with overhead mechanical agitator. Brij S100 strearyl 7.2 g was added and mixed thoroughly. Once solubilized, 2.4 g butane diol and 90 g of diol from Example 11 were added. Methyl diphenyl diisocyanate (MDI) 30 g was melted and was added to the reactor at room temperature under agitation. It was mixed until exotherm was exhausted. The solution was then heated to 90° C. for 2 hours until the viscosity was above 50 cps @ 50° C. as measured by a cone & plate Brookfield viscometer. The material was recovered by precipitation into hexane.
Although the invention has been described with reference to preferred embodiments thereof, it is understood that various modifications may be made thereto without departing from the full spirit and scope of the invention as defined by the claims which follow. | 1a
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to baseball statistic recording cards and more particularly pertains to a new baseball score card and method for providing a reusable device for keeping records of the events occurring during a baseball game.
2. Description of the Prior Art
The use of baseball statistic recording cards is known in the prior art. More specifically, baseball statistic recording cards heretofore devised and utilized are known to consist basically of familiar, expected and obvious structural configurations, notwithstanding the myriad of designs encompassed by the crowded prior art which have been developed for the fulfillment of countless objectives and requirements.
Known prior art includes U.S. Pat. No. 402,700; U.S. Pat. No. 5,664,780; U.S. Pat. No. 2,145,664; U.S. Pat. No. 1,601,119; U.S. Pat. No. Des. 352,956; and U.S. Pat. No. 5,556,135.
While these devices fulfill their respective, particular objectives and requirements, the aforementioned patents do not disclose a new baseball score card and method. The inventive device includes a planar sheet member having a front face and a rear face. Each face includes sections having indicia arranged for facilitating keeping records of the events occurring during a baseball game. The faces are selectively markable to correspond to play results. In an embodiment, the planar sheet member is laminated to permit wiping away of markings in the sections on each face.
In these respects, the baseball score card and method according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in so doing provides an apparatus primarily developed for the purpose of providing a reusable device for keeping records of the events occurring during a baseball game.
SUMMARY OF THE INVENTION
In view of the foregoing disadvantages inherent in the known types of baseball statistic recording cards now present in the prior art, the present invention provides a new baseball score card and method construction wherein the same can be utilized for providing a reusable device for keeping records of the events occurring during a baseball game.
The general purpose of the present invention, which will be described subsequently in greater detail, is to provide a new baseball score card and method apparatus and method which has many of the advantages of the baseball statistic recording cards mentioned heretofore and many novel features that result in a new baseball score card and method which is not anticipated, rendered obvious, suggested, or even implied by any of the prior art baseball statistic recording cards, either alone or in any combination thereof.
To attain this, the present invention generally comprises a planar sheet member having a front face and a rear face. Each face includes sections having indicia arranged for facilitating keeping records of the events occurring during a baseball game. The faces are selectively markable to correspond to play results. In an embodiment, the planar sheet member is laminated to permit wiping away of markings in the sections on each face.
There has thus been outlined, rather broadly, the more important features of the invention in order that the detailed description thereof that follows may be better understood, and in order that the present contribution to the art may be better appreciated. There are additional features of the invention that will be described hereinafter and which will form the subject matter of the claims appended hereto.
In this respect, before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting.
As such, those skilled in the art will appreciate that the conception, upon which this disclosure is based, may readily be utilized as a basis for the designing of other structures, methods and systems for carrying out the several purposes of the present invention. It is important, therefore, that the claims be regarded as including such equivalent constructions insofar as they do not depart from the spirit and scope of the present invention.
Further, the purpose of the foregoing abstract is to enable the U.S. Patent and Trademark Office and the public generally, and especially the scientists, engineers and practitioners in the art who are not familiar with patent or legal terms or phraseology, to determine quickly from a cursory inspection the nature and essence of the technical disclosure of the application. The abstract is neither intended to define the invention of the application, which is measured by the claims, nor is it intended to be limiting as to the scope of the invention in any way.
It is therefore an object of the present invention to provide a new baseball score card and method apparatus and method which has many of the advantages of the baseball statistic recording cards mentioned heretofore and many novel features that result in a new baseball score card and method which is not anticipated, rendered obvious, suggested, or even implied by any of the prior art baseball statistic recording cards, either alone or in any combination thereof.
It is another object of the present invention to provide a new baseball score card and method that may be easily and efficiently manufactured and marketed.
It is a further object of the present invention to provide a new baseball score card and method that is of a durable and reliable construction.
An even further object of the present invention is to provide a new baseball score card and method which is susceptible of a low cost of manufacture with regard to both materials and labor, and which accordingly is then susceptible of low prices of sale to the consuming public, thereby making such baseball score card and method economically available to the buying public.
Still yet another object of the present invention is to provide a new baseball score card and method which provides in the apparatuses and methods of the prior art some of the advantages thereof, while simultaneously overcoming some of the disadvantages normally associated therewith.
Still another object of the present invention is to provide a new baseball score card and method for providing a reusable device for keeping records of the events occurring during a baseball game.
Yet another object of the present invention is to provide a new baseball score card and method which includes a planar sheet member having a front face and a rear face. Each face includes sections having indicia arranged for facilitating keeping records of the events occurring during a baseball game. The faces are selectively markable to correspond to play results. In an embodiment, the planar sheet member is laminated to permit wiping away of markings in the sections on each face.
Still yet another object of the present invention is to provide a new baseball score card and method that provides a number of preprinted indicia positioned within sections of a sheet, the indicia corresponding to possible play results.
Even still another object of the present invention is to provide a new baseball score card and method that permits temporary marking of a sheet to correspond to highly individualized results while simultaneously providing an organized neat set of indicia for marking corresponding to more common play results in the sport of baseball.
These together with other objects of the invention, along with the various features of novelty which characterize the invention, are pointed out with particularity in the claims annexed to and forming a part of this disclosure. For a better understanding of the invention, its operating advantages and the specific objects attained by its uses, reference should be made to the accompanying drawings and descriptive matter in which there are illustrated preferred embodiments of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be better understood and objects other than those set forth above will become apparent when consideration is given to the following detailed description thereof. Such description makes reference to the annexed drawings wherein:
FIG. 1 is a front view of a new baseball score card and method according to the present invention.
FIG. 2 is a rear view of the present invention.
FIG. 3 is an enlarged view of the area designated as 3 in FIG. 1 .
FIG. 4 is a side view of a marker of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
With reference now to the drawings, and in particular to FIGS. 1 through 4 thereof, a new baseball score card and method embodying the principles and concepts of the present invention and generally designated by the reference numeral 10 will be described.
As best illustrated in FIGS. 1 through 4, the baseball score card and method 10 generally comprises a sheet member 12 having a front face 14 and a rear face 16 , and a marker 13 having a fine point 19 for marking on the sheet member. The front face and the rear face each includes a top section 20 , medial section 22 and a lower section 24 .
In an embodiment of the invention, the sheet member has a smooth surface for facilitating marking on the sheet member with either an erasable or dry erase type marker. Also in an embodiment of the invention, the sheet member is constructed of plastic or is laminated.
The top section of the front face and the rear face each include a respective one of a home team line indicia 25 and an away team line indicia 26 , each line indicia being designed for facilitating legible marking of a home or away team name above the respective team line indicia.
The top section of the front face and the rear face each include a respective date line indicia 27 designed for facilitating marking of a date of game played above the respective date line indicia.
The medial portion of the front face and the rear face each includes a single lineup column 30 of lineup spaces 31 aligned proximate respective sides 32 and 33 of the sheet member. Each of the lineup spaces is designed for marking a player indicator such as a name or number within the lineup space.
The medial portion of the front face and the rear face each further includes a plurality of result columns 39 positioned adjacent to the lineup column. Each activity column includes a plurality of activity spaces 34 . The result columns are positioned to form a plurality of activity space rows 35 aligned with a respective one of the lineup spaces.
Each activity space includes a first region 36 adjacent to a first side 37 of the activity space. Each first region also includes a list of result indicia 38 positioned within the first region.
Each activity space further has a second region 40 having a diamond indicia 41 positioned within the second region. Each diamond indicia includes a lowermost point 42 positioned along a lower edge 43 of the activity space. Each diamond indicia also includes an uppermost point 44 positioned within an interior portion 45 of the second region of the activity space.
In an embodiment, the plurality of activity columns comprises nine columns, each column corresponding to one inning of a nine inning baseball game. Greater or fewer numbers of columns may be provided to correspond to the appropriate number of innings for a level of play or to provide additional columns for extra innings.
The top sections of the front face and the rear face each includes a positional indicator 50 . Each positional indicator has position indicia 51 in the general shape of a playing surface of a baseball diamond including a generally arcuate outfield representational portion 52 . The position indicia are numbered such that each number corresponds to a baseball player position. Typically, 1 indicates the pitcher, 2 indicates the catcher, 3 indicates the first baseman, 4 indicates the second baseman, 5 indicates the third baseman, 6 indicates the shortstop, 7 indicates the left fielder, 8 indicates the center fielder, and 9 indicates the right fielder.
In an embodiment, the front face and the rear face also each including a key portion 55 positioned between the top section and the medial section. The key portion has a plurality of alphanumeric indicators 56 , each alphanumeric indicator being associated with a corresponding play result. Typically, 1 B indicates a single, HR indicates a home run, 2 B indicates a double, 3 B indicates a triple, BB indicates a walk or base on balls, HP indicates a hit batsmen, K indicates a strike out, F indicates a fly ball, G indicates either a ground ball or a ground out, and E indicates an error.
The lower section of the front and rear faces each includes a plurality of run columns 61 . Each run column is divided into an upper and a lower division 62 and 63 . Each division is for recording a number of runs scored by a respective team associated with each respective division 62 or 63 .
In use, the marker 13 is used to record a lineup of players into the lineup column by recording one respective player name in each lineup space. Each player's results are then recorded in an activity space aligned with the player's lineup space and a column of activity spaces corresponding to the inning in the baseball game in which the result occurred. For clarity the results are recorded using one of the result indicia within the first region or marking a corresponding alphanumeric indicator from the key portion within the second region.
Runs per inning are recorded in the run column corresponding to the inning of the baseball game in which the runs were scored.
As to a further discussion of the manner of usage and operation of the present invention, the same should be apparent from the above description. Accordingly, no further discussion relating to the manner of usage and operation will be provided.
With respect to the above description then, it is to be realized that the optimum dimensional relationships for the parts of the invention, to include variations in size, materials, shape, form, function and manner of operation, assembly and use, are deemed readily apparent and obvious to one skilled in the art, and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present invention.
Therefore, the foregoing is considered as illustrative only of the principles of the invention. Further, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention. | 1a
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CROSS REFERENCE TO RELATED APPLICATION
This application is a Continuation-in-Part of copending application Ser. No. 849,950 filed Apr. 8, 1986, now U.S. Pat. No. 4,781,175 and entitled Electrosurgical Conductive Gas Stream Technique of Achieving Improved Eschar for Coagulation which is of common ownership with the present application, the disclosure of which is hereby incorporated by reference.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to electrosurgery, and more particularly to a new and improved electrosurgical technique for achieving coagulation or a hemostatic effect, i.e. fulguration and desiccation, by conducting radio frequency (RF) electrical energy through a conductive inert gas stream to the tissue. In addition, the present invention relates to an electrosurgical fulguration arcing technique of creating an eschar and tissue effects offering a substantially improved capability for coagulation. Further still, the present invention relates to an electrosurgical non-arcing desiccation technique and equipment for applying electrical energy to tissue to achieve superior thermal desiccative effects.
2. Description of the Prior Art
Electrosurgery involves the application of radio frequency electrical energy to tissue. The electrical energy originates from an electrosurgical generator (ESG) and is applied by an active electrode to the tissue. The active electrode typically has a small cross-sectional or limited surface area to concentrate the electrical energy at the surgical site. An inactive return electrode or patient plate contacts the patient at a remote location from the surgical site to complete the circuit through the tissue to the ESG. The patient plate is relatively large in size to avoid destructive energy concentrations. Alternatively, a pair of active electrodes may be used in a "bipolar" mode in which the electrosurgical energy flows directly through the tissue between the two active electrodes, and the electrosurgical effects are confined to the tissue directly located between the two closely-spaced electrodes.
A variety of different electrosurgical effects can be achieved, depending primarily on the characteristics of the electrical energy delivered from the ESG. Among the effects are a pure cutting effect, a combined cutting and hemostasis effect, a fulguration effect and a desiccation effect. Desiccation and fulguration are usually described collectively as coagulation. Many conventional ESG's offer the capability to selectively change the energy delivery characteristics and thus change the electrosurgical effects created.
Satisfactory fulguration effects have been particularly difficult to obtain. Some surgeons have preferred to use older spark gap generators known as "Bovie" devices for fulguration, but use other more modern ESG's for cutting or cutting with hemostasis. Indeed, spark gap ESG's have been the standard against which modern solid state ESG's have been measured for achievement of satisfactory fulguration effects. One modern ESG which achieves substantially improved fulguration effects, compared to both spark gap and previous solid state ESG's is described in U.S. Pat. No. 4,429,694, assigned to the assignee hereof. Despite the improvements available in fulguration, certain disadvantages remain for which there have been no satisfactory alternatives.
Conventional fulguration is characterized by electrical arcing through the air from various locations on the metal surface of the active electrode, with the arcs contacting the tissue in somewhat of a random non-predictable manner. In many cases, arcs leave the active electrode in an initial trajectory traveling away from the tissue before actually curving around and striking the tissue surface. The result is an uneven, randomly concentrated or distributed delivery of arcing energy. An uneven eschar of variable characteristics is created on the surface of the tissue.
The random delivery of the arc energy creates holes which are significantly disparate in diameter (or cross-sectional size) and in depth. Larger, deeper holes are formed by repeated arcs contacting the tissue at approximately the same location. Smaller arc holes are also present in the tissue but they are unevenly distributed about the larger arc holes. The smaller arc holes are created by single individual arcs, or the less repetitious arcing to the tissue at the same location. The smaller arc holes are relatively small in diameter or cross-section and relatively shallow in depth, compared to the larger arc holes. Significant variations in cross-sectional size and depth between the large and small arc holes occur. Significant variations exist in the spacing and in the amounts of tissue between the large and small arc holes, causing the substantial variations in the surface distribution of the holes.
Thermal necrosis occurs in the tissue between the arc holes. The degree of thermal necrosis varies between total carbonization between the more closely spaced larger holes, to necrosis without charring or carbonization between the more widely separated smaller arc holes.
The eschar created has two distinct layers above the unaffected viable tissue. An arc hole reticulum of the tissue subjected to necrosis is created by the pattern of arc holes. The arc hole reticulum extends to greater depths in the areas of the deeper arc holes, and to substantially shallower depths in the areas of the shallower arc holes. Due to the random distribution and depth of the arc holes, the arc hole reticulum is relatively uneven in depth. Significant variations in the depth of the arc hole reticulum layer are typical. A layer of thermally desiccated tissue is located below the arc hole reticulum layer. Tissue necrosis in the thermally desiccated layer occurs as a result of the current heating effects of the electrical energy dissipating from the arcs. The desiccation layer is also uneven in depth and location due to the nonuniform application of the arcing energy over the arc hole reticulum layer. Significant variations in the depths of the desiccation layer are also typical.
Over a given area of tissue, certain locations are only moderately affected by the arcing energy. A thin arc hole reticulum and a thin desiccation layer result. Other areas have a relatively thick eschar formed therein. Very thick carbonized eschars tend to be fragile and are prone to crack when flexed, usually resulting in renewed bleeding from the unaffected tissue below the desiccation layer. Thin eschars are more flexibile and therefore more desirable, but it has been difficult to obtain sufficient coagulation effects from thin eschars.
Causes of the uneven eschar created by prior fulguration techniques are not known with certainty, but numerous factors are theorized to play a role. One of the more significant contributory factors is probably changes in impedance in the arc pathway between the active electrode and the tissue. Impedance changes may result from variations in the distance which the arcs travel through the air, due to the changes in ionization potential between the active electrode and the tissue. It is virtually impossible for the surgeon to maintain the active electrode at a consistent distance from the tissue, particularly if the tissue is moving due to pulsation, or due to puckering and swelling as a result of applying the electrical energy. The arcing from random locations on the active electrode also creates different arc length pathways and hence impedances. The combined impedance of the tissue and the eschar changes with the application of electrical energy. The volatilization of the cells and vaporization of the moisture in the cells changes the relative impedance in a localized spot-to-spot manner on the surface of the tissue. The formation of the charred material also influences the arc pathways, presenting an opportunity for subsequent arcs to return to the tissue at the same location and thereby enlarge the pre-existing arc hole and create even further charring.
Another problem with conventional electrosurgery is that it is very difficult if not impossible to achieve effective fulguration on spongy or vascular tissue such as the liver or the spleen, or on other tissues from which there is a tendency for blood to continually ooze over the surface from the highly developed vascular network within the tissue. Often, only the surface of the oozing blood is coagulated, with no penetration to the surface of the tissue below the layer of blood. A superficial coagulum results on the surface of the blood, but this coagulum quickly sloughs away resulting in only temporary hemostasis. Of course, once the temporary coagulum sloughs away, bleeding continues. Even if a coagulation effect on the tissue surface can be established, it is easily destroyed or perforated by the arcs returning to the same locations causing the longer, deeper arc holes. The deeper arc holes perforate the eschar and extend into the viable tissue below the eschar to provide a pathway for continued bleeding. The heat created by the arcs causes boiling of moisture below the eschar, and the pressure of resulting vapor can also rupture the eschar to reinitiate bleeding.
Apart from the tissue disadvantages of conventional electrosurgical fulguration, certain other practical problems exist. Arcing from the active electrode rapidly increases the temperature of the active electrode. Electrode heating is responsible for a number of problems. If the heated active electrode contacts the tissue, as it inevitably will, or if the active electrode is immersed in fluid such as blood, proteins from the tissue or the blood are denatured and stick to the active surface of the electrode. The buildup of charred material on the electrode eventually creates a sufficiently high impedance so that adequate power can no longer be delivered. The surgeon must continually clean the electrode by wiping or scraping the charred material, which disrupts, distracts, and prolongs the surgical operation. Freshly created eschars can be detached in an effort to free a sticking electrode from the tissue surface. The random accumulation of charred material on the active electrode creates more random delivery of the arcing energy, even further increasing the random delivery pattern. Because of the variable nature of the impedance of the charred material, consistent power application is difficult or impossible. The accumulation of the charred material can obscure the surgeons view of the surgical site. The temperature of the active electrode may reach sufficiently elevated levels to transfer molten metal from the electrode to the patient, creating questionable effects. Because the electrode contacts the tissue, there is a potential for cross-contamination between viable tissues and diseased tissues. Although the clinical problems associated with cross contamination are not fully understood at the present time, the advantages of eliminating the possibility are evident. A significant smoke plume also results from the burning tissue because of the air environment in which the electrosurgery occurs. Not only does the plume produce a noxious odor, but there may be some evidence that particulates in the smoke plume from burning tissue may contain hazardous chemicals, virus, bacteria, neoplastic cells and other hazards. Of course, the oxygen environment in which the electrosurgery is conventionally conducted exhibits a potential for igniting paper drapes, surgical sponges and the like.
Some of the typical problems associated with creating and applying the arcs in conventional electrosurgery can be improved by optimizing the operating and other characteristics of the electrosurgical generator. U.S. Pat. No. 4,429,694 discloses an improved ESG which reduces some of the described disadvantages during fulguration. However, many of the disadvantages cannot be avoided and many of the characteristics cannot be improved by conventional electrosurgical techniques and equipment, due to the limitations previously inherent in electrosurgery.
The conventional technique of obtaining thermal desiccation by use of a conventional ESG is to apply electrical energy from a flat surface of the active electrode placed in contact with the tissue. An electrical resistance heating effect is created by the current flowing into the tissue from the active electrode. Because the active electrode contacts the tissue surface over a relatively large area, no arcing is intended to occur. To spread the thermal desiccation effect over a substantially large area, the active electrode is moved from location to location. It is very difficult to apply a level of energy which will obtain thermal desiccation but which will not cause the tissue to stick on the flat surface of the active electrode or arcing from the active electrode to non-contacted surface areas. The thermal desiccation effects are unevenly distributed because the active electrode is moved from spot to spot. Overlapping the spots of energy application can enhance the probability for tissue sticking and exaggerate the variable depth effects. Of course, moving the active electrode from spot to spot is very time consuming in an operation where time is very important or critical.
The prior art desiccation technique can only be applied to create surface desiccation effects. Furthermore, the inability to accurately control the amount of power, tissue sticking effects, and the like have prevented the prior use of electrosurgery on very thin fragile tissue such as the mesentary, and in other surgical techniques.
It is against this abbreviated background of previously existing disadvantages and problems in electrosurgery that the advantages and improvements of the present invention can be better appreciated.
SUMMARY OF THE INVENTION
In general, the electrosurgical technique and equipment for achieving coagulation in accordance with the present invention involves conducting a predetermined ionizable gas in a directed or generally laminar jet stream to the tissue at a predetermined flow rate sufficient to clear natural fluids from the tissue and to substantially expose the underlying tissue, while simultaneously conducting electrical energy at a predetermined primary radio frequency range in the gas jet stream through ionized conductive pathways. To achieve fulguration, the electrical energy is conducted as arcs in the ionized pathways. To achieve desiccation, the electrical energy is conducted in the ionized pathways as a non-arcing diffuse current.
The electrosurgical equipment of the present invention includes a nozzle which is removably mounted on a handle in a unique manner so as to be reliably sealed thereto to prevent the leakage of gas. The nozzle also supports an electrode along a small portion of its length so that a substantial portion of the electrode is exposed to the gas in a mixing chamber portion of the nozzle to improve initiation of the ionization of the gas.
The hose which supports the nozzle and the handle at a leading or free end thereof has its opposite end connected to a gas delivery apparatus by a connector element which also establishes a positive seal through a removable connection technique. The connector element is rotatably connected to the gas delivery apparatus in a manner so as to prevent the leakage of gas while permitting rotation of the hose to prevent kinks from forming in the hose as the surgeon is manipulating the handle and nozzle.
Many other significant features are inherent in the present invention, as well as many improvements over prior art coagulation techniques and equipment. These various features and improvements are discussed more completely in the following detailed description of the preferred embodiment taken in conjunction with the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective representation of a nozzle, hand piece, cord and connector of the present invention.
FIG. 2 is an enlarged exploded perspective view of the nozzle and the mating end of the hand piece illustrated in FIG. 1.
FIG. 3 is a fragmentary enlarged perspective view of the connector end of the cord illustrated in FIG. 1.
FIG. 4 is an enlarged section view of the cord taken along line 4--4 of FIG. 1.
FIG. 5 is an enlarged section view of the nozzle and front end of the hand piece taken along line 5--5 of FIG. 1 with parts removed to condense the size.
FIG. 6 is an enlarged section view taken along line 6--6 of FIG. 5.
FIG. 7 is an enlarged section view taken along line 7--7 of FIG. 5.
FIG. 8 is an enlarged section view taken along line 8--8 of FIG. 5.
FIG. 9 is an enlarged section view of the connector taken along line 9--9 of FIG. 1.
FIG. 10 is a section view taken along line 10--10 of FIG. 9.
FIG. 11 is a section view taken along line 11--11 of FIG. 9.
FIG. 12 is a section view taken along line 12--12 of FIG. 9.
FIG. 13 is a generalized schematic view of an electrosurgical unit (ESU) embodying the present invention, illustrating an electrosurgical generator (ESG), a gas delivery apparatus, a segment of tissue shown illustratively in cross-section, and the elements of the invention shown in FIG. 1.
DESCRIPTION OF THE PREFERRED EMBODIMENT
An electrosurgical unit (ESU) which embodies the present invention is shown generally in FIG. 13 and is referenced 40. The ESU 40 includes three major components, a pencil 42 which is manipulated by the surgeon, gas delivery apparatus 44 and an electrosurgical generator (ESG) 46. A flexible cord 48 connects the gas delivery apparatus 44 and the ESG 46 to the pencil 42. The gas delivery apparatus 44 delivers a preselected gas through a plurality of individual hose passageways or lumens 50 in the cord 48 to the pencil 42. The gas issues from a nozzle 52 of the pencil 42 in a directed or substantially laminar flow stream or jet 54.
The ESG 46 supplies electrical energy over a supply conductor 56 of the cord 48 to the pencil 42. The conductor 56 is electrically connected in the pencil to a needle-like electrode 58 which forms a part of the nozzle 52. The electrical energy supplied by the ESG 46 is of predetermined characteristic sufficient to ionize the gas flowing through the nozzle 52 and to create ionized pathways in the jet 54. The electrical energy travels in the ionized pathways in the jet 54 to a body tissue 62 where it creates a predetermined electrosurgical effect on the tissue 62.
In the fulguration mode of operation of the ESU, electrical energy is transferred in the ionized pathways in the form of arcs 60. The arcs 60 travel within the jet 54 until they reach the tissue 62 at the electrical surgical site. The jet 54 expands slightly above the surface of the tissue 62 and the arcs 60 disburse over a slightly enlarged area of the tissue surface compared to the cross-section of the jet 54. Electrical energy of the arcs is transferred into the tissue 62 and creates the upper arc hole reticulum or layer 30 and a desiccated layer 32 therebelow. The arc hole reticulum 30 and the desiccated layer are schematically illustrated in FIG. 13.
In the desiccation mode of operation of the ESU, the ionized pathways in the jet 54 transfer electrical energy from the electrode 58 as a non-arcing, conductive current. A gentle coupling effect is created at the tissue which does not cause holes in the tissue, because arcs are not present. As is described more completely in the parent application, Ser. No. 849,950, a desiccative electrosurgical effect is created, and only a desiccation layer similar to that schematically shown at 32 in FIG. 13 is formed on the surface of the tissue. The normal unaffected tissue structure such as that at 34 exists below the surface desiccated layer 32. The jet expands slightly at the surface of the tissue to couple the nonarcing electrical current over a slightly enlarged area of the tissue surface compared to the cross-sectional size of the jet. This type of desiccative coagulation electrosurgical effect has heretofore not been obtainable in the field of electrosurgery except through the apparatus disclosed in the parent application hereto. The desiccative effects on the tissue offer the possibility of accomplishing substantially new and different types of electrosurgical procedures by use of an ESU.
The electrical energy delivered through the jet 54 travels through the tissue 62 to a return electrode or patient plate 70 which contacts the tissue 62. The patient plate 70 is connected by a return electrical conductor 72 to the ESG 46. A complete electrical circuit is thus established for conducting the energy from the ESG 46, to the pencil 42, through the jet 54, to and through the tissue 62, to patient plate 70, through the return conductor 72 to the ESG 46.
The pencil 42 includes a handle portion 76 and the nozzle 52 with the nozzle being threadedly connected to the handle for easy removal therefrom. As is best illustrated in FIGS. 2 and 5-8, the handle portion 76 of the pencil includes a generally cylindrical dielectric body 78 which may be ceramic. The cylindrical body 78 has a central axial passageway 80 therethrough which is relatively narrower at a leading end than at a trailing end as created by a relatively thick wall 82 at its leading end. The open leading end of the handle has internal threads 84 which form exemplary means for releasably and connecting receiving the nozzle 52 as will be described in more detail hereinafter.
A socket insert 86 is disposed internally of the handle portion 76 at the forwardmost extent of the large diameter portion 80L of the passageway through the handle. The socket insert 86, as is best illustrated in FIGS. 5 and 8, is also of cylindrical configuration having an outer diameter substantially the same as the inner diameter of the handle 76 at the location where the insert is positioned within the handle. At the trailing end of the socket insert 86, a disc-like wall 88 is formed having a plurality of circumferentially spaced openings 90 therethrough adapted to align with the passageways or lumens 50 through the hose 48. The wall 88 also has a central opening 92 therethrough adapted to accommodate the conductor 56 which passes through the hose and takes the form of a braided metal wire. A forwardly projecting internal cylindrical sleeve 94 projects forwardly from the disc-like wall 88 and confines and supports an electrical connector means such as a metallic socket 96 adapted to receive the electrode 58 of the nozzle as will be discussed later. The metallic socket 96 also includes a receptacle for receiving and retaining the leading end of the braided metal wire 56 which projects thereinto from the leading end of the hose 48.
The leading end of the hose 48 is also received in the enlarged diameter trailing portion 80L of the passageway 80 through the handle portion 76 and abuts the trailing end of the socket insert 86. The hose is aligned with the socket insert so that the passageways 50 through the hose are in alignment with the openings 90 through the disc-like wall 88 of the insert whereby gas can pass freely from the hose through the insert 86 and subsequently through the nozzle. The hose is retained in its fixed relationship with the handle portion by an outer covering 98 which encompasses the handle portion 76 and overlaps a portion of the hose where the hose enters the trailing end of the handle portion. The covering 98 is of a soft pliable material such as silicone and also overlaps the leading end of the handle portion leaving the opening through the leading end of the handle portion unobstructed. It is important to note, however, that a portion of the covering does overlap the leading end of the handle forming a boot 100 which facilitates the establishment of a hermetic seal between the nozzle and the handle.
The nozzle 52 includes inner and outer dielectric component parts 51 and 53 with the electrode 58 being supported axially within the inner part. As mentioned previously, the nozzle is adapted to be releasably connected to the handle 76 to define the pencil 42. The inner part 51 of the nozzle has a forwardly projecting cylindrical-body 102, an integral intermediate enlarged cylindrical body 104 at the trailing end of the forwardly projecting cylindrical body 102, and an integral trailing cylindrical body 106 protruding rearwardly from the intermediate body. The intermediate body 104 at its trailing end has a plurality of inwardly directed ribs 108 which support the trailing body 106. The ribs 108 define passageways 110 therebetween through which gas is enabled to pass from the hose 48 through the socket insert 86 in the handle portion and subsequently through the passageways 110 for exposure to the electrode 58 within a nozzle passageway or mixing chamber 112 defined by the cylindrical inner spaces of the forward and intermediate bodys 102 and 104 respectively of the inner part 51. The trailing body 106 of the inner part has a cylindrical passage 114 therethrough adapted to mate with and receive the electrode 58 which is made of a conductive metal material and secured in the trailing body 106 in any suitable manner. The electrode 58 protrudes rearwardly from the trailing body of the inner part 51 so as to be receivable in the metal socket provided in the socket insert 86 of the handle portion. It is important to note that the trailing body of the inner part supports the electrode 58 along a small or minority portion of its length, and as such and in conjunction with the ribs are one example of support means for supporting the electrode. In a preferred embodiment, the support for the electrode extends only along a relatively short length of the electrode, for example, less than 20% of its length, exposing a significant portion of the electrode to the mixing chamber 112 and thus the gases flowing therethrough to improve initiation of the ionization of the gas. It has been determined that the initiation of the ionization process is facilitated by a greater exposure of the electrode to the gas jet stream 54 and for this reason, this feature of the invention is of significant value.
The outer part 53 of the nozzle 52 includes an enlarged frusto-conical head 116 and a trailing reduced diameter cylindrical portion 118 having external threads 120 adapted to mate with and be received in the internal threads 84 at the leading end of the handle portion. The outer part of the nozzle is affixed to and is unitary with the inner part 51 of the nozzle so that as the outer part is threaded into the leading end of the handle portion, the trailing end of the electrode 58 is inserted into the metallic socket in the handle portion in a positive manner. Also, it is important to note that the frusto-conical head 116 has a trailing circular radially disposed surface 122 which abuts with the boot 100 or overlapping portion of the handle cover to positively establish a hermetic seal between the nozzle and the handle portion. This seal is of critical importance in preventing the escape of gas and the possible transmittal of electrical energy to the surgeon's hand.
The opposite or trailing end of the hose 48 is connected to the gas delivery apparatus 44 and the ESG 46 through a connector 124. The connector is best illustrated in FIGS. 3 and 9-12 as including a female mating portion of member 126 which is directly fastenable to the gas delivery apparatus and ESG to receive gas and electrical energy therefrom and a male mating portion of member 128 secured in a unitary fashion to the trailing end of the hose. An intermediate sleeve member 130 is also provided which permits the hose to be positively secured to the female member 126 in a rotative relationship so that the hose will not form kinks as the pencil 42 is manipulated by a surgeon.
The female member 126 of the connector is probably best seen in FIG. 9 and is formed from a block of dielectric material such as plastic which is secured to the gas delivery apparatus 44 and ESG 46 such that a hollow interior passageway 132 through the female member can be aligned with a gas delivery opening 134 in the gas delivery apparatus and an electrical connector or contact means such as a metallic socket 136 which is in electrical communication with the ESG through a conductor 138. The female member is screwed or otherwise operatively secured to the gas delivery apparatus and ESG in a positive manner (not shown).
The female member 126 includes an outer cylindrical opening 140 adapted to receive the trailing end of the hose 48 with the opening 140 having internal threads 142 formed therein. A rear wall 144 of the female member supports a forwardly projecting central cylindrical hub 146 which extends into the cylindrical opening 140 in the female member for approximately a third of its length. The cylindrical hub 146 has a cylindrical wall 148 and a plurality of radial inwardly directed ribs 150 defining therebetween a central axial passage 152 for receiving an a connecting electrode 154 on the trailing end of the hose. The metallic socket 136 in the gas delivery apparatus and ESG protrudes forwardly into the central axial passage 152 in a position to receive the electrode 154 in a manner to be described hereinafter. The forward edge of the cylindrical hub has a tapered surface 156 which is frusto-conical and rearwardly convergent and is continuous with the forward edges of the ribs at the locations where the ribs 150 are contiguous with the tapered surface 156. This frusto-conically tapered surface is adapted to cooperate with the trailing end of the hose in establishing a rotating hermetic seal as will become more clear later.
The male member 128 of the connector 124 includes a body made of a moderately resilient material such as rubber and an internal supporting insert 158 that is received within the body. The body has an enlarged head 160 defined by two axially aligned frusto-conical surfaces 162 and 164 and a cylindrical extension portion 166 protruding forwardly away therefrom and adapted to receive the trailing end of the hose. The extension portion 166 has an internal cylindrical passageway 168 into which the hose 48 is inserted and retained in any suitable manner. The insert 158 is of generally cylindrical configuration having a protruding radial rib 170 around its trailing end which is adapted to be received within an annular recess 172 formed internally of the head 160. The seating of the radial rib 170 in the recess 172 retains the insert in a positive relationship with the male member. The insert has a plurality of openings 174 therethrough which are aligned with the passageways or lumens 50 through the hose so that gas can pass readily from the gas delivery apparatus 44 to the hose. The insert further includes an internal cylindrical sleeve 176 defining a cylindrical recess 178 in which the electrode 154 can be inserted and retained in any suitable manner. The electrode has a recess 180 defined in its leading end which is adapted to receive the end of the braided metal wire 56 that passes through the hose to establish an electrical connecting means and relationship between the braided metal wire and the electrode.
The enlarged head 160 includes a solid interior wall 181 having circular openings 183 therethrough in alignment with the openings 174 through the insert 158. The wall 181 is integral with and supports a rearwardly projecting cylindrical sleeve 182 through a plurality of ribs 184 shown best in FIGS. 9 and 11. The sleeve 182 has an internal passageway 185 therethrough which receives the electrode 154 in a manner such that the electrode protrudes a short distance from the rearward end of the sleeve. The male and female members 128 and 126 respectively of the connector are dimensioned such that the rearwardmost frusto-conical surface 164 on the head 160, which defines a generally circular trailing edge 186 of the head and a rearwardly opening frusto-conical recess 187, engages the cylindrical hub 146 of the female member when the electrode 154 is positively seated in the metal socket 136. The circular opening 183 and the recess 187 form a center opening for passing gas into the hose 48. The cylindrical hub of the female member engages the frusto-conical surface 164 at a circular edge or annular manner so as to establish a hermetic seal therewith and to allow the male member to rotate relative to the female member while maintaining that seal.
The male member 128 is positively retained in the female member 126 by the intermediate sleeve 130 which is of generally cylindrical configuration having a larger diameter trailing end 188 and a smaller diameter leading end 190. The smaller diameter leading end 190 is rotably disposed about the cylindrical extension portion 166 of the male element and defines a radial abutment shoulder 192 against which is disposed a washer member 194 preferably made of a fluoroplastic or other low friction material. The washer 194 fills a space between the radial abutment shoulder 192 on the intermediate sleeve and a radial shoulder 196 at the leading end of the enlarged head 160 of the male element so as to provide a low friction bearing surface between the intermediate sleeve and the male member. The large cylindrical end 188 of the intermediate sleeve has external threads 198 formed therein adapted to be received in the internal threads 142 of the female member and the portion of the sleeve rearwardly of the threads projects forwardly into a cylindrical socket 200 defined within the female member. The trailing end of the sleeve is adapted to abut the rear wall 144 of the female member when the sleeve 130 is fully threaded thereinto and at this same relative positioning of the intermediate sleeve with the female member, it will be appreciated that the male member is positively positioned relative to the female member as illustrated in FIG. 9 to establish the rotating seal between the male member and the female member along the frusto-conical surfaces 164 and 156. Also, the electrode 154 is positively positioned in the socket 136 of the gas delivery and ESG apparatus such that electricity is dependably transferred along the rear electrode 154 and the braided metal wire to the electrode 58 in the nozzle 52 as desired. Further, a clear passageway is established for the gas which emanates from the gas delivery apparatus and passes first through the female connector member and subsequently the male connector member and the hose for delivery to the nozzle.
It is important to note that the male member is easily connected to the female member through the threaded relationship of the female member with the intermediate sleeve 130 and that this connection permits full rotation of the hose relative to the female member while maintaining a hermetic seal to prevent the leakage of gas.
The electrosurgical unit 40 herein described is used in accordance with the technique fully described in the aforenoted parent application which has been incorporated herein by reference and accordingly a description of that technique is not repeated.
Although the present invention has been described with a certain degree of particularity, it is understood that the present disclosure has been made by way of example, and changes in detail or structure may be made without departing from the spirit of the invention, as defined in the appended claims. | 1a
|
BACKGROUND OF THE INVENTION
[0001] Egg albumen, or egg whites, are a known food ingredient in a number of foodstuffs, particularly baked foodstuffs, for example angel food cakes. Due to the expense of egg whites, extenders or replacements for egg whites have been developed.
[0002] U.S. Pat. No. 4,238,519 (Chang) discloses an egg albumen extender comprised of a protein-containing composition having certain characteristics and other ingredients, including gums such as xanthan, but preferably carrageenan. Xanthan gum, along with water and wheat starch is suggested as a partial replacement for egg whites in angel food cakes by L. L. Miller, et al., “Xanthan Gum in a Reduced Egg White Angel Food Cake”, Cereal Chemistry, 60(1): 62-64 (1983).
SUMMARY OF THE INVENTION
[0003] In one aspect, this invention relates to a composition useful as an extender for egg whites in a baked foodstuff comprising a major amount of a potato starch and a minor amount of granular xanthan gum, said granular xanthan gum having a mean particle size greater than 40 micrometers. In a related embodiment, the composition is further comprised of a minor amount of a dextrin, preferably a white dextrin.
[0004] In another aspect, this invention relates to a method of replacing egg whites in a baked foodstuff comprising adding water, a major amount of a potato starch and a minor amount of granular xanthan gum, said granular xanthan gum having a mean particle size greater than 40 micrometers (and preferably a minor amount of a dextrin), to replace a portion of the egg whites in a baked foodstuff.
[0005] In another aspect, this invention relates to a baked foodstuff comprised of egg whites, wherein at least a portion of the egg whites are replaced with a major amount of a potato starch and a minor amount of granular xanthan gum, said granular xanthan gum having a mean particle size greater than 40 micrometers (and preferably a minor amount of a dextrin).
[0006] It has been found that if xanthan gum of a relatively coarse grind is used as a partial replacement for egg whites to prepare a baked foodstuff, such as an angel food cake, then improved properties of the baked foodstuffs are obtained as compared to the use of xanthan gum of a relatively fine grind.
DETAILED DESCRIPTION
[0007] Potato starch is starch extracted from potatoes. The cells of the root tubers of the potato plant contain starch grains (leucoplasts). In a typical process to extract the starch, the potatoes are macerated or crushed and the starch grains are released from the destroyed cells. The starch is then washed out, collected, and dried to powder. The potato starch is preferably used in its native state, i.e. as isolated from the cells of the potato and after washing and drying. The potato starch may also be starch recovered from aqueous process streams that are the by-product of the processing of potatoes. The starch may be minimally modified prior to use, e.g. physically, thermally or chemically, if desired, but is preferably used in its native state.
[0008] Xanthan gum is an extracellular polysaccharide secreted by the micro-organism Xanthomonas campestris . Xanthan gum is soluble in cold water and solutions exhibit highly pseudoplastic flow. The bacterium Xanthomonas campestris produces the polysaccharide at the cell wall surface during its normal life cycle by a complex enzymatic process. Commercially, xanthan gum is typically produced from a pure culture of the bacterium by an aerobic, submerged fermentation process. The bacteria are cultured in a well-aerated medium containing glucose, a nitrogen source and various trace elements. To provide seed for the final fermentation stage, the process of inoculum build-up is carried out in several stages. When the final fermentation has finished the broth is pasteurized to kill the bacteria and the xanthan gum is recovered by precipitation with isopropyl alcohol. Finally, the isolated product is dried to a crude form and the crude form is then milled to form granules. The particle size of the crude xanthan gum can be reduced using milling machines such as the ball mill, vertical roller mill, hammer mill, roller press or high compression roller mill, vibration mill, or jet mill, among others. The particle size of the granules of milled xanthan gum can be adjusted by conventional dry sieving with appropriately sized sieves.
[0009] The particle size of the granular xanthan gum is determined by particle analysis using laser diffraction. Laser diffraction analysis depends upon analysis of the “halo” of diffracted light produced when a laser beam passes through a dispersion of particles in air or in a liquid and is based on the Fraunhofer diffraction theory, stating that the intensity of light scattered by a particle is directly proportional to the particle size. The angle of the laser beam and particle size have an inversely proportional relationship, where the laser beam angle increases as particle size decreases and vice versa. A useful particle size analyzer is the LS Particle Size Analyzer, LS 13 320, available from Beckman Coulter, Inc., 250 South Kraemer Boulevard, Brea, Calif. The mean particle size obtained by the use of this apparatus is volume based.
[0010] The mean particle size of the granular xanthan gum, as measured by laser diffraction, will be greater than 40 micrometers. Typically, the mean particle size is greater than about 45 micrometers, more typically greater than about 50 micrometers, and even more typically greater than about 60 micrometers. Preferably, the mean particle size is greater than 70 micrometers or about 80 micrometers, more preferably greater than about 90 micrometers, and even more preferably greater than about 100 micrometers. Even more preferred granular xanthan gums have a mean particle size of greater than about 110 micrometers, and even more preferably greater than about 115 micrometers. The mean particle size will typically range from about 100 micrometers to about 200 micrometers, more typically from about 110 micrometers to about 150 micrometers and even more typically from about 115 micrometers to about 125 micrometers.
[0011] The granular xanthan gum will typically have a narrow particle size distribution. Typically, the ratio of the mean particle size to median particle size will be less than about 1.5:1, more typically less than about 1.2:1, an even more typically less than about 1.1:1. Preferably, the ratio of the mean particle size to median particle size will be less than about 1.05:1. The granular xanthan gum will typically contain less than about 20%, and more typically less than about 10%, by volume of particles outside the range of from about 100 micrometers to about 200 micrometers, more typically from about 110 micrometers to about 150 micrometers and even more typically from about 115 micrometers to about 125 micrometers, and more typically less than about 5% by volume of particles outside these ranges.
[0012] The amounts of potato starch and granular xanthan gum in the compositions of this invention can vary widely, but potato starch will constitute more than 50% by weight of the blend, preferably from about 90% to about 99, more preferably from about 92% to about 96%, and even more preferably from about 93% to about 95%, by weight. Thus, the weight ratio of potato starch to xanthan gum will be greater than 1:1, preferably from about 9:1 to about 99:1, more preferably from about 11.5:1 to 24:1 and even more preferably from about 13:1 to about 19:1.
[0013] The compositions of this invention may also contain a dextrin in a minor amount by weight in addition to the major amount of potato starch and minor amount of granular xanthan gum. As used herein, the term “dextrin” means the products made by heating dry starch with or without acid. During the reaction, greater or lesser amounts of hydrolysis, transglycosidation, and repolymerization occur. According to which reaction predominates, the product is a white dextrin, a yellow dextrin, or a British gum. Preferred dextrins are white dextrins, especially those exhibiting low solubility, solution stability and dispersed viscosity. The weight ratio of potato starch to dextrin will typically range from about 1.5:1 to about 6:1, and more typically from about 2:1 to about 4:1, and even more typically from about 2.5:1 to about 3.5:1.
[0014] The baked foodstuffs of this invention can be any of a variety of baked goods, including without limitation, cakes, including angel food cake, yellow cake, sponge cake, chiffon cake, cookies, muffins, pancake and waffle mix, gluten free bread, gluten free rolls, gluten free cakes, gluten free muffins, gluten free cookies, and gluten free pancake and waffle mix. Preferred baked foodstuffs include aerated baked goods such as angel food cakes. The baked foodstuff will typically also contain a reduced amount of egg whites, typically from about 20% to about 60% less egg whites, more typically from about 30% to about 50%, less egg whites, and even more typically from about 35% to about 45% less egg whites, by weight. Water is also added to the baked good to compensate for the water contained in the omitted egg whites, in addition to the composition of this invention. It has been found that replacing only a portion of the water present in the omitted egg leads to increased cake height and reduced gumminess compared to replacing all of the water present in the omitted egg whites. Thus, it is advantageous to reduce the amount of water added to compensate for the omitted egg whites by from about 5% to about 35%, more typically from about 10% to about 30%, and even more typically from about 15% to about 25%, based on the weight of the water present in the omitted egg whites.
[0015] The baked foodstuff will also typically be comprised of wheat flour, and may also contain other ingredients typically used in baked goods such as sweeteners, food acids (e.g. cream of tartar), leavening agents, flavorings such as vanilla, and water. The amount of wheat flour in relation to the amounts of egg whites and the composition of this invention in the baked foodstuffs of the invention will vary depending upon the specific nature of the baked foodstuff, but the ratios of wheat flour to egg whites to starch/gum composition will generally range from about 2-60:0.5-2:1, more typically from about 3-50:0.75-1.50:1, and even more typically from about 4-45:0.85-1.3:1, by weight.
[0016] The baked foodstuff may also contain other starch-based ingredients. One such ingredient is a dextrin, e.g. a tapioca dextrin, which will aid in forming a stable emulsion in a batter. The dextrin is typically added in an amount of from about 0.5% to 5% by weight, more typically from about 1% to about 2% by weight, of the baked foodstuff formulation. The dextrin may be present in the formulation as a result of pre-blending with the potato starch and granular xanthan gum.
[0017] The following examples will serve to illustrate the invention and should not be construed to limit the invention, unless otherwise provided in the appended claims.
EXAMPLES
Procedure for Making Angel Food Cake
[0018] Angel food cake was prepared using a 20 quart Hobart 3-speed mixer. Reconstituted egg whites were made by mixing egg white powder (12%, plus assuming egg white powder has 10% moisture) and distilled water (88%) with a whisk until particulates of egg white powder is no longer visible and allowing to hydrate for at least 1 hour with periodic mixing. Reconstituted egg whites were then added to mixing bowl with vanilla extract and formula water. Temperature of this mixture was measured to be between 62 and 72° F. Using a whisk Hobart mixer attachment, the mix was mixed for 2 minutes at Speed 2. Part A (sugar plus cream of tartar) was then added and the mixture was continued to be foamed for 11 minutes (foam checked after 7 minutes for consistency). The temperature of the foam was measured to be between 64-74° F. A specific gravity of the foam was also taken and measured to be between 0.12-0.18. Part B (remaining dry ingredients) were then added to the foam in three parts. The mixer was turned on for a very short time after each part was added at speed 1 to hydrate the ingredients (approximately 5-7 seconds). The temperature and specific gravity was measured again and recorded. The angel food cake complete batter was then added to tube angel food cake pans (with detachable bottom) to 800 grams cake weight, and the batter was smoothed with a plastic bowl scraper to make the surface of the batter even and flat. The cakes were then baked in a MIWE electric conduction oven (available from MIWE Michael Wenz GmbH) for 43 minutes at 350° F. The MIWE oven has a heated top and bottom slab (both were on medium setting) and the vent system was assured be closed during baking. After baking, the cakes were taken out of the oven and then flipped over for cooling for approximately 1 hour. The cakes were then taken out of their pans and continued to be cooled to completion for another 30 minutes. The cakes were then packaged into 2-gallon re-sealable plastic bags and then placed into a deep freezer immediately. Prior to running any further analysis, the cakes were thawed.
Cake Height Measurement:
[0019] Angel food cakes were thawed for approximately 24 hours prior to taking measurement. Cake height of the angel food cake was done using digital calipers by measuring the cake at four points (each 90° apart) at the outside of the cake ring, the inside of the cake ring, and the middle point of the cake ring. The diameter of the ring was also taken at four points. An average was taken from the four points measured and recorded as the dimension of the cake.
Instrumental Texture Analysis of Angel Food Cake:
[0020] Angel food cakes were thawed for approximately 6 hours prior to taking measurement. Instrumental texture analysis of the angel food cake was done by using a TPA procedure using a TA-XT Plus (StableMicrosystems, Scarsdale, N.Y.) Texture Analyzer.
[0000] The following Texture Analyzer setting was used:
[0021] Pre-test Speed: 1 mm/s,
[0022] Test Speed: 5 mm/s),
[0023] Post-test speed: 5 mm/s
[0024] Compress to % Strain
[0025] Percent Strain: 50%
[0026] Trigger force: 5 g
[0027] Delay time between compressions: 5 seconds.
[0028] 1 inch cylinder acrylic probe used
[0029] Texture properties that were recorded include hardness, springiness, resilience, cohesiveness, and gumminess and were calculated using the Stable Microsystems software. Hardness value was the peak force experienced during the first compression of the product (Units in grams). The Cohesiveness value was measured by the area under the curve of the second compression divided by the area under the curve of the first compression (no units). Resilience value was calculated by measuring by dividing the area under the curve of the withdrawal of the first compression divided by the area under the curve of the downstroke of the first compression (not units). Springiness was calculated by the detected height of the product on the second compression divided by the detected height of the product of the first compression (no units). Gumminess value was calculated by multiplying hardness by cohesiveness value (units in grams).
[0030] The starches used in the examples are described in Table 1, below.
[0000]
TABLE 1
Starch
Number
Starch Name and Manufacturer
Description
1
NOVATION ® 1900 starch, available
Dry thermally inhibited potato starch, 20% Max
from Ingredion, 10 Finderne Ave.,
Moisture, 250-550 MVU viscosity
Bridgewater, New Jersey
2
PURAMYL ™ HF 6% starch, available
Lower moisture spec potato starch, Less than
from Avebe, Prins Hendrikplein 20
8% moisture
9641 GK Veendam
The Netherlands
3
ELIANE ™ 100 starch, available from
Waxy Potato Starch, 20.5% moisture (max)
Avebe
4
AVEBE ®NS 450 starch, available from
Physically modified native potato starch, 18.5-20%
Avebe
moisture, 1900 BU viscosity, less than 71
deg C. peak viscosity temp
5
Regular Wheat Starch, available from
Native Regular Wheat Starch
MGP Ingredients, 100 Commercial
Street, Atchison, Kansas
6
Waxy Wheat Starch, available from
Native Waxy Wheat Starch
MPG Ingredients
7
WESTARCH ™ 100, available from
Native potato starch, less than 20% moisture,
Western Polymer, Moses Lake, WA
500-122 BU viscosity
Examples 1-5 and Comparative Examples A-H
[0031] The amounts of the ingredients used in making the angel food cakes and properties of the resulting cakes are shown in Tables 2 and 3, below.
[0000]
TABLE 2
Example
A
1
B
2
C
3
D
4
5
Starch Number
1
1
2
2
3
3
4
4
4
Starch Source
Potato
Potato
Potato
Potato
Potato
Potato
Potato
Potato
Potato
Part A
Wt. %
Wt. %
Wt. %
Wt. %
Wt. %
Wt. %
Wt. %
Wt. %
Wt. %
Sugar (Part A)
20.55
20.55
20.55
20.55
20.55
20.55
20.55
20.55
20.55
Cream of Tartar
0.51
0.51
0.51
0.51
0.51
0.51
0.51
0.51
0.51
Part B
Sugar (Part B)
20.55
20.55
20.55
20.55
20.55
20.55
20.55
20.55
20.55
Cake Flour
16.29
16.29
16.29
16.29
16.29
16.29
16.29
16.29
16.29
Salt
0.18
0.18
0.18
0.18
0.18
0.18
0.18
0.18
0.18
Starch 1
3.42
3.42
3.42
3.42
3.42
3.42
3.42
3.42
3.42
Tapioca Dextrin 2
1.14
1.14
1.14
1.14
1.14
1.14
1.14
1.14
1.14
Xanthan Gum -
0.2
0
0.2
0
0.2
0
0.2
0
0
Fine Grind 3
Xanthan Gum -
0
0.2
0
0.2
0
0.2
0
0.2
0.2
Coarse Grind 3
Part C
Reconstituted
26.21
26.21
26.21
26.21
26.21
26.21
26.21
26.21
26.21
Egg Whites
Vanilla Extract
0.51
0.51
0.51
0.51
0.51
0.51
0.51
0.51
0.51
Water
10.43
10.43
10.43
10.43
10.43
10.43
10.43
10.43
10.43
TOTAL
100
100
100
100
100
100
100
100
100
Cake Height (mm)
53.75
64.28
55.13
63.03
55.35
64.47
56.00 4
65.38
60.06
Cake Hardness
1460
972
1346
1172
1465
1094
1349 5
992
1122
Cake Gumminess
789
579
824
734
930
679
808 6
524
686
1 See table above for details on starches used.
2 Tapioca Dextrin used was CRYSTAL TEX ® 644 dextrin, available from Ingredion.
3 Xanthan Gum used was KELTROL ® brand xanthan, CP KELCO, 3100 Cumberland Boulevard, Atlanta, Georgia;
Fine grind had mean particle size of 39.58 micrometers, and Coarse grind had mean particle size of 122.2 micrometers.
4 Height of 51.99 mm for a second set of replicates.
5 Hardness of 1558 for a second set of replicates.
6 Gumminess of 840 for a second set of replicates.
Conclusions:
[0032] The results in Table 2 show that coarse grind xanthan gum performed significantly better as an egg white extender in angel food cake with the tested potato starches than fine grind xanthan gum in terms of cake height, hardness, and gumminess. The cakes with fine grind xanthan gum were significantly harder, had a lower cake height, and were gummier.
[0000]
TABLE 3
Positive
Negative
Example
Control
Control
E
F
G
H
Starch Number
—
—
5
5
6
6
Starch Source
—
—
Wheat
Wheat
Wheat
Wheat
Part A
Wt. %
Wt. %
Wt. %
Wt. %
Wt. %
Wt. %
Sugar (Part A)
20.10
20.52
20.55
20.55
20.55
20.55
Cream of Tartar
0.50
0.51
0.51
0.51
0.51
0.51
Part B
Sugar (Part B)
20.10
20.52
20.55
20.55
20.55
20.55
Cake Flour
15.93
16.26
16.29
16.29
16.29
16.29
Salt
0.18
0.18
0.18
0.18
0.18
0.18
Starch 1
0
0
3.42
3.42
3.42
3.42
Tapioca Dextrin 2
0
0
1.14
1.14
1.14
1.14
Xanthan Gum -
0
0
0.2
0
0.2
0
Fine Grind 3
Xanthan Gum -
0
0
0
0.2
0
0.2
Coarse Grind 3
Part C
Reconstituted
42.70
26.16
26.21
26.21
26.21
26.21
Egg Whites
Vanilla Extract
0.50
0.51
0.51
0.51
0.51
0.51
Water
0.00
15.34
10.43
10.43
10.43
10.43
TOTAL
100
100
100
100
100
100
Cake Height (mm)
73.06
46.50
54.93
62.09
54.53
54.25
Cake Hardness
740
1397
1308
932
892
1303
Cake Gumminess
546
885
784
667
642
822
1 See table above for details on starches used.
2 Tapioca Dextrin used was CRYSTAL TEX ® 644 dextrin, available from Ingredion.
3 Xanthan Gum used was KELTROL ® brand xanthan, CP KELCO, 3100 Cumberland Boulevard, Atlanta, Georgia;
Fine grind had a mean particle size of 39.58 micrometers, and Coarse grind had a mean particle size of 122.2 micrometers.
Examples 6-8 and Comparative Example I
[0033] Traditional yellow layer cakes were made using an egg white extender of the invention.
[0000] Ingredients Wt. % Part A Sugar 26.78 Cake Shortening-US DDA Emulsified 12.28 Part B Cake Flour 23.59 Baking Powder 0.90 Salt 0.22 Nonfat Dry Milk 2.52 Dry Egg Whites 0.71 Potato or Wheat Starch 0.51 Xanthan Gum - Coarse Grind 0.028 Tapioca Dextrin - CRYSTAL TEX ® 644 0.17 Part C Egg yolk-liquid 5.25 Part D Water 26.29 Vanilla Extract 0.75 TOTAL 100.00
A control yellow cake formula is below:
[0000]
Ingredients
Wt. %
Part A
Sugar
26.78
Cake Shortening-US DDA Emulsified
12.28
Part B
Cake Flour
23.59
Baking Powder
0.90
Salt
0.22
Nonfat Dry Milk
2.52
Dry Egg Whites
1.41
Part C
Egg yolk-liquid
5.25
Part D
Water
26.29
Vanilla Extract
0.75
TOTAL
100
[0034] The cakes were manufactured by following the steps below:
Preparation:
[0000]
1. Sift together all of the dry ingredients (B). Set aside.
2. Cream the shortening and sugar (A) together in a Hobart N50 mixer at Speed 1 for 1.5 minutes and Speed 2 for 1.5 minutes
3. Add the eggs gradually while mixing at Speed 1. After all eggs are incorporated, mix at Speed 1 for 30 seconds, then Speed 2 for 1.5 minutes.
4. Blend the water and vanilla (D) together.
5. Alternately add A and liquid in 3 parts at Speed 1. Scrape bowl. Mix for additional 1.5 minutes at Speed 2
6. Stop mixing when batter is uniform. Do not overmix.
7. Pour batter into a 8-inch cake pan and bake for 27 minutes @350° F. 500 grams per pan in a conduction oven
Results:
[0042]
[0000]
TABLE 4
Starch
Cake
Example
Number
Starch Name
Height
Sensory Description
6
4
AVEBE ® NS
44 mm
Firm Bite, Slightly
450
cohesive in mouth
after initial chew.
Very good
crumb structure
7
2
PURAMYL ®
46 mm
More chewy and firm.
HF 6%
More cohesive
8
7
WESTARCH ™
43 mm
Less firm than
100-Western
AVEBE ® NS 450,
Polymer
slightly cohesive
I
5
Regular Wheat
44 mm
Least firm of all
Starch
samples, slightly drier
than rest
[0043] All yellow cakes made generated a cake height that were similar. They also had a crumb structure that were similar to a control yellow cake. They all were slightly cohesive, with the exception of the PURAMYL™ starch that was more cohesive than the rest. The Regular Wheat starch was also slightly drier than the rest.
Examples 9-11 and Comparative Example J
[0044] Muffins were made using the following formulas:
[0000]
TABLE 5
Positive
Negative
Example
Control
Control
9
10
J
11
Ingredients
Wt. %
Wt. %
Wt. %
Wt. %
Wt. %
Wt. %
All Purpose Flour
27.92
29.03
28.587
28.587
28.587
28.587
Sugar
17.79
17.79
17.79
17.79
17.79
17.79
Baking Powder
1.49
1.49
1.49
1.49
1.49
1.49
Salt
0.23
0.23
0.23
0.23
0.23
0.23
Milk Powder-
2.23
2.23
2.23
2.23
2.23
2.23
nonfat, hi-heat
Shortening
11.86
11.86
11.86
11.86
11.86
11.86
Whole eggs-
8.9
4.45
4.45
4.45
4.45
4.45
Liquids
Starch No. 4
0
0
0.801
0
0
0
(Potato)
Starch No. 7
0
0
0
0.801
0
0
(Potato)
Starch No. 5
0
0
0
0
0.801
0
(Wheat)
Starch No. 2
0
0
0
0
0
0.801
(Potato)
Dextrin 1
0
0
0.267
0.267
0.267
0.267
Xanthan Gum -
0
0
0.045
0.045
0.045
0.045
Coarse Grind 2
Water
19.13
22.47
21.8
21.8
21.8
21.8
Blueberries
9.91
9.91
9.91
9.91
9.91
9.91
Vanilla Extract
0.54
0.54
0.54
0.54
0.54
0.54
Total
100
100
100
100
100
100
1 Tapioca Dextrin used was CRYSTAL TEX ® 644 destrin, available from Ingredion.
2 Xanthan Gum used was KELTROL ® brand xanthan, CP KELCO, with a mean particle size of 122.2 micrometers.
Results:
[0045]
[0000]
TABLE 6
Example
Starch
Height
Sensory Description
Positive
—
53 mm
Good crumb structure, firm, slightly dry
Control
Negative
—
49 mm
Slightly shorter, cohesive and
Control
gummy and wet in mouth
9
No. 4
50 mm
Slightly cohesive, gummy after chewdown
10
No. 7
49 mm
Less cohesive than Example 9
J
No. 5
52 mm
Drier than all samples, somewhat
crumbly and less cohesive
11
No. 2
51 mm
Very cohesive and firmer. Dense and wet
[0046] All muffins were of similar height and were slightly shorter than control. All samples had good crumb structure with some slight tunneling. | 1a
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BACKGROUND OF THE INVENTION
The invention concerns a medical electrode, in particular for energy transmission, comprising at least one electrically contactable conductor surface preferably provided with a connecting bar or the like.
Such electrodes are applied to the skin of the patient for the most widely varying purposes, for example in order to monitor bioelectrical processes of the body or to introduce into or take from the body currents—which are mostly of relatively high frequency—(for example neutral electrodes, stimulation electrodes and defibrillation electrodes). The structure of those electrodes can be of various different kinds, in general such electrodes have a rearward carrier remote from the skin and comprising a foam material. Provided on the carrier, possibly with the interposition of intermediate layers, are electrically conductive conductor surfaces, for example an aluminum laminate. It is however also possible to provide non-metallic conductor surfaces. In the case of neutral electrodes, they are not directly in contact with the skin, to avoid the occurrence of high local current densities. On the contrary, there is provided an adhesive gel which is electrically conductive for the alternating currents used and which makes the contact with the skin.
In the case of neutral electrodes for taking current from an area of operation it is already known for those electrodes to be equipped with at least two electrically separate conductor surfaces, wherein an electronic evaluation device individually monitors the currents taken from the respective conductor surfaces and gives an alarm in the event of an excessive difference being detected. The purpose of that procedure is to ensure that both conductor surfaces of the neutral electrode afford good electrical contact with the skin in order to exclude local heat-generation phenomena at the skin of the patient. In the case of the known neutral electrode, there are for example two substantially rectangular conductor surfaces which are arranged on a common carrier in mutually juxtaposed relationship with a gap between them. So that this neutral electrode together with the monitoring device connected thereto is operable, the gap must be precisely oriented with respect to the area of operation as otherwise the two conductor surfaces are supplied differently with current.
SUMMARY OF THE INVENTION
In order to improve the apportioning of current, in particular in the case of neutral electrodes for taking off current, and to make such apportioning more uniform, it is provided in accordance with the invention that there is at least one uncontacted conductor surface which is arranged at a spacing and electrically separated from the at least one electrically contactable conductor surface.
The uncontacted conductor surface which is free from connecting bars can for example surround the contacted conductor surface in the form of a circular ring. It is also possible to provide two or more such uncontacted conductor surfaces on a common carrier with the contactable conductor surface or surfaces. It is also possible for the uncontacted conductor surface to extend into the intermediate space between two spaced contacted conductor surfaces.
As already mentioned the aim of those uncontacted conductor surfaces is to improve current apportionment, in particular in the case of neutral electrodes which take off current, and to make it more uniform. Particularly in the case of such neutral electrodes which preferably have two or more electrically contactable conductor surfaces, an additional non-contacted conductor surface ring can result in uniform apportionment of the current to be taken off, to the two electrode portions (conductor surfaces). That therefore overall affords better current density distribution and thus a lower level of thermal loading for the patient.
In order to provide a medical electrode having at least two electrically separated conductor surfaces which permit uniform detection of biopotentials or energy transmission, a preferred embodiment provides that one conductor surface at least partially surrounds another conductor surface, as viewed in plan.
The inner conductor surface is preferably of a round circular configuration and the outer conductor surface surrounds that inner conductor surface in the form of a circular ring. The gap between the two electrically separated conductor surfaces then extends in the form of an annular gap between the inner and the outer conductor surfaces. In accordance with an embodiment, by suitable dimensioning and configuration thereof, it is possible for the surface areas and/or peripheral lengths of the two conductor surfaces which are however different in configuration to be nonetheless substantially equal, in particular in order to provide substantially identical conditions in terms of taking off current in the case of the neutral electrode and to ensure a high level of orientational tolerance.
A substantial advantage of such a preferred electrode configuration provides that, apart from a compact structural shape, it can be stuck on the skin in many different orientations without having to accept a substantial variation in current conductivity (high orientational tolerance, that is to say flexile orientability for example in relation to an area of operation). In that respect it is particularly desirable if the outer conductor surface surrounds the inner over an angular range of over 90°, preferably over 270°. While in the previous neutral electrode in accordance with the state of the art, the gap always had to be oriented accurately with respect to the area of operation, the medical staff can now stick the novel electrode on the skin in virtually any orientation. That makes use considerably easier.
In spite of the fact that the conductor surfaces surround each other with their active regions, it is desirable for the connecting lugs to be taken out laterally in parallel mutually juxtaposed relationship in order to permit simple connection of the multi-pole electrode cable.
A further embodiment of the invention is based on the realisation that higher local current densities can occur at the corners of the conductive regions. In order to avoid that this embodiment of the invention provides that the conductive regions are of a substantially round configuration, preferably being of a round circular configuration. In that way it is possible to avoid the disadvantageous corners and in addition to ensure insensitivity in relation to different orientations when applying the electrode.
BRIEF DESCRIPTION OF THE DRAWING
Further advantages and details of the invention are described in greater detail with reference to the specific description hereinafter.
FIG. 1 diagrammatically shows the arrangement of two electrically separate conductor surfaces in an electrode, wherein the carrier, for example a sticky foam support, is shown in broken line.
FIGS. 2 through 11 further arrangements of conductor surfaces for an electrode, in particular a neutral electrode, wherein carrier materials or possible skin-side, electrically conducting, sticky gels are not shown for the sake of simplicity. In this respect FIGS. 4 , 6 , 7 , 8 , 9 , 10 and 11 show the uncontacted conductor surface according to the invention.
DETAILED DESCRIPTION OF THE INVENTION
The medical skin electrode shown in FIG. 1 has on a carrier 2 two electrically separate conductor surfaces 1 a and 1 b provided with connecting bars 3 . The outer conductor surface 1 b surrounds the inner conductor surface 1 a , as can be seen in a plan view as shown in FIG. 1 . The inner conductor surface 1 a is of a substantially round circular configuration and the outer conductor surface 1 b is substantially in the form of a circular ring, with a gap 4 of constant width being arranged therebetween. It is particularly appropriate if the outer conductor surface 1 b surrounds the inner conductor surface over an angular range which is as large as possible. That should be at least 90°, preferably over 270°. With such an arrangement it is possible for the electrode to be disposed in virtually any orientation with respect to the area of operation while nonetheless always achieving reliable current take-off which is distributed uniformly to the two surface portions 1 a and 1 b . When connecting a monitoring apparatus which forms part of the state of the art and which measures the relative currents from the two conductor surfaces 1 a and 1 b , the situation therefore does not involve an unwanted alarm being triggered off when the electrode is stuck on the skin in virtually any orientation relative to the area of operation. The electrode can thus be applied quickly and in an uncomplicated fashion by the medical specialist staff.
In order to provide conditions which as far as possible are identical for current take-off (in general terms: energy transmission) for the two conductor surfaces 1 a and 1 b the surface areas of the two surfaces 1 a and 1 b are here selected to be equal.
In the case of the electrode shown in FIG. 2 the inner conductor surface 1 d has a multiply curved outside edge in order to increase the peripheral length thereof so that it substantially corresponds to the peripheral length of the outer hook-shaped or circular ring-shaped conductor surface element 1 b.
FIG. 3 shows a ‘double hook geometry’ in which the conductor surfaces 1 a and 1 b have hook-shaped projections which are interleaved one into the other in order to achieve uniform current distribution to the two half-electrodes.
The electrode shown in FIG. 4 also has two electrically contacted conductor surfaces 1 a and 1 b which are interleaved one into the other or which at least partially surround each other. In accordance with the invention this electrode also has two uncontacted rings 4 and 5 which, in contrast to the conductor surfaces 1 a and 1 b , do not have any connecting elements 3 for an electrode cable. The outer uncontacted ring encloses all inner conductor surfaces while the inner uncontacted ring additionally also extends into the gap between the two contacted conductor surfaces 1 a and 1 b (the actual active electrode surfaces). The purpose of such uncontacted conductor surfaces or rings 4 and 5 of that kind is to achieve uniform current apportionment. Tests on a patient with neutral electrodes have shown that the use of such uncontacted rings involves a substantially lower level of thermal loading by virtue of improved current density distribution.
Desirably those uncontacted rings and the contacted conductor surfaces 1 a and 1 b will be arranged on a carrier (not shown in FIG. 4 ), for example of foam, and, if this is desired, covered with an electrically conducting gel at the skin side. In principle however it is also possible for the uncontacted, electrically conducting rings or the contactable conductor surfaces 1 a and 1 b to be applied independently of each other to the patient in the form of separate components.
In order to avoid corners being present on rectangular electrode elements, the shape of the conductor surfaces is desirably so selected that they are of a round, preferably round circular external contour (with the exception of the connecting bars 3 ). Such an embodiment is diagrammatically shown in FIG. 5 where the two conductor surfaces 6 a and 6 b are of a clearly evident round circular outside contour 7 . It will be appreciated that such a simple, round, double-surface double electrode may also be surrounded by an additional uncontacted ring 4 which at least partially encloses the outside contour. In that way once again the rise in temperature of the electrode with the flow of current in the course of medical use can be kept particularly low and uniform. In the embodiment illustrated in FIG. 7 there is also a further ring 4 ′ disposed outside the uncontacted ring 4 , that is to say a total of two uncontacted rings which result in the current flow in use being rendered still more uniform. It is also possible for the uncontacted conductor surface 4 to have an extension 4 a which extends into the region between the two electrically contacted conductor surfaces.
The idea of a medical electrode with an electrically uncontacted, preferably annular conductor surface 4 or 5 respectively can also be embodied in electrodes with only one electrically contacted conductor surface 6 , as is shown in FIGS. 9 , 10 and 11 . In regard to FIG. 11 it should also be mentioned that here the current-carrying contacted electrode 6 is of a substantially hook-shaped configuration, wherein the contact-less outer ring 4 extends inwardly with an extension 4 ′ a and thus also covers the inside of the hook electrode. | 1a
|
CROSS-REFERENCE
[0001] This application claims priority from and incorporates the entire disclosure of U.S. Provisional Patent Application No. 60/361,901 filed Feb. 28, 2002.
BACKGROUND
[0002] 1. Technical Field of the Invention
[0003] The present invention relates to orthopedic supports and, more particularly, but not by way of limitation, to an orthopedic support for a knee having a hinge that may be adjustably positioned for anatomically correct support of knees and legs of varying sizes and shapes.
[0004] 2. History of Related Art
[0005] It is common in the Sports Medicine Industry to utilize orthopedic supports for various body parts subject to injury. The most common support areas include the knees, elbows, and ankles. Often injuries to these areas of the body can be treated by the utilization of the appropriate orthopedic support. In the event surgery, rehabilitation is sometimes augmented by the utilization of such supports.
[0006] The design of orthopedic supports has changed considerably over the past two decades. The types of material used as well as the fastening and hinging mechanisms associated with orthopedic supports have been the subject of considerable study and improvement. U.S. Pat. No. 4,986,264 to Miller, teaches a knee brace having an interior tibial shell and an interior femoral which are closely configured to the shape of the lower leg and thigh respectively and which are joined by a frame in the form of a pair of polycentric hinge joints. U.S. Pat. No. 4,856,501 to Castill et. al. teaches a knee brace having adjustable width frame pivoted to cuffs. The brace as set forth therein includes first and second frame members disposed on opposite sides of the joint to be supported, and first and second hinge members disposed substantially adjacent to joint and connected to the frame members to pivot the frame members about the joint.
[0007] Another example of related art is shown in U.S. Pat. No. 4,494,534 to Hudson. This patent teaches a universal leg brace system for controlling the degree of motion permitted by wearer's knee characterized by respective flexible sheets of cushioned material adapted for snugly wrapping around the wearer's thigh and calf. U.S. Pat. No. 5,554,104 to Grim likewise teaches a custom formed knee brace. This brace is taught to support weakened or injured knees by having formed components which conform to the unique configuration of an individual's leg surfaces. Other references include U.S. Pat. No. 6,066,110 to Nauert; U.S. Pat. No. 5,810,752 to Grifka; U.S. Pat. No. 5,624,389 to Zepf; U.S. Pat. No. 4,873,967 to Sutherland; U.S. Pat. No. 5,921,946 to Tillinghas; and U.S. Pat. No. 5,562,605 to Taylor.
[0008] As seen from the patents listed above, the aspect ofjoint support, flexibility, and rehabilitation have received considerable attention in prior orthopedic support design. One area of continued concern is, however, the adaptability of a single support to human body parts of varying size and shape. For example, knee braces require that the area of the thigh above the knee as well as the area of the leg beneath the knee be securely fitted within the brace. Some legs are shaped differently than others. Some individuals have larger thighs than other individuals and thus various modifications must be made to the particular brace to accommodate large and/or smaller leg portions. This is particularly true when an upper leg portion in the area of the thigh is considerably larger than the portion below the knee. When hinge structures are utilized in conjunction with orthopedic supports for such knees, the appropriate alignment of the oppositely disposed hinges becomes critical. If the hinges are not diametrically opposed one to the other, the appropriate hinge action cannot smoothly occur. In fact, various stresses can be imparted to the orthopedic support as well as the knee when misalignment is present. Such a problem is contrary to the purpose of the orthopedic support and will not maximize efficiency and healing. The alignment ofthe hinges should, therefore, be a primary consideration in orthopedic support design construction and fitting. The present invention addresses such design manufacturer and fitting issues by providing an orthopedic support with adjustable hinge sections to permit appropriate diametrically opposed hinge alignment therewith to accommodate a variety of a body shapes and sizes.
SUMMARY OF THE INVENTION
[0009] The present invention relates generally to orthopedic supports having hinge elements associated therewith. More particularly, one aspect of the invention includes an orthopedic support facilitating better fit for legs of varying shape, including the cone-shaped leg and the positioning of the support around the thigh. In one aspect of the present invention, hinges disposed for positioning above the patella have unique hook and pile adjustments to fit larger or smaller thighs (from child sizes to adult sizes) and allow proper balanced support on opposite sides of the knee. In another aspect a posterior elastic segment on velcro straps prevent any tourniquet effect. Moreover, the present invention may, in one embodiment, provide a universal right or left leg applicability with removable, adjustable half-horseshoe buttress.
[0010] Another aspect of the present invention relates to a hinged knee support utilizing adjustable hinges. The knee support is particularly adapted for individuals having larger thigh regions. Thus, the hinged knee support is adapted to open in the upper region thereof to accommodate various sizes and shapes of thigh portions and to further include means for adjustably positioning the lateral hinges so that they are oppositely disposed about knee to provide the most appropriate support, irrespective of the shape and size and
[0011] In another aspect of the present invention, the present invention includes a large popliteal opening for added comfort by the user. A multitude of hinges may be used including both the single axis and a polycentric type of hinge.
[0012] In still another aspect of the present invention, a spiral stay may be used so that as the knee is bent by a user, the stay encourages the present invention to return to a neutral position after each movement. In this manner, as the knee is returned to a neutral position such that pressure exerted on the knee neither pushes or pulls the tissues of the knee apart.
[0013] In yet another aspect of the present invention, hook and pile inter-engagement is used to facilitate the positioning and securement of the hinges in the most appropriate location relative to the knee.
[0014] And yet a further aspect of the present invention, a hinged knee support is provided with a patient friendly configuration having a closed bottom section for covering the calf of the patient and an upper region that may be open and adjusted to the appropriate size for accommodating a variation in the size of the thigh of the user. The hinged knee further incorporates the adjustable hinge feature as described above therein facilitating structural support of patients having a wide variation of certain anatomical regions thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] A more complete understanding of embodiments of the present invention can be achieved by reference to the following Detailed Description when taken in conjunction with the accompanying Drawings wherein:
[0016] [0016]FIG. 1 is a perspective view of an orthopedic support constructed in accordance with the principles of the present invention;
[0017] [0017]FIG. 2 is an enlarged, side elevation, fragmentary view of the hinged attachment area of the knee support of FIG. 1 illustrating various positioning of the hinge thereon and a means of for attachment thereto;
[0018] [0018]FIG. 3 is a front elevation view of the knee support of FIG. 1 illustrating the accommodation of a relatively large thigh therein and the manner of accommodation provided in accordance with the principles of the present invention;
[0019] [0019]FIG. 4 is a front elevation view of the knee support of FIG. 3 illustrating closure of the kneec thigh and the use of hook and pile closure straps for securement ofthe knee support to the user's leg;
[0020] [0020]FIG. 5 is a side elevation view of the knee support of FIG. 1 further illustrating the construction of thereof;
[0021] [0021]FIG. 6 is a front elevation view of the knee support of FIG. 1 further illustrating the construction thereof and the positioning of the medial and lateral hinges so that said hinges are anatomically correct relative to the knee of the user; and
[0022] [0022]FIG. 7 is a flow chart illustrating the method of using the present invention.
DETAILED DESCRIPTION
[0023] It has been discovered that many commercial braces do not fit certain sizes and shapes in the most appropriate manner. This is particularly true of legs with large thighs and smaller calf regions. These leg shapes are referred to herein as “cone-shaped” legs and illustrated in certain ones of the following drawings. Further, the present invention may be adapted to fit the leg shapes of both children and adults.
[0024] Referring now to FIG. 1, there is shown an adjustable hinged knee support 10 constructed in accordance with the principles of the present invention. The knee support 10 facilitates a better fit for users having large thighs or “cone-shaped” legs 12 . An adjustable upper fastener assembly 14 accommodates the various thigh sizes. As shown in FIG. 1, a large patella opening 16 (or alternatively, a large popliteal opening) is also provided for added comfort. On opposite sides of opening 16 are removable, adjustable half-horseshoe buttress' 21 for comfort and support (see also FIG. 2). As described below, the upper fastener assembly 14 and the lower fastener assembly 18 may be constructed with hook and pile portions to facilitate adjustability and ease of use by the user. Still referring to FIG. 1, a hinge 20 is distinctly placed along the medial portion of the knee support 10 . Hinge 20 may be either a polycentric (double axis) hinge, single axis hinge, complex hinge, or a spiral stay. Other types of hinges may also be used As will be shown in more detail below, a second hinge 20 is disposed opposite hinge 20 , and is positioned on the outside portion ofthe knee to balance the support about the knee. It has been observed in prior art that knee braces do not accommodate variations in size of the user's thigh, the position ofthe respective hinges may vary in accordance with the principles of the present invention.
[0025] Referring now to FIG. 2 there is shown an enlarged fragmentary, side elevation view of an upper portion 22 of hinge 20 of the knee support 10 of FIG. 1. The position of the upper portion 22 of hinge 20 is shown to be positionable about a hook and pile surface 24 of the knee support 10 . A retaining strap 26 is shown in a position for securement of hinge 20 . In this manner, the position of the hinge 20 relative to the leg of the user, as shown in FIG. 1, may be selectively adjusted to accommodate variations in the size of the thigh of the user. In other words, the medial and lateral hinges (described below) are adjusted to allow the knee support 10 to be anatomically correct relative to the knee.
[0026] Referring now to FIG. 3 there is shown the knee support 10 positioned about the leg 12 of a user. In this particular embodiment it may be seen that the thigh 30 is much larger than the calf 32 of the user. For this reason, the knee support 10 is constructed with opposing flaps 34 and 36 which as shown in FIG. 1, when closed comprise an upper portion 52 of the knee support 10 . In this particular illustration, it may be seen that the flaps 34 and 36 are in an open position, which permit the fitting of the knee support 10 about the leg 12 of the user. The flaps 34 and 36 are constructed with hook and pile surfaces 38 (one which is shown on flap 34 ) to facilitate securement about the leg 12 of the user. A portion of the hook and pile surface 38 comprises a portion of the adjustable upper fastener assembly 14 , illustrated in FIG. 1. The adjustable upper fastener assembly 14 further includes a strap 40 extending outwardly from flap 36 . Still referring to FIG. 3, the lower region 50 of the knee support 10 , in this particular embodiment, is of fixed size and thus is not adjustable. The lower region 50 does, however, include a support strap 52 that affords securement of the knee support 10 about the leg 12 of the user.
[0027] Referring now to FIG. 4 there is shown the knee support 10 of FIG. 3 positioned about the leg 12 of the user with the flap 38 closed and positioned over the flap 36 as described above. A region 38 a of hook and pile material, which is not visible in FIG. 3, is illustrated as it appears on the outer portion of the flap 36 . It should be noted that the term “hook and pile fasteners” is a recognized structure to one skilled in the art and is often sold under the trademark Velcro®. It is also well known that the hook and pile enter and engage one another. Therefore, if surface 38 , as shown in FIG. 3, is a hook surface then the region 38 a of FIG. 4 would be a pile surface. It is to be understood that further reference herein to a “hook and pile surface” refers to either a hook or a pile surface.
[0028] Still referring to FIG. 4, it may be seen that the lower region 50 of the knee support 10 conforms about the calf 32 , with the patella opening 16 more clearly illustrated by the closure of flap 38 over flap 36 . Various stitching 54 is shown upon flap 38 as well as stitching 56 shown around the patella opening 16 . This stitching is shown for purposes of illustration only, and other stitching embodiments maybe incorporated herein. All illustrations thereof should not be deemed limited in any respect relative to the principles of the present invention.
[0029] Referring now to FIG. 5 there is shown the knee support 10 with the lower strap 52 securing the lower region 50 ofthe knee support 10 while the upper fastener assembly 14 secures the upper region of the knee support knee 10 about the leg 12 of the user. It may be seen that the hinge 20 is positioned on the hook and pile surface 24 in a position most appropriate to support of knee of the user as will be described in more detail below.
[0030] Referring now to FIG. 6, there is shown the knee support 10 in a front elevation view. This particular view it may be seen that the hinge 20 comprises medial and lateral hinges 20 . Because the knee brace may be used on either left or right knees, it is not necessary to differentiate which hinge 20 is medial or lateral. This definition is relative to the leg of the user. The present description is intended to provide an understanding that the position of the medial and lateral hinges 20 may be adjusted so that they are anatomically correct. As described above, the ability to adjust the position of the hinges 20 , and the ability to position the upper portion 22 of the hinge 20 about the hook and pile surface 24 against which it may be secured, facilitates anatomically correct adjustment.
[0031] In one embodiment of the present invention, a sheet of material 60 covers the hinge 20 . The underside of the sheet 60 has a mating hook and pile surface to engage the hook and pile surface 24 , which provides securement of the upper portion 22 of hinge 20 (FIG. 2) thereto.
[0032] In operation, the present invention accommodates various leg sizes. This is clearly shown in FIG. 3, where the above described upper fastener assembly 14 and strap 40 therein described allow the user to position the knee support 10 around the leg 12 of the user in a manner facilitating a wide variety of thigh sizes. Because thigh sizes will vary (especially between children and adults), the knee support 10 ofthe present invention may be provided in a variety of basic sizes, such as small, medium, large, and extra large, to further provide accommodation of varying leg sizes.
[0033] Still referring to FIGS. 1 - 6 in combination, FIG. 4 illustrates the anterior hook and pile closure “wrap around” configuration that affords ease in the use of the present invention. However, other fasteners can be used. Likewise FIG. 5 illustrates the securement of the bottom strap 52 of the present invention around the calf 32 of the user prior to the securement of the upper fastener assembly 14 . This is the preferred method of securing the knee support 10 around the leg 12 of the user.
[0034] Finally, FIG. 6 clearly illustrates the ability to adjust the medial and lateral hinges 20 in an anatomically correct configuration relative to the legs of the user. It is necessary to provide the hinges 20 on opposite sides of the user's knee, no matter the shape of the user's thigh so as to provide appropriate support about the knee. Thus, the present invention, which utilizes hook and pile adjustable “wrap around” fasteners, provides a better fit for “cone-shaped” legs than those found in the prior art. The large patella opening 16 provides additional comfort, while a posterior elastic segment on the hook and pile straps 40 and 52 (FIG. 3) prevent any tourniquet effect. As described above, the adjustable, hinged knee support 10 with adjustable hinges is interchangeable for use on either the right or left leg.
[0035] Referring now to FIG. 7, the method of using the present invention allows users having different leg sizes and shapes, including a generally cone-shaped upper leg portion to be fitted with an effective knee support. The user positions the open knee support on the user's leg and adjusts the hinges as described above so as to position each hinge relative to the user's knees on opposite size thereof The hook and pile fasteners permit the user to secure the hinge in the position that is most appropriate for the user's particular leg shape, and further secure the hinge with the straps pulled there around. It is possible to use multiple hinges, and in one aspect of the present invention four different hinges and/or stays may be used. It has been shown to the applicant that not everyone requires a heavy hinge and hinges that simply lockout at either 90 degrees or vertical are in some instances appropriate to prevent hyper extension ofthe user's knee. In accordance with the principles of the present invention, the use of a polycentric hinge (a double axis type of hinge) has also been found to be useful. It should be understood, however, that any type of hinge may be used.
[0036] One advantage of the present invention is the adjustable hinges. This is because adjustable hinges 20 , as is illustrated in FIG. 2, allow the user to position the hinges 20 about the hook and pile material so as to position them above the knee wherein the hinges are neither to far interior nor to far posterior prior to final securement.
[0037] Another advantage is in the use of a flexible spiral stay, which allows use ofthe knee support 10 for various injuries where it is beneficial for the knee support apparatus to return to a neutral position for proper healing. Spiral stays are made from hardened, galvanized spring steel round wire which is coiled and flattened, and is generally referred to in the trade as “spiral boning”. Such material provides support rigidity for partially immobilizing the knee, yet can be flexed, when placed under pressure, to conform to the body contours of the wearer, as illustrated in FIG. 5.
[0038] Yet another advantage is in the ample strap length provided, which allows a wide range of adjustability relative to the sizes of the user's leg. Since adjustability is a key aspect of the present invention, straps with hook and pile material are an advantage.
[0039] Finally, the present invention may be adapted to fit both children and adults. The present invention will be supplied in wide variety of sizes to accommodate the needs of various users.
[0040] Although an embodiment of the method and apparatus of the present invention has been illustrated in the accompanying Drawings and described in the foregoing Detailed Description, it will be understood that the invention is not limited to the embodiment disclosed, but is capable of numerous rearrangements, modifications and substitutions without departing from the spirit of the invention as set forth and defined herein. | 1a
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BACKGROUND OF THE INVENTION
This invention relates to the manufacture of an electrically conductive coated product suitable for medical applications and especially to such conductive products having a metal substrate on which a conductive hydrogel polymer layer is formed.
Electrically conductive coated products have been made with an electrically conductive hydrogel which has been cured on the surface of an metal substrate such as in U.S. Pat. Nos. 4,391,278 and 4,581,821 issued to Cahalan et al. Laminated conductive products can be purchased in roll form from the Promeon Division of Medtronic, Inc. For example, a product designated RG-51 is a product which includes three layers. A first layer is an aluminum/polyester laminate; a second layer is a hydrogel based on 2-acrylamido-2-methylpropanesulfonic acid; and a third layer is a release liner. It was noted that in the conventional process for producing this product, localized corrosion of the aluminum substrate occurred after the product was made. The result was unacceptable pitting of the substrate and a high scrap rate for the finished product.
It would therefore be desirable to provide an improved process for making metal/hydrogel products by which the corrosion of the finished product is prevented.
BRIEF DESCRIPTION OF THE INVENTION
This and other objects have been accomplished by the present invention. We have discovered a method for making a conductive coated product comprising the steps of abrading a conductive metal substrate, applying to the conductive metal substrate a layer of a curable composition which includes 2-acrylamido-2-methylpropanesulfonic acid, water and/or alcohol, and a curing agent and curing the composition on the substrate. We have also discovered that when a metal substrate is coated with a layer of a curable composition which includes 2-acrylamido-2-methylpropanesulfonic acid, water and/or alcohol, and a ultraviolet sensitive curing agent and the composition is then cured on the substrate, the application of a heat treatment to the cured coating and substrate can also reduce the incidence of corrosion on the finished product. Preferably, these two methods are combined to provide a product free of visible corrosion.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic representation of the method according to the present invention.
FIG. 2 is an expanded schematic representation of the abrading station of FIG. 1 together with optional means for removing particulate residue.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to FIG. 1, the method of making a conductive coated product is shown schematically. Metal substrate material in roll form 10 is unwound in a web 12 which passes through an abrading station 15 which produces an abraded substrate 14, a coating station 20 which adds a layer of uncured hydrogel material onto the abraded substrate 14, and a curing station 25 which cures the hydrogel material. Release liner material in roll form 30 is unwound in a web 32 and is joined with the web with cured coating 16. The resulting laminate 40 is wound into a roll 42. The roll 42 is placed into an oven 50 where it is heated to form a finished roll product 60.
The metal substrate material 10 is typically a thin foil of metal laminated on a polymeric backing material. A polyester backing material such as a polyester terephthalate film with a thin coating (e.g. 0.001 inch) of aluminum or tin on one side can be used. The metal substrate material 10 used is substantially free of rolling oil and other contaminants. The metal substrate material 10 extends as a web 12 to an abrading station 15 where the metal side of the web 12 is mildly abraded to provide a microscopically rough surface. The abrasions are preferably less than 25 μm apart and between about 2 μm and 10 μm in depth and more preferably, between about 2 μm and 20 μm apart and between about 3 μm and 6 μm apart. The abrasions are preferably aligned predominantly in the same direction as the direction of travel for the web 12. Referring now also to FIG. 2, the abrasions can be produced by an abrasion wheel 70 such as an ultra fine silica carbide flap brush (e.g. 3M Company Scotch-Brite® Finishing Flap Brush Grade ULF). The metal substrate 12 is drawn between a backup roll 72 and the counter-rotating abrasion wheel 70. It will be appreciated by those skilled in the art that the degree and uniformity of abrasion is controlled by the combination of the speed of the web 12, the pressure applied between the abrasion wheel 70 and the backup roll 72, and the rotational speed of the abrasion wheel 70. In a preferred embodiment of the invention, the abraded substrate 14 is also cleaned to prevent stray particles from marring the appearance of the finished product 60. Cleaning can be accomplished, for example, by providing a housing 75 enclosing the abrasion wheel 70 and the abraded substrate 14 and attaching a vacuum source 77 to the housing 75 whereby particles released by the abrasion process can be swept away. In yet another method for cleaning a separate cleaning station 80 can be optionally employed in which a web 82 of paper or cloth is pressed against the abraded substrate 14 and moved in a direction opposite to the direction of movement of the abraded substrate 14.
Although the abrasion station 15 is shown to be a part of a continuous production system, it has also been found that it is possible to abrade the metal substrate material 10 in a separate operation, store the abraded substrate for a desired period of time and then apply a coating to the pre-abraded material to make the product 60 without again abrading the substrate.
The coating station 20 adds a layer of uncured hydrogel material to the abraded surface of the substrate 14. The uncured hydrogel material is a mixture of 2-acrylamido-2-methylpropanesulfonic acid (AMPS) or one of its salts, copolymers of the acid, copolymers of the salts of the acid and their various mixtures with water and/or an alcohol. Such compositions are set forth more fully in U.S. Pat. Nos. 4,391,278 and 4,581,821 issued to Cahalan et al. which are incorporated herein by reference. The compositions can include a variety of additives and modifiers including humectants such as glycerol or propylene glycol, thickeners such as polyvinylpyrrolidone or polyvinyl alcohol, monomers such as acrylic acid or acrylamide, crosslinking agents such as methylene-bis-acrylamide, fillers such as silica, ionizable metal salts such as potassium chloride or sodium chloride, pH modifiers such as sodium hydroxide, and various curing agents. A particularly useful curing agent for this process is hydroxycyclohexylphenylketone which can be added to the AMPS and other ingredients in a solution of isopropanol. It produces a cure of the hydrogel coating when it is exposed to ultraviolet light. The uncured hydrogel material can therefore be premixed and applied to the substrate by conventional coating equipment. Preferably, the uncured hydrogel material is handled in an atmosphere that is dry and substantially free of oxygen.
The curing station 25 provides the necessary conditions for the hydrogel coating on the abraded substrate 14 to cure. For example, heat or ultraviolet light can be applied depending on the curing agent used Curing by application of ultraviolet light is preferred. After the hydrogel coating is cured, the release liner material in roll form 30 is unwound in a web 32 and is joined with the web with cured coating 16. The resulting laminate 40 is wound into a roll 42.
If the material has been cured by application of ultraviolet light, the roll 42 then undergoes a heat treatment operation whereby it is placed into an oven 50 at a temperature of at least 45° C. and preferably in the range of about 50°-65° C. for at least 10 hours and preferably for more than 24 hours to make a finished product 60. The time required to accomplish the heat treatment will, of course, depend upon the size of the roll 42 and its heat transfer characteristics. Heat treatment could be accomplished in as little as one hour for a small sample.
It will be appreciated by those skilled in the art that while the invention has been described above in connection with particular embodiments and examples, the invention is not necessarily so limited and that numerous other embodiments, examples, uses, modifications and departures from the embodiments, examples and uses may be made without departing from the inventive concepts. | 1a
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FIELD OF THE INVENTION
[0001] The present invention relates to the use of nucleic acids as biomaterials, and more specifically to the use of a nucleic acid as a polymer alone or in combination with a copolymer suitable for use as a biocompatible material.
BACKGROUND OF THE INVENTION
[0002] During the last 20 to 30 years, several biocompatible polymers have been developed for use in the body and approved for use by the U.S. Food and Drug Administration (FDA). These FDA-approved materials include polyglycolic acid (PGA), polylactic acid (PLA), Polyglactin 910 (VICRYL®), polyglyconate (MAXON®) and polydioxanone (PDS). Many other biocompatible polymers are under development. In general these materials biodegrade in vivo in a matter of months, although certain forms may biodegrade more slowly. These materials have been used in orthopedic applications, wound healing applications, and extensively as sutures. More recently some of these polymers have also been used in tissue engineering applications.
[0003] Tissue engineering is a field that develops tissue products that restore, maintain, or improve tissue function. The need for this approach has arisen out of the lack of suitable donor tissue to repair and restore the body.
[0004] In general there are three distinct approaches to engineer new tissue. These are 1) infusion of isolated cells or cell substitutes, 2) use of tissue inducing materials and/or tissue regeneration scaffolds (guided tissue repair) and 3) implantation of cells seeded in scaffolds.
[0005] In open scaffold systems and guided tissue repair, tissue engineering materials have normally been fabricated from natural protein polymers such as collagen or from synthetic polymers. These materials often do not have the specific mechanical requirements that a scaffold needs to provide until the new tissue is developed. These materials may also handle poorly, be difficult to suture or may not maintain the desired form or strength for a long enough period of time. Thus it is desirable to develop bioabsorbable and/or biocompatible polymers that extend the range of properties available.
SUMMARY OF THE INVENTION
[0006] The present invention includes the use of nucleic acids, particularly DNA, as a polymeric biomaterial. The nucleic acids may be used alone, or as copolymers with other degradable or non-degradable biomaterials. The invention includes such biomaterials, methods of formation and methods of use.
[0007] In certain embodiments of the invention, the nucleic acids are used primarily for their biodegradable polymer properties and not for their information coding aspects. However, in other embodiments, both the polymer and information coding aspects of nucleic acids may be used.
[0008] One embodiment of the present invention relates to a nucleic acid biomaterial including an isolated, modified nucleic acid.
[0009] In other embodiments, the biomaterial includes a suture material or a biomaterial matrix including an isolated, modified nucleic acid.
[0010] In another specific embodiment, the biodegradable polymer may be formed a drug carrier or a wound dressing.
[0011] More specific embodiments include biomaterial made of at least 50% nucleic acid by weight or volume. Other specific embodiments include biomaterial made of at least 5% 10%, 20%, 30%, 40%, 60%, 70%, 80%, 90%, or 95% nucleic acid by weight or volume In another specific embodiment, the biomaterial may be modified by capping, crosslinking, methylation, ethylation and attachment of a protein or small molecule.
[0012] In yet another specific embodiment, the modified nucleic acid comprises at least 5%, 10%, 20%, 30%, 40$, 50%, 60%, 70%, 80%, 90% or 95% DNA per total nucleic acid.
[0013] In another specific embodiment, the biomaterial includes a biodegradable copolymer. More specifically, this copolymer may be polylactic acid, polyglycol alginate, polyglycolic acid, poly amino acids, polysaccharides, cellulose acetate, hyaluronic acid and/or collagen.
[0014] In other embodiments, the biomaterial may include a hydrogel and/or a tissue scaffold.
[0015] In certain embodiments, the nucleic acid of the biomaterial may encode a protein. More specifically, it may include a wound healing factor.
[0016] An embodiment of the invention also includes a method of making a biomaterial by purifying a nucleic acid, modifying the nucleic acid and forming a biomaterial from the nucleic acid.
[0017] In specific embodiments the biomaterial may be a suture material formed by forming a nucleic acid filament. More specifically, the filament may formed by extruding the isolated nucleic acid through a spinneret and drying the extruded nucleic acid.
[0018] In other specific embodiments, the biomaterial may be a biomaterial matrix formed by preparing a solution of the nucleic acid and foaming the solution with supercritical carbon dioxide.
[0019] In another specific embodiment, the biomaterial may be a biomaterial matrix formed by freezing an aqueous solution of the nucleic acid and lyophilizing the frozen aqueous solution.
[0020] In yet another specific embodiment the biomaterial may be formed by creating a hydrogel including the nucleic acid.
[0021] In a specific embodiment, the nucleic acid comprises at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% DNA per total nucleic acid.
[0022] In another specific embodiment, the nucleic acid is modified by capping, crosslinking, methylation, ethylation, and/or attachment of a protein or small molecule.
[0023] In another specific embodiment a biodegradable copolymer may be added to the modified nucleic acid. More specifically, this biodegradable copolymer may be polylactic acid, polyglycol alginate, polyglycolic acid, poly amino acids, polysaccharides, cellulose acetate, hyaluronic acid and/or collagen.
BRIEF DESCRIPTION OF THE DRAWING
[0024] The invention may be better understood by reference to the drawings and detailed description of specific embodiments presented herein.
[0025] FIG. 1 is a schematic drawing of a collagen/DNA copolymeric suture material according to one embodiment of the present invention.
[0026] FIG. 2 is a schematic drawing of a DNA polywater biomaterial according to one embodiment of the present invention. All water molecules are not shown in the drawing.
[0027] FIG. 3 is a schematic drawing of a silica/DNA biomaterial according to one embodiment of the present invention.
[0028] FIG. 4 is a schematic drawing of a silica/glass/DNA biomaterial according to one embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0029] The present invention broadly relates to the use of nucleic acids as biomaterials, which are biocompatible. Although nucleic acids have been utilized extensively as sources of information, which may be used to produce various biological effects, potential uses based largely upon the polymeric aspects of nucleic acids have been neglected. The present invention capitalizes upon the polymeric properties of nucleic acids, although in certain embodiments it may also relate to their information coding aspects as well.
[0030] The present invention encompasses the use of nucleic acids from any source as a polymeric biomaterial. Sources include naturally occurring nucleic acids as well as synthesized nucleic acids. Nucleic acids suitable for use in the present invention include naturally occuring forms of nucleic acids, such as DNA (including the A, B and Z structures), RNA (including mRNA, tRNA, and rRNA together or separated) and cDNA, as well as any synthetic or artificial forms of polynucleotides. The nucleic acids used in the present invention may be modified in a variety of ways, including by crosslinking, intra-chain modifications such as methylation and capping, and by copolymerization. Additionally, other beneficial molecules may be attached to the nucleic acid chains. The nucleic acids may have naturally occurring sequences or artificial sequences. The sequence of the nucleic acid may be irrelevant for many aspects of the present invention. However, special sequences may be used to prevent any significant effects due to the information coding properties of nucleic acids, to elicit particular cellular responses or to govern the physical structure of the molecule.
[0031] Nucleic acids may be used in a variety of crystalline structures both in finished biomaterials and during their production processes. Nucleic acid crystalline structure may be influenced by salts used with the nucleic acid. For example, Na, K, Bi and Ca salts of DNA all have different precipitation rates and different crystalline structures. Additionally, pH influences crystalline structure of nucleic acids.
[0032] The physical properties of the nucleic acids may also be influenced by the presence of other physical characteristics. For instance, inclusion of hairpin loops may result in more elastic biomaterials or may provide specific cleavage sites.
[0033] The nucleic acid polymers and copolymers produced may be used for a variety of tissue engineering applications including, inter alia, to increase tissue tensile strength, improve wound healing, speed up wound healing, as templates for tissue formation, to guide tissue formation, to stimulate nerve growth, to improve vascularization in tissues, as a biodegradable adhesive, as device or implant coating, or to improve the function of a tissue or body part. The polymers may also more specifically be used as sutures, scaffolds and wound dressings. The type of nucleic acid polymer or copolymer used may affect the resulting chemical and physical structure of the polymeric biomaterial.
[0034] 1. Sources of Nucleic Acids
[0035] Naturally occurring nucleic acids may be harvested from almost any biological material. Harvesting techniques, including those capable of producing commercial volumes of nucleic acids (including nucleic acids with a specific sequence or group of sequences) are known in the art. Nucleic acids may be extracted from almost any biological source. Two common sources of non-specific DNA are fish sperm and calf thymus. Almost any source, animal or plant-based, yeast or bacterial may be used. These sources may be specifically developed for nucleic acid harvest or may be waste products of other commercial processes, as in the case of calf thymus.
[0036] Because many embodiments of the invention employ nucleic acids for their polymeric properties alone, and not their information coding properties, the sequences of nucleic acids may be irrelevant in such applications. However, it is possible that a given source may be undesirable because the nucleic acid retains its information coding aspects, which may give rise to unwanted side effects. For instance, in some examples it may be desirable to avoid use of bacterial nucleic acid sources if there is a danger of transformation of local bacteria with new sequences as the nucleic acid polymer degrades. Similarly, it may be best to use plant-derived nucleic acids in some applications in mammals to avoid transcription or translation of mammalian nucleic acids formed by polymer breakdown. Additionally, specific sequences may be desirable to product certain physical effects, such as hairpin loops.
[0037] In other aspects of the present invention it may be desirable for nucleic acids to become accessible for transcription or translation either in the form of the initially supplied polymeric biomaterial or as breakdown products thereof. For instance, the nucleic acids may encode proteins useful in association with the biomaterial, such as cytokines or wound healing factors. These proteins may be produced in mammalian cells or in bacteria resident around the biomaterial. They may promote an activity in mammalian tissue, result in destruction of unwanted bacteria, or have other benefical effects.
[0038] Nucleic acids, in certain examples, may be produced by solubilization of cellular material with a detergent, followed by extraction of nucleic acids from the aqueous layer with an alcohol. Various additional steps and additives may assist in the removal of protein to obtain purer nucleic acids. RNase inhibitors may be used to obtain better RNA yield. Various nucleases and extraction techniques may be employed to destroy unwanted forms of nucleic acids, such as RNA in a DNA sample. Such techniques are well known in the art. Techniques for obtaining nucleic acids of a given sequence or sequences are also known.
[0039] Nucleic acids may also be synthesized artificially from nucleotides. For instance, surface catalysis techniques or oligonucleotide synthesizers may be used. Artificial nucleic acids allow for ready control of sequence. This may be significant in avoiding unwanted side effects, or for obtaining beneficial effects as described above.
[0040] 2. Capping, Crosslinking and Nucleic Acid Modifications
[0041] Nucleic acids have different rates of degradation, which may be modified and exploited. Additionally, particular degradation products may be desired (for instance, nucleic acids with a given sequence). The sites or timing of degradation may be modified so as to obtain these products.
[0042] First, the type of nucleic acid selected may affect degradation. RNA will likely degrade much more rapidly than DNA. Different DNA structures may have different degradation rates. This may also vary by the tissue in which the nucleic acid is used. Various disease states or injuries may also affect degradation.
[0043] Second, in particular embodiments of the present invention, purified nucleic acids may be cross-linked to reduce degradation. Cross-linking may be accomplished in a variety of ways, including hydrogen bonds, ionic and covalent bonds, ππ bonds, polarization bonding, van der Wals forces. More specifically, crosslinking may be accomplished by UV radiation, esterification, hydrolysis, intercalating agents, neoplastic agents, formaldehyde, formalin, or silica compounds. One specific example includes the use of siloxane bridges as described in U.S. Pat. No. 5,214,134.
[0044] More than one type of crosslinking may be used within a given biomaterial. For example, use of a type of crosslinking easily degraded in a cell coupled with a more degradation resistant type of crosslinking may result in a biomaterial that is opened in two phases, one when the easily degraded crosslinks are broken and second when the more resistant crosslinks or the nucleic acid itself are degraded.
[0045] Crosslinking may occur between two strands of a double stranded nucleic acid or between the strands of two separate double strands. It may also occur between two separate single strands. Double strand to single strand crosslinking is also possible, as is crosslinking between different regions of one strand. Increased levels of crosslinking will generally slow degradation of nucleic acids. Linkers such as small organic molecules (esters, amines) or inorganic molecules (silicas, siloxanes), including microparticles or nanoparticles thereof, may be used to attach copolymers to nucleic acids.
[0046] Third, nucleic acids may be methylated, ethylated, alkylated, or otherwise modified along the backbone to influence degradation rates. Generally, methylated, hemi-methylated, ethylated, or alkylated nucleic acids will degrade more slowly. Other backbone modifications affecting degradation rates include the use of heteroatomic oligonucleoside linkages as described in U.S. Pat. No. 5,677,437. Additionally, modifications may be used to prevent the nucleic acid from being transcribed or translated in a given tissue or organism.
[0047] Fourth, nucleic acids may be capped to prevent degradation. Such caps are generally located at or near the termini of the nucleic acid chains. Examples of capping procedures are included in U.S. Pat. Nos. 5,245,022 and 5,567,810. In specific embodiments of the present invention, inorganic caps are used.
[0048] 3. Copolymerization
[0049] Biomaterials of the present invention also include copolymers. Copolymers that are also biodegradable and non-toxic to mammals may be preferred. However, polymers in which only one polymer (e.g. the nucleic acid portion) degrades, leaving a non-biodegradable framework may also be desirable in certain situations.
[0050] Examples of biomaterials that may be used as copolymers with nucleic acids include, but are not limited to, poly(amino acids), including PGA, PLA, PLGA and poly(proline), polysaccharides, such as cellulose, chitin and dextran, proteins, such as fibrin and casein, VICRYL®, MAXON®, PDS, poly(e-caprolactone), polyanhydirdes, trimethylene carbonate, poly(β-hydroxybutyrate), poly(DTH imino carbonate), poly(bisphenol A iminocarbonate), poly(ortho ester), polycyanoacrylate, polyphospohazene and hyaluronic acid.
[0051] Polymers may be formed in a variety of ways, depending upon the copolymer used and the desired properties of the finished polymer. The copolymer may be attached to the nucleic acid by covalent, ionic or hydrogen bonds or by Van der Wals forces. Linkers such as small organic molecules (esters, amines) or inorganic molecules (silicas, siloxanes), including microparticles or nanoparticles thereof, may be used to attach copolymers to nucleic acids. The finished biomaterial may contain the nucleic acids and copolymers arranged in a variety of fashions including, substantially end-to-end, end-to-side, side-to-side, or any mixture thereof with one or more linkages securing such attachments. Copolymers may also fall into the general forms or block copolymers and graft copolymers.
[0052] The nucleic acids in such copolymers may be selected or treated as described above for nucleic acid polymers.
[0053] 4. Polymer Modifications and Additions
[0054] Chemical and biological properties of nucleic acid polymers of the present invention may be influenced by modifications of the polymers, such as modification of the hydrophobicity or hydrophilicity of the polymers or copolymers. Additionally, any inorganic or organic molecules, including amino acids, silicas, cytokines, such as interleukins, biologics and drugs may be added to the nucleic acid polymers to produce certain biological effects. Nucleic acids provide a variety of molecular attachment sites and therefore facilitate covalent, ionic and hydrogen bonding, as well as Van der Wals attachments, or other forms of attachment.
[0055] 5. Sutures and Filamentous Biomaterials
[0056] Polymers of the present invention may be used to form filamentous polymeric biomaterials. Nucleic acids are filamentous by nature. This may allow formation of sutures or thread-like biomaterials simply by crosslinking nucleic acids. Techniques to draw the polymers into a filamentous form may also be used. Filament formation techniques may be particularly advantageous where a copolymer in the filament is not naturally filamentous. Such techniques include those known in the art for preparation of polymer filaments. Embodiments of filamentous polymers may be extruded, precipitated, woven and monofilamentous, inter alia. In specific embodiments, extrusion methods are used to produce filamentous biomaterials.
[0057] Formation of filamentous nucleic acid polymers may be facilitated by methods in which crosslinking, copolymerization, or other processes that define the overall structure of the polymer are not complete until after filament formation.
[0058] In one embodiment of the invention, the filamentous nucleic acid polymers may be used to form sutures. Filaments may used as initially produced or they may be twisted or braided, as is common in suture preparation. The composition of the nucleic acid polymers may be varied depending upon the length of time such sutures need to remain intact. Additionally, the sutures may be designed to produce bacteriocidal or healing factors as they degrade, or may be initially coated with such factors. Other treatment methods in use with other suture material may also be applied to sutures of the present invention.
[0059] 6. Structural Biomaterials
[0060] Polymers of the present invention may also be shaped into structural biomaterials, such as sponge-like forms for tissue growth or dental implants. Such structures may be formed using current methods for manipulation of biological materials, such as extracellular matrix material. They may also be formed by supplying the nucleic acid polymer to a mold or form before it is completely set in its final polymerized, crosslinked or other end state.
[0061] Structural biomaterials may include or produce as breakdown products a number of biological factors. For instance, angiogenic factors may be used to induce vascularization of tissue growing in the structural biomaterial. Structural biomaterials, in particular, may benefit from a multi-stage degradation wherein a certain crosslinker or other bond is broken early after introduction of biological cells or tissues or placement in a patient, but other crosslinkers or bonds retain the basic structure until sometime later.
[0062] Structural, wound healing and other biomaterials of the present invention may also be formed using a variety of techniques also used for other biomaterials. In particular embodiments, extrusion techniques may be used. For example, a spongelike biomaterial may be formed using a rotating extrusion device.
[0063] 7. Wound Healing Biomaterials
[0064] Polymers of the present invention may be used for wound healing in a variety of ways. First, nucleic acid polymers may be used to form hydrogels for use in a wound. They may also be shaped into patches or dressings to be placed in or over wounds.
[0065] A hydrogel is typically a three-dimensional network of polymers held together by association bonds. These networks are able to hold a large quantity of water within their structure without dissolving. They may have superior chemical and physical properties such as increased elasticity. The polymer portions of hydrogels may be formed first, with the aqueous components added later to allow easier transport, and more flexibility in terms of the solution added. For instance, an aqueous solution with a soluble drug may be used to hydrate the hydrogel. The desired soluble drug may vary for a given application. Hydrogels may also be in the form of a polywater, in which substantially all water in the hydrogel is in association with the nucleic acid polymer and accordingly limited in its movement.
[0066] Wound dressings may be formed as patches or 3D structures and they may be woven from filamentous nucleic acid polymers. Wound dressings in particular may benefit from the inclusion of bacteriocidal, clotting, or other factors on the nucleic acid polymers. Wound dressings intended to remain in place may encode healing factors, which may be designed to become expressible at particular stages of polymer degradation and wound healing. Wound dressing may also be formed from polywater hydrogels.
[0067] 8. Other Biomaterials
[0068] The present invention includes the use of nucleic acids polymers as any sort of degradable biomaterial. Such materials may be used in vitro or in vivo. They may be modified in any manner typical of other biodegradable materials for a given use.
[0069] Specifically, the nucleic acid polymers of the present invention may also be used as adhesives, drug carriers, coatings for surgical pins and plates or other materials, inhalers, fillers, membranes, cloths, castings, implants and as any other type of biocompatible material. In specific embodiments, nucleic acid biomaterials may be processed in any way PVA is processed and may be put to similar uses.
[0070] Water content of the various biomaterials of the present invention may be altered depending upon the intended use. For example, if the biomaterials are to be used as a wound dressing, water content may be at least 90%. For sutures water content may be as low as 5% or lower. In general water content may be similar to that of other materials put to similar uses.
[0071] The following examples are provided to illustrate certain aspects of the present invention. They are not intended to encompass and fully describe the entire invention or any aspect thereof.
EXAMPLES
Example 1
DNA-Based Suture Material
[0072] Suture material according to one embodiment of the present invention may be prepared using waste DNA. Such DNA may be harvested from calf thymus, fish sperm or other animal waste. It may be extracted from plant waste such as spoiled vegetation.
[0073] The tissue may be solubilized by first processing it to a pulp, then adding a detergent such as SDS. Proteinases such as Proteinase K may be added to destroy excess protein. RNases may be added to destroy RNA in the sample.
[0074] DNA may be extracted by adding Tris-phenol/chloroform or chloroform/isoamylalcohol. Approximately 70% or greater alcohol, such as ethanol or methanol may also be used to extract DNA. If phenol or isoamylalcohol are used to extract the DNA it may be lyophilized to help remove residual chemical.
[0075] Extracted DNA may be washed by repeated solubilization in water and extraction with alcohol to remove additional protein components. Special steps in which proteinases and RNases are added under digestion conditions may also aid in enhancing DNA purity.
[0076] For longer lasting sutures, the DNA may be crosslinked, capped and methylated or ethylated. It may also be treated by other methods described above to increase degradation resistance.
[0077] After any degradation resistance treatments, the DNA may be suspended in an aqueous solution with low alcohol content to form a viscous gel. This gel may then be extruded a spinneret similar to those used in collagen processing into a solution which causes DNA to condense, such as a high-alcohol content aqueous solution. DNA filaments thus formed may then be collected from the solution and dried.
[0078] The alcohol contents of the low-alcohol content and high-alcohol contents solution may vary depending upon whether the DNA is treated to reduce degradation. For untreated DNA the low-alcohol content aqueous solution may be approximately between 5 and 30% alcohol. The high-alcohol content solution may be between 80 and 95% alcohol.
[0079] The DNA filaments may be twisted or braided in the same manner as other suture filaments to produce stronger and more durable suture material.
Example 2
DNA/Collagen-Based Suture Material
[0080] DNA may be prepared and treated as described above. DNA in an aqueous solution of approximately 30% alcohol or less and containing little to no residual proteinase may then be crosslinked with collagen. The DNA solution be selected to contain DNA of only a certain molecular weight range.
[0081] Collagen may be prepared from animal tendons such as the flexor tendons of cattle. The tendons are cleaned, frozen, sliced and treated with ficin. They are then swollen with dilute cyanoacetic acid to produce a viscous gel. The DNA solution may be added to this gel along with a crosslinking agent such as 4% paraformaldehyde, or the gel may be subjected to ultraviolet radiation in order to crosslink the DNA and collagen. For many applications of the present invention, the crosslinking agent or method should be selected so that toxic by products will not be formed during degradation of the suture material.
[0082] The crosslinked solution may then be extruded through a spinneret into an aqueous solution containing high levels of acetone and alcohol, in which it will condense into fibers that may be dried. See FIG. 1 .
[0083] This general scheme may also be used with other polypeptides such as poly(amino acids) or hydrogenated keratins. Additionally, PVA may be used in place of or in addition to the polypeptides.
Example 3
DNA-Based Tissue Scaffold
[0084] DNA may be prepared as described in Example 1. The viscous solution of DNA may be resuspended in an aqueous solution with alcohol content between approximately 5 to 20%. This solution may then be poured into an appropriately shaped mold and frozen. Alcohol can then be evaporated from the frozen material. The solution may then be lyophilized to leave a porous material formed from the DNA. Exclusion of the DNA from the solvent crystal phase leaves a porous skeleton of material. The pore size of the material may be varied by varying the rate of freezing and the alcohol content. Freezing methods that result in larger crystals tend to produce larger pores. Additionally, temperature gradients in the frozen solution can be used to produce a material with a gradient of pore sizes.
[0085] In an alternative procedure, the DNA solution may be dried in the presence of supercritical carbon dioxide, which acts as a foaming agent.
[0086] Membranes such as these may be used for guided tissue regeneration, including tissue regeneration in patients. For instance, they may be used in applications where bone must grow below the membrane and fibroblasts on top. Using current technology, the membrane must usually be removed one regeneration has begun. This results in additional danger and discomfort to the patient. Membranes of the present invention may be designed to degrade at appropriate times, eliminating the need for removal.
Example 4
Hydrogel Formation
[0087] Hydrogels based on DNA may be formed with techniques used to produce polywater with PVA. See FIG. 2 . Essentially, a solution of about 20% DMSO, 79% water and 1% DNA by volume may be prepared and frozen. In the frozen state, a shell of water forms around the DNA molecules, which tend to be evenly spaced. DMSO and water may then be removed so that the only water substantially held in place around the DNA remains. This results in a composition of up to 99% water by volume, but with very little free water. This produces a substance that is capable of retaining moisture while allowing exchange of gasses. Such a substance may be formed into a membrane and used as a wound dressing.
Example 5
Silica-Based Nucleic Acid Biomaterials
[0088] Biomaterials of the present invention may also be formed by bonding DNA or other nucleic acids to silica particles. In specific embodiments the DNA may bond substantially at the end of the DNA molecule. The DNA molecule may be bound to a silica particle at either end and possibly at other points along the DNA strand. Multiple DNA molecules may be bound to a silica particle. Example embodiments may contain up to 50% silica by weight or volume. See FIG. 3 .
[0089] In another embodiment, DNA may be bonded at one end to a glass microparticle, such as a 1 μm diameter glass fiber, with the other end of each DNA molecule bonded to an SiO 2 nanoparticle, such as a 1 nm diameter particle. See FIG. 4 .
[0090] Biomaterials of the present invention additionally include nucleic acids coated on silica surfaces.
Example 6
Wound Dressings Containing TNFα
[0091] Hypertrophic scarring is a significant problem in many types of wounds, especially burns. Research indicates that hypertrophic scar tissue contains abnormally low levels of TNFα when compared to normal scar tissue. Hydrogels are commonly used to treat burns and sometimes lead to less scarring, but presently available hydrogels are unable to address the TNFα deficiencies that lead to hypertrophic scarring.
[0092] To address this problem, a hydrogel containing TNFα may be prepared using the DNA as described in Example 1. The DNA may be formulated into a hydrogel by suspension in an aqueous solution of no more than approximately 20% alcohol. Prior to hydrogel formation, TNFα may be linked to the DNA using a degradable crosslinker or bond, such as an ester bond. The strength and nature of this bond or crosslink will determine the rate of TNFα release. Additionally, multiple types of bonds or crosslinks may be used to obtain an even longer time-frame of TNFα release.
[0093] Other proteins may also be incorporated in the wound dressing. Such proteins include growth factors such as FGF, EGF and VEGF, fibronectin, vitronectin, adhesion factors and steroids. These and other proteins may be added to various other biomaterials of the present invention.
Example 7
Wound Dressing Encoding TNFα
[0094] A wound dressing DNA hydrogel may be prepared as described above. However, the DNA used for the hydrogel may be specifically selected to encode TNFα with an operable promoter. Such specific DNA may be prepared using any methods known to the art. Preparation of DNA in a mammalian or even yeast cell bioreactor may be preferable to the use of a bacterial source to limit the possibility of endotoxins. The DNA may also be treated to facilitate uptake by cells.
Example 8
Drug Encapsulation
[0095] DNA prepared according to the methods of the present invention may also be used as a drug encapsulent. It may be used as a spray, film, membrane or solid bead. For example, the nucleic acid may be partially solubilized in alcohol such as ethanol, acetone or a volatile organic solvent then sprayed onto the drug and the solvent then evaporated. It may also be foamed using a carbon dioxide agent.
Example 9
Delivery Agent
[0096] Nucleic acid polymers of the present invention may also serve as delivery agents for other materials. This may be their primary function or an additional function. Materials may be delivered by or absorption onto the surface of the nucleic acid biomaterial. For instance, the biomaterial may contain on its surface antibiotics, antioxidants, antivirals and/or growth factors, inter alia.
Example 10
Dispensation
[0097] Nucleic acid biomaterials of the present invention may be formed into shapes as described above. They may also be provided in saline solutions, buffered solutions, alcohol solutions, DMSO solutions and other solutions. These solutions may be designed to promote stability during storage.
[0098] Although only exemplary embodiments of the invention are specifically described above, it will be appreciated that modifications and variations of the invention are possible without departing from the spirit and intended scope of the invention. | 1a
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent application Ser. No. 12/582,621, filed Oct. 20, 2009, the entirety of which is incorporated herein by reference and is to be considered part of this specification.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The invention relates to the systems and methods for guiding, steering and advancing an invasive medical device in a patient.
[0004] 2. Description of the Related Art
[0005] The use of control cursors in catheter guidance systems is not unique. Prior art uses control cursors to locate the desired position of the catheter tip, but it does not bind the position and orientation to the achievable bounds of the system.
[0006] Blume et al, U.S. Pat. No. 6,014,580 describes a cursor for specifying the desired position of a catheter using a cross-hair type cursor. This is a simple pointing device which is capable of specifying a static location or locations within a workspace, but does not give a prediction of how the catheter will be situated with respect to the mapping data.
SUMMARY
[0007] The system described herein solves these and other problems by incorporating a catheter guidance and imaging system simulated model into a catheter control system and applying it to the use of predictive guidance, dynamic response, and full simulation of surgical procedures.
[0008] In one embodiment, a catheter guidance simulation is used to generate a secondary simulated catheter which may be controlled by the operator as an interactive cursor that realistically predicts the motion and end disposition and orientation of a catheter, and which is then used as a desired position target for the closed-loop regulator to guide a real catheter to that disposition.
[0009] In one embodiment, a catheter line is graphically rendered relatively realistically on a display, and constrained by the mapped geometry, between the live catheter position and the live sheath position.
[0010] In one embodiment, a catheter line is rendered realistically, and constrained by the mapped geometry, between a simulated catheter position and a live sheath position, as to connect a catheter control cursor to the actual catheter entry location.
[0011] In one embodiment, a catheter guidance simulation is used to train operators in the use of a catheter guidance system in the absence of a patient or control hardware. The range of motion and expected stability of catheter placement may be assessed in the absence of guidance and control hardware.
[0012] In one embodiment, a catheter guidance simulation is used to approximate the performance of a closed-loop regulator before it is tested on position control hardware. The dynamic response and interaction with geometric models present real-world scenarios for assessing the stability of closed-loop position control.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 is a block diagram of the placement of a catheter guidance and control simulation within a catheter guidance control and imaging system.
[0014] FIG. 2 is a block diagram of the internal algorithms of the simulated catheter physics and obstacle detection module.
[0015] FIG. 2B is a block diagram detail of the data in and out of the catheter flexure kinematic module.
[0016] FIG. 2C is a block diagram detail of the derivation of the net torque and force on the catheter tip based on the difference in actual and desired position.
[0017] FIG. 2D is a block diagram detail of the obstacle collision detection calculation adding contact normal vectors to the data for the physics calculations.
[0018] FIG. 2E is a block diagram detail of the torque, force and collision data to increment the simulated catheter's position.
[0019] FIG. 3 is an illustration of one embodiment of the invention where the simulation is used to create a virtual catheter cursor.
[0020] FIG. 4A is an illustration of a simulated catheter in proximity to an obstacle within the mapping geometry.
[0021] FIG. 4B is an illustration of a simulated catheter touching an obstacle.
[0022] FIG. 4C is an illustration of a simulated catheter touching an obstacle and rotating.
[0023] FIG. 4D is an illustration of a simulated catheter touching and obstacle and being forced back and downwards.
[0024] FIG. 5 is a block diagram of the catheter guidance system used as a simulator without any live patient data or hardware control.
[0025] FIG. 6 is a block diagram of the placement of the physics simulation within the navigation and control system rendering software that is used to generate data for a realistic catheter line.
[0026] FIG. 7 is an illustration of a flexible catheter line being constrained by a geometric mesh.
[0027] FIG. 8 is an illustration of the elements used to simulate the flexible catheter line being constrained by a geometric mesh with the associated constraint vectors.
DETAILED DESCRIPTION
[0028] FIG. 1 is a block diagram of the placement of a catheter guidance and control simulation within a guidance control and imaging system. A patient 1 is placed in a guidance control and imaging system in a standard configuration. A position detection system 3 is used by a position detection and mapping system 4 to continuously monitor the location and orientation of the tools within the patient. A guidance system's navigation and closed-loop control system 7 receives the live tool position data 5 from the position detection and mapping system 4 , as well as the 3D geometry 6 created by the mapping process. The navigation and closed-loop control module 7 outputs a set of control parameters 8 to the position control system 9 . These control parameters are the closed-loop control feedback that is used to synchronize the tool's actual position (AP) 5 with the operator's desired position (DP) 2 . FIG. 1 further shows that simulated tool position data 13 and simulated mapping geometry 11 from stored computer data 10 can be used in parallel with live data in the navigation and closed-loop control system 7 by the use of a simulated catheter physics and obstacle detection computer algorithm 12 . The input of this algorithm is the real and simulated tool position and mapping data, and the output of this algorithm is the simulated position data 13 based on the real navigation and closed-loop control system's position control regulator output 8 .
[0029] FIG. 2 is a block diagram of the internal algorithms of the simulated catheter physics and obstacle detection module 12 . The closed-loop regulator's position control regulator output 8 is first used to calculate the rest position of the tool under the current regulator parameters. This is done with a predetermined model for catheter flexure kinematics 12 . 1 that relates the regulator parameters to the tool position and orientation at a rest state. The difference between the actual position of the tool and the kinematic rest position is used to calculate the force and torque on the simulated tool using the actual position to desired position force and torque algorithm 12 . 2 . This actual position to desired position force and torque algorithm compiles the difference between the force and torque at the desired position and the force and torque at the current position, as specified by the predetermined kinematic model. Both real and simulated world space objects ( 5 , 6 and 11 ) are used by the obstacle collision detection algorithm 12 . 3 to calculate the torques and forces that oppose the tool's motion. These forces and torques are then used by the physics momentum calculation and obstacle collision force algorithm 12 . 4 to adjust the instantaneous velocity and rotation of the tool. These dynamic properties are used by the time step incremental position change algorithm 12 . 5 to give a discrete position change of the tool based on the closed-loop time increments. The new simulated tool position 13 is output back to the guidance and imaging system.
[0030] FIG. 2B is a block diagram detail of the data in and out of the catheter flexure kinematic module. The position control regulator's output 8 passes the key regulation parameters to the kinematic model 12 . 1 , including the magnetic field direction and magnetic field gradient and the length of the catheter. The kinematic model takes these parameters and outputs the ultimate static rest position and the physical forces on a catheter under the influence of those control system settings 12 . 11 .
[0031] FIG. 2C is a block diagram detail of the derivation of the net torque and force on the catheter tip based on the difference in actual and desired position. The theoretical net forces 12 . 11 on the catheter are given by the kinematic model for both the current actual position of the catheter (AP) and the desired static rest position (DP) of the catheter under the current control forces. These are subtracted by the actual position to desired position torque and force module 12 . 2 to give the net torque and force on the catheter 12 . 21 which is passed to the physics momentum calculation module 12 . 4 (see FIG. 2E ).
[0032] FIG. 2D is a block diagram detail of the obstacle collision detection calculation adding contact normal vectors to the data for the physics calculations. Industry standard routines 12 . 3 are used to detect collisions between the world space objects ( 5 , 6 and 7 ) and the catheter which output the contact locations and contact normal vectors 12 . 31 to the physics momentum calculation module 12 . 4 . The net torque and force 12 . 21 is also passed on from the previous module.
[0033] FIG. 2E is a block diagram detail of the torque, force and collision data to increment the simulated catheter's position. The net forces on the catheter tip from the control system and object collisions 12 . 31 are used by the physics momentum calculation and obstacle collision forces algorithm 12 . 4 to incrementally increase the linear and angular velocity of the catheter tip. Obstacle collisions are used to terminate the velocity in specific directions, and to impart an additional angular velocity due to off-axis collisions. The net linear and angular velocity are stored and used by the time step incremental position change algorithm 12 . 5 to incrementally change the catheter actual position and orientation (AP) 13 .
[0034] FIG. 3 is an illustration of one embodiment where the simulation is used to create a virtual catheter cursor. This provides the operator with an interactive cursor which gives a realistic view of the range of catheter motion and potential interaction with the geometric mapping data. The live position of the physical catheter 14 and the physical introducer sheath 15 , based on their electrode positions ( 14 . 1 , 15 . 1 ), are displayed from the position detection and mapping system data 5 . The catheter and introducer sheath are graphically rendered to depict the catheter 14 emerging from the sheath 15 . The simulated regulator output, indicated by the magnetic control arrow 17 is based on the operator input and is used to calculate and render a simulated catheter 16 which is also shown to emerge from the live physical sheath 15 . The flexible shaft of the simulated catheter 18 behaves as a physical catheter would, which gives the operator a visual reference of the amount of catheter in the chamber and the probable disposition of the catheter line about the chamber.
[0035] FIG. 4A is an illustration of a simulated catheter in proximity to an obstacle within the mapping geometry. The obstacle 19 may be either from the real-world mapping system data or a simulated object. The catheter 16 emerges from the sheath 15 , and the catheter's flexible section 18 is depicted as a smooth tangent curve.
[0036] FIG. 4B is an illustration of a simulated catheter touching an obstacle. The simulated catheter 14 is just making contact with the obstacle 19 , so the catheter line 18 is depicted as a smooth tangent curve.
[0037] FIG. 4C is an illustration of a simulated catheter touching an obstacle and rotating. The simulated catheter 14 is making strong contact with the tip, causing the tip to rotate. The catheter line is depicted as having a non-tangent “s” curve due to the applied torque to the tip.
[0038] FIG. 4D is an illustration of a simulated catheter touching an obstacle and being forced back and downwards. The catheter line is depicted as having a relatively sharp downward pinch, indicating that the catheter is being pushed back and downward.
[0039] FIG. 5 is a block diagram of the catheter guidance system used as a simulator without any live patient data or hardware control. The user's desired position input 2 is used by the navigation and closed-loop control module 7 to send position control regulator output 8 to the simulated catheter physics and obstacle detection engine 12 . The simulated position data 13 is based on the user's desired input 2 and the simulated mapping geometry 11 from stored data 10 . In one embodiment of the invention, the simulator may be used to develop and tune the closed-loop regulation of the navigation and closed-loop control module 7 as to give an approximation of the expected performance before the control loop is used with the sensitive hardware. In another embodiment of the invention, the simulator can be used to train operators without the patient and control hardware.
[0040] FIG. 6 is a block diagram of the placement of the physics simulation within the navigation and control system rendering software that is used to generate data for a realistic catheter line. A simple physics simulation 20 , such as the open source Tokamak Game Physics SDK, is used to generate additional location data needed to render the line between the sheath 15 and the catheter tip 16 . The navigation and closed-loop control module 7 passes the live position data 5 for the catheters, live mapping data 6 , simulated mapping geometry 11 from stored data files 10 and simulated catheter position data 13 through to the 3D rendering engine 21 and the catheter line physics simulation 20 . The rendering engine renders the catheters by their electrode location data ( 5 , 13 ). The catheter line physics calculations 20 insert the additional catheter line position data before the catheters are rendered 21 and displayed 22 . These control points 18 . 1 (see FIG. 8 ) are used by the rendering engine 21 in a similar fashion as the electrode location data to render the geometric spline meshes.
[0041] FIG. 7 is an illustration of a flexible catheter line being constrained by a geometric mesh. The catheter line 18 emerges from the sheath 15 and connects to the catheter tip 16 . The catheter tip 16 and sheath 15 locations are defined and rendered according to their electrode positions, 15 . 1 and 16 . 1 . The catheter line 18 is rendered according to the control points 18 . 1 (see FIG. 8 ) generated by a simple physics simulation 20 , such as the open source Tokamak Game Physics SDK, which generates a realistic interaction between the control points and all real and simulated geometric objects (see FIG. 1 , assemblies 5 , 6 , 11 and 13 ) including the spherical mesh obstacle 19 . The end constraints 18 . 2 (see FIG. 8 ) are the catheter tip 16 and sheath 15 locations. The length of the catheter line 18 . 3 is passed to the physics engine by the navigation and closed-loop control module 7 .
[0042] FIG. 8 is an illustration of the elements used to simulate the flexible catheter line being constrained by a geometric mesh with the associated constraint vectors. The catheter line that emerges from the sheath 15 and connects to the catheter tip 16 has been represented as a series of control points 18 . 1 , each with its own constraints. The simple physics simulation creates a realistic interaction between the elements and all of the live and simulated geometric objects ( 5 , 6 , 11 and 13 ). Where the flexible catheter line segment 18 makes contact with the chamber geometry or obstacle 19 , the line conforms to the shape and does not pass through the wall, behaving like a physical catheter. The acquired location of the physical or simulated catheter tip 16 and the physical sheath 15 become the end constraints 18 . 2 for the flexible segment control points 18 . 1 . The length of the segment within the chamber 18 . 3 , the geometric models ( 6 , 11 ) and the end constraints are sent to the physics engine 20 to generate the location of the catheter line control points 18 . 1 .
DETAILED DESCRIPTION
[0043] In the field of catheter guidance systems, a predictive kinematic algorithm can be used for determining the movement of a catheter based on control parameters is common. The operator either manually steers the catheter through the use of a joystick or similar fixture, or places a cursor where they wish the catheter to go and a predictive kinematic algorithm is used by the closed-loop control system to guide the catheter to that location.
[0044] In one embodiment, the operational parameters are commonly determined through finite element analysis and control loop feedback calculations, which are useful for predicting the general kinematics of the mechanical apparatus and stability of the control loop. The operator's experience with the ergonomics and responsiveness of the system are later tested in the completed guidance system. A simulated model of the catheter guidance system and its response to a variety of operator inputs and dynamic models is not generally available.
[0045] In the graphical rendering of catheters within a mapping system, the catheter electrode locations are used to reconstruct the location and size of the catheter as it exists between the electrodes. Those portions of the catheter that are not in close proximity to an electrode are not generally rendered, as there is no reliable positional reference. Where the catheter has an associated introducer with positional electrodes, there is no attempt to graphically connect the catheter tip to its origin from within its introducer.
[0046] Training for use of catheter guidance systems can be done by the use of a human analog model which is placed within the system and used as a physical representative of the anatomical structures. These models contain either static or moveable structures to allow the operator to practice the targeting of tissue locations and navigating around obstacles with the catheter guidance system.
[0047] It is to be understood that the illustrated embodiment has been set forth only for the purposes of example and that it should not be taken as limiting the invention as defined by the following claims. For example, notwithstanding the fact that the elements of a claim are set forth below in a certain combination, it must be expressly understood that the invention includes other combinations of fewer, more or different elements, which are disclosed in above even when not initially claimed in such combinations. A teaching that two elements are combined in a claimed combination is further to be understood as also allowing for a claimed combination in which the two elements are not combined with each other, but can be used alone or combined in other combinations. The excision of any disclosed element of the invention is explicitly contemplated as within the scope of the invention.
[0048] The definitions of the words or elements of the following claims are, therefore, defined in this specification to include not only the combination of elements which are literally set forth, but all equivalent structure, material or acts for performing substantially the same function in substantially the same way to obtain substantially the same result. In this sense, an equivalent substitution of two or more elements can be made for any one of the elements in the claims below or that a single element can be substituted for two or more elements in a claim. Although elements can be described above as acting in certain combinations and even initially claimed as such, it is to be expressly understood that one or more elements from a claimed combination can in some cases be excised from the combination and that the claimed combination can be directed to a sub combination or variation of a sub combination.
[0049] Insubstantial changes from the claimed subject matter as viewed by a person with ordinary skill in the art, now known or later devised, are expressly contemplated as being equivalently within the scope of the claims. For example, although the specification above generally refers to a ferrous substance, one of ordinary skill in the art will recognize that the described ferrous substances can typically be any suitable magnetic material such as, for example a ferrous substances or compounds, nickel substances or compounds, cobalt substances or compounds, combinations thereof, etc. Therefore, obvious substitutions now or later known to one with ordinary skill in the art are defined to be within the scope of the defined elements. Accordingly, the invention is limited only by the claims. | 1a
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to the disinfection of refuse such as garbage. The present invention more particularly relates to an apparatus for the disinfection of garbage and the like especially when received from marine vessels and under quarantine.
2. General Background and Prior Art
In the marine industry, it has been commonplace in past years for the garbage which accumulates on the ship and like refuse to be merely cast overboard during the journey into the surrounding ocean.
The dumping of such refuse or garbage at sea has now become illegal and seamen are required to dispose of their accumulated garbage at the port which is their destination.
In the United States, refuse, garbage and the like is quarantined by the Food and Drug Administration as soon as the garbage reaches the dock.
Inspectors from the Food and Drug Administration will normally require that the crewmen seal up the refuse or garbage in an approved container and, thereafter, demand that it be disposed of by suitable means to prevent the transfer of harmful disease or bacteria to the continental United States.
One prior art method for dealing with this problem has been the incineration or burning of the garbage which itself contributes to environmental pollution.
It would be desirable to have a method and apparatus for the disinfection of garbage, refuse and like materials accumulated on the ships which system for disinfection could quickly and easily rid the shipowner of the refuse problem.
Several prior art devices have been patented which attempt to disinfect or sterilize garbage, refuse or the like in some sort of container.
U.S. Pat. No. 4,017,980 issued to R. A. Kleinguenther, entitled "Apparatus and Process for Treating Wood and Fibrous Materials" teaches the use of an apparatus and process for treating wood and other fibrous materials within a hermetically sealed, heat insulated chamber at a certain atmospheric pressure and temperature range, the purpose of which would be to dry the fibrous materials to increase the tensile strength.
U.S. Pat. No. 1,955,289 issued to B. Greenfield, entitled "Steam Cooking Process" would teach the use for a method for cooking foods wherein the food may be cooked at various temperatures out of contact with the fuel gases and under a flowing pressure of a premixed stream of air and steam, by allowing the cooking chamber to have continuous ventilation to the atmosphere.
U.S. Pat. No. 4,160,445 issued to Paul Kunz, entitled "Pressure Vessel and Method for Cooking Food in a Pressure Vessel" would teach the use of a pressure vessel having therein a first zone in which solid material is introduced, and a second zone in the lower portion of the vessel where liquid is accumulated during the cooking process.
U.S. Pat. No. 3,721,527 issued to W. Lodige, et al, entitled "Method for Sterilizing Bulk Materials" teaches the use of sterilization by means of steam or hot gas, wherein batches of material are centrifuged in a closed chamber with simultaneous addition of sterilizing medium. Thereafter, the sterilizing medium is separated out from the material at a sub-atmospheric pressure with centrifuging of the material.
U.S. Pat. No. 1,902,625 issued to A. L. Dunham, entitled "Method and Apparatus for Sterilizing" teaches a method of sterilization by the use of superheated steam, in a closed chamber which is heated to a desired temperature by the introduction of the superheated steam at comparatively low pressure. The sterilization would take place in a dry atmosphere in order to maintain the temperature within the chamber above the point of steam condensation.
U.S. Pat. No. 4,050,388 issued to John A. Boyd, entitled "Refuse Treatment Apparatus" teaches the treatment of refuse by directing the non-pulverized refuse material into a furnace. A steam supply is introduced into the inlet end of the drum to admix with the refuse material being fed thereinto. The non-pulverized refuse material emerging from the outlet end of the drum would then pass through a series of treatment steps.
U.S. Pat. No. 2,260,710 issued to J. F. Gschwind entitled "Autoclave and the Like" would teach the use of an arrangement of direct and indirect heat sources in autoclaves to assure a quick heating up and a minimum of the heat and condensate losses. The invention would further prevent the loss of any heating fluids during the curing period inasmuch as there is no need for additional heating.
GENERAL DISCUSSION OF THE PRESENT INVENTION
The present invention solves these prior art problems and shortcoming by providing a disinfection device for use with garbage and refuse from shipowners which provides a spacious container having an inner refuse or garbage holding portion with movable lids which allow the addition of garbage or the like to the container and can thereafter be shut to seal the refuse inside. If desired, a plurality of lifting eyes can be located on the container which adapted for lifting onto the deck or into the hold of a ship where the garbage to be disinfected can be added to the container.
A continuous elongated steam sparger is provided on the inner portion of the container adjacent but spaced from the bottom. One end portion of the sparger outcrops the side wall portion of the container where a valve, for example, can be provided for valving the flow of steam to the inner portion of the container through the steam sparger.
In the preferred embodiment, the sparger comprises an elongated pipe having perforations which are spaced a desired distance and are patterned, for example, to spray steam downwardly toward the floor of the container at an angle with respect to the container floor. In the preferred embodiment, the sparger is formed by a plurality of generally parallel pipe sections which are joined at their end portions using, for example, elbow connections. Thus, a continuous elongated sparger is provided covering substantially an entire container floor and providing for substantially equal distribution of steam over the entire floor of the apparatus. During operation, water is preferably added to the container to a degree which fills the container with water to a level which submerges the entire steam coil sparger in water prior to the disinfection of garbage by the introduction of steam.
A garbage product to be added is added to the interior of the container with the sparger being spaced off the bottom of the container and with the openings being directed downwardly to prevent clogging.
Thus, it is an object of the present invention to provide a system for the disinfection of garbage which can be easily adapted for disinfection of garbage from ocean-going vessels, ships and the like.
It is another object of the present invention to provide a disinfection apparatus which disinfects garbage, refuse and the like using steam.
Another object of the present invention is to provide a garbage disinfection apparatus which quickly and easily disinfects garbage in relatively large quantities in a relatively short period of time.
It is another object of the present invention to provide an apparatus for the disinfection of garbage which is simple and easy to use.
It is another object of the present invention to provide an apparatus for the disinfection of garbage which is mobile, and can be easily transported from a vessel generating the garbage to an area where steam can be added to the apparatus and thence to a dump sight.
It is another object of the present invention to provide a garbage disinfection apparatus which can be easily sealed to safely contain quarantined garbage or the like which must thereafter be disinfected.
BRIEF DESCRIPTION OF THE DRAWINGS
For a further understanding of the nature and objects of the present invention, reference should be had to the following detailed description, taken in conjunction with the accompanying drawings, in which like parts are given like reference numerals and wherein:
FIG. 1 is a perspective, partially cut away view of the preferred embodiment of the apparatus of the present invention;
FIG. 2 is a sectional view taken along lines 2--2 of FIG. 1; and
FIG. 3 is a bottom view of the steam coil sparger portion of the preferred embodiment of the apparatus of the present invention, which is also a sectional view taken along lines 3--3 of FIG. 2.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 best illustrates the preferred embodiment of the apparatus of the present invention designated generally by the numeral 10. In FIG. 1, there can be seen a garbage disposal apparatus 10 which comprises generally a container 12 having lid portions 18, 16 attached hingedly thereto with the lids being movable in a pivotal fashion to open and close the provided upper opening 20 to container 12 which allows the entry of garbage, refuse or the like into the inner space 22 portion of container 12.
Container 12 provides within its inner space 22 and more specifically on the bottom portion thereof a continuous steam coil sparger 30 which sparger has an inlet 32 end portion provided with a valve 35 for controlling or valving the flow of steam into container 12 through sparger 30, the inflow of steam being schematically illustrated by the arrow 36 in FIG. 1.
Sparger 30 can be, for example, in the form of a plurality of substantially parallel pipe members 37 (12 being preferred) which are connected alternately at the end portions by elbow fittings 40.
The extreme end portion of sparger 30 from inlet 32 provides a cap 42. It will be understood by one skilled in the art, that the flow of steam from inlet 32 will be generally toward cap 42 with steam between inlet 32 and cap 42 leaving sparger 30 through provided openings 45 (see FIG. 3).
A pair of spacer support racks 50, 51 are seen best in FIGS. 1 and 2. Support racks 50, 51 are provided to space sparger 30 a distance D above the floor F of container 12 with a four to six inch spacing D being preferable.
Container 12 comprises generally a floor F portion and four sidewalls each being designated by the letter S.
In FIG. 3, there is seen a detail of a single sparger pipe 37 with discharge openings 45 being shown thereon. Openings 45 could be, for example, equally spaced a distance of six inches apart with each consecutive opening 45 being placed at an orientation of forty-five degrees (45°) downwardly with respect to the horizontal while alternating in forwardly and rearwardly disposed positions. Thus, steam would be distributed to the left and to the right of each sparger pipe 37 to provide an even distribution of steam within the inner space 22 of container 12.
As schematically shown in FIG. 2, water would preferably be added to inner space 22 above floor F of container 12 to a level WS which would submerge sparger 30 minutes before the introduction of steam at inlet 32. This has been found to provide a method and apparatus for the quick and complete disinfection of any mass of garbage which is added to container 12 through opening 22.
A plurality of lifting eyes 61-64 can be provided for attaching container 12 to a crane or the like for elevating container 12 onto the deck of a vessel where a mass of garbage to be disinfected can be added thereto.
The container of the present invention thus provides an easily movable container apparatus 10 which can be lifted onto the vessel, with the garbage or refuse product thereafter added and the container sealed on the vessel by appropriate authorities.
Container 12 could be, for example, welded steel construction while sparger could be in the form of a continuous sparger comprised of a plurality of pipe sections, each being preferably of extra heavy thickness steel pipe or the like.
Because many varying and different embodiments may be made within the scope of the inventive concept herein taught, and because many modifications may be made in the embodiments herein detailed in accordance with the descriptive requirement of the law, it is to be understood that the details herein are to be interpreted as illustrative and not in a limiting sense. | 1a
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BACKGROUND OF THE INVENTION
Golf has been a popular sport for many years and various different forms of carts heretofore have been provided to support a golfer's bag of clubs while the golfer plays a particular golf course. Some forms of carts are non-powered and must therefore be pushed or pulled by a golfer and other forms of carts are powered and include provisions thereon for supporting the golfer as well as his bag of clubs.
Such powered carts are sufficient in size to support other items such as coolers, seats, umbrellas, and other golfing accessories, but most handcarts include structure for supporting little more than a bag of golf clubs.
In the past, persons who used handcarts did so either because of the unavailability of powered carts or because of financial or physical exercise reasons and if motorized carts were available to the more affluent golfers such persons would rent motorized golf carts.
However, the recent increase of interest in physical conditioning has prompted even the affluent golfer to use a handcart rather than a motorized cart. The more affluent golfer is accustomed to many of the golfing accessories which previously could be carried only on a motorized golf cart. These accessories include drink coolers, seats, umbrellas and the like. Accordingly, a need exists for a golf cart of the hand type and which may be used by golfers wishing to receive maximum physical exercise while golfing and yet which will be capable of supporting numerous of the golfing accessories previously limited to motorized golf carts.
Examples of various different forms of golf carts including some of the general structural and operational features of the instant invention are disclosed in U.S. Pat. Nos. 2,711,027, 2,772,113, 2,780,508, 2,806,711, 3,147,988, 3,162,461, 3,164,339, 3,620,546, 3,707,279, 3,733,086, 3,866,934, 4,032,054 and 4,262,928.
BRIEF DESCRIPTION OF THE INVENTION
The golf cart of the instant invention incorporates, generally, an upstanding wheeled frame including a lower horizonal shelf projecting from the rear side of the frame and a retractable forwardly projecting handle carried by an upper portion of the frame. A first side of the frame includes a retractable support for supporting a cooler therefrom while the other side of the frame retractably mounts a seat structure. In addition, structure is provided on the frame for support of an umbrella and the handle of the cart supports a ball caddy, a scorecard support, a golf tee support and a drink container support. Further, one disclosed form of the invention includes a resettable distance travelled indicator operated by one of the wheels of the cart.
The main object of this invention is to provide a golf cart to be used by golfers wishing to obtain maxiumum exercise while golfing and wherein the cart is provided with structure for supporting a golf bag as well as a plurality of golf accessories therefrom and which may be collapsed into a compact state for ready storage and transport within the luggage compartment of a vehicle.
Another object of this invention is to provide a golf cart which will be capable of supporting various different types of golfing accessories such as a golf ball receiver, a score pad, golf tees, a drink container holder and an umbrella.
Another very important of this invention is to provide a golf cart also including retractable structure for supporting a cooler therefrom as well as a seat structure.
Yet another object of this invention is to provide a golf cart which will be able to indicate distance travelled from each golf tee.
A final object of this invention to be specifically enumerated herein is to provide a golf cart in accordance with the preceding objects and which will conform to conventional forms of manufacture, be of simple construction and each to use so as to provide a device that will be economically feasible, long lasting and relatively trouble free in operation.
These together with other objects and advantages which will become subsequently apparent reside in the details of construction and operation as more fully hereinafter described and claimed, reference being had to the accompanying drawings forming a part hereof, wherein like numerals refer to like parts throughout.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a first form of golf cart constructed in accordance with the present invention;
FIG. 2 is an enlarged front elevational view of the golf cart and with retracted positions of the cooler support and seat structure illustrated in phantom line;
FIG. 3 is a vertical sectional view taken substantially upon the plane indicated by the section line 3--3 of FIG. 2 and with the handle of the cart in a slightly more lowered position;
FIG. 4 is a fragmentary horizontal sectional view taken substantially upon the plane indicated by the section line 4--4 of FIG. 3;
FIG. 5 is an enlarged perspective view of the handle of the golf carts;
FIG. 6 is a fragmentary elevational view of the lower end of the frame of the golf cart with portions of the two axle assemblies thereof in exploded position and other portions illustrated in vertical sections;
FIG. 7 is a front elevational view of the golf cart on somewhat of a reduced scale and with the various foldably retractable portions thereof in retracted positions;
FIG. 8 is a fragmentary perpective view of the upper portion of the frame of the golf cart illustrating the adjacent handle portion in foldably retracted position;
FIG. 9 is an enlarged vertical sectional view taken substantially upon the plane indicated by the section line 9--9 of FIG. 5.
FIG. 10 is a side elevational view of a simplified modified form of golf cart; and
FIG. 11 is a fragmentary enlarged horizontal sectional view taken substantially upon the plane indicated by the section line 11--11 of FIG. 10.
DETAILED DESCRIPTION OF THE INVENTION
Referring now more specifically to the drawings, the numeral 10 generally designates a first form of golf cart constructed in accordance with the present invention. The golf cart 10 includes an upstanding frame referred to in general by the reference numeral 12 and the frame 12 includes upstanding opposite side members 14 and 16 interconnected at their lower ends by means of a horizontal transverse member 18. The upper end portions 20 and 22 of the opposite side members 14 and 16 are upwardly convergent and secured together by an upper end gooseneck stem 24 secured therebetween. One end of an elongated handle arm is pivotally anchored to the gooseneck stem 24 by a friction washer equipped pivot connection 28 and the handle arm 26 includes a free end equipped with a handgrip 30 and is swingable between the extended positions of the handle arm 26 illustrated in FIGS. 1, 2 and 3 and a folded collapsed position such as that illustrated in FIGS. 7 and 8.
With attention now invited more specifically to FIG. 6 of the drawings, it may be seen that the side member 14 has a collared sleeve 32 supported therefrom and that a live axle 34 upon which a wheel 36 is stationarily mounted is journalled through the sleeve 32 and equipped with a point cam 37 on its inner end. The point cam 37 is enclosed by a removable cover 38 supported from the flange 40 of the sleeve 32 and the axle is journalled in the sleeve 32 by flange bearings 42 and retained through the sleeve 32 by a hex nut 44.
The side member 16 of the frame 12, on the other hand, has a sleeve 46 supported therefrom through which a slidable adjustable and removable axle 48 is journalled. The sleeve 46 supports a spring biased locking pin 50 therefrom and the pin 50 is selectively engageable in either of two circumferential grooves 52 formed in the axle 48 and spaced longitudinally therealong. Of course, each of the axles 34 and 48 has a second support wheel 36 mounted thereon, the support wheels 36 being of lightweight metal construction and including resilient peripheral tread rings 56 supported therefrom.
In addition, the side member 16 has the bifurcated right angulated base end 58 of a support arm 60 pivotally supported therefrom as at 62 and the support arm 60 mounts a seat cushion 64 therefrom and has a support leg 66 pivotally supported from its outer end as at 68, the free end of the support leg 66 including a horizontally enlarged foot 70.
The pivot structure 62 between the bifurcated base end 58 and the side member 14 includes frictional washers (not shown) whereby the support arm 60 may be frictionally retained in the raised phantom line position thereof illustrated in FIG. 2 of the drawings. In addition, the pivot connection at 68 also includes similar frictional washers whereby the support leg may be frictionally retained in the phantom line retracted position thereof illustrated in FIG. 2 of the drawings between opposing flanges of the support arm 60.
The side member 14 has the bifurcated base end 72 of a second support arm 74 supported, therefrom by a friction washer equipped pivot connection 76 and the support arm 74 mounts a support table 78 therefrom equipped with a peripheral railing 80 disposed above the table 78. The table 78 is adapted to receive a cooler 82 thereon, see FIG. 1.
The upper end portion 20 also mounts an L-shaped bracket 84 therefrom equipped with a first "Velcro" panel 86 and a distance indicator of the LED or LCD readout and resettable type such as that indicated by the reference numeral 88 is removable from the bracket 84, the readout 88 being provided with a second type of "Velcro" panel for coaction with the panel 86 in order to removably anchor the readout 88 to the bracket 84. The readout 88 is, of course, electrically connected to a point assembly (not shown) also enclosed within the cover 38 and actuable by the point cam 37. In this manner, the distance travelled by the wheel mounted on the axle 34 may be indicated by the readout 88. The lower portions of the upper end portions 20 and 22 include a plurality of vertically spaced bar members 90 supported and extending therebetween (see FIG. 2) and the bar members 90 may be utilized to support any suitable articles such as a cloth or piece of clothing. In addition, the upper end portion 22 supports a hook 92 therefrom which may also be used to support a selected article.
The handle arm 26 mounts one longitudinal edge of a scorecard supporting panel 94 therefrom (see FIG. 5) and the other longitudinal edge of the panel 94 supports a pair of scorecard engageable clips 96 therefrom. The panel 94 extends longitudinally of the handle arm 26 and the marginal edge of the panel 94 remote from the handle arm 26 includes a depending apertured panel 98 supported therefrom. The panel 98 includes a plurality of apertures 100 formed therethrough and golf tees 102 may be wedged in the apertures 100 for support from the panel 98. Also, the end of the panel 94 remote from the handgrip 30 thereof includes a notched support 104 from which writing instruments may be supported and the underside of the panel 94 supports a tubular magazine 106 therefrom closed at its end remote from the handgrip 30 and including ball retaining fingers 108 at its end adjacent the handgrip 30. The magazine 106 includes a coiled compression spring (not shown) disposed therein and a plurality of golf balls 110 may be telescoped into magazine 106 against the biasing action of the aforementioned spring, the ball retaining fingers 108 preventing the outermost ball 110 from being discharged from the magazine 106. Further, from FIG. 9 of the drawings, it may be seen that the interior of the magazine 106 is lined with a smooth plastic sleeve 112. Also, if it is desired, the interior spring within the magazine 106 may be omitted and the golf ball 110 closest to the ball retaining fingers 108 may be discharged from the open end of the magazine toward the fingers 108 merely by tilting cart to a position such that the handle arm 26 is in a forward and downwardly inclined position.
From FIGS. 1, 2, 5 and 7 of the drawings, it may also be seen that the handle assembly supports a drinking container holder 114 therefrom, the holder 114 being pivotally mounted as at 116, see FIG. 5, or oscillation about a horizontal axis extending transversely of the handle arm 26.
The juncture between the upper end portions 20 and 22 of the side members 14 and 16 supports a rigid horizontal and rearwardly opening semi-cylindrical brace 118 therefrom with whose free ends a flexible and longitudinally stretchable elongated tension member 120 may be releasably engaged. The brace 118 and the tension member 120 encircle the upper end of a conventional golf bag 122 therefrom. A similar semi-cylindrical brace 124 is supported by a depending shank 126 from the central portion of the transverse member 18 and has the opposite ends of a second elongated flexible and longitudinally stretchable tension member 127 removably anchored to its opposite ends. The central portion of the transverse member 18 also includes a horizontally rearwardly projecting base 128 from whose outer free end of the base end 130 of a horizontally outwardly projecting and horizontally swingable kick stand 132 is pivotally mounted as at 134. The outer end of the kick stand 132 includes downwardly facing foot 136.
From FIGS. 1 and 2, it may be seen that an upstanding sleeve 140 is supported from the upper end portion 20 and equipped with a thumb screw 142. The lower end of an upstanding umbrella shank 144 is adjustably anchored in the sleeve 140.
It will be noted that the major components of the cart 10 are constructed of lightweight material such as aluminum, exclusive of the axles 34 and 48 from which the wheels 36 are supported as well as other minor components which may be constructed of other metals or plastic, and FIG. 8 of the drawings illustrates an adjustable set screw 148 by which upward swinging movement of the handle arm 26 may be adjustably limited.
With attention invited more specifically to FIGS. 10 and 11 of the drawings, there will be seen a modified form of golf cart referred to in general by the reference numeral 10' and which is substantially identical to the cart 10, except that the cart 10' includes vertically spaced horizontal plates 11 and 13 through which upper and lower end portions, respectively, of golf club shaft support tubes 15 and an umbrella support tube 17 are supported. The tubes 15 are used in lieu of the golf bag supporting braces 118 and 124 and the cart 10 may be provided with a tube corresponding to the tube 17, if desired. Otherwise, the cart 10' is substantially identical to the cart 10.
The foregoing is considered as illustrative only of the principles of the invention. Further, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention. | 1a
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TECHNICAL FIELD
This invention relates to novel peptide antagonists of luteinizing hormone.
BACKGROUND OF THE INVENTION
In the mammal, the anterior pituitary gland is located at the base of the brain, but is separate from it. A special set of closed circulation blood vessels connect the anterior pituitary to the brain at the region of the hypothalamus. It is the activity of the hypothalamus which largely regulates the production of luteinizing hormone, (LH), and follicle stimulating hormone, (FSH), by the anterior pituitary.
Within the hypothalamus, neurosecretory cells manufacture and release gonadotropic releasing hormones such as luteinizing hormone releasing hormone, (LHRH), also know as gonadotropic releasing hormone, (GnRH). LHRH enters a closed system of blood vessels directly connecting the hypothalamus with the anterior pituitary. As LHRH contacts neurosecretory cells located within the anterior pituitary these cells are stimulated to release luteinizing hormone into the systemic blood stream. In a similar manner, the hypothalamus causes the anterior pituitary to release FSH.
A developing mammalian egg, an oocyte grows to maturation within an ovarian follicle. Cyclically, the hypothalamus secretes follicle stimulating hormone releasing factor into the closed capillary system attaching the hypothalamus to the anterior pituitary. Once FSHRH contacts the anterior pituitary, it stimulates neurosecretory cells to produce FSH. FSH causes the mammalian follicle to grow both in size and number of cells. The follicle cells in turn secrete estrogen which stimulates the growth of the uterine wall in preparation for implantation of an embryo should fertilization occur. A feedback phenomenon occurs as estrogen level production stimulated by FSH rise causing both a direct reduction in the output of FSH by the anterior pituitary as well as an indirect effect by means of reducing hypothalamic stimulus of the anterior pituitary.
As the follicle reaches full maturity, the hypothalamus responds to the rising estrogen levels by secreting LHRH or luteinizing hormone releasing hormone into the closed capillary system connecting the hypothalamus with the anterior pituitary. As LHRH reaches the anterior pituitary, it stimulates release of luteinizing hormone. Luteinizing hormone stimulates the completion of maturation of the follicle and ovum. LH is also known as interstitial cell-stimulating hormone since it acts upon the interstitial cells of the testes in stimulating production of testosterone. After the mature follicle has released an ovum into the oviduct, the corpus luteum, which is derived from the remnant granulosa and theca cell of the ruptured follicle cells, becomes the equivalent of an endocrine gland secreting progesterone under the influence of LH.
If a fertilized egg is implanted, chorionic gonadotropin or CG is secreted by the placental tissues. CG prevents the corpus luteum from degenerating and allows it to continue its production of progesterone. Progesterone maintains the growth of cells of the endometrium as well as maintaining an adequate blood supply to nourish an implanted embryo.
Normally, as outlined above, the function of LH and FSH are biologically positive. FSH stimulates the mammalian follicle to produce estrogens while LH stimulates the corpus luteum to produce progesterone and the interstitial cells of the testes and ovaries to produce testosterone and estrogen respectively. FSH and LH have a synergism. That is to say, LH, when administered by itself has little or no effect, but combined with a small dose of FSH induces follicular maturation. Likewise, a small amount of LH greatly augments the response of the response of tissue to a small amount of FSH. For this reason, LHRH antagonists also affect the activity of FSH.
The above discussed hormones may be classified as gonadotropic as they stimulate growth and function of reproductive tissue. However, there are certain situations in which the gonadotropic effects of these hormones may deleteriously affect the health of an individual. Certain tumors derived of hormone dependent tissue are stimulated by the same gonadotropic hormones that stimulate healthy tissue. If such tumors are exposed to the normal anabolic effect of such hormones, rapid growth, and in the case of malignant tumors, metastasis is encouraged.
Various treatment modalities have been available for treating disease of hormone responsive tissue. Basically, these treatment modalities may be classified as those involving estrogen, androgen, and progestin additive therapy, or ablative procedures involving orchidectomy and removal of the ovaries.
Treatment of hormone dependent pathology such as uterine fibroids, breast, prostatic and testicular interstitial cancer, endometriosis and certain human papillomavirus associated tumors may be accomplished through altering the amount of circulating estrogen, progesterone, or testosterone. Precocious puberty may be treated by reducing the levels of circulating gonadotropic hormones.
Ablation, or castration therapy has been utilized in treating tumors derived from organs which are normally responsive, or dependent upon hormones. Ablative surgery has been used extensively in women with breast carcinoma. Removal of the ovaries is most beneficial to premenopausal women in whom there has been a long interval between mastectomy and recurrence or who have mainly osseous and soft-tissue metastases.
Orchidectomy has been utilized to treat carcinoma of the prostate. As with other ablative treatments, hormone therapy is sometimes used in place of excision. In prostate carcinoma, estrogen therapy has been utilized with some measure of success. Castration is especially effective in men with breast cancer and results in a response rate of nearly 70 percent. Thorn et al., Harrison's Principles Of Internal Medicine, eighth ed. pp. 1753, (1977).
Filicori et al., GnRH Agonists and Antagonists Current Clinical Status, Drugs 35:63-82 (1988) discloses the clinical application of GnRH analogues. The article discloses the use of these agonist drugs in successfully treating precocious puberty, prostatic cancer, breast cancer, female contraception, male contraception, endometriosis, uterine leiomyoma, and polycystic ovarian disease. However, although promising results in treating these various pathologies are disclosed, the need for effective LHRH antagonist is strongly emphasized.
LHRH antagonist drugs of the past have required extensive modifications in the native LHRH to obtain a potent antagonistic effect as compared to the relatively minor changes required for formulating superactive GnRH agonists. It has been believed that the number and the type of amino acid substitutions and the resulting conformation of the antagonist that affects LHRH receptor binding.
There is currently much research directed to the use of gonadotropic antagonists such as LHRH antagonists in treating pathological conditions which are normally responsive to a reduction in plasma levels of gonadotropic hormones such as uterine fibroids, precocious puberty, endometriosis and hormone dependent carcinomas. These antagonist peptides strongly inhibit LH secretion and have some effect, as explained above in diminishing FSH activity.
Well known examples of LHRH antagonists are those described by A. V. Schally and others in Proc. Natl. Acad. Sci. (USA), Vol 85, pp. 1637-1641 (1988). K. Folkers and others in Tetrahedron, Vol 46, pp. 33297-3304 (1990), also in Proc. Natl. Acad. Sci. (USA) Vol 85, pp. 8236-8240 (1988).
Although LHRH antagonists offer a promising alternative in treating hormone responsive disease, peptide antagonists synthesized so far have demonstrated serious deficiencies and side effects. Presently, sufficient potency has not been demonstrated in vivo, for the antagonistic peptides. Furthermore, serious side effects such as histamine release, anaphylactoid reactions, and hypotension occur. LHRH antagonists have also caused local vascular permeability changes and associated edematogenic effects, poor water solubility and inadequate duration of action.
What is needed is a water soluble LHRH antagonist peptide which exhibits sufficient potency so as to achieve an effective therapeutic effect, while minimizing anaphylactoid reactions of past antagonists described above.
SUMMARY OF THE INVENTION
Now in accordance with the present invention a luteinizing hormone releasing hormone, (LHRH) antagonist has been discovered which effectively reduces the amount of luteinizing hormone and follicle stimulating hormone produced by the anterior pituitary gland. The LHRH antagonist of the present invention reduces the level of circulating estrogen, progesterone and testosterone in mammals which are treated with a therapeutically effective dose of said antagonist.
The preferred embodiment of the LHRH antagonist peptide of the present invention is characterized by the following formula:
SEQ ID NO.: #1 wherein the Alanine residue at SEQUENCE position 1 is N-acetyl-D-3-(2-naphthyl)-Ala; the Phenylalanine residue at SEQUENCE position 2 is D-3-(4-chlorophenyl)-alanine; the Alanine residue at SEQUENCE position 3 is D-3(3-pyridyl)-Ala; the Lysine residue at Sequence position 6 is D-6-carbamoyl lysine; the Lysine residue at SEQUENCE position number 8 is Nε-isopropyl-Lys; and the Alanine residue at SEQUENCE position 10 is D-Ala-NH 2 .
An alternative embodiment of the present invention is characterized by the following formula:
SEQ ID NO.: 2 wherein the Alanine residue at SEQUENCE position 1 is N-acetyl-D-3-(2-naphthyl)-Ala; the Phenylalanine residue at SEQUENCE position 2 is D-3-(4-chlorophenyl)alanine; the Alanine residue at SEQUENCE position 3 is D-3(3-pyridyl)-Ala; the Lysine residue at Sequence position 6 is D-6-carbamoyl lysine; the Lysine residue at SEQUENCE position number 8 is Nε-isopropyl-Lys; and the Proline residue at SEQUENCE position 9 is Pro-NHCH 2 CH 3 .
In another embodiment of the present invention a method for reducing circulating levels of estrogen, progesterone and testosterone is provided wherein an LHRH antagonist according to the present invention is administered to a subject mammal at a therapeutically effective dosage so as to reduce said levels. As is well known in the art, the therapeutically effective dosage for any given hormone antagonist is dependent on various factors identified with each subject to be treated such as subject weight, age, metabolic rate and plasma levels of gonadotropic hormones. However, the human dosage for the LHRH antagonists of the present invention generally ranges between about 0.1 and 1.0 mg/day in order to achieve a castration level of estradiol or testosterone.
The LHRH antagonist peptides of the present invention may be utilized as an alternative to ablation treatment in treating disease of estrogen and androgen responsive tissue which is ordinarily responsive to reduction of plasma levels of these hormones. When utilized for this purpose, individual subjects should be titrated to ablation levels of plasma testosterone or estrogen (estradiol). As discussed above, a daily dosage of from about 0.1 to 1.0 mg is used to achieve the required castration level.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The LHRH antagonist peptides of the present invention may be utilized in the treatment of prostatic cancer. The antagonist is titrated to a dosage required to simulate castration levels in order to substantially reduce the circulating androgen level.
The peptides of the present invention may be utilized alone, or in combination with anti-androgens such as flutamide, cyproterone acetate, and ketoconazole. These anti-androgen preparations are required where significant androgen production occurs in the adrenal gland. Since adrenal production of androgens are not affected by LHRH anti-androgens may be combined with the peptides of the present invention in order to block androgen activity from adrenal origin.
The LHRH antagonist peptides of the present invention may be used as an alternative to ovariectomy in the palliative treatment of breast cancer of premenopausal women. Because of the relatively low level of estrogen in post menopausal women, and in women who have undergone ovariectomies, any reduction of this hormone through utilization of the LHRH antagonist peptide of the present invention would be of limited value.
The peptides of the present invention must be titrated so as to achieve profound pituitary and gonadal suppression. Such suppression occurs, as discussed above, with a daily average dosage range of about 0.1 to 1.0 mg/day.
The peptides of the present invention may be utilized in the treatment of endometriosis; the ectopic occurrence of endometrial tissue generally within the abdominal cavity. By suppressing gonadal steroid secretion, growth of endometrial tissue decreases to the level of atrophy, thus effectively reducing endometrial tissue island formation within the myometrium or in the pelvic cavity outside the uterus. Thus an alternative to anterior pituitary drugs such as Danazol (pregna-2, 4-dien-20-yno[2,3d]isoxazol-17-ol), and surgical excisions of implants through laparoscopy, in a method of treating endometriosis is provided wherein cardiovascular side effects and mild androgenic effects associated with such drugs are avoided, and the need for surgical excision is either eliminated or reduced.
The LHRH antagonist peptides of the present invention additionally provide a method for treating uterine leiomyoma in pre-menopausal women. By titrating patient estrogen levels to those levels found in post menopausal women, control of tumor growth, and regression is possible. Thus the peptides of the present invention provide an alternative to the only known (non-surgical) existing medical treatment of uterine leiomyoma; LHRH agonist therapy. Complete anterior pituitary suppression is required in order to ensure effective treatment of uterine leiomyoma.
The LHRH antagonist peptides of the present invention provide a method for treating polycystic ovarian disease. The increased androgen secretion associated with this disease may be associated with either ovarian or adrenal secretion. Since adrenal secretion is not responsive to variations in gonadotropic hormone levels, the LHRH antagonist of the present invention may alternatively be used as a diagnostic tool in differentiating the source of elevated plasma levels of androgen. By administering a castration level of the peptides of the present invention to a subject with polycystic ovarian disease, the level of androgen will profoundly decrease if ovarian tissue (LH-responsive tissue) is responsible for the unusually high levels of androgen. If, on the other hand, no substantial decrease in androgen level is detected, it is the adrenal gland which is responsible for the elevated androgen levels. If the ovarian tissue is responsible for elevated levels of androgen, the LHRH antagonist peptide of the present invention may be utilized, (at a castration level), in order to control polycystic disease and associated ache and hirsutism.
LHRH antagonist peptides of the present invention may be prepared utilizing automated peptide synthesis techniques well known to the art. The following examples disclose two methods utilizing standard techniques, however, one skilled in the art may readily adapt other techniques to different synthesizers.
EXAMPLE 1
A synthesis of an LHRH antagonist peptide according to the present invention was carried out by the solid-phase-method on a benzhydrylamine resin on a polystyrene support using the LABORTEC peptide Synthesizer (SP 650, LABORTEC AG, 4416-Bubendorf, Switzerland) using Fmoc-amino acids (FMOC=9-Fluorenylmethyloxycarbonyl) and following the manufacturers instructions.
Optionally Boc-amino acids,(Boc-t-butyloxycarbonyl) can be used. Both natural and unnatural amino acids were obtained by Bachem AG, Bubendorf, Switzerland. Purification of the crude peptide was accomplished by gel permeation chromatography on Sephadex G 25 followed by permeation chromatography on Sephadex G 25 followed by preparative HPLC purification on silica gel.
The following peptide was thus obtained. SEQ ID NO.: 1 wherein the Alanine residue at SEQUENCE position 1 is N-acetyl-D-3-(2-naphthyl)-Ala; the Phenyl-alanine residue at SEQUENCE position 2 is D-3-(4-chlorophenyl)-alanine; the Alanine residue at SEQUENCE position 3 is D-3(3-pyridyl)-Ala; the Lysine residue at Sequence position 6 is D-6-carbamoyl lysine; the Lysine residue at SEQUENCE position number 8 is Nε-isopropyl-Lys; and the Alanine residue at SEQUENCE position 10 is D-Ala-NH2.
The molecular weight of the LHRH antagonist so synthesized is 1459.2 g/mol. The amino acid analysis yielded the following results: Serine 0.92, Proline 1.07, Alanine 0.98, Tyrosine 1.03. The product is freely soluble in water.
EXAMPLE 2
Utilizing substantially the same procedure as in Example 1, the following LHRH antagonist of the present invention was obtained. SEQ ID NO.: 2 wherein the Alanine residue at SEQUENCE position I is N-acetyl-D-3-(2-naphthyl)-Ala; the Phenylalanine residue at SEQUENCE position 2 is D-3-(4-chlorophenyl)alanine; the Alanine residue at SEQUENCE position 3 is D-3(3-pyridyl)-Ala; the Lysine residue at Sequence position 6 is D-6-carbamoyl lysine; the Lysine residue at SEQUENCE position number 8 is Nε-isopropyl-Lys; and the Proline residue at SEQUENCE position 9 is Pro-NHCH 2 CH 3 .
EXAMPLE 3
The LHRH antagonist peptide of Example 1 was converted into a slightly soluble pamoate salt. An aqueous solution of the peptide of Example 1 was mixed with an aqueous solution of sodium pamoate. The resultant mixture was then filtered so as to allow collection of a sparingly soluble peptide pamoate salt which was thus formed.
EXAMPLE 4
The water soluble peptide of Example 2 was converted into a sparingly soluble stearate salt by mixing an aqueous solution of said peptide with an alcoholic (ethanol) solution of stearic acid and filtering the resulting stearate salt thus formed.
EXAMPLE 5
Six rats were utilized to test the LHRH antagonist peptide of Example 1 of the present invention for anaphylactoid properties. Each of the six rats was injected with 5 mg/kg of the test peptide. No mortality or other signs of anaphylactoid reactions were observed over a 24 hour period.
The effect of an LHRH antagonist peptide of Example 1 of the present invention was compared to the effect of "Antide", cf. A. Ljungqvist et al., Biochem. Biophys. Res. Comm., 148, 849-858 (1987)., an LHRH antagonist of the prior art. Both LHRH antagonists were intermuscularly injected into 6 rats at a dosage of 300 mcg/kg. The following results were obtained:
TABLE 1______________________________________Group 0 hr 24 hr 48 hr______________________________________Saline 3.60 ± 2.04 2.74 ± 1.05 3.41 ± 2.14i.m."Antide" 3.35 ± 2.51 0.78 ± 0.37** 1.96 ± 0.95300 μg/kgi.m.Peptide of 5.46 ± 3.32 0.067 ± 0.030***0.84 ± 0.28*Example 1300 μg/kgi.m.______________________________________
As can be seen by the above data in Table 1, the LHRH antagonist peptide of Example 1 is more than about ten times as effective as Antide, an LHRH antagonist of the prior art, at 24 hour suppression of plasma testosterone in rats. The data for 48 hours indicates the peptide of Example 1 is more than twice as effective as Antide.
For the intended therapeutic uses, the peptides of the invention are formulated in suitable pharmaceutical compositions, using well known techniques and excipients such as disclosed, for instance, in Remington's Pharmaceutical Sciences Handbook, Mack Pub. Co., N.Y. USA, XVII ed. The compositions of the invention will be preferably suited for the parenteral or intranasal delivery: for the parenteral administrations, pharmaceutical delivery systems consisting of a biodegradable and biocompatible polymer as a matrix are particularly preferred whereas for the intranasal delivery the combined use of pharmaceutically acceptable peptidase inhibitors and/or pharmaceutically acceptable mucosal penetration enhancers (surfactants, quaternary ammonium salts, betaine derivatives and the like) is preferred.
The daily dosage peptides will range from 0.1 to 1 mg of the peptides of the invention, suitably formulated.
While it is apparent that the invention herein disclosed is well calculated to fulfill the objects above stated, it will be appreciated that numerous modifications and embodiments may be devised by those skilled in the art, and it is intended that the appended claims cover all such modifications and embodiments as fall within the true spirit and scope of the present invention.
__________________________________________________________________________SEQUENCE LISTING(1) GENERAL INFORMATION:(iii) NUMBER OF SEQUENCES: 2(2) INFORMATION FOR SEQ ID NO:1:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 10 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:AlaPheAlaSerTyrLysLeuLysProAla1510(2) INFORMATION FOR SEQ ID NO:2:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 9 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:AlaPheAlaSerTyrLysLeuLysPro15 | 1a
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FIELD OF INVENTION
[0001] The present invention relates to the uses of Curculigo latifolia ( C. latifolia ) extracts.
[0002] BACKGROUND OF INVENTION
[0003] Heterogeneous metabolic disorder such as Type 2 diabetes mellitus is mainly caused by inadequacy of insulin-producing β-cells to keep up with demand and insulin resistance occurring in peripheral tissues such as liver, adipose and muscle tissues. Apart from that, the combinations of sedentary lifestyle, unhealthy dietary habits, and genetic predisposition are the main reasons for this problem. If the condition is not controlled, it can lead to other health problems like obesity, cardiovascular diseases, kidney failures and lost of vision.
[0004] Recently, hypoadiponectin, insulin resistance and defect in glucose uptake activity become a central issue in the pathogenesis of type 2. Adiponectin is a cytokine which has been secreted exclusively by adipose tissue during adipocyte differentiation. It plays a role in metabolism to improved insulin sensitivity, glucose tolerance and lipid profile. However, in diabetes situation, the adiponectin level is decrease and it can contribute into insulin resistance and hyperinsulinemia occurrence. Insulin resistance can be defined as insulin-mediated glucose clearance into target tissues which is a peripheral tissue. In normal scenario, insulin induce glucose uptake in these tissues by binding to the insulin receptor proteins at the surface of the cell. Then, it will activate a series of protein within the cell to translocate GLUT4 onto the cell surface to uptake the glucose from the bloodstream into the cells but in type 2 diabetic condition, the glucose uptake activity is being defect and glucose remains in the bloodstream. These mechanisms highlight that hypoadinopectin, hyperinsulinemia and hypergiucosemia are type 2 diabetes symptoms.
[0005] Ethnobotanicals have been used widely for many years in East Asian countries mainly in developing countries. Meanwhile, in Western countries, the herbal supplements usage has steadily increased over the last decades. However, there are limited scientific evidences are reported for the efficacy of these ethnobotanicals. Recently, the use of ethnobotanicals in diabetes mellitus treatment has vigorously increased. This emerging interest has led to collaborative works among the scientists to search and study on plants which may have potentials as antidiabetic agents. Many studies have shown that some of ethnobotanicals may improve blood glucose levels in type-2 diabetes mellitus patients and also prevent diabetes-related long term complication. Further studies demonstrated that antidiabetic agents in these plant components display characteristics of insulin sensitization in peripheral tissues and/or insulinotropic action from pancreatic β-cells.
[0006] C. latifolia is a stemless herb that grows in Western Malaysia and its fruits have been used by the natives as sweetener. Interestingly, the sweet taste is from the isolated protein, curculin presence in the C. latifolia fruit. This protein exhibits both sweet-tasting and taste-modifying activities. However, there are no proper studies about their potential use neither as an antidiabetic agent nor as an artificial sweetener for diabetic patients since it has been shown that the fruits of C. latifolia are 9000 times sweeter than sucrose.
[0007] Currently, some work showed that artificial sweetener consumptions like saccharine, aspartame and cyclamate have side effects such as psychological problems, mental disorders, bladder cancer, heart failure and brain tumors. In order to overcome this problem, the search for non-carbohydrate sweeteners from natural sources has led to the discovery of many intensely sweet-tasting over artificial sweeteners. Since they are natural, they could be safer than aspartame and other sweeteners. This is a new approach to the potential treatment of diabetes, obesity and other metabolic disorders.
SUMMARY OF INVENTION
[0008] Accordingly, the present invention provides Curculigo latifolia ( C. latifolia ) extracts, wherein the extracts extracted from different parts of a plant such as fruits, roots and leaves, individually and in any combinations thereof, characterized in that the extracts are used as an agent for treating and preventing metabolic disorder diseases such as diabetes mellitus, obesity, cardiovascular, and atherosclerosis.
[0009] The present invention consists of several novel features and a combination of parts hereinafter fully described and illustrated in the accompanying description and drawing, it being understood that various changes in the details may be made without departing from the scope of the invention or sacrificing any of the advantages of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The present invention will be fully understood from the detailed description given herein below and the accompanying drawings which are given by way of illustration only, and thus are not imitative of the present invention, wherein:
[0011] FIG. 1 a shows the effect of C. latifolia extracts on BRIN-BD11 pancretic cell lines viability;
[0012] FIG. 1 b shows the effect of C. latifolia extracts on 3T3-L1 adipocyte cell lines viability;
[0013] FIG. 1 c shows the effect of C. latifolia extracts on L6 myotubes cell lines viability;
[0014] FIG. 2 shows the effect of C. latifolia extract on BRIN-BD11 cell in insulin secretion after 30 minutes treatment;
[0015] FIG. 3 a shows the C. latifolia fruit extract effect on glucose uptake activity in differentiated 3T3-L1 adipocytes in presence and absence of insulin;
[0016] FIG. 3 b shows the C. latifolia root extract effect on glucose uptake activity in differentiated 3T3-L1 adipocytes in presence and absence of insulin;
[0017] FIG. 3 c shows the C. latifolia leaf (hot water) extract effect on glucose uptake activity in differentiated 3T3-L1 adipocytes in presence and absence of insulin;
[0018] FIG. 3 d shows the C. latifolia leaf extract effect on glucose uptake activity in differentiated 3T3-L1 adipocytes in presence and absence of insulin;
[0019] FIG. 4 a shows the C. latifolia fruit extract effect on glucose uptake activity in differentiated L6 myotubes in presence and absence of insulin;
[0020] FIG. 4 b shows the C. latifolia root extract effect on glucose uptake activity in differentiated L6 myotubes in presence and absence of insulin;
[0021] FIG. 4 c shows the C. latifolia leaf (hot water) extract effect on glucose uptake activity in differentiated L6 myotubes in presence and absence of insulin;
[0022] FIG. 4 d shows the C. latifolia leaf extract effect on glucose uptake activity in differentiated L6 myotubes in presence and absence of insulin;
[0023] FIG. 5 shows the effect of C. latifolia extracts on differentiated 3T3-L1 adipocyte in adiponectin secretion after 30 minutes treatment with absence of insulin.
[0024] FIG. 6 shows the effect of C. latifolia extracts on differentiated 3T3-L1 adipocyte in adiponectin secretion after 30 minutes treatment with presence of insulin.
[0025] FIG. 7 a shows the effect of C. latifolia extracts on body weight in high fat-fed diet and low dose STZ induced diabetic rats;
[0026] FIG. 7 b shows the effect of C. latifolia extracts on fasting blood glucose in high fat-fed diet induced diabetic rats;
[0027] FIG. 7 c shows the effect of C. latifolia extracts on insulin level in high fat-fed diet induced diabetic rats; and
[0028] FIG. 7 d shows the effect of C. latifolia extracts on adiponectin level in high fat-fed diet induced diabetic rats.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0029] The present invention relates to the uses of Curculigo latifolia ( C. latifolia ) extracts. Hereinafter, this specification will describe the present invention according to the preferred embodiments of the present invention. However, it is to be understood that limiting the description to the preferred embodiments of the invention is merely to facilitate discussion of the present invention and it is envisioned that those skilled in the art may devise various modifications and equivalents without departing from the scope of the appended claims.
[0030] More particularly, the present invention relates to a method for ameliorating blood glucose, glucose uptake activity, insulin and adiponectin level. The method of treatment involves administration of C. latifolia extracts.
[0031] Accordingly, it is an object of the present invention to provide C. latifolia extracts which can modulate diabetes mellitus by administrating an effective amount of C. latifolia extracts to the subject, wherein the amount of C. latifolia extracts modulates the symptoms of diabetes mellitus.
[0032] In order to achieve the above object, the extensive studies in in vitro and in vivo have been conducted. In in vitro, an effective amount of C. latifolia extracts have been tested in cell lines: BRIN-BD11, 3T3-L1 adipocytes and L6 myotubes. Meanwhile, in in vivo, C. latifolia extracts has been administered orally to subjects.
[0033] Accordingly, it is a method of cytotoxicity of BRIN-BD11, 3T3-L1 adipocyte and L6 myotubes treated with C. latifolia extracts, wherein the amount of C. latifolia extracts is found to be non-toxic towards those cell lines.
[0034] The preferred embodiment of the present invention is a method of glucose uptake in 3T3-L1 adipocyte and L6 myotubes cell lines treated with C. latifolia extracts, wherein the amount of C. latifolia extracts is found to increase glucose uptake activity in 3T3-L1 adipocyte and L6 myotubes cell lines.
[0035] Further embodiment is a method of secretion of insulin in BRIN BD11 cell line and adiponectin in 3T3-L1 adipocytes cell line treated with C. latifolia extracts, wherein the amount of C. latifolia extracts is found to increase secretion of insulin in BRIN BD11 cell line and adiponectin in 3T3-L1 adipocyte.
[0036] According to above objects, the subject has been induced to develop diabetes mellitus by combination of high fat diet (HFD) and low dose streptozotocin (STZ).
[0037] Diabetes mellitus is non-insulin dependent diabetes mellitus (NIDDM). The symptoms of diabetes mellitus can be selected from the group that showing hyperglycemia, obesity, increased insulin level, polyphagia, polydipsia and polyuria.
[0038] Yet further, subject has been administered orally with an effective dose is about 100 mg/kg body weight per day. More specifically, subject has been administered for a 30 days.
[0039] An embodiment of the present invention is a method of reducing blood glucose in a diabetes mellitus subject by administering an effective amount of C. latifolia extracts.
[0040] According to the method for ameliorating blood glucose level of the present intervention, fasting blood glucose and oral glucose tolerance are monitored.
[0041] It is envisioned that the C. latifolia extracts reduce blood glucose level and increase insulin and adiponectin levels in the subject.
[0042] Further envisioned of the present study, C. latifolia extracts increase oral glucose tolerance in the subject.
[0043] Still further, another envisioned is C. latifolia extracts increased food intake and body weight in a subject.
[0044] The C. latifolia extracts according to the present invention can be prepared in accordance with the following process.
Example 1
Preparation of Plant Extract
[0045] C. latifolia Fruit Extract
[0046] Fresh C. latifolia fruits were washed with distilled water. Then, 50 g of C. latifolia fruits were extracted with 2 l of distilled water in 5 l beaker for 24 hours with continuous stirring at room temperature. This extract was filtered through Whatman no.1 filter paper. The filtrate was then collected and lyophilized. The lyophilized sample was kept at −80° C. until use.
[0000] C. latifolia Leave Extract
Two Types of Extracts Used:
(1) Hot Water Extract
[0047] Five grams of C. latifolia leave powder were placed in 200 ml boiling (distilled) water. Then it was removed from the heat source and allowed to infuse for 15 min. This suspension was filtered with Whatman no. 1 filter paper. The filtrate was then collected and lyophilized. The lyophilized sample was kept at −80° C. until use.
(2) Normal Water Extract
[0048] Five grams of C. latifolia leave powder were extracted with 200 ml of distilled water and were soaked for 24 hours with continuous stirring at room temperature. This extract was filtered through Whatman no.1 filter paper. The filtrate was then collected and lyophilized. The lyophilized sample was kept at −80° C. until use.
[0000] C. latifolia Root Extract
[0049] Five grams of C. latifolia root powder were extracted with 200 ml of distilled water and were soaked for 24 hours with continuous stirring at room temperature. This extract was filtered through Whatman no.1 filter paper. The filtrate was then collected and lyophilized. The lyophilized sample was kept at −80° C. until use.
Example 2
[0050] In Vitro Cytotoxicity Study of C. latifolia Extracts Tested on 3T3-L1 Adipocyte, L6-Myotubes and BRIN-BD11 Pancreatic Cell Lines
Cell Culture
[0051] BRIN-BD11 cell line was cultured and maintained in RPMI 1640 medium supplemented with 10% foetal bovine serum, 1% penicillin-streptomycin and 1% glutamine at 37° C. in a humidified atmosphere of 5% CO 2 . Meanwhile, 3T3 adipocytes and L6 myotubes cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with streptomycin/penicillin antibiotics and 10% fetal bovine serum. Both cells were maintained in humidified atmosphere of 5% CO 2 at 37° C. Cells were subcultured every 2 to 3 days at approximately 80% confluence using trypsin-EDTA to detach the cell from the culture flask. Cell counting was done using hemocytometer. For differentiation, L6 cells were transferred to DMEM with 2% fetal bovine serum, 4-6 days post-confluence. The extent of differentiation was established by observing multinucleation of cells and >90% fusion of myoblasts into myotubes were considered. Meanwhile, differentiation of 3T3 preadipocyte was grown in the plates to reach confluence in 3 days. At this point (day 0) cells were switched to differentiation medium (DMEM, 10% FBS, 0.25 μM dexamethasone, 0.25 mM IBMX, and 1 μg/ml insulin) for 3 days, with one medium change in between. On day 3, the dexamethasone and IBMX were removed leaving insulin on the cells for an additional 4 days, changing the medium every 2 days. Thereafter the cells were maintained in the original propagation DMEM, changing medium every 2-3 days, until use. Plates where cells were >90% differentiated were used for experiments between days 9 to 12 post-induction.
Cell Viability Assay
[0052] To date various methods have been developed and introduced to measure the viability cell. The CellTiter 96® aqueous non-radioactive cell proliferation assay (Promega, Madison, Wis.) is one of them. The cells were seeded onto 96-well plates at a concentration 2×10 5 cells/well in 100 μl of medium culture and allowed to attach for 24 hours. The cells monolayer were washed with phosphate-buffered saline (PBS) to remove unattached cells; the attached cells were incubated in fresh serum free media with different concentrations of C. latifolia fruit, leave and root extracts for 72 hours. Cells were then incubated with 20 μl of tetrazolium salt solution for four hours. The absorbance of each well was measured at 490 nm using a Microplate reader (Opsys MR, Thermolabsystems) to quantify the formazon product. The number of living cells in culture is proportional to quantity of formazon product presence.
[0053] FIGS. 1 a, 1 b and 1 c show the effect of C. latifolia extracts on MIN BD11, 3T3-L1 adipocyte and L6 myotubes cell lines, respectively.
Example 3
Insulin Secretion In Vitro
[0054] BRIN-BD11 cell line was used to evaluate insulin secretion. Insulin secretion activity was determined using 24-well plates. Cells were seeded at a concentration 2×10 5 cells/well in RPMI 1640 containing 10% foetal bovine serum, 1% antibiotic and 1% glutamine and allowed attachment overnight. Cell were then washed thrice with Kreb's—Ringer bicarbonate buffer (KRB; 115 mM NaCl, 4.7 mM KCl, 1.28 mM CaCl2, 1.2 mM KH 2 PO 4 , 1.2 mM MgSO 4 , 24 mM NaHCO 3 , 10 mM Hepes-free acid, 1 g/l bovine serum albumin, 1.1 mM glucose; pH 7.4) and preincubated for 40 minutes in KRB buffer at 37° C. Cells were then incubated for 30 min with 1 ml KRB buffer in the absence and presence of C. latifolia extracts and glibenclamide as positive control. Aliquots were removed from each well and stored at −20° C. for insulin assay later.
Insulin Assay
[0055] In order to quantify the insulin concentration, aliquot from insulin secretion in in vitro study were used and assay was done using Mercodia Rat Insulin ELISA (Uppsala, Sweden) protocol. The absorbance of each well was measured at 450 nm using a Microplate reader (Opsys MR, Thermolabsystems) to quantify the insulin concentration.
[0056] FIG. 2 shows the effect of C. latifolia extract on BRIN-BD11 cell in insulin secretion after 30 minutes treatment.
Example 4
2-Deoxy-D-[1- 3 H] Glucose (2-DOG) Uptake
[0057] Glucose uptake was measured in fully differentiated L6 myotubes and 3T3 adipocyte. Cells were rinsed thrice with Krebs-Ringer HEPES buffer (pH 7.4) before treated with C. latifolia extracts in the presence and absence of insulin (100 nM). This treatment was allowed to proceed for 30 min. After 30 min, 1 μCi/ml of 2-deoxy-D-[1- 3 H] glucose was added and allowed 30 min incubated. Before the cells were digested, the medium was collected to vials and frozen at −20° C. for adiponectin analysis and the collected process has done on a bed of ice. Then, plates were washed thrice with ice-cold KRH buffer and cells were digested with 0.1% SDS. An aliquot was used to measure the radioactivity by using scintillation counter (Tri-Garb 2300TR, Perkin Elmer Life and Analytical Services, Boston, Mass., USA) using Ultima Gold™ LLT as the scintillation cocktail (Perkin Elmer, Boston, Mass., USA). Glucose uptake was expressed as disintegrations per minute (dpm).
[0058] FIGS. 3 a , 3 b , 3 c and 3 d show the C. latifolia extracts effect on glucose uptake activity in differentiated 3T3 adipocytes, respectively, whereas, FIGS. 4 a , 4 b , 4 c and 4 d show the C. latifolia extracts effect on glucose uptake activity in differentiated L6 myotubes, respectively.
Example 5
Adiponectin Assay
[0059] BioVision Rat Adiponectin ELISA assay (Mountain View, USA) was used to screen C. latifolia extracts to potentiate the adiponectin secretion in differentiated 3T3 adipocytes.
[0060] Aliquot collected from glucose uptake assay were used and assay was done according to the kit procedure.
[0061] FIG. 5 shows the C. latifolia extracts effect on adiponectin secretion activity in differentiated 3T3 adipocytes with absence of insulin whereas FIG. 6 shows the C. latifolia extracts effect on adiponectin secretion activity in differentiated 3T3 adipocytes with presence of insulin.
Example 6
Animals
[0062] A total of 42 male Sprague-Dawley (SD) rats (160-200 g) were used for this study. They were housed individually in polypropylene cages and maintained under controlled room temperature (22±2° C.) and humidity (55±5%) with 12:12 h light and dark cycle. All rats were provided with free access to water and commercially available rat normal pallet (NPD) prior to acclimatize period. All experimental protocols for animal care and use was approved by the Animal Care and Use Committee (ACUC) of Faculty of Medicine and Health Sciences, Universiti Putra Malaysia.
Experimental Design
Phase I
Preparation of High-Fat (HF) Diet
[0063] The HF diet was formulated based on the composition provided by Levin et. al. (1989). It will be prepared from a mixture of 50% normal rat chow pallet, 24% of corn oil (Mazola brand), 20% of full-cream milk powder (Nespray brand from Nestlé) and 6% sugar.
[0000] Development of HFD-Fed and Low Dose STZ-Treated Type 2 Diabetic Rats Rats were allocated into two groups based on dietary regimens; NPD and HFD and they were fed for a month. After a month on either diet, rats which were introduced with HFD will be anesthetized with diethyl ether after an overnight fast and then inject with STZ (35 mg/kg) via intravenous. Rats were continued to their original diets (chow or fat) and water after the STZ injection. After seven days of STZ injection, diabetes conditions were identified by polydipsia, polyuria and by measuring fasting blood glucose level; glucose level >170 mg/dl were included in the study.
[0064] Body weight, food consumption and fasting blood glucose were determined weekly.
Phase II
[0065] The animals are randomly divided into seven groups of three animals each.
Group 1: Normal control (normal pellet diet, non-diabetic, untreated) rats Group 2: Diabetic control (high fat-fed diet, diabetic, untreated) rats
[0068] Group 3: Diabetic control (high fat-fed diet, induced with STZ, diabetic, untreated) rats
Group 4: Diabetes test rats (high fat-fed diet, induced with STZ, diabetic, treated), treatment with glibenclimide 600 μg per b.w Group 5: Diabetic test rats (high fat-fed diet, induced with STZ, diabetic, untreated), treatment with C. latifolia fruit extract 100 mg per b.w Group 6: Diabetic test rats (high fat-fed diet, induced with STZ, diabetic, untreated), treatment with C. latifolia root extract 100 mg per b.w Group 7: Diabetic test rats (high fat-fed diet, induced with STZ, diabetic, untreated), treatment with combination of C. latifolia root and fruit extract 100 mg per b.w
[0073] Body weight, food consumption and fasting blood glucose are determined weekly.
Oral Glucose Tolerance Test (OGTT)
[0074] Fasting blood glucose level of each rat was determined at zero-time (after overnight fasting with free access to water). Glucose (2 g/kg b.w) was orally administered 30 minutes after an oral administration of the C. latifolia extracts or glibenclamide. Blood glucose concentration was measured just before and 30, 60 and 120 minutes after the oral administration of test sample.
Biological Assays
[0075] Blood samples were collected at the end of every phase of treatments. Plasma was collected by cardiac puncture for various biological assays. Physical and biochemical parameters were obtained such as changes in body weights, food intake, plasma glucose, insulin and adiponectin level. Insulin level was measured using an Insulin ELISA kit (Mercodia AB, Uppsala, Sweeden) with rat insulin as a standard. Adiponectin level is measured using BioVision Rat Adiponectin ELISA assay (Mountain View, USA).
[0076] FIG. 7 a shows the effect of C. latifolia extracts on body weight in high fat-fed diet and low dose STZ induced diabetic rats whereas FIG. 7 b shows the effect of C. latifolia extracts on fasting blood glucose in high fat-fed diet induced diabetic rats.
[0077] On the other hand, FIG. 7 c shows the effect of C. latifolia extracts on insulin level in high fat-fed diet induced diabetic rats whereas FIG. 7 d shows the effect of C. latifolia extracts on adiponectin level in high fat-fed diet induced diabetic rats | 1a
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CROSS-REFERENCE TO RELATED APPLICATION
This application is a division of U.S. patent application Ser. No. 10/954,227, which was filed on Oct. 1, 2004, the entire subject matter of which is incorporated by reference in its entirety.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a spine fixation apparatus, and more particularly to a pedicle screw implanted into a spine and an operating device for the pedicle screw capable of easily inserting a rod to a head section of the pedicle screw in order to securely fix the spine.
2. Description of the Prior Art
As generally known in the art a spine fixation apparatus is provided for treating patients who have vertebral disease caused by traffic accidents or fall accidents. For instance, the spine fixation apparatus connects bones forming the spine to each other so as to assist patients with vertebral fracture to be restored to health.
A patient makes a living with a spine fixation apparatus implanted into the spine of the patient. Thus, a subsidiary implanted into a body of the patient must have a simple structure and must not be deformed or released even if the patient takes an active life for a long period of time.
FIG. 1 shows a conventional spine fixation apparatus. Referring to FIG. 1 , the conventional spine fixation apparatus includes a pedicle screw 100 provided with a rod 104 and a coupling screw 102 which are coupled to an upper portion of the pedicle screw 100 .
The pedicle screw 100 is provided at an upper end thereof with a head section 110 and a lower end thereof with a screw section 120 . The rod 104 is inserted into a recess 114 of the head section 110 . The recess 114 is defined by first and second sidewalls 111 and 112 and receives the rod 104 therein.
When the rod 104 has been received in the head section 110 of the pedicle screw 100 , the coupling screw 102 is screw-coupled into the upper portion of the pedicle screw 100 so as to prevent the rod 104 from being separated from the pedicle screw 100 . The first and second sidewalls 111 and 112 of the head section 110 are formed at inner portions thereof with screw sections such that the coupling screw 102 is securely fixed to the head section 110 of the pedicle screw 100 .
The screw section 120 of the pedicle screw 100 is screw-coupled into a bone of a spine of a patient so that the pedicle screw 100 is implanted into a body of the patient. The pedicle screw 100 is connected to the other pedicle screw, which is screw-coupled with the other bone of the spine of the patient, through the rod 104 .
The rod 104 is inserted into the pedicle screw 100 from an upper portion of the pedicle screw 100 when the pedicle screw 100 is implanted into the patient. Accordingly, it is necessary to make elongated incisions in the patient's back. That is, the back of the patient must be incised corresponding to a length of the rod 104 . Reference numeral 116 represents an inner bottom surface of the head section 110 .
The current tendency of a surgical operation is to minimize an incision part in a human body. Thus, there has been suggested a method capable of minimizing an incision part in the back of a patient when a pedicle screw is implanted into the body of the patient. According to the above method, a rod is inserted into the pedicle screw from a lateral portion of the pedicle screw instead of inserting the rod from an upper portion of the pedicle screw. In this case, two pedicle screws can be implanted into the body of the patient without incising the back of the patient in a long size by forming only three incisions (two is for pedicle screws and one is for the rod) in the back of the patient.
When the rod is inserted into the pedicle screw from the lateral portion of the pedicle screw, one end of the rod must be easily inserted into a recess part of the pedicle screw. In addition, it is necessary to prevent the rod from being easily separated from the recess part. The rod is inserted into the recess part of a head section of the pedicle screw and fixedly coupled thereto by means of a coupling screw. Accordingly, the rod can be easily separated from the head section of the pedicle screw before the coupling screw is coupled thereto.
For this reason, if the conventional pedicle screw is used for the minimum incision surgery, the pedicle screw may be separated from the pedicle screw while the surgery operation is being carried out, resulting a delay or a failure of the surgery operation.
In addition, since the minimum incision surgery is carried out while making several incisions in the back of the patient while keeping the size of the incisions quite small, a position of the pedicle screw is not exposed to an exterior. Thus, it is difficult to determine a coupling position of a screw section of the pedicle screw having a diameter of about 5 mm with respect to the spine of the patient.
In the meantime, the minimum incision surgery requires great skill when determining the coupling position of the pedicle screw with regard to the spine of the patient and inserting the rod into the pedicle screw from the lateral portion of the pedicle screw. This is because the incisions made in the back of the patient tend to be clogged by skin and the operator cannot see the pedicle screw, which has already been implanted in the body of the patient. Thus, the operator must perform the surgical operation while gripping the pedicle screw with one hand in order to couple the pedicle screw to a precise position of the spine of the patient.
That is, since the minimum incision surgery is carried out while making several incisions in the back of the patient and keeping the size of the incisions quite small the location of the pedicle screw is “subcutaneous”, so that the operator cannot easily carry out minimum incision surgery.
Therefore, it is necessary to provide an apparatus to facilitate minimum incision surgery capable of allowing the operator to easily couple a pedicle screw to the spine of the patient and insert a rod into the pedicle screw from a lateral portion of the pedicle screw.
SUMMARY OF THE INVENTION
Accordingly, the present invention has been made to solve the above-mentioned problems occurring in the prior art and an object of the present invention is to provide a pedicle screw including a support unit which connects a first sidewall of a head section to a second sidewall of the head section in order to prevent a rod, which is inserted into the head section of the pedicle screw from a lateral portion of the pedicle screw, from being separated upward from the head section.
Another object of the present invention is to provide a pedicle screw including an indicator protruding from an end of a screw section of the pedicle screw for precisely indicating an insertion point of the pedicle screw during minimum incision surgery.
Still another object of the present invention is to provide an operating device for a pedicle screw allowing an operator to easily perform minimum incision surgery while making several incisions for the pedicle screw and a rod in the back of a patient.
To accomplish the above objects, according to one aspect of the present invention, there is provided a pedicle screw comprising: a head section including a recess part defined by first and second sidewalls; a screw section; and a support unit formed at an upper portion of the recess part of the head section while connecting the first sidewall to the second sidewall.
According to the preferred embodiment of the present invention, the pedicle screw has a guide hole extending from an inner bottom surface of the head section to a lower end portion of the screw section.
To accomplish the above objects, according to another aspect of the present invention, there is provided an operating device for a pedicle screw, the operating device comprising: a screw coupling rod having an elongated pipe shape; a body having a first side coupled to the screw coupling rod; a rotating member having a first end coupled to a second side of the body in such a manner that a second end of the rotating member rotates about the first end thereof, and a rod receiver coupled to the second end of the rotating member.
According to the preferred embodiment of the present invention, the body includes a coupling hole into which the first end of the rotating member is inserted and an elongated rod having a coupling slot for coupling the screw coupling rod.
The screw coupling rod is coupled to the body by means of a coupling member, the elongated rod extends by passing through the coupling member, and the coupling member is provided with a first screw, which is screw-coupled with the coupling slot, and a second screw for supporting the screw coupling rod.
The rod receiver has a curved shape in the form of an arc and the rod is detachably coupled to one end of the rod receiver. The rod receiver is provided at an inner portion thereof with a flexible shaft which is screw-coupled with one end of the rod, and the rod is coupled with or separated from the rod receiver according to a rotational direction of the flexible shaft.
The screw coupling rod has an upper end portion coupled to the body and a lower end portion into which a pedicle screw is inserted. The screw coupling rod is formed at a lower end portion thereof with a rod hole.
BRIEF DESCRIPTION OF THE DRAWINGS
The above and other objects, features and advantages of the present invention will be more apparent from the following detailed description taken in conjunction with the accompanying drawings, in which:
FIG. 1 is a perspective view showing a conventional spine fixation apparatus;
FIG. 2 is a front view of a pedicle screw according to one embodiment of the present invention;
FIG. 3 is a plan view of a pedicle screw according to one embodiment of the present invention;
FIG. 4 is a perspective view of a pedicle screw according to one embodiment of the present invention;
FIG. 5 is a perspective view showing usage of a pedicle screw according to one embodiment of the present invention;
FIG. 6 is a perspective view showing usage of a pedicle screw according to one embodiment of the present invention;
FIG. 7 is a perspective view showing an operating device for a pedicle screw according to one embodiment of the present invention;
FIG. 8 is a front view showing an operating device for a pedicle screw according to one embodiment of the present invention;
FIG. 9 is a plan view showing an operating device for a pedicle screw according to one embodiment of the present invention;
FIG. 10 is a perspective view showing an operational state of an operating device for a pedicle screw according to one embodiment of the present invention;
FIG. 11 is an enlarged sectional view showing a rod inserted into a rod receiver according to one embodiment of the present invention; and
FIG. 12 is an enlarged sectional view showing a rod being separated from a rod receiver according to one embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Hereinafter, a preferred embodiment of the present invention will be described with reference to the accompanying drawings.
FIGS. 2 to 4 are front, plan and perspective views of a pedicle screw according to one embodiment of the present invention Referring to FIGS. 2 to 4 , the pedicle screw includes a head section 10 formed with first and second sidewalls 11 and 12 . A recess 14 is formed between the first and second sidewalls 11 and 12 and a support unit 18 is formed at an upper portion of the recess 14 in order to connect the first sidewall 11 to the second sidewall 12 .
The support unit 18 horizontally connects upper portions of the first and second sidewalls 11 and 12 to each other. Thus, the support unit 18 forms a hole having a predetermined size together with the recess 14 . The shape and position of the support unit 18 may vary so far as the support unit 18 connects the first sidewall 11 to the second sidewall 12 and prevents a rod (not shown) from being separated upwardly of the recess 14 . As shown in FIG. 3 , the recess 14 is formed with a screw hole 17 such that a coupling screw ( 102 , see FIG. 6 ) can be screw-coupled with the recess 14 from an upper portion of the support unit 18 . Since the coupling screw 102 is screw-coupled with the screw hole 17 of the recess 14 , the support unit 18 must be aligned such that it does not block a movement path of the coupling screw 102 .
A guide hole 19 is formed at a center of an inner bottom surface 17 of the head section 10 formed between the first and second sidewalls 11 and 12 of the head section 10 . The guide hole 19 downwardly extends from the inner bottom surface 17 of the head section 10 to a lower end of a screw section 20 through an inner portion of the screw section 20 .
FIG. 5 is a perspective view showing usage of a pedicle screw according to one embodiment of the present invention. Referring to FIG. 5 , the pedicle screw is located at a precise position of the spine by means of a position indication driver 30 .
The position indication driver 30 has a handle 34 and an elongated needle 32 extending downward from the handle 34 . The elongated needle 32 is inserted into the guide hole 19 by passing through the screw hole 17 of the recess 14 .
The elongated needle 32 downwardly protrudes beyond a lower end of the screw section 20 of the pedicle screw and makes contact with the spine. When the elongated needle 32 is moved into a precise position of the spine by moving the position indication driver 30 , the pedicle screw is also located in the precise position of the spine. In this state, the pedicle screw is inserted into the spine by rotating the pedicle screw. After that, the position indication driver 30 is separated from the pedicle screw by upwardly pulling the position indication driver 30 .
Thus, it is not necessary for the operator to move the pedicle screw while enlarging an incision part in order to find a coupling position of the pedicle screw with regard the spine because the elongated needle 32 can point the coupling position of the pedicle screw. The pedicle screw is rotatably inserted into the spine by means of a separate driver (not shown).
FIG. 6 is a perspective view showing usage of a pedicle screw 1 according to one embodiment of the present invention. Referring to FIG. 6 , the rod 104 is inserted into the pedicle screw 1 from a lateral portion of the pedicle screw 1 . In this case, the rod 104 is prevented from being separated upwardly from the pedicle screw 1 due to the support unit even if the operator does not conduct any additional procedures.
When the rod 104 has been inserted into the recess 14 from the lateral portion of the recess 14 , the coupling screw 102 is screw-coupled into the screw hole 17 while pressing the rod 104 downward. Since the rod 104 is prevented from upwardly moving from the recess 14 , it is necessary to push the rod 104 in the lateral di on when removing the rod 104 from the recess 14 .
In short due to the support unit 18 , the rod 104 inserted into the recess 14 is prevented from being separated from the recess 104 even if the coupling screw 102 has not been screw-coupled with the recess 14 , so the operator can easily perform the surgical operation.
Although it is described that the head section of the pedicle screw is integrally formed with the screw section, the present invention can be applicable for a multi-axial pedicle screw in which a head section is separated from a screw section so that the screw section can move with regard to the head section.
FIG. 7 is a perspective view showing an operating device for a pedicle screw according to one embodiment of the present invention, FIG. 8 is a front view showing the operating device for the pedicle screw, and FIG. 9 is a plan view showing the operating device for the pedicle screw. Referring to FIG. 7 to 9 , the operating device for the pedicle screw includes a body 230 , a rotating member 210 rotatably coupled to a rear portion of the body 230 , at least two screw coupling rods 250 vertically coupled to a front portion of the body 230 , and a rod receiver 220 provided at a second end 212 of the rotating member 210 in the form of a curved rod and extends toward a lower end of the screw coupling rods 250 .
The rotating member 210 preferably has a reverse “L” shape and a first end of the rotating member 210 is coupled to the rear portion of the body 230 through a rotary screw shaft 214 such that the rotating member 210 can rotate about the rotary screw shaft 214 . The second end 212 of the rotating member 210 is formed with a hole so as to receive the rod receiver 220 therein. As the rotating member 210 rotates, the rod receiver 220 is also moved in up and down directions.
An upper end portion of the rod receiver 220 is coupled with the second end 212 of the rotating member 210 . In addition, the rod 104 is detachably coupled with a lower end portion of the rod receiver 220 . The rod receiver 220 has a curved structure in the form of an arc having a predetermined curvature. As the rotating member 210 rotates, the rod receiver 220 also rotates along a predetermined circular route. Preferably, the rod 104 inserted into the lower end portion of the rod receiver 222 has a curved structure with a predetermined curvature identical to the curvature of the rod receiver 220 . Reference numeral 224 represents a fastening screw 224 .
The rotating member 210 is connected to the screw coupling rod 250 through the body 230 . Preferably, the body 230 has a “ ”-shaped structure when looking at the body 230 from the upper region of the body 230 . The body 230 is provided at a middle portion thereof with a central protrusion 232 and one end of the rotary screw shaft 214 is inserted into the central protrusion 232 while interposing the first end of the rotating member 210 therebetween. The body 230 includes an elongated rod 234 . The central protrusion 232 is provided at a middle portion of the elongated rod 234 . A coupling slot 236 is longitudinally formed along an upper portion of the coupling screw 234 . At least two screw coupling rods 250 are vertically coupled to the elongated rod 234 in such a manner that the angel of the screw coupling rods 250 can be slightly adjusted.
The screw coupling rod 250 has a hollow pipe shape and an upper end of the screw coupling rod 250 is coupled to the elongated rod 234 . A pedicle screw (not shown) is inserted into a lower end of the screw coupling rod 250 . The screw coupling rod 250 is formed with a perforated hole 254 . A driver (not shown) may be inserted into the perforated hole 254 of the screw coupling rod 250 in order to manipulate the pedicle screw. Preferably, a rod hole 256 is formed at a lower lateral portion of the screw coupling rod 250 . The rod hole 256 receives a head section of the pedicle screw. That is, as the rotating member 210 rotates, the rod 105 inserted into the second end 222 of the rod receiver 220 is introduced into the head section of the pedicle screw by passing through the rod hole 256 . Coupling members 240 are provided to couple the screw coupling rods 250 to the elongated rod 234 of the body 230 . Each of the coupling members 240 has a hexahedral structure and the elongated rod 234 of the body 234 passes through the coupling member 240 . In addition, a protrusion 258 of the screw coupling rod 250 is inserted into the coupling member 240 . A first screw 242 is screw coupled into the coupling member 240 in order to fix the elongated rod 234 and a second screw 252 is screw coupled into the coupling member 240 in order to fix the protrusion 258 of the coupling rod 250 .
The first screw 242 is inserted into the coupling slot 236 of the elongated rod 234 . The first screw 242 extends toward an inner portion of the coupling member 240 by passing through an upper surface of the coupling member 240 so that an end portion of the first screw 242 is inserted into the coupling slot 236 of the elongated rod 234 . When releasing the first screw 242 , the coupling member 240 can move along the elongated rod 234 . In addition, the coupling member 240 can be fixed to predetermined portion of the elongated rod 234 when fastening the first screw 234 .
The second screw 252 is screw-coupled into the coupling member 240 in order to adjust a rotational angle or a gradient of the screw coupling rod 250 . The protrusion 258 inserted into the coupling member 240 is provided at an upper end portion of the screw coupling rod 250 and the second screw 252 makes contact with the protrusion 258 of the screw coupling rod 250 by passing through the coupling member 240 .
The protrusion 258 has a cylindrical shape and is rotatably inserted into the coupling member 240 . As the protrusion 258 rotates, the screw coupling rod 250 is slightly moved by a predetermined angle. Thus, a position of the screw coupling rod 250 is adjusted in a state that the second screw 252 is slightly released. Then, the second screw 252 is fastened such that the second screw 252 fixedly presses the protrusion 258 , so the position of the screw coupling rod 250 is fixed with respect to the body 230 .
FIG. 10 is a perspective view showing an operational state of the operating device for the pedicle screw according to one embodiment of the present invention. Referring to FIG. 10 , the pedicle screw 1 is inserted into a lower portion of the screw coupling rod 250 . In this state, the rod 104 is inserted into the pedicle screw 1 by rotating the rotating member 210 in the downward direction.
That is, the pedicle screw 1 is coupled with the screw coupling rod 250 and the position of the body 230 is determined according to the position of the screw coupling rod 250 . As the rotating member 210 coupled with the body 230 rotates in the downward direction, the rod receiver 220 and the rod 104 connected to the second end 212 of the rotating member 210 may be directed toward the rod hole 256 formed at the lower end portion of the screw coupling rod 250 .
Thus, the operator can easily insert the rod 104 into the pedicle screw 1 without performing additional inspection work by simply rotating the rotating member 210 in the downward direction thereof. Therefore, if two incisions for two pedicle screws 1 and one incision for the rod 104 and the rod receiver 220 are made in the back of the patient, the rod 104 can be easily inserted into the pedicle screw 1 .
When the rod 104 coupled with a detachment section 222 of the rod receiver 220 has been placed in the head section of the pedicle screw 1 due to the rotation of the rotating member 210 , the coupling screw 102 (see, FIG. 1 ) is inserted into the perforated hole of the screw coupling rod 250 and the driver is also inserted into the perforated hole of the screw coupling rod 250 in order to fasten the coupling screw 102 , thereby fixedly securing the rod 104 to the pedicle screw 1 . After that, the rod 104 is separated from the rod receiver 220 and the rotating member 210 is rotated in the upward direction, thereby removing the rod receiver 220 from the back of the patient.
FIG. 11 is an enlarged sectional view showing the rod inserted into the rod receiver according to one embodiment of the present invention, and FIG. 12 is an enlarged sectional view showing the rod being separated from the rod receiver according to one embodiment of the present invention. Referring to FIGS. 11 and 12 , the rod 104 is partially inserted into the detachment section 222 of the rod receiver 220 . The detachment section 222 is formed at a lower end portion of the rod receiver 220 in order to detachably receive the rod 104 . The rod 104 is formed at one end thereof with a female screw section 104 a such that the rod 104 can be screw-coupled with the rod receiver 220 . The female screw section 104 a is formed at an inner wall part of a hole formed in the rod 104 . A flexible shaft 226 is positioned in the rod receiver 220 . A male screw section 226 a of the flexible shaft 226 is located in the vicinity of the detachment section 222 of the rod receiver 220 . The rod 104 has a curved shape in the form of an arc and the female screw section 104 a formed at one end of the rod 104 is screw-coupled with the male screw section 226 a of the flexible shaft 226 .
The flexible shaft 226 is made from a synthetic resin material, such as plastic, which can be easily bent without deforming a shape thereof. An upper portion of the flexible shaft 226 is connected to a fastening screw 224 provided at an upper end portion of the rod receiver 220 . As the fastening screw 224 rotates, the flexible shaft 226 also rotates.
The male screw section 226 a of the flexible shaft 226 may be coupled with the female screw section 104 a of the rod 104 or released from the female screw section 104 a of the rod 104 according to a rotational direction of the fastening screw 224 . If the flexible screw 226 rotates in one direction as shown in FIG. 8 , the rod 104 is separated from the flexible screw 226 . Accordingly, the rod 104 can be easily implanted into the spine of the patient through the steps of inserting the rod 104 into a target position in the pedicle screw 1 , separating the rod 104 from the flexible screw 226 by rotating the fastening screw 224 , and lifting the rotating member 210 .
As described above, the pedicle screw according to the present invention has a support unit capable of preventing a rod from being easily separated from the pedicle screw, thereby facilitating minimum incision surgery.
In addition, the pedicle screw according to the present invention is formed with a guide hole, which receives a position indication driver, so the operator can easily detect a precise insertion point of the pedicle screw during minimum incision surgery.
In addition, the present invention provides an operating device for the pedicle screw, capable of implanting a plurality pedicle screws into the body of the patient while making several incisions for the pedicle screws and the rod in the back of the patient and keeping the size of incisions quite a small.
Furthermore, the operating device for the pedicle according to the present invention may allow an operator to easily insert the rod into the pedicle screw inserted into the incision made in the patient's back without checking the location of the pedicle screw and the rod with the naked eye.
In addition, the operating device for the pedicle according to the present invention can easily separate the rod from the pedicle screw after the rod has been inserted into the pedicle screw.
The operating device for the pedicle according to the present invention includes a screw coupling rod, so the number of pedicle screws used for minimum incision surgery may increase without limitation.
Although a preferred embodiment of the present invention has been described for illustrative purposes, those skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.
The present disclosure relates to subject matter contained in Korean Patent Application Nos. 10-2002-0056911, filed on Jul. 21, 2004, and 10-2004-0056912, filed on Jul. 21, 2004, the contents of both are herein expressly incorporated by reference in their entireties. | 1a
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REFERENCE TO RELATED APPLICATION
This application claims the priority of European Patent Application No. 10 011 329, filed Sep. 28, 2010, and of U.S. Provisional Application No. 61/387,309, filed Sep. 28, 2010, the entire contents of which are incorporated herein by reference.
FIELD OF THE INVENTION
The invention relates to an implant set for the lamina of a vertebra, comprising several implants that each comprise a main body with bearing surfaces on the vertebra and a fastening device.
The spinal column in humans comprises a multiplicity of vertebrae arranged in a load-bearing manner one above another and interconnected in an articulated manner. The vertebrae differ in shape depending on where they are located in the spinal column, but they nonetheless have some features in common. Thus, each vertebra has a solid vertebral body with two osseous projections (pedicles) which extend laterally and to the rear and which, in their rear part, are connected by an osseous arch. In the connection area, the osseous arch is shaped as a broad plate (lamina) and has, at its center, a rearwardly protruding spinous process. The spinous process and two further transverse processes on the side surfaces of the pedicles form articulation points for muscles and ligaments. In the area where the pedicles merge into the broad lamina, an upper and a lower articulating process are arranged on each side. These each form part of a facet joint (zygapophyseal joint) with an adjacent upper or lower vertebra. A vertebra is also connected to its adjacent upper and/or lower vertebra via an intervertebral disk, the latter being arranged at the bottom and/or top on the relatively flat cover surfaces of the vertebral body. The space bounded by the rear side of the vertebral body and by the vertebral arch forms a hollow space in which nerve fibers running parallel to the spinal column are accommodated.
Many different forms of back pain can occur as a result of disease or injury. These can be caused in particular by defects of the intervertebral disk or of the facet joints and/or by the nerve fibers extending through the hollow space becoming pinched or trapped. In the latter case, it is known that pressure exerted on the nerve fibers by protrusions of the intervertebral disk or by osseous growths in the area of the hollow channel can be avoided by removal of these protrusions and/or growths. For this purpose, an access route to the hollow space is created through the rear side of the vertebral arch, that is to say generally through the lamina, and the growths causing the problems are removed from there by means of suitable instruments known per se. In this way, the pressure is removed from the nerve fibers, whereupon the pain induced by the pressure is correspondingly reduced. In this method, also known as laminectomy or decompression, the access created in the lamina, that is to say the opening present therein, is in most cases not closed after the operation. It has been shown that this weakens the mechanical stability of the vertebra.
BACKGROUND OF THE INVENTION
The object of the invention is to reduce or avoid the occurrence of these ensuing problems.
The solution according to the invention lies in the features broadly disclosed herein. Advantageous developments of the invention are the subject matter of the detailed disclosure.
An implant set comprises several reinforcing implants for insertion into the lamina of the vertebra, which reinforcing implants each comprise a main body with bearing surfaces on the vertebra and a fastening device, wherein according to the invention the main body has a front surface, a rear surface, and medial and lateral side surfaces, wherein the medial side surface is offset rearwardly in relation to the lateral side surface, and the medial and lateral side surfaces are designed to bear on sectioned surfaces of the lamina, and wherein a rearwardly protruding extension with a lateral bearing surface on the spinous process is arranged on the rear surface, and wherein the reinforcing implants of the set differ from one another in terms of the distance between medial side surface and lateral side surface.
The invention is based on the concept of making available a plurality of block-like reinforcing implants which differ in terms of their thickness, so as to be able to fill and reliably close resection openings of different widths in the lamina. The fastening device ensures that the reinforcing implant is fixed securely in its position in the lamina. By virtue of the reinforcing implant, the vertebral arch interrupted by the resection opening is completely closed again. Not only does this provide better protection for the nerve fibers running in the hollow channel, the mechanical stability of the vertebral arch is also restored and recovers the original values at the very latest when the implant has become incorporated.
The invention in this respect exploits the fact that, in the unilateral resection that is performed particularly often in practice (this is understood to mean access through the lamina only on one side, that is to say either to the left or right of the spinous process), sufficiently extensive and mechanically stable fastening to the spinous process is possible, and this possibility is made use of to fasten the reinforcing implant according to the invention. The claimed shape with the mutually offset side surfaces, which bear on the resected surfaces of the lamina after the resection, ensures a geometrically favorable integration of the reinforcing element in the vertebral arch, specifically in such a way that the reinforcing implant does not cause problems by protruding into the hollow space for the nerve fibers and also does not extend substantially outward. In other words, the main body of the reinforcing implant remains substantially inside the area that was filled by the corresponding part of the lamina prior to the resection. The danger of undesired irritation of the nerve fibers inside the hollow channel and also of the surrounding tissue is thus effectively countered.
A further advantage of the reinforcing implant according to the invention is that, after the correct reinforcing implant has been chosen from the set, only this part has to be inserted, and no other assembly work or adjustment work is needed deep within the operating site. It suffices to insert the implant of appropriate size and to fix it at the intended location by means of the fastening device, in the simplest case a bone screw. This ease of implantation thus safeguards against incorrect implantation and thereby contributes directly to improved outcomes.
Although the side surfaces are in most cases parallel to each other, they can form a wedge shape tapering slightly toward the front, the wedge angle measuring between 0 and 20°. The wedge angle is preferably less than 10°, more preferably less than 5°.
By virtue of the mutually offset arrangement of the side surfaces, the front surface and rear surface are oblique with respect to the two side surfaces, and they are in fact preferably substantially parallel or deviate from this by a maximum of 20°.
Advantageously, the side surfaces are not only mutually offset toward the front and rear, but also upward and downward. The main body thus expediently has a rhomboidal shape in two different planes. The rhombus angle (smaller internal angle) is here preferably between 35 and 75° in the vertical with respect to the underside and 30 to 60° in a plane orthogonal to the rear surface.
The lateral surface arranged further forward preferably forms a rounded apex angle with the front surface. This facilitates the insertion of the main body into the opening created by the resection, since the rounding prevents the implant from catching on the lamina in the event of an uneven shape of the resected surfaces, and the acute angle facilitates insertion, if appropriate with slight elastic widening (to achieve what is called a press fit), to the full thickness.
In order to avoid the reinforcing implant being inserted too far into the hollow space, a shoulder-shaped projection is preferably formed on one side surface and functions as an abutment. This ensures that a secure fit of the implant at the intended location can be achieved even without close visual monitoring and, in particular, it avoids a situation where the implant is pushed in too far and exerts pressure on the nerve fibers located in the hollow space. The danger of operating errors is thus effectively countered. It has proven useful that the shoulder-shaped projection is located at a distance from the front surface corresponding to approximately 0.8 to 2.2 times the thickness of the main body. It has proven useful to have a linear relationship with offset, such that, starting with a thickness of 3 mm, the distance is 6 mm, and the distance increases by 0.5 mm for each 1 mm of additional thickness.
A fastening hole is expediently provided on the rearwardly protruding extension. This not only provides securing by means of the lateral bearing surface and the force-fit thereof on the spinous process, it is also possible to achieve a form-fit fastening to the spinous process by insertion of a suitable fastening means (for example a screw). For this purpose, the fastening hole is preferably designed for the polyaxial reception of a screw. This is understood to mean that the screw with its head has a secure planar contact in the area of the fastening hole not only in an exactly central position, but also at angular deviations of up to 15° in each direction. In this way, even with a different anatomy of the vertebra, the screw can always be fitted in an orientation favorable for the fastening, preferably a translaminar screw. With this, a particularly secure hold can be achieved in the intact part of the lamina lying on the other side of the spinous process. However, a screw connection can also be provided directly on the spinous process; this is generally recommended when the opposite part of the lamina also has a defect. For this purpose, a screw dowel device is advantageously used. It permits secure fastening even in the case of a thin spinous process and in all situations in which, because of the small size of the fastening means used here, sufficiently reliable transfer of force would not be guaranteed by the screw thread alone. It comprises a dowel and a dowel screw. The dowel is preferably of sleeve-shaped configuration, with several segments which are connected at a near end and are free at their far end and have outwardly facing retainer hooks. They are dimensioned such that, when the dowel is pushed into the spinous process, they emerge on the other side and there engage behind the edge of the opening. The retainer hooks are preferably arranged in several steps with a height increasing toward the fixed end, in order to achieve a secure hold in spinous processes of different thicknesses.
The medial and lateral side surfaces are preferably provided with spikes. Proven shapes of the spikes are conical tips, pyramids, prismatic V-shaped elevations of different extent and height. They are advantageously configured asymmetrically, specifically in such a way that they have a greater bevel toward the front than in the opposite direction. This makes the implant easier to insert and provides a barb effect against undesired rearward migration. Secure primary fixation can be achieved in this way. In order to additionally increase the secondary fixation, the medial and lateral side surfaces are preferably provided with a coating that promotes bone growth. This can in particular be hydroxyapatite or other osteoinductive substances.
A laterally protruding fixing tongue is preferably provided on the rear edge of the lateral side surface. It is designed such that, in the implanted state, it rests on an outer surface of the so-called pars. In order to achieve good contact independently of the individual anatomy, the angle of the fixing tongue to the lateral side surface can preferably be changed. This can be achieved in practice, in a particularly expedient manner, by a flexible design of the fixing tongue, preferably with a reduced material thickness in the area of the transition between fixing tongue and main body. The fixing tongue can have a fastening hole, which advantageously has several defined receiving positions for a second fastening element, in particular a pars screw. The defined receiving positions make it possible to provide different positions for the pars screw in relation to the fixing tongue, wherein the pars screw is mounted with a form fit in each position, which is not the case in an oblong hole. As is also the case in the fastening of the translaminar screw, the receiving positions of the fixing tongue are preferably designed for polyaxial reception of a screw. In this way, the pars screw can be arranged not only with a translational degree of freedom but also with two rotational degrees of freedom in relation to the fixing tongue, which permits reliable fastening even in difficult anatomical situations. The angle range for the polyaxial receipt of the screw preferably once again measures approximately ±15° in each direction.
The reinforcing implant preferably has a tool receiver on its rear surface. This tool receiver allows the reinforcing implant to be received and held securely on a tool serving for the implantation. It is thus made easier for the operating surgeon to bring the reinforcing implant safely and precisely to the intended implantation site and to fasten it in place there. For this purpose, the tool receiver preferably has a longitudinal groove. This can be in one part or can be formed from several (also round) recesses. An unambiguous orientation of the reinforcing implant with respect to the tool can thus be achieved. A pulling thread is advantageously formed at the bottom of the tool receiver. It is thus possible, in combination with a holding screw on the tool, to secure the reinforcing implant on the tool and thereby not only to protect it against falling out and being lost, but also maintain it in a correct angular orientation.
A holding tool is preferably provided for this purpose, specifically such that it has a foot with an elongate gripper foot designed for interaction with the tool receiver. This gripper foot comprises, at the front end, a protruding area designed for complementary engagement in the longitudinal groove. It preferably comprises a connection of the gripper foot to a handle on a long hollow shaft through which a clamping element is guided that engages in the pulling thread. In this way, from the handle, the reinforcing implant can be clamped firmly on the gripper foot for safe implantation and, when the implantation site is reached, can be released therefrom, without the surgeon having to work deep within the operating site. It has proven useful in practice to arrange, at the rear end of the hollow shaft, a laterally extending projection, which has a predefined orientation with respect to the elongate gripper foot. The projection can preferably be a part of the grip. Thus, by taking hold of the instrument, it is already clear to the operating surgeon in which orientation the reinforcing implant clamped on the gripper foot is located. The danger of incorrect implantation as a result of incorrect orientation is thus reduced.
The material provided for the reinforcing implant is preferably a titanium alloy or pure titanium. This has the advantage of a high degree of biocompatibility in combination with good mechanical processing and load-bearing. Other materials that have proven useful are alloys of titanium/aluminum/vanadium, titanium/niobium/vanadium or cobalt/chromium/molybdenum, and also biocompatible plastics, such as polyether ether ketone (PEEK), or combinations of these materials.
The main bodies of the set according to the invention have different distances between medial side surface and lateral side surface (this distance is designated as the thickness). A range of between 3 and 15 mm has proven useful, and it has proven sufficient in practice to provide a gradation of in each case 2 mm. A millimeter gradation can also be provided for a finely graduated implant set.
The set according to the invention preferably additionally comprises mirror-inverted implants, which are likewise provided in different thicknesses. A treatment adapted to the anatomy can in this way be provided both in the left-hand area and also in the right-hand area of the lamina.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention is explained below on the basis of advantageous illustrative embodiments and by reference to the attached drawing, in which:
FIG. 1 shows a bottom view of a first illustrative embodiment of a right-hand reinforcing implant;
FIG. 2 shows a view, obliquely from behind, of the illustrative embodiment shown in FIG. 1 ;
FIG. 3 shows a set with reinforcing implants of different thickness;
FIG. 4 shows a rear view with inserted fastening screw;
FIG. 5 shows a view from the right with inserted fastening screw;
FIG. 6 shows an instrument for the implantation;
FIGS. 7 a - c show a vertebra with a resected lamina and with an inserted implant in a rear view from below; and
FIG. 8 shows a fastening means according to a second illustrative embodiment.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 depicts a first illustrative embodiment of a reinforcing implant according to the invention, which is designated in its entirety by reference number 1 . It has a forwardly facing oblique front surface 20 , a rearwardly facing and similarly oblique rear surface 21 , and also a lateral side surface 22 and a medial side surface 23 . An underside 14 and, opposite the latter, a top surface 15 (see FIG. 2 ) are also provided, which merge via rounded edges into the front surface 20 . These surfaces delimit a main body 2 , which has a double rhomboidal shape.
The front surface 20 , the rear surface 21 and the two side surfaces 22 , 23 form a rhombus with a rhombus angle α of 45° measured in a plane orthogonal to the rear surface 21 . (Rhombus angle is understood as the smaller of the internal angles.) The lateral and medial side surfaces 22 , 23 are oriented parallel to each other, although this does not rule out the possibility of their forming a wedge angle. The front surface 20 and the rear surface 21 are likewise arranged parallel to each other. There is also a rhomboidal shape with respect to the front surface 20 , rear surface 21 , underside 14 and top surface 15 (see FIG. 2 ). Here, the rhombus angle β measures approximately 55°. Arranged on the side surfaces 22 , 23 , there are spikes 28 which are for primary fixation and are beveled toward the front.
At the rear end of the medial side surface, a rearwardly protruding extension 4 is arranged in the area of the transition to the rear surface 21 . This extension 4 has, on its medial side, a bearing surface 43 for bearing on the spinous process of a vertebra. The bearing surface 43 and the medial side surface 23 are preferably in one plane. The extension is relatively thin and has a material thickness of up to 1.5 mm.
An abutment shoulder 27 is formed in the area of the transition between the lateral side surface 22 and the rear surface 21 . The rearwardly facing side is oblique and forms a plane with the rear surface 21 , while its forwardly facing side is oriented perpendicular to the lateral side surface 22 . It thus forms, with its front side, an abutment which limits the depth of insertion of the implant into the resection opening. The implant is inserted until the abutment shoulder 27 rests with its front side on the bone of the lamina.
A fixing tongue 3 is articulated on the abutment shoulder 27 . It has a substantially oval configuration and is mounted bendably, via a portion of reduced material thickness 30 , on the abutment shoulder 27 of the main body 2 . The fixing tongue 3 has a similar opening 31 which, on its two long sides, is divided into three areas by two projections 32 . The edge of the opening is shaped obliquely such that, together with the projections 32 , a conical contact surface is formed for a round receiving head, which can be mounted in a total of three positions in the opening 1 : an upper position, a middle position between the pairs of projections 32 , and a lower position. They serve to receive a pars screw (see FIG. 5 ). The pars screw 6 is mounted in a receiving position 33 in the opening 31 of the fixing tongue 3 such that it can adopt different axes (polyaxial) through ±15° in two directions. On account of the different receiving positions 33 , the pars screw 6 can be moved by 4 mm in the opening 31 .
A similar polyaxial seat for a laminar screw 7 is provided in the extension 4 . For this purpose, an opening 41 is formed which, at its edge 42 , likewise has bevels in order to permit, together with the screw head, a polyaxial mounting about ±15° (see FIG. 4 ). The opening 41 is designed as an oblong hole and allows the laminar screw to be arranged in different positions along a length of 3.5 mm.
Moreover, a tool receiver 5 is arranged in the rear surface 21 . It comprises a longitudinal groove 51 with a blind hole, which is arranged in the middle of the groove bottom and has a pulling thread 52 . The longitudinal groove 51 receives, at the correct angle and in a manner secure against rotation, the gripper foot of a holding tool, onto which the implant is drawn via the pulling thread 52 by a clamping screw contained in the tool.
An embodiment of a corresponding instrument 8 is shown in FIG. 6 . It comprises an elongate shaft 80 , which is provided with a hollow bore along the central axis. A laterally protruding handle 81 is arranged at one end and is fixed in terms of its angle to the hollow shaft 80 . At the other end of the hollow shaft 80 , there is a gripper foot 82 which, at its outer end, has a ridge extending transversely with respect to the axis of the hollow shaft 80 . The ridge is shaped in such a way that, with respect to its length and width, it can be introduced into the complementary seat in the longitudinal groove 51 of the main body 2 . A clamping screw 84 with a rotary grip 85 at the handle end and with a threaded head 86 at the opposite end is fitted in the hollow shaft 80 . The threaded head 86 is designed such that it engages in the thread 52 at the bottom of the longitudinal groove 51 and clamps this against the gripper foot. In this way, the implant 1 is mounted on the instrument 8 firmly and in a manner secure against rotation. Through suitable orientation of the handle 81 , the operating surgeon knows exactly at what angle the implant 1 is located and can insert the latter in a targeted manner, specifically until the abutment shoulder 27 prevents further insertion. The implant 1 is thus positioned. All that then has to be done is, using suitable drills and screwdrivers, to insert the pars screw 6 and laminar screw 7 that are required for further fastening.
FIGS. 7 a - c show an example of the arrangement of the implant in a vertebra 9 . FIG. 7 a is a rear view of the vertebra 9 showing a resection in the area of the lamina 93 , more precisely in the area to the right of the spinous process 92 . Sectioned surfaces 94 , 95 can be seen that have been made on the left and right edges of the opening. The implant 1 is inserted into this opening by means of the instrument 8 in the manner described above. The implant 1 is chosen from the set (see FIG. 3 ), in terms of its thickness d, such that it completely fills the space between the two sectioned surfaces 94 , 95 of the lamina. The spikes 28 on the lateral and medial side surfaces 22 , 23 of the main body 2 engage in the sectioned surfaces 94 , 95 and thus provide primary fastening of the implant. In order to further protect the implant against migration and against twisting, further anchoring is provided by the pars screw 6 in the pars interarticularis 91 of the vertebra 9 and by means of the laminar screw 7 in that part of the lamina 93 located on the other side of the spinous process 92 . The arrangement of the screw is symbolized for illustrative purposes in the partially cutaway view in FIG. 7 c.
An alternative means of fastening using a screw dowel device is shown in FIG. 8 . It comprises a dowel 71 with several segments 72 that are divided by longitudinal slits and that are connected to one another at one end and are free at the other end. Arranged at each free end, there is an outwardly facing retainer hook 73 , which is designed to engage behind the opening edge of the bore through which the dowel is plugged. In order to achieve sufficiently secure engagement even in through-bores of different lengths, the retainer hook is preferably designed in several steps (with three steps in the illustrative embodiment shown). Each step has a lower height than the adjacent one lying further to the outside. The dowel is also provided with an internal thread 74 . A fixing screw 70 provided with a corresponding external thread engages in the internal thread and is inserted, instead of the laminar screw 7 , through the opening 41 in the extension 4 . Secure anchoring on the spinous process 92 can be achieved in this way.
Examples of implants 1 in different sizes are shown in FIG. 3 . The implants 1 , 1 ′, 1 ″, 1 ′″ are substantially identical and differ only in respect of their thickness d, that is to say the distance between lateral side surface 22 and medial side surface 23 . They also differ in terms of the distance of the front side of the shoulder 27 from the rounded front edge of the lateral side surface 22 which, in the illustrative embodiment shown, is approximately 0.9 times the thickness d. The set further comprises similar but mirror-inverted implants 11 , 11 ′, 11 ″, 11 ′″, which together form an implant set 11 . In this way, dedicated implants adapted to the anatomy can be used for implantation in the lamina on the left-hand side and on the right-hand side.
The individual steps involved in the implantation are outlined below. After an opening has been created (cf. FIG. 7 a ), a test implant is used to determine the width of the opening and therefore the suitable size of the implant 1 from the implant set according to the invention. The test implant also comprises sample bores on the extension 4 and on the fixing tongue, in order to form bores for receiving the pars screw 6 and the laminar screw 7 using the test implant as drill jig. In a next step, the implant is mounted and secured on the tool 8 in the manner shown and, finally, inserted into the resected space in the lamina 93 . The fastening devices used for securing, particularly in the area of the extension 4 , are introduced. The implant is definitively secured by tightening of the fastening screws. | 1a
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. patent application Ser. No. 12/916,229, filed Oct. 29, 2010, now allowed, the disclosure of which is hereby incorporated by reference herein.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention generally relates to treating patients for health issues, and more specifically relates to systems, devices and methods that use muscle response testing and multi-polar magnetic devices for treating patients for health issues.
[0004] 2. Description of the Related Art
[0005] For centuries, particular locations on the body, referred to as acupuncture or acupressure points, have been used to aid the body in healing. Each of the points on a human body correlates to a particular electromagnetic line, meridian or “flow” that runs through the body. Hieroglyphics and pictographs from the Shang Dynasty, circa 1600-1100 B.C., suggest that acupuncture was in use during that time period. Chinese documents from the beginning of the first century contain the earliest written record of acupuncture points.
[0006] The mummified remains of Ötzi, an iceman estimated to be 5,300 years old, had tattoos on various locations of his body that correlate to acupuncture and meridian points. DNA evidence suggests that Ötzi had genetic markers associated with reduced fertility. It was also found that Ötzi had whipworm, an intestinal parasite, which would have caused him to have abdominal complaints. Ötzi was also found to be suffering from arthritis. Among the tattoos found on his body, the tattoo behind his left knee is the location used today for individuals suffering from abdominal complaints, reproductive organ complaints, and vertigo, to name a few. The tattoo located on the inside of his ankle is used for improving digestion. In addition, his fingernails indicated that he had been sick three times in the six months prior to his death (cause of death was a wound), the last time lasting about two weeks. One of the tattoos is at an area of rejuvenation for the body. The placement of tattoos on Ötzi's body fits his scientifically discovered medical history perfectly, and in fact, if Ötzi went to a practitioner today, there is a good chance that those very same acupuncture points would be chosen to treat his ailments.
[0007] The use of acupuncture and acupressure has a more recent history as well. In 1683, a Dutch physician named Willem Ten Rhijne studied acupuncture for two years in Japan, and he mentioned it in an essay he wrote in a medical text on arthritis.
[0008] In 1943, Dr. Reinhold Voll, a medical doctor in Germany, was diagnosed with bladder cancer. Western medicine provided him with no hope of a cure so he tried acupuncture and was able to completely heal himself. This experience started his quest to learn more about acupuncture. During his studies of acupuncture, he learned that the points used on the body for acupuncture were in fact more conductive of electricity than the tissue surrounding it. From this discovery he was able to develop the EAV Device (Electromagnetic Acupuncture according to Voll), which is a diagnostic machine that is still widely used today. It is believed that the extra conductivity at or around the acupuncture points is what makes the placement of therapeutic devices at these locations so effective in the treatment of health issues.
[0009] Today, acupuncture and other healing arts, such as Jin Shin Jyutsu®, are widely accepted. Medical acupuncture is taught in Harvard Medical School and the Helms Medical Institute, as well as at other well-respected medical schools. Acupuncture, Jin Shin Jyutsu, as well as other similar therapeutic techniques based on traditional Chinese medicine (TCM), have been implemented in many hospitals to help with pain and healing. Although not always fully understood in the West, the value of these ancient healing arts is finally being appreciated by Western medicine.
[0010] Magnetism has been used for centuries for healing health complaints, and is possibly even older than acupuncture. Magnetic energy influences every cell in the body. If the cells become depolarized, it has been observed that an individual will tire. Thousands of years ago, the Eastern belief was that the life force or Chi is generated by the Earth's magnetic field. Its use is recorded in ancient Egyptian writings and it is known that Cleopatra wore magnetic jewelry (i.e., a lodestone) on her head in the belief that it would help her maintain a youthful appearance.
[0011] The existence of electromagnetic energy and its effect on the human body is being studied more and more in Western medicine. Many prestigious institutions have made it a focal point of clinical trials with such research being conducted at Harvard Medical School, Vanderbilt University Medical Center, and the University of Texas Medical Branch. Today magnetic therapies are accepted and used in many countries.
[0012] In 1964, Dr. George J. Goodheart, a doctor of chiropractic medicine, realized that basic chiropractic adjustments were not providing complete and long-term relief for patients' physical complaints. In response, Dr. Goodheart combined the knowledge of those before him with his own experiences involving the muscles of the body in relation to acupuncture therapy to create Applied Kinesiology, a unique method of balancing the electromagnetic lines or flows that run throughout the body. Applied Kinesiology describes a branch of holistic medicine that studies the relationship between muscle movement and the health of the human body.
[0013] He achieved significant results using his new methods and found a very important and specific relationship between the muscles and the rest of the body. He later discovered a diagnostic and treatment tool that he called therapy localization. He observed that if a patient touched a part of the body where there was a problem or “blockage,” a weak muscle would become strong. From that observation, Dr. Goodheart realized he could use a muscle that was strong and go to various points on the body to detect a reflex or organ that created weakness. This weakness would show up in the muscle that was being tested. In this way problem areas could be identified and solutions could be found. For example, he discovered that if an individual was exposed to supplements that could help a patient, that the physical exposure of the individual to the correct supplement would make a weak muscle strong again.
[0014] There are many references that describe the underlying principals of Applied Kinesiology including “Applied Kinesiology,” written by Tom and Carole Valentine of Rochester, Vt. (1985); “Your Body Doesn't Lie,” written by John Diamond of New York, N.Y. (1980); and “Thorsons Introductory Guide to Kinesiology—Touch for Health,” written by Maggie La Tourelle and Anthea Courtenay of London, England (1992).
[0015] Building upon the efforts of Dr. Goodheart and Applied Kinesiology, there is a growing body of medical evidence that indicates that many health issues, whether physical, mental or emotional, are rooted in the electromagnetic lines or flows of the body. Different flows feed different sections of the body and a disruption in the flow will cause various health issues. The electromagnetic lines, also referred to as meridians, work in the body in a similar way as the electrical wiring in a house. When a circuit breaker “blows,” a section of the house fed by that current line loses power. It has long been observed that the removal of “blockages” of the meridian lines will restore good health. Different means have been used to stimulate these lines such as sharp stones, bone needles, and eventually metal needles, as well as hand techniques. Other methods used to “open” the blockages in electromagnetic lines include taping stationary magnets to a patient, magnetic beds, foot pads, plasters, etc, as well as various other types of machines.
[0016] Muscle response testing is a diagnostic methodology that uses the principals of Applied Kinesiology for determining a body's needs. Muscle response testing (MRT) is used widely by medical doctors, acupuncturists, chiropractors, osteopaths, veterinarians, and holistic dentists. There have been a number of books written on MRT including a seminal work written by Dr. David R. Hawkins in 1995.
[0017] During MRT, medical personnel will push down on a patient's extended arm while the patient resists the downward pressure. If the patient's nervous system is irritated for a period of time, a temporary short circuit will arise in the nervous system causing the arm being tested to momentarily weaken. During testing, medical personnel will irritate the nervous system by touching a sensitive area of the body, an acupuncture point or even by generating uncomfortable or irritating thoughts. Medical personnel may also ask a series of “yes/no” questions of the nervous system, looking for a weak or a strong response of the patient's extended arm. The weak or strong response reveals information about troubled areas in the body and provides additional information to medical personnel on how to treat the troubled areas.
[0018] MRT is used for virtually any question that can be asked of the body to make determinations about physiology, skeletal trauma, allergies, nutritional imbalances, emotional states or anything that may affect the body or the mind. MRT is a diagnostic tool that is only limited to the creativity of the practitioner's ability to ask a proper question. Once the information is ascertained, muscle testing may then be used to find out what the body or mind will respond to in terms of a resolution to the problem. Another benefit of MRT is that many of the problems that may be detected using MRT cannot be detected using conventional lab and exam tests and thus, are not discoverable except when using MRT.
[0019] There have been many efforts directed to using muscle response testing and applied kinesiology techniques. For example, U.S. Pat. No. 5,188,107 discloses a bi-digital O-ring test for imaging and diagnosis of internal organs of a patient. During the test, a patient forms an O-ring with a first hand by placing the finger tips of his thumb and one of his remaining fingers together, and a sample of tissue of an internal organ is placed in contact with the patient's second hand. The patient's internal organ is non-invasively externally probed with a probing instrument. The internal organ is the same type of organ as that of the sample. Simultaneously, a tester attempts to pull apart the O-ring shape of the first hand by means of the tester placing his thumb and one of the remaining fingers of each of his hands within the O-ring shape of the patient to form interlocking O-rings and pulling the thumb and the finger of the patient apart due to an electromagnetic field of the tissue of the sample interacting with an electromagnetic field of the internal organ being probed. This interaction is detected by the ability to pull apart O-ring shape, thereby permitting imaging of the boundaries of the internal organ being probed.
[0020] U.S. Pat. No. 5,855,539 discloses a kinesiology testing apparatus having a base, and a foot treadle having a first end and a second end. The first end of the foot treadle is pivotally attached to the base. The apparatus includes a line having a first end and a second end, whereby the second end of the line is secured adjacent to the second end of the foot treadle. Means is provided for securing the first end of the line to a person's arm. When a person has his arm extended out parallel to a floor, a downward force exerted by a foot of the person upon the foot treadle transmits, via the line, a downward force upon the persons arm.
[0021] In spite of the above advances, there remains a need for improved systems, devices and methods for efficiently diagnosing medical conditions using muscle response testing and treating the medical conditions using magnetic devices.
SUMMARY OF THE INVENTION
[0022] In one embodiment, the present invention discloses a method and system for placing one or more magnetic devices, such as an octapolar magnetic device, at a location on the body that is determined through using muscle response testing (MRT). The placement of the one or more magnetic devices preferably stimulates the electromagnetic lines in the body causing the bioelectrical energy in the body to flow freely. When the rivers of bioelectrical energy flow freely (as taught by traditional Chinese, Japanese, Indian, and Korean medicine), the individual feels better and heals faster.
[0023] In one embodiment, the present invention relates to systems, device, and methods for the treatment of health issues related to the blockage of the electromagnetic lines of the body. A blockage may result from either a lack of sufficient bioelectrical energy flow, or because of too much flow in one line and not enough in another. It has long been known that when these electromagnetic lines in the body are hindered in some way it causes disease. By stimulating the bioelectrical flow (Chi in Traditional Chinese Medicine (TMC) and Ki in Japanese Medicine), a physical healing of a variety of issues may take place.
[0024] In one embodiment of the present invention, multi-polar magnetic devices are placed on one or more points or locations on the body that have long been used for the stimulation of bioelectrical energy flow that is crucial to good health. In one embodiment, a multi-polar magnetic device has two positive and two negative poles alternating diagonally at the corners within a square 2×2 grid within the same plane. A flux field produced by the magnetic device opens magnetic lines at the desired point for healing the patient.
[0025] In one embodiment, the magnetic device has four disc-shaped magnetic bodies that are housed in a non-metallic enclosure that holds the magnetic bodies in place and in relative alignment with one another. It is believed that the relative orientation of the magnetic discs relative to one another enhances the performance of the device, because their collective orientations combine to produce a suitable field gradient that properly stimulates the electromagnetic lines of the body. The magnetic device includes an enclosure that has a prominent directional arrow, which is an important element contributing to the effectiveness of the systems and methods disclosed herein because it enables medical personnel to properly orient the magnetic devices for maximizing therapeutic benefit.
[0026] More than one device may be worn at a time. The two or more devices are preferably used at different points or locations on the body, whereby the points or locations are determined through Muscle Response Testing (MRT). The multi-polar magnetic devices are preferably not used in close proximity to one another, as doing so has been found to disrupt the field gradient of each apparatus.
[0027] The particular locations on the body used for the placement of the magnetic devices have been used for centuries in Eastern medicine. The placement of the magnetic devices at acupuncture points on the body is customized to a patient's needs. Through the relatively new science of Muscle Response Testing (MRT) or Manual Applied Kinesiology, blockages or points of correction on the body are located. After the exact placement points are identified, MRT is used again to determine one or more of the following: 1) the order of placement or placements, 2) the duration that each magnetic device will be left in place, 3) determining whether two or more device should be placed on the body at the same time or whether they should be placed one at a time in a series, and 4) determining whether the same placement series will be repeated or a new placement series will be used.
[0028] These and other preferred embodiments of the present invention will be described in more detail below.
BRIEF DESCRIPTION OF THE DRAWING
[0029] FIG. 1 shows a system for treating a patient including a pair of multi-polar magnetic devices, in accordance with one embodiment of the present invention.
[0030] FIGS. 2A-2C show a multi-polar magnetic device, in accordance with one embodiment of the present invention.
[0031] FIG. 3 shows a schematic top plan view of a multi-polar magnetic device, in accordance with one embodiment of the present invention.
[0032] FIGS. 4 and 5 show cross-sectional views of the multi-polar magnetic device of FIG. 3 .
[0033] FIGS. 6A-6F show a method of attaching a multi-polar magnetic device to a patient, in accordance with one embodiment of the present invention.
[0034] FIG. 7 shows acupuncture points and the main meridian channels on a human body.
[0035] FIGS. 8A-8D show Jin Shin Jyutsu points on a human body.
[0036] FIG. 9 shows meridian lines in a human body.
[0037] FIGS. 10A and 10B show a method of testing a patient, in accordance with one embodiment of the present invention.
[0038] FIGS. 11A-11C show a method of testing a patient, in accordance with one embodiment of the present invention.
[0039] FIGS. 12A-12C show a method of testing a patient, in accordance with one embodiment of the present invention.
[0040] FIGS. 13A-13B and 14 show some examples of the direction of energy flow through a human body.
[0041] FIG. 15A shows ascending energy flow through a human body.
[0042] FIG. 15B shows descending energy flow through a human body.
[0043] FIGS. 16 and 17 show the relationship between the teeth and parts of the human body.
[0044] FIG. 18 shows a method of treating a patient, in accordance with one embodiment of the present invention.
[0045] FIG. 19 shows a method of treating a patient, in accordance with one embodiment of the present invention.
[0046] FIG. 20 shows a method of treating a patient, in accordance with one embodiment of the present invention.
[0047] FIGS. 21A-21B show a method of treating a patient, in accordance with one embodiment of the present invention.
[0048] FIGS. 22A-22C show a method of treating a patient, in accordance with one embodiment of the present invention.
[0049] FIG. 23 shows a method of treating a patient, in accordance with one embodiment of the present invention.
[0050] FIG. 24 shows a method of treating a patient, in accordance with one embodiment of the present invention.
[0051] FIG. 25 shows a method of treating a patient, in accordance with one embodiment of the present invention.
DETAILED DESCRIPTION
[0052] Referring to FIG. 1 , in one embodiment, a system 100 for treating medical conditions preferably includes a storage case 102 having a base 104 and a cover 106 that is hingedly connected with the base. The base 104 is adapted to receive and hold a pair of octapolar magnetic devices 108 A, 108 B, which may be removed from the base 104 for being applied to a patient. The cover 106 preferably includes an underside 110 adapted to receive a plurality of adhesive discs 112 for adhering the magnetic devices to a patient and an instruction manual 114 that provides instructions for using the octapolar magnetic devices 108 A, 108 B. An elastic band 116 is preferably secured to the underside 110 of the cover 106 for storing the adhesive discs 112 , and the instruction manual 114 within the cover 106 of the case 102 .
[0053] Referring to FIGS. 2A-2C , in one embodiment, an octapolar magnetic device 108 desirably includes a housing 118 made of a non-metallic material, such as a plastic or polymer material, that is adapted to house a plurality of permanent magnets therein. In one embodiment, the housing 118 has a top surface 120 , a bottom surface 122 , and a side wall 124 extending between the top and bottom surfaces. The side wall 124 preferably defines a pentagon shape and desirably includes a first side wall section 126 , a second side wall section 128 , a third side wall section 130 , a fourth side wall section 132 , and a fifth side wall section 134 . The first and second side wall sections 126 , 128 preferably join one another at an acute angle that defines an apex 136 . The housing 118 also preferably includes an alignment marker 138 that is formed in the top surface 120 of the housing. A leading edge 140 of the alignment marker 138 is preferably aligned with the apex 136 of the housing 118 . The top surface 120 of the housing 118 also preferably includes a central marker 142 that is desirably centered between the four magnetic discs located within the housing. As will be described in more detail herein, the alignment marker 138 enables the octapolar magnetic device 108 to be properly aligned on a patient's body for maximizing therapeutic benefit.
[0054] Referring to FIGS. 3-5 , in one embodiment, the octapolar magnetic device 108 desirable includes four magnetic discs 144 , 146 , 148 , and 150 that are held by the housing 118 in a particular orientation that accounts for the magnetic properties of each magnetic disc, and so that the magnetic device 108 may be easily handled without altering the arrangement of the magnetic discs. In one embodiment, each of the magnetic discs is preferably a cylindrical, center-charged permanent magnet with each magnetic disc being of equal size and strength. The magnetic poles of the magnetic discs are desirably disposed substantially in two parallel planes, with each plane containing opposing positive and negative magnetic poles. Referring to FIG. 3 , in one embodiment, first and third magnetic discs 144 , 148 have their negative charged faces in a first plane and second and fourth magnetic discs 146 , 150 have their positively charged faces in the first plane. Collectively, the four magnetic discs form an octapolar magnetic device.
[0055] In one embodiment, a first face 152 of the first magnetic disc 144 lies in a first plane P 1 and is negatively charged and a second face 154 of the first magnetic disc 144 lies in a second plane P 2 and is positively charged. Thus, a negative magnetic pole of the first magnetic disc 144 is centered on the first plane P 1 , while a positive magnetic pole of the first magnetic disc 144 is centered on the second plane P 2 . The housing 118 holds the second magnetic disc 146 adjacent the first magnetic disc 144 . A first face 156 of the second magnetic disc 146 lies in the first plane P 1 and is positive charged and a second face 158 of the second magnetic disc 146 lies in the second plane P 2 and is positively charged. Thus, a positive magnetic pole of the second magnetic disc 146 is centered on the first plane P 1 , while a negative magnetic pole of the second magnetic disc 146 is centered on the second plane P 2 .
[0056] The four magnetic discs 144 , 146 , 148 , 150 are desirably oriented to define four vertices of a quadrilateral shape. The four magnetic poles in each of the two parallel planes comprise two positive and two negative poles, the two positive poles defining two diagonal vertices and the two negative poles defining the diagonal vertices of the quadrilateral shape. The distance between the poles in each plane is such that the magnetic field generated by each pole has a significant magnitude at each of the other poles
[0057] Referring to FIG. 3 , the negatively charged faces of magnetic discs 144 and 148 and the positively charged faces of magnetic discs 146 , 150 are in the first plane P 1 ( FIG. 4 ). The two negative poles on discs 144 , 148 define opposite diagonal vertices of the quadrilateral shape, while the two positive poles on discs 146 , 150 define opposite diagonal vertices. Each of the four magnetic poles is magnetically attracted by the two oppositely charged poles and is magnetically repelled by the like charged pole
[0058] Referring to FIGS. 3 and 5 , the magnetic discs preferably have the same diameter, height and shape. In one embodiment, each magnetic disc has a diameter of about 12.7 mm and a height of about 3.2 mm. However, larger or smaller magnetic discs may be used and still fall within the scope of the present invention. When cylindrical magnetic discs with opposite poles on opposite faces are utilized, both major faces of the octapolar magnetic device 108 will exhibit the same magnetic field. Thus, each major face of the octapolar magnetic device can be considered to have a quadrapolar configuration
[0059] In one embodiment, each of the magnetic discs preferably center-charged, which means the magnetic energy is concentrated on the central axis of each magnetic disc rather than being distributed uniformly over the face of the magnet. The magnetic induction field over the center-charged face has a steeper gradient than the field over a non-center-charged face. Suitable center-charged magnets are manufactured by Delco Remy, a division of General Motors Corporation.
[0060] The housing 118 preferably holds the magnetic discs 144 , 146 , 148 and 150 in the desired orientation. The housing 118 may be made of a thermoplastic material in which the four magnetic discs are held.
[0061] The alignment marker on the magnetic device has great importance regarding the treatment methods disclosed herein because the energy flow in bodies can become disrupted, thereby causing a variety of health issues. Energy can become stagnated, thus needing to be dispersed or it can be lacking in an area and need more from other areas to bring it into balance. In Jin Shin Jyutsu and other similar techniques, this is done by directional hand placement. The energy flow of the body is influenced by the way the hands are placed while the patient is being worked on by the practitioner. In the present invention, it is done by the use of the alignment marker and how the magnetic devices are oriented on the body. This is very important in achieving the re-establishment of proper energy for resulting in the elimination of disease. The alignment marker on the magnetic device influences the path and the direction of the energy flow in the body in the same way.
[0062] Referring to FIGS. 1 and 6 A- 6 F, in one embodiment, at least one of the octapolar magnetic devices 108 is attached to a patient's body. Referring to FIGS. 1 and 6A , one of the magnetic devices 108 and at least one adhesive disc 112 is removed from the case 102 . Referring to FIGS. 6A and 6B , a pair of tabs 160 A, 160 B is peeled away from a sheet 162 to expose a top face of an adhesive disc 164 , which is preferably transparent. Referring to FIG. 6C , the bottom major face 122 ( FIG. 2C ) of the housing 118 is preferably pressed against the exposed adhesive disc 164 on the sheet 162 to secure the adhesive disc to the housing 118 . The adhesive disc 164 is preferably attached to the bottom major face of the housing 118 so that the alignment marker 138 on the top major face 120 may be used for aligning the magnetic device on a patient.
[0063] FIG. 6D shows the adhesive disc 164 after it has been attached to the bottom major face 122 of the housing 118 . Referring to FIG. 6E , the housing 118 is preferably secured to a patient's body by pressing the adhesive disc 164 ( FIG. 6D ) and the bottom major face 122 of the housing 118 against the patient's skin. The alignment marker 138 on the housing 118 is used for properly aligning the magnetic device 108 on the patient for maximizing therapeutic benefit. In FIG. 6E , the alignment marker 138 and the magnetic device 108 are aligned at a six o'clock position. In FIG. 6F , the alignment mark 138 and the magnetic device 108 are aligned at a nine o'clock position. The orientation of the alignment marker is determined through muscle response testing as will be described in more detail herein.
[0064] In one embodiment, one or more magnetic devices are placed at locations or points on the body that are widely used in acupuncture, acupressure, Shiatsu, Jin Shin Jyutsu, and reflexology. The locations may also be acupuncture points, electromagnetic lines, meridians, points used in traditional Chinese medicine, locations on the body used in Jin Shin Jyutsu, and locations on the body used in Ki-Iki Jutsu® and Shiatsu. FIG. 7 shows the location of traditional acupuncture points and the main meridian lines on a human body. FIGS. 8A-8D show the location of Jin Shin Jyutsu points on a human body. These points have been observed to have more electrical current than surrounding areas of the body so that they may be used to stimulate the electromagnetic lines or flows of the body. FIG. 9 shows the electromagnetic lines that extend through a human body.
[0065] There is a very strong connection between the brain and the muscles of the body. The brain uses electrical current to direct muscular movement. This relationship makes the muscles very sensitive to the electrical flows of the body, thus making them good indicators of the strengths and weaknesses of the meridian lines or flows.
[0066] In one embodiment, a patient is assessed using Muscle Response Testing (MRT) or Manual Applied Kinesiology (AK). MRT is an effective way of determining energy pathways that are disrupted.
[0067] In one embodiment, one muscle is isolated, usually the deltoid, and consistent pressure is put upon it by gently but firmly pressing downward on the arm. Other muscles may be tested, however, the deltoid muscle is most commonly used for testing. When meridian line or flow weakness or blockage is identified through the electrical response of the muscle, the same technique may be used to determine which therapies are needed to strengthen the line and restore flow once again. The process is somewhat similar to finding a “blown” fuse in an electrical system in a house and replacing it to restore the electrical circuit and its flow of current.
[0068] When a patient/client is about to be tested, the first step is to check the polarity of the individual. As used herein, the terms patient and client may be used interchangeably. The Earth is a huge magnet and the body acts as an electromagnetic. There is a magnetic difference between the top of a patient's head (North Pole), and the bottoms of the patient's feet (South Pole). There is also a difference in the patient's hands, with the palm of the hand being the South Pole and the back of the hand being the North Pole.
[0069] Normal Polarity. Referring to FIGS. 10A and 10B , when the back of the hand is placed on the top of the patient's head, if the individual's polarity is correct, the deltoid (or whatever muscle is being used) will register weakness, and the arm will weaken. The reason for this is that the patient has two like magnetic poles. The top of the head is North, and the back of the hand is North, and as with any other type of magnet two similar poles will repel each other. The patient cannot feel the repulsion but the brain and the nervous system perceive it immediately and the inner reflexes to all the muscles are slightly weakened.
[0070] Normal Polarity. When the patient places the palm of the hand on the top of the head, if the individual's polarity is correct, the deltoid (or whatever muscle is being used) will register strength. The reason for this is that the patient has two opposite poles. The top of the head is North and the palm of the hand is South so there is an attraction, whereupon the computer in the brain is not affected so that the muscles keep their strength.
[0071] Unstable Polarity. Unstable polarity exists when the palm of the hand is placed on the top of the head and there is no change in the strength of the muscles. If the patient places the palm of the hand on the top of the head and the muscles weaken, this is an indication of a problem that must be corrected before the test can begin. The usual causes of polarity issues in the body are lack of water, structural ankle issues, heavy jewelry (metal will disrupt electrical flow), and occasionally cell phones. When the above polarity disturbances occur, which is not common, they must be corrected before continuing.
[0072] In one embodiment, Muscle Response Testing (MRT) is used to determine if the system and methods will work for the patient. Referring to FIGS. 11A-11C , in one embodiment, the patient can hold a magnetic device in their hand and the muscles will respond with either strength or weakness. If the arm tests strong while holding the device, that indicates that the magnetic therapy will work well for the body in promoting healing. If the muscle displays weakness while the individual holds the device that indicates that the therapy would not be the optimum method to promote healing. If the patient touches the magnetic device and the muscle displays strength that indicates that the system and methods will work well and help promote healing. The patient can also touch a device and if their arm is weak it would not be the best method to promote healing in their case.
[0073] After getting a positive response that the magnetic devices will benefit the patient, a determination is made regarding where the device is to be placed on the patient's body. This is once again determined by MRT. The locations or points chosen are ones used for centuries to stimulate the electromagnetic lines or flows in the body. The patient's symptoms help guide the practitioner to the proper location but finding the exact spot of placement is a process of elimination. Referring to FIG. 8B , in one embodiment, point # 4 located at the base of the skull on the right side of the body is used. When the # 4 location is pointed to and the deltoid responds with strength the tester knows there is not problem along this energy flow or line. If the # 4 location is pointed to and the response is a weakening of the deltoid muscle the indication is there are issues with this line or flow in the body and a device should be placed there. This process is used to check the points or locations of the body that could be used for possible device placement. The confirmation of the # 4 location is in agreement with the patient's symptoms because they suffer with headaches that occur mostly in the area of the forehead, they get neck pain, and have a very stubborn personality, all of which originate with a malfunctioning of the # 4 flow.
[0074] Next, MRT is conducted for determining the direction of the arrow on the magnetic device when the device is placed on the patient's body. The direction of the arrow will directly impact the success of the treatment methodology because the electromagnetic lines or flows run in many different directions. The tester uses a process of elimination. Testing is conducted with the arrow on the magnetic device pointed in each direction, one at a time, by either placing the device on the patient or letting the patient hold the device and shift the arrow each time a test is conducted. Referring to FIG. 12A , in one embodiment, the alignment marker 138 on the magnetic device 108 is pointed to the individuals left, the deltoid goes weak, which is a negative response, and the body's answer is “no.” Referring to FIG. 12B , in one embodiment, the alignment marker 138 on the magnetic device 108 is pointed down, the deltoid goes weak, which is a negative response, and the body's answer is “no.” Referring to FIG. 12C , in one embodiment, the alignment marker 138 of the magnetic device 108 is pointed to the patient's right, the deltoid muscle is strong, and the body's answer is “yes.” Based upon the above scenario, the magnetic device is placed on the # 4 point, on the right side of the body, with the directional arrow pointing to the patient's right.
[0075] If none of the tested arrow directions (i.e., up, down, left or right) provided a “yes” response, then the MRT testing will be conducted using the face of a clock. In one embodiment, the directional arrow is placed between 1 and 3 o'clock. The deltoid muscle is weak so the patient's body does not want the arrow in this direction. Next, the placement arrow is positioned between 3 and 6 o'clock, the deltoid is weak, a negative response, the body does not want the arrow in this direction. Next, the directional arrow is positioned between 6 and 9 o'clock, the deltoid muscle is strong indicating a positive or a yes, which means that the body wants the directional arrow pointing between 6 and 9 o'clock. Because it was already determined that the body did not test for the arrow direction to be down or to the right or left, there is no need to test for the 6 o'clock or 9 o'clock directions. The next test is the 7 o'clock direction, the deltoid goes weak, a negative response, the body does not want the 7 o'clock direction. The directional arrow is then placed in the 8 o'clock direction and the deltoid muscle is strong indicating a positive response, the body wants the arrow pointed in this direction. The testing indicates that the magnetic device should be placed on the right # 4 location with the directional arrow pointing to 8 o'clock.
[0076] In one embodiment, a determination is made regarding how long the magnetic device should be worn on the body. Again, this determination is preferably made through a process of elimination using MRT. In one embodiment, time is grouped in blocks to facilitate the test. For example, the device will be worn for 10 hours, the deltoid goes weak, a negative response, it will not be worn for 10 hours. The device will be worn under 10 hours, the deltoid is weak, a negative response, the device will not be worn under 10 hours. The device will be worn over 10 hours, the deltoid is strong, a positive response. How much over 10 hours? The device will be worn for 15 hours, the deltoid is weak, and will not be worn for 15 hours. The device will stay on for under 15 hours, the deltoid is strong, indicating a positive response by the body. This result indicates that the device should be worn for between 11 and 14 hours. The test continues. The device will stay on the body for 11 hours, the deltoid is weak, a negative response. The device will be left on the body for 12 hours, the deltoid is weak, a negative response. The device will be left on for 13 hours, the deltoid is weak, a negative response. The device will be left on for 14 hours, the deltoid is strong, a positive response. The test results indicate that the device should be placed on the right # 4 location with the arrow direction at 8 o'clock for 14 hours.
[0077] The next stage of testing is used to determine if the device placement will be re-applied. This can be determined by asking “will the placement need to be re-applied?” or having the patient hold the device by the # 4 location. If the deltoid is weak, the answer is negative, a no. If testing indicates the deltoid is strong, the answer is positive, a yes.
[0078] During testing, statements are verbalized initiating a response from the brain that affects the deltoid (or whatever muscle is chosen for testing). The device placement on the body will be re-applied two times, the deltoid is strong, a positive response, it will be repeated two times.
[0079] For determining whether the device should be reapplied in the location, duration, and direction, the following questions are asked. The device placement will be worn two days in a row, the deltoid is weak, a negative response, it will not be worn two days in a row. The statement is then made that the device placement on the body is spaced every other day, the deltoid is weak, a negative response, it will not be repeated every other day. Placement on the body will be repeated every third day, the deltoid is strong, a positive response, the device will be worn on the body for 14 hours, taken off, and repeated again for 14 hours 3 days later.
[0080] Based upon the above responses, the device needs to be worn on the right # 4 location with the arrow toward 8 o'clock, for 14 hours. After the 14 hours is complete, the device is to be removed. On the third day after removal the device is to be reapplied to the body at the same location, with the arrow direction to be the same, and the amount of time left on the body to be the same.
[0081] MRT is conducted to determine if a second placement is needed to further improve line flow. The deltoid is weak, a negative, no. Another placement will not be needed. If the test had been positive, the above process would be repeated for determining the location, direction, and length of time for placement of the second device.
[0082] Multiple Device Placement. The number of placements on the body may vary. In one embodiment, a determination is made if the method will benefit the health of the patient. The patient touches the device on a table, the deltoid is strong, a positive response, the individual would benefit from the method. The patient holds one device in their hand and a statement is made that only one location will be needed. The deltoid goes weak, indicating a negative response. The patient holds two devices in their hands and a statement is made that two locations will be needed. The deltoid is strong, indicating a positive response, the body wants devices in two locations on the body.
[0083] Testing is now conducted to determine where the two separate locations are on the body. The average number of devices is usually between one and three but can go higher in some cases. Another way to test for locations is to have the patient touch one device on a table, if the deltoid is weak, it is a negative response and more than one device is needed.
[0084] The patient touches two devices on the table, the deltoid is strong, a positive response from the body. This indicates that there should be two locations on the body for placement of the devices.
[0085] The patient is tested to determine if the locations to be used are used in Jin Shin Jyutsu, the deltoid is strong, indicating a positive response, we are looking for locations used in Jin Shin Jyutsu.
[0086] To facilitate the test, the body is broken up into sections. The points are located below the waist on the front of the body. The deltoid is weak, a negative response, the locations are not on points below the waist on the front of the body. The points are located below the waist on the back of the body. The deltoid is weak, a negative response, the locations are not on points below the waist on the back of the body. The points are located above the waist, the deltoid muscle is strong, a positive response, either one or both will be located above the waist. Testing has indicated that the point or points are located above the waist. The next section tested is above the waist on the back of the body. The deltoid muscle is weak, a negative response, the location is not on the back of the body.
[0087] Through a process of elimination it is determined that at least one or both of the locations are on the front of the body. This is confirmed by further testing. The deltoid muscle is strong indicating the device or devices will be placed on locations on the front of the body above the waist.
[0088] To find the exact location, each point will be tested by either the patient or the practitioner pointing to the area. In this case a weakness on the spot is the signal by the brain via the deltoid muscle indicating a line flow problem. One location has been found on the front of the body, the energy lock or sphere # 22 ( FIG. 8A ). When the left # 22 location was touched either by the patient or the practitioner, the deltoid weakened indicating line flow disruption. The directional arrow is then tested as previously discussed and the arrow will be facing to the patients' right.
[0089] At this stage, only one of the two locations has been identified for the particular placement. The testing continues for the second location by testing the arms. The deltoid is strong when the right arm is tested, a positive, yes. The second area of placement is located on the right arm. Again by process of elimination the points on the right arm are each tested and the location that shows up as weakness in the deltoid, indicated by the arm becoming weak, is the # 19 ( FIG. 8A ) by the bend of the elbow. Through a process of elimination, it has been determined that the second location is the energy lock or sphere # 19 on the right arm. The directional arrow will then be tested as described previously. In this case the arrow direction will by facing down toward the fingers.
[0090] For the double device placement it has been determined that the areas of placement will be the left # 22 and the right # 19 . Testing is then conducted to determine if both devices are placed on the body at the same time. The deltoid is weak, a negative response from the body. The devices will not be placed on the body at the same time.
[0091] Testing is conducted to determine if the # 19 will be placed on first, the deltoid muscle is weak, a negative response, the # 19 will not be placed on the body first. Testing is conducted to determine if the # 22 will be placed on the body first, the deltoid is strong, a positive response from the body, the device will be placed on the # 22 first with the arrow direction pointing to the patient's right. The amount of time it will be worn on the body alone is then tested as described previously. It is determined that the left # 22 will be worn on the body first, with the arrow direction to the patient's right, and is worn alone on the body for 5 hours.
[0092] Testing is then conducted to determine what will occur after the 5 hours have passed. The # 19 device is placed on the right arm. Both the # 22 and the # 19 devices are worn on the body together for a MRT time of 10 hours. Testing is conducted to determine what will occur after the 10 hours is complete. The # 22 is to be removed and the # 19 will stay on the arm another 5 hours alone on the body. After the 5 hours is complete all devices are removed. Testing is conducted to determine if the placements will be repeated when the 20 hours of initial placement is completed, or will another placement or placements be needed after the first round of placements. The deltoid muscle is strong, a positive response, another placement or placements will be needed.
[0093] In one embodiment, an individual may conduct MRT on himself, which enables the individual to quickly care for an injury or illness. Teaching MRT to a non-practitioner will enable individuals to care for common health issues such as virus, flu, injuries, etc. Deeper levels of line correction would require a qualified practitioner or trained medical professional.
[0094] Self test method # 1 . In one embodiment, the finger pad of the thumb and the finger pad of one of the fingers, usually the pointer or middle, are gently slid against each other. If the fingers are dry there should be very little to no resistance to this movement. If something is placed in the opposite hand that is good for the body, the individual will feel resistance between the two fingers and a feeling of tackiness will develop. If something is placed in the opposite hand that is not good for the body, then there will be no change or the slip of the fingers increases. This method can also be used to isolate locations on the body that show blockage. The regular protocol for MRT can be followed.
[0095] Self test method # 2 . This method uses a finger loop. The muscles of the fingers are used to evaluate the needs of the body. The fingers on one hand create a loop and, using the finger of the opposite hand, an individual gently applies pressure to try to break the looped fingers apart. If the individual cannot pull the finger through the loop that would be a strong or positive test. It is making the body's electrical flow stronger. If the individual is able to pull the finger through it is making the body's electrical flow weaker. This test uses the same principle that are used when MRT the arm. Once again the MRT protocol for the therapy is followed. Although two self tests are disclosed, there are other self test methods that may be used.
[0096] Other ways to access line or flow blockages. Taking a pulse reading, which is used extensively in TCM, can help determine which lines or flows are problematic. From this information, the practitioner or medical professional can press on the locations that correlate to the lines having difficulty. The areas where devices should be placed will most likely be tender, and sometimes even painful. They can also feel like small hard nodules or lumps, and at times can feel as though there is a little electrical buzz or a pulse. It would then be up to the discretion of the practitioner as to how many devices would be needed, the duration, and the direction of the arrows.
[0097] Any method of identifying meridian or line flow blockage can be adapted to the methods disclosed herein in the same manner as described herein. Methods to access line or flow issues range from machines that use points on the feet and hands, using points on the body, TCM face reading techniques, nail reading, iridology (reading the eye), and sclarolegy (reading the whites of the eyes).
[0098] As can be seen by FIGS. 13A , 13 B, and 14 , energy flow in the body takes many directions. There is also a daytime and evening general energy direction that occurs naturally in the body. In the daytime the flow travels from the feet up the front of the body and down the back. This is called ascending energy. In the evening when the body is ready to rest in sleep the energy flow should reverse and flow from the feet up the back and down the front of the body. This is called descending energy. The proper flow of the ascending and descending energy is very important to good health. Disruption of these flows will effect sleep patterns and fatigue, and impair the proper function of other electromagnetic current lines.
[0099] FIG. 15A shows the ascending energy (flow from feet to head) being stimulated by the hands. The left hand fingers toward the head and the right hand fingers toward the feet are placed on the mid-line of the body. To achieve the same effect with the present invention, a first magnetic device is placed on the navel with the directional arrow pointing down, and a second magnetic device is placed on the coccyx tip with the directional arrow facing up.
[0100] In FIG. 15B , the opposite energy flow is being addressed. The hands are positioned with the right hand on the upper portion of the body with the fingers toward the head and the left hand positioned on the lower part of the body with fingers toward the feet to address the descending energy. To address this energy, the first magnetic device is placed on the navel with the directional arrow facing up, and the second magnetic device is on the coccyx tip with the directional arrow facing down.
[0101] Energy can also become pooled in a certain area of the body. These areas of stagnation can be located by a hardness that is felt just under the skin. The area can be small (¼ inch) or quite large (3-4 inches). These areas are strongly affected by the direction of hand placement on the body or the direction of the alignment markers on the magnetic devices disclosed in the present invention. Thus, hand placement to correct energy flow problems correlates to the alignment markers on the magnetic devices disclosed in the present invention.
[0102] The present invention preferably has many valuable uses in dentistry because the teeth can have a huge impact on the health of an individual. Many electromagnetic lines run through the teeth. So when the teeth have issues, it will affect the lines or flows that pass through them causing disruption.
[0103] We can see how teeth impact the health of an individual when we examine the connection tooth # 3 , the first molar on the upper right side of the mouth, has with the rest of the body. Referring to FIG. 16 , a serious problem with this tooth can affect the pancreas, small intestine, larynx, mammary gland on the right breast, stomach, medial ankle, anterior knee, anterior hip, TMJ on the right side of the jaw, maxillary sinus, tongue, and thyroid.
[0104] Another example is tooth # 25 , the central incisor right lower. Referring to FIG. 17 , serious problems with this tooth could affect the adrenal glands, nose, sphenoid sinus, frontal sinus, sacrao-coccygeal joint, posterior hip and knee, kidney on the right side, bladder, genitor-urinary, ovaries, uterus, testicles, prostate, and the right ear.
[0105] A relatively new discovery in dentistry is a condition that can occur when a tooth is extracted, called a cavitation or “NECO” (Neuralgia Inducing Cavitational Osteonecrosis) lesion. The term NECO was given because some specialists feel that this dental issue could be responsible for Trigeminal Neuralgia as well as other types of facial pain.
[0106] A cavitation is a hole in the bone, which usually occurs where a tooth has been removed. In an X-ray, this area will show up as a shadow of a tooth. After a tooth is extracted, some feel that the membrane of the tooth remains behind so that the bone at this location never fills in. It may also be caused by the lines or flows that feed that particular tooth. If the lines or flows are experiencing a weakened condition, the space left behind after an extraction will have difficulty healing. The result is a spongy spot in the jaw at the extraction site. Other traumas can also cause cavitations.
[0107] There are many health dangers associated with a cavitation. These areas become breeding grounds for bacteria and the toxins they give off. They can also harbor mercury, and are very detrimental to the balanced flow of the energy lines, acting almost like a “leak” in the bioelectrical energy of the body. It is almost impossible to completely correct weakened flows that run through a cavitation or NECO lesion, which makes them a silent cause of recurring health issues.
[0108] Prior to the present invention, surgery would have been the recommended course to handle a cavitation. Surgery is very costly, painful, and can leave behind scar tissue which carries its own set of health issues. In one embodiment of the present invention, a magnetic device may be placed on an area of the face that correlates with cavitation location in the jaw so that the cavitations or NECO lesions can be stimulated to heal.
[0109] Muscle Response Testing is used to determine 1) the proper location for the magnetic device on the face, 2) the direction of the arrow on the magnetic device, and 3) the amount of time needed for placement of the magnetic device. In one embodiment, the average time the magnetic device will be worn on the face to correct a cavitation is around 56 hours.
[0110] The methods disclosed herein may also be used for other dental issues. When magnetic devices are placed near location # 18 ( FIG. 8A ) on the thumb, it can calm the gag reflex some experience during dental work. It may also help speed healing with any type of dental procedure by addressing the energy lines that affect the particular area of the mouth that is being worked on. These placements are very individualized and are not necessarily placed at the site of the actual dental work. As an example, a person who received a root canal may wear the magnetic device on location # 20 ( FIG. 8A ) on the forehead. This facilitates healing, which, in turn, helps with pain and discomfort. The patient is able to go about their business as through dental work had not been performed. This type of placement would follow the same procedure that has been outlined herein for placement of devices on an individual.
[0111] The present invention may be used to treat patients having a wide variety of conditions and diseases as discussed in case studies 1 - 10 below.
[0112] Case Study # 1 . A young girl about 10 years old had a fear of the dark. Whenever the family would arrive home at night, she couldn't enter the house until lights were turned on. MRT was conducted to determine if the present invention would work to help her alleviate her phobia of the dark. Energy flows or lines are responsible for anything the body experiences; they are even responsible for phobias that individuals may have. To test the patient, she was asked to think about the dark, which weakened her deltoid muscle, registering as weakness in her arm when gentle pressure was applied. The patient was then told to hold one of the magnetic devices in her hand and she was asked to think about the dark. This time the deltoid muscle was strong, indicating that the present invention would help her overcome her fear of the dark. Once again, the patient was asked to think about her phobia and tested which contact points on her body showed weakness as described previously under the method. These would be the locations that affected the lines or flows responsible for the phobia.
[0113] Referring to FIG. 18 , during MRT testing, through a process of elimination, it was discovered that the energy sphere or lock # 16 on the outside of the left ankle was registering weakness when she thought about the dark. It was determined that only one device was needed because only one location made the deltoid muscle go weak, indicated by the arm weakening. Also, when the young patient held one device in her hand, her deltoid muscle was strong but when another was added, it weakened, indicating her body only needed one device placed in one location. The location would be the left # 16 on the outside of the ankle.
[0114] The device was placed against the area and tested the strength of the deltoid by process of elimination as described in the method, it was determined that the arrow direction would be down. Then through asking the body verbal questions while muscle testing, it was determined that she would need to wear the device on the left # 16 for 10 hours which, because of her age, and the fact that she was in school, she wore while she slept. Arrow direction would be down. Through MRT we determined the apparatus would be worn three nights in a row. The Result Her fear of the dark is vastly diminished.
[0115] Case Study # 2 . A patient had not been feeling well for a few weeks and through muscle response testing it was determined that this was bacterial in origin. As with Case Study # 1 , MRT was conducted to determine which point on the body was the root of the problem. The location of the problem would show up as a weakness in the deltoid muscle reflected in the testing arm weakening when light pressure was gently applied, and the problem location was touched.
[0116] The patient then held the magnetic device to see if the body would respond to the new therapy. The response was a strengthening of the arm when the weak area was touched while the individual held the apparatus. Then the number of devices needed was tested. The patient needed only one device because when two were placed in his hand, the patient's deltoid went weak, and only one location was found when points on the body were tested. Referring to FIG. 19 , the location needed was the left # 3 on the top of the shoulder blade close to the spine. This location fits with the prior test that indicated that the problem was bacterial in nature as the # 3 point is considered the body's natural antibiotic. A test for arrow direction was conducted by moving the arrow on the # 3 location until the arm registered strength. This happened when the arrow was toward the patient's right.
[0117] The test continued using verbal questions to determine the amount of time the patient would need to wear the device. The length of time was 10 hours and even though it did not have to be applied at a specific time (occasionally the time of application does matter as noted in the Chinese meridian clock) the patient wished to sleep with it on. When the patient woke up the next day, he reported that the symptoms he had been suffering with were gone.
[0118] Case Study # 3 . This case involved a tooth extraction that would possibly have led to a cavitation in the area due to the fact that the lines or flows that passed through that tooth were already showing signs of weakness or blockage. Cavitations or NECO lesions are caused by a lack of blood flow to the area of the extraction leaving the tissue in a necrotic state. In a sense it's a black hole. Since many of these energy lines run through the teeth, cavitations can cause problems along those lines or flows. These are very difficult to correct if the cavitation or NECO lesion is not addressed.
[0119] Referring to FIG. 20 , the tooth extracted was # 15 , the second molar. This tooth correlates with the parathyroid, tongue, maxillary sinus, left jaw TMJ, anterior hip, anterior knee, medial ankle joint, spleen, stomach, left breast, bladder, and pancreas. The area was MRT by pointing to different locations on the outside of the mouth close to the extraction site until the deltoid weakened. When the weakened area was located, the apparatus was applied over the location on the outside of the mouth.
[0120] The direction of the arrow was then tested, and it was to point toward the back of the head. Through verbal questions it was discovered that the device was to be left on for a total of 59 hours straight (there are cases where the time can be broken up). When examined three days later, the area of extraction was almost totally healed, the patient felt better, and the patient reported that her skin was healthier. Due to the fast healing of the area, pain was kept to a minimum as well.
[0121] Case Study # 4 . A patient had a pinched nerve in his neck. He was unable to move his head to the left or the right. The pain was so intense that it was to the point of nausea. This went on for about three weeks while other methods were tried unsuccessfully. The patient was tested to see if the new method would work for him and it was determined that it would, by the muscles of his arm registering strength. The patient was then tested to see which locations of the body would be used to correct his problem. Referring to FIGS. 21A and 21B , three locations were determined through MRT, which were the area of the # 12 on the left side of the neck, the # 15 on the left side of the groin area, and the # 24 on the top of the left foot. At each location, the arrow direction was then tested and it was determined that the arrows at all three locations would be facing to the right of the individual. The patient was then tested to determine length of treatment and it was determined that all three devices were to be applied at the same time and were to stay on together for a total of 12 hours. It was also determined through MRT that at the end of the 12 hours the # 15 and # 24 were to be removed and the # 12 was to remain on the neck for another 12 hours. Before the devices were placed on the body, the patient could not move his head to the right or left. After treatment, the patient could freely move his head and the pain had almost entirely disappeared. He reported being about 70-80% better than the day before. A second set of devices were recommended to reach 100% correction, but the patient felt so good he never applied them.
[0122] Case Study # 5 . A 28 year old patient was having a lot of health problems after he was in a serious car accident. The testing point for the vagus nerve was determined to be very weak, which is an indicator for major structural problems, probably as a result of the car accident. These structural problems were affecting the lines or flows for the gallbladder, umbilicus, and bladder energies. He was experiencing most of the symptoms that these blocked lines will manifest.
[0123] After identifying the problem lines or flows, MRT was used to determine which lines needed to be addressed first. Through MRT, it was determined that the gallbladder line needed to be worked on first. This determination was made by verbal questions. It was also determined that two locations were to be used to restore flow to the gallbladder line. Referring to FIGS. 22A-22B , the devices were placed on the # 14 located along the rib cage on the left side of the body, and the # 16 located on the left outer ankle. MRT was conducted to determine that the arrow on the # 14 was to be pointing to the individual's left, and on the # 16 , the arrow pointed down.
[0124] Both apparatuses were to be applied to the body at the same time and were to be left on together for a total of 10 hours. After the 10 hour placement was completed, the # 16 was to be removed, but the # 14 was to stay on another 10 hours by itself. After the # 14 was worn on the body for a total of 20 hours, it was to be removed also. It was determined through MRT that the patient would need a second placement series, but a space of a week would be needed between the two placement series. The patient reported, in the seven days between placements, that he felt a bit better every day. He reported that it was the first time he felt better since the accident.
[0125] Case Study # 5 —Second Round of Placements. The second round of placements was necessary to balance out a flow called the 5 th stratum, and the umbilicus line. Referring to FIGS. 22B and 22C , once again, two devices would be needed, with one placed on the left # 19 on the arm by the elbow, and the other on the left ring finger. The arrow on the device placed on the left # 19 would be facing to the right of the patient as would the device placed on the ring finger. It was determined that the # 19 was to be placed on the body first and would remain on the body alone for a total of 10 hours. After the completion of the 10 hours another apparatus was added to the finger. Both devices were to stay on together for another 10 hours. When the 10 hours were complete, the ring finger device was to be removed, and the device on the # 19 was to remain on for another 5 hours. This second set brought the patient's vagus point into complete balance, as indicated by the deltoid muscle registering strength when the point was tested. At the end of treatment, it was determined that the patient was symptom-free.
[0126] Case Study # 6 . The patient was suffering from flu-like symptoms. Referring to FIG. 23 , it was determined that one device would be needed, and it was to be placed on the left # 23 , with the arrow pointing to the individual's left. The apparatus was to be left on the left # 23 for 3-4 hours (with influenza it can stay on as long as 9 hours). In three hours all symptoms of influenza were gone.
[0127] Case Study # 7 . The patient was suffering from a stomach virus, experiencing diarrhea, and abdominal rumbling and discomfort. Referring to FIG. 24 , MRT determined that a device needed to be placed on the right # 15 with the arrow direction pointing down toward the feet. The apparatus was to be left on for about 5 or 6 hours. The patient started feeling better shortly after application of the device and by the time 5 hours had passed, the patient felt no symptoms of illness at all.
[0128] Case Study # 8 . This case study involved a patient that needed a root canal procedure. Referring to FIG. 25 , MRT testing indicated that the device should be placed on the forehead on the left # 20 location. MRT was also conducted to determine whether the device or devices need to be placed on before, during, or after the procedure. It was determined through MRT that one device was to be placed prior to the dental procedure and left on until the procedure was completed, which facilitated the healing of the area and helped eliminate much of the discomfort experienced after the procedure. No pain medication of any kind was needed after the procedure, not even an aspirin.
[0129] While the foregoing is directed to embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, which is only limited by the scope of the claims that follow. For example, the present invention contemplates that any of the features shown in any of the embodiments described herein, or incorporated by reference herein, may be incorporated with any of the features shown in any of the other embodiments described herein, or incorporated by reference herein, and still fall within the scope of the present invention. | 1a
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to a therapeutic device, and more particularly to a self-operated mini therapeutic device that can use pressure wave and magnetic stimulation to prevent and treat venous thrombus.
[0003] 2. Description of the Prior Arts
[0004] According to clinical observation, the peoples after operation, anesthesia, long time bedridden or the disabilities, such as the patients suffering from paraplegia, out of conscious, or the healthy peoples after long time of sitting or standing, they are susceptible to so-called deep venous thrombus which happens in the deep vein at the patients' thigh or buttocks. The thigh muscles lack of exercise or the partial blood vessels are injured or the blood viscosity of the lower part of the body is too high, all these factors will engender the venous thrombus. Clinics show that if a blood clot moves from deep vein to lung, which can lead to sudden death by lung clot, or it will interfere the cardiovascular blood circulation that also endangers the life of the patient.
[0005] Humen are susceptible to varicose veins of lower limbs because we walk on two legs, which results in valve failure and stagnant blood. The pregnant women are also susceptible to varicose veins of lower limbs due to the increment of the progestational hormone and hypervolemia.
[0006] The solution of eliminating or preventing the above-mentioned symptoms is to improve the blood circulation and make it flow smoothly. The blood circulation depends not only on the cardiac contraction but also on the muscle contraction. Since over half of the muscles are located in lower limbs, the legs play the role of a “second heart”.
[0007] In clinical practices or in particular environments, besides medicines can be used to improve the blood circulation, it is also very important to take some auxiliary measures to prevent, control or treat such kind of deceases.
[0008] Conventional method is to apply intermittent compression to patient's legs so as to improve the blood circulation. According to a thesis of “External Pneumatic Intermittent Compression on Fibrinolysis in Man” by Allenby et al published in “The Lancet” of Dec. 22, 1973, which discloses that the Fibrinolysis in patient's body will be inhibited after operation, and the pneumatic intermittent compression in the thighs will encourage the fibrinolysis. The author further discloses that the best way of preventing the after-operation venous thrombus is to apply pneumatic intermittent compression to the patent's shank in or after operation.
[0009] Furthermore, from hemorheological point of view, the blood viscosity can be decreased only when subjected to enough shearing stresses, especially the blood in the deep vein of the legs needs more high shearing stresses then the blood circulation can be activated and improved. Since the veins have venous valves, the axial shearing stresses in the veins should be maintained in a higher level then the blood circulation runs smoothly.
[0010] However, due to the structural limitation of the air sacs of the conventional portable pneumatic therapeutic device for treatment of venous thrombus, which only uses the vertical compression of the air sacs to the body surface. As disclosed in U.S. Pat. No. 6,290,662 of Sep. 18, 2001, wherein a portable self-operated device for deep venous thrombus prophylaxis only has vertical compression on the patient's body so that the viscose blood in the deep and shallow veins will only reciprocate between two or several venous valves, and the blood circulation cannot be improved. Moreover, since the air sac is too big, it needs long time to inflate the air to a desired pressure.
[0011] In addition, many documents have disclosed that magnetic stimulation has positive effect on muscle nerves, e.g. Wen-Hau Lin disclosed in U.S. Pat. No. 6,213,933 of Apr. 10, 2001, that magnetic stimulation could stimulate fibrinolysis. However, so far the magnetic stimulation device of prior arts is not portable, let alone a mini therapeutic device with functions of pneumatic compression and magnetic stimulation.
[0012] So far, all the devices with the similar functions, whatever portable or not, they have very limited treatment effect due to the strength and the acting level are inappropriate which cannot satisfy the demands of the physiological pulsation of the deep veins and the peripheral nerves and muscle tissues. The way the devices operate is monotonic and some effects are even unsuitable. And the portability of the so-called “portable” is also limited due to the air sacs should be big enough for maintaining useful effect.
[0013] The present invention has arisen to mitigate and/or obviate the afore-described disadvantages of the conventional therapeutic device.
SUMMARY OF THE INVENTION
[0014] The primary object of the present invention is to provide a self-operated mini therapeutic device for venous thrombus prophylaxis that not only can produce an effect of waving osmotic pressure that meets the demands of the physiological pulsation, but also can provide flexible and multiple compression effects, besides, it also can provide magnetic stimulation for the target parts of the patient's body.
[0015] The self-operated mini therapeutic device for venous thrombus prophylaxis in accordance with one aspect of the present invention comprises plural air passages and plural magnets defined in an air cushion, a mouth of the respective air passages connected to diverting valve via pipes, the diverting valve connected to an inflating and extracting mechanism via the pipes, so as to form air paths for inflation and extraction of the respective air passages in the air cushion, a control circuit employed to control the diverting valve.
[0016] The air cushion can be attached to the target parts, such as shank or rear portion of the shank, the foot or sole or the instep of the foot, the buttocks and the arms, etc. A mini air pump can inflate and extract the air passages according to the predetermined program, so as to produce transversal contraction and relief of the deep veins and the neighboring muscles and cause vertical waving movement. Meanwhile, the magnets on the surface of the air passages can move a little along with the movement of the air passages, such that the motion of the magnetic lines will induce the changes of the bioelectricity that located at the adjacent of the deep veins of the muscle tissues.
[0017] The self-operated mini therapeutic device for venous thrombus prophylaxis can treat the muscle nerves and the deep vein around the air cushion with waving osmotic pressure and magnetic stimulation, such that the deep venous thrombus can be effectively prevented and the blood circulation is improved. In addition, the structure of the air passages of the present invention can effectively improve the useful works, and the self-operated mini therapeutic device is compact and portable.
[0018] The present invention will become more obvious from the following description when taken in connection with the accompanying drawings, which shows, for purpose of illustrations only, the preferred embodiments in accordance with the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] FIG. 1 is an illustrative view of a self-operated mini therapeutic device for venous thrombus prophylaxis in accordance with one aspect of the present invention;
[0020] FIG. 2 is a cross sectional view taken along the line A-A of FIG. 1 ;
[0021] FIG. 3 is amplified view of FIG. 2 ;
[0022] FIG. 4 is an operation block diagram of the self-operated mini therapeutic device for venous thrombus prophylaxis in accordance with one aspect of the present invention;
[0023] FIG. 5 is a circuit diagram of the self-operated mini therapeutic device for venous thrombus prophylaxis in accordance with one aspect of the present invention;
[0024] FIG. 6 is an illustrative view for showing the inflation and extraction in the air passages;
[0025] FIG. 7 is a stereographic view for showing the self-operated mini therapeutic device for venous thrombus prophylaxis attached to user's shank;
[0026] FIG. 8 is a perspective view for showing the self-operated mini therapeutic device for venous thrombus prophylaxis attached to user's foot;
[0027] FIG. 9 is a perspective view for showing the self-operated mini therapeutic device for venous thrombus prophylaxis attached to user's pants.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0028] Referring to FIGS. 1-3 , wherein a self-operated mini therapeutic device for venous thrombus prophylaxis in accordance with one aspect of the present invention is shown, which comprises: an air cushion 4 has a non-elastic outer layer 13 adhered with a flexible inner liner, the air cushion 4 is interiorly formed with air passage, it can be a single air passage, double air passages or multiple passages, the air passages are parallel with each other, or formed in the shape of “Z”. The width of the respective air passages is approximately 50-300 mm, on the surface of the air passages is evenly provided with tiny magnets. The magnetic field strength of each tiny magnet is approximately 2-120 T. The longitudinal and the lateral distances between each adjoining magnets are approximately 10-30 mm. An inflating and extracting mechanism includes a diverting valve 6 , a mini air pump 8 , a baroceptor 9 and a relief valve 10 which are connected to a multi-way connector 7 via pipes 5 . The max input pressure of the inflating and extracting mechanism is approximately 20-300 mmHg. A passage 1 or 3 is connected to the diverting valve 6 , with the pipes 5 the diverting valve 6 is connected to the mini air pump 8 , the baroceptor 9 and the relief valve 10 via the multi-way connector 7 . A control circuit 11 is used to control the mini air pump 8 , the baroceptor 9 , the relief valve 10 and the diverting valve 6 . The control circuit 11 is provided with power source and switch 12 .
[0029] When the pressure of the air in the air passages 1 or 3 inflated by the mini air pump 8 reaches a desired value, the baroceptor 9 will send signals to the control circuit 11 , then the control circuit 11 will accordingly control the diverting valve 6 so as to make the mini air pump 8 inflate another air passage. In case that the air cushion 4 is provided with two air passages, the diverting valve 6 can work as a relief valve. If the air cushion 4 is provided with more than two air passages, the air passages can be additionally equipped with the relief valve 10 , which is under the control of the control circuit 11 to relieve or maintain the air pressure in the respective air passages. The pressure reduction of the air passages 1 or 2 or other respective air passages can be fulfilled through natural leakage after a period of inflation.
[0030] The control circuit 11 includes an oscillator comprised of a set of programming switches and a general purpose integral circuit, a NAND Gate and an output circuit. The control circuit 11 can use program to control the speed of the air inflation/extraction, the sequence of inflation/extraction of the respective air passages, and the working period of the self-operated mini therapeutic device for venous thrombus prophylaxis.
[0031] To prolong the service life of battery, a detector for detecting the movements of limbs and trunk (muscular movements) can be used to signal to stop the self-operated mini therapeutic device for venous thrombus prophylaxis whenever the user is walking or doing other activities.
[0032] To make it more adaptive to physiological requirements, the self-operated mini therapeutic device for venous thrombus prophylaxis can be additionally equipped with a monitoring equipment which serves to monitor pulses and blood pressure, and the detected data and parameters can be inputted to the control circuit as a basis for the mini therapeutic device to decide the mode of operations.
[0033] FIG. 4 is an operation block diagram of the self-operated mini therapeutic device for venous thrombus prophylaxis in accordance with one aspect of the present invention.
[0034] FIG. 5 is a circuit diagram of the self-operated mini therapeutic device for venous thrombus prophylaxis in accordance with one aspect of the present invention, wherein the control circuit comprises DC power supply of 2.5-6V, oscillating circuit, amplifier circuit, programmer, kinesthetic receptor and switch. A control circuit consisting of a 555 IC, a set of programmable switches (K 1 , K 2 , K 3 , . . . . Ki), NAND Gate and output is used to drive the load RL, the load RL can be mini air pump or relay (with the relay to drive the mini pump). When the switch K is closed, the output end of the IC is at high electric level, and a current-limiting resistor R 4 and an inverter 1 are used to trigger the input end of a NAND 2 of the IC 1 . At this moment, if pressure is not at a predetermined level, position P is at high electric level, thereby the output end T of the control circuit is in fully conducted state, such that the load RL is in operating state. After a period of operation of the load RL, the pressure will reach the predetermined level, the position P is at a low electric level, the output end T of the control circuit is in a cut-off state, and thus the load RL will stop. Power resource Vcc can be dry battery. With this optimized electrical circuit, the work time of the battery can be prolonged up to several weeks.
[0035] According to real needs, period of inflation/extraction cycle can be changed from once per minute to once per 10-20 minutes with the change of the resistance of the programmable switches.
[0036] In operation, with the mini air pump, the pressure in the air passages can reach a level that is high enough to increase the venous blood return. Through proper adjustment or improvement of the electric circuit, the max pressure can be adjusted. The control circuit of the present invention employs a controllable multi-way diverting valve to realize faster air extraction and flexible multiple-passage air extraction. The air pressure in the air passages can be maintained for a period of time according to needs.
[0037] The operation of the self-operated mini therapeutic device for venous thrombus prophylaxis in accordance with the present invention is further explained in FIG. 6 . The power is turned on at time of 18 , and the programmable switches in FIG. 5 are used to adjust the frequency. During the first period 17 , the mini air pump 8 inflates the respective air passages for a first time 20 until the baroceptor 9 detects a predetermined max pressure (at the end of the time 20 ), the circuit starts to count time, that means a first lag phase 14 is started. The diverting valve 6 and the relief valve 10 operate in a coordinate manner during the first lag phase 14 , so as to relieve or maintain the air pressure in the respective air passages.
[0038] Time count stops at the moment the first lag phase 14 is terminated, then starts a second period 19 , the mini air pump 8 operates for a second time 15 . In the second period 19 , under the control of programmable circuit, the mini air pump 8 starts to choicely inflate the air passages which are selected by the diverting valve 6 until all the air passages in the air cushion 4 to be inflated have been inflated, such that an inflation cycle is finished, and then the next inflation cycle starts until the power is off. The maintenance or relief of the air pressure in the respective air passages can be achieved by the coordination between the relief valve 10 and the diverting valve 6 that is controlled by the programmable circuit. An extreme condition is that with a predetermined program, all the respective air passages in the air cushion are inflated to a predetermined pressure and then the air passages are released in turn, that is to say, with a more complicated programmable circuit or microprocessor, the inflation speed, the time delay of pressure-release or the periodical change between the air inflation and release can be adjusted synchronously or respectively according to their corresponding time functions. Therefore the self-operated mini therapeutic device for venous thrombus prophylaxis in accordance with the present invention is not only conductive to specific treatment but also helpful to the service life of the battery.
[0039] As shown in FIG. 7 , wherein the air cushion 4 is attached to a user's shank 23 and fixed with a nylon buckle 21 , the air passages 1 or 3 are connected to a control box 22 for air path and circuit. The diverting valve 6 , the inflating and extracting mechanism and the circuit for controlling them are enclosed in the control box 22 . A rotary knob is defined on the control box 22 , when the power is turned on, the mini air pump 8 in the control box 22 will inflate or extract the respective air passages, so as to massage the shrank with wave pressure, meanwhile a magnet 2 in the air cushion also will have effect on the shrank.
[0040] Referring to FIG. 8 , wherein the air cushion in accordance with another embodiment of the present invention is disposed in the user's shoe 24 at a position corresponding to the sole and the side of the foot. The mini air pump 8 and the control box 22 can be positioned on the front uppers of the shoe and connected to the air passages 1 via the pipe 5 .
[0041] Referring to FIG. 9 , wherein the air cushion with multiple air passages in accordance with another embodiment of the present invention is fixed to pants. In this embodiment, the air passages 1 are respectively located at the positions of the buttock, the thigh and the shank. In consideration of limitation of the position and the power capacity, wherein the air cushion at the positions of the buttock, the left thigh and shank, and the right thigh and shank are connected to three air paths via three pipes 5 and controlled by the control box 22 . Obviously, if pneumatic component parameter can meet the desired power requirements, they can be combined together, the arrangements of the air paths and the magnets include but are not limited to the positions as shown in Figures. In real operation, the user only needs to fasten the nylon buckle 21 to desired parts of the body and turn the power on, and then the self-operated mini therapeutic device for venous thrombus prophylaxis works immediately.
[0042] While we have shown and described various embodiments in accordance with the present invention, it should be clear to those skilled in the art that further embodiments may be made without departing from the scope of the present invention. | 1a
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority under 35 USC §119 to U.S. Provisional Patent Ser. No. 61/061,111, filed on Jun. 12, 2008, and titled “Transmission Fluorometer”; and also claims priority under 35 USC §119 to U.S. Provisional Patent Ser. No. 61/061,114, filed on Jun. 13, 2008, and titled “Transmission Fluorometer,” the entire contents of both of which are hereby incorporated herein by reference in their entirety.
FIELD OF THE INVENTION
[0002] This disclosure relates generally to a system and method for performing non-invasive and non-destructive transmissive mode and/or fluorescent measurements of chemical analytes in samples that exhibit detectable transparency to both excitation light transmitted through the sample and light fluoresced by the analytes transmitted through the sample. More specifically, a system and method are disclosed to monitor levels of fluorescent chemicals in blood. For such medical applications, the system is safe, easy and sanitary to use compared to existing methods, more convenient than invasive tests, and provides immediate feedback. A major application of the system is field-based non-invasive blood testing of micro-nutrient deficiency and diseases resulting from it, such as iron deficient anemia. The system can potentially be used to initially screen patients for problems, such as micronutrient deficiencies or disease, and may help reduce or eliminate the need for blood drawing, sending the sample to a blood lab and having to wait for a result.
BACKGROUND
[0003] Generally, legacy fluorometry systems employ either “right angle” or “front face” optics. Right angle optics is where the detector is placed at right angles to the excitation source. This serves to minimize interference from the excitation source. However, these systems are subject to “inner filtering” problems where the light fluoresced by the sample is filtered out by the sample under test. Front facing optics is where the detector is placed at an angle between either 30-40 degrees or 50-60 degrees to the excitation source. Front facing optics overcomes inner filtering but is unable to relate fluorescent intensity to analyte concentration over a very broad range for analytes having a high extinction coefficient. These problems have limited the application of fluorometry techniques in the area of noninvasive analysis, particularly blood and tissue analysis.
[0004] Significant advances in modern technology have failed so far to provide any relief for such problems.
[0005] Many of these technologies are disclosed in a broad spectrum of patents and patent applications, including:
[0006] U.S. Pat. No. 6,252,657 to Bohnenkamp discloses a reflection fluorometer using light guides to test samples placed in a capillary tube. However this approach is not suitable for non-invasive measurement.
[0007] U.S. Pat. No. 5,785,658 to Benaron discloses a tool for nondestructive interrogation of the tissue including a light source emitter and detector which may be mounted directly on a surgical tool in a tissue contacting surface for interrogation or mounted remotely and guided to the surgical field with fiber optic cables. This device is also invasive.
[0008] U.S. Pat. No. 5,933,232 to Atzler discloses a measurement station for microtitration plates. The system applies fluorometry to solutions in curvettes, which are not compatible with non-invasive use.
[0009] U.S. Pat. No. 6,013,034 to Da Cunha Vaz discloses an Ocular Fluorometer for use in taking non-invasive reflective fluorometric readings of the human eye.
[0010] U.S. Pat. No. 4,178,917 to Shapiro discloses a method and system for the non-invasive detection of zinc protoporphyrin (ZPP) in erythrocytes wherein a light source is applied to the skin of the patient. However, the approach uses front facing optics so it is subject to the inherent limitations of front facing optics discussed above.
[0011] In summary, the prior art provides a broad range of alternatives to invasive fluorescent spectroscopy. The prior art also provides some solutions to non-invasive spectroscopy using either front facing or reflective optics. However these non-invasive solutions are subject to problems of inner filtering and/or inability to correlate fluorescent intensity to analyte concentration. As a result, existing solutions are inapplicable to a whole host of new applications (such as blood analyte measurement) which demand non-invasive testing, accuracy, broad diagnostic capability and convenient usage.
SUMMARY
[0012] The present disclosure addresses the aforementioned problems by providing a novel transmission fluorometry system that can take advantage of the transparency presented by the target material to the exciting and fluorescing wavelengths to measure the relative concentration of analytes. One or more of the following aspects may be realized by the systems and/or methods taught herein:
[0013] One aspect of the disclosure relates to non-destructive, non-invasive, fluorescent measurement of samples in the transmission mode. Examples include paper, glass, plastic and in-vivo living tissue such as plant and animal matter.
[0014] Another aspect of the disclosure relates to non-invasive blood measurement. Noninvasive Transmission Fluorometry provides a portable, quick, accurate, safe and sanitary system for in vivo, non-invasive detection of several blood ailments such as Iron Deficient anemia.
[0015] Another aspect of the disclosure relates to non-invasively detecting multiple blood components using only one excitation wavelength. For example, 365 nm can be used to simultaneously and non-invasively detect Zinc Protoporphyrin, Protoporphyrin IX and Fluorescent Herne Degradation Product, 395 nm can be used to non-invasively detect Zinc Protoporphyrin and Protoporphyrin IX.
[0016] Another aspect of the disclosure relates to non-invasively detecting multiple blood components using multiple excitation wavelengths. For example, a sensor head containing both a 425 nm LED and a 346 nm LED can be used to non-invasively detect Zinc Protoporphyrin and Retinol (Vitamin A) simultaneously.
[0017] Another aspect of the disclosure relates to normalizing the spectral measurements by dividing each intensity reading in the transmitted spectrum by the height of the excitation wavelength intensity, Normalization allows different readings taken independently to be compared.
[0018] One aspect of the disclosure relates to field usage. Most fluorometry systems cannot be used in the field because they are bulky and/or invasive. The present system can potentially be smaller than some fluorometry systems since it may employ relatively small components. As such the instrument can be taken to the subject and does not necessarily require the subject to be brought to the instrument as is the case with existing fluorometers. In addition, the system sensors can be used in vivo on live subjects, as opposed to invasive systems which generally require a sample of the subject to be inserted in a curvette.
[0019] Another aspect of the disclosure relates to the measurement point on the subject. Even at high power, UV does not penetrate far enough to go through traditional measurement points such as an earlobe or a finger. In addition, the usage of UV precludes testing the palebral conjunctiva due to safety considerations. However, the method described in the present disclosure, namely shining an excitation wavelength through a section of loose skin on the subject (such as webbing between finger and thumb), can produce the desired results. In an embodiment, a clamping system can be employed whereby the thickness of the sample can be intentionally reduced to a suitable thickness, such as, for example, a thickness ranging from about ⅛ th inch or less, such as approximately 1/16 th inch. In an embodiment, the clamping system may also result in the sample being blanched, thereby reducing the concentration of analytes.
[0020] Another aspect of the disclosure relates to sensor size. Most Sensor/Fluorometer systems cannot be used in the field, due to their bulkiness. In addition to permitting portable “in vivo” measurement, the sensor in the preferred embodiment is narrow enough to pinch the skin between thumb and forefinger in a child's hand.
[0021] Another aspect of the disclosure relates to measuring and reporting a broad spectrum of analyte ratios simultaneously. Some analyte ratios (e.g. ratio of oxygenated hemoglobin to total hemoglobin) are most easily measured using absorption spectroscopy. The system of the present disclosure can perform “mixed mode” measurements involving both fluorometry and absorption spectroscopy on the subject simultaneously, via reflectance if necessary, in order to report a broader range of analyte ratios.
[0022] Further aspects of this disclosure will become apparent in the Detailed Description and by reference to the attached drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] FIG. 1 illustrates a system overview and components, according to an embodiment of the present disclosure.
[0024] FIG. 2 illustrates a signal processing functional diagram, according to an embodiment of the present disclosure.
[0025] FIG. 3 shows a light source driver control, according to an embodiment of the present disclosure.
[0026] FIG. 4 illustrates a sample holding device, according to an embodiment of the present disclosure.
[0027] FIG. 5 illustrates a configuration with multiple sample holding devices, according to an embodiment of the present disclosure
[0028] FIG. 6 is a flowchart illustrating a method performed by the fluorescent measurement system.
[0029] FIG. 7 is a diagram illustrating how to normalize a transmission fluorometer reading.
DETAILED DESCRIPTION
[0030] In the following description, reference is made to the accompanying drawings, which form a part hereof, and which show, by way of illustration, specific embodiments or processes in which the teachings of the present disclosure may be practiced. Where possible, the same reference numbers are used throughout the drawings to refer to the same or like components. In some instances, numerous specific details are set forth in order to provide a thorough understanding of the present disclosure. The teachings of the present disclosure, however, may be practiced without the specific details or with certain alternative equivalent devices and methods to those described herein. In other instances, well-known methods and devices have not been described in detail so as not to unnecessarily Obscure aspects of the present disclosure.
I. SYSTEM OVERVIEW AND COMPONENTS
[0031] FIG. 1 illustrates the system overview and components of an embodiment of the transmission fluorometry system 100 of the present disclosure. In the embodiment shown in FIG. 1 , the system 100 comprises a power supply 110 coupled to a light source driver control 120 . The light source driver control 120 is coupled via any suitable electrical connection 190 to a source-receiver assembly 130 , which comprises a light source 140 and receiving optics 160 . A spectrometric assembly 170 can be coupled to the receiving optics 160 via any suitable optical link 195 for providing a spectral data output of the light transmitted through and/or emitted from the sample 150 . The spectral data 170 can be fed into a computer 180 for analysis.
[0032] In operation, the power supply 110 powers light source driver control 120 . Any suitable power supply can be employed. Examples of suitable power supplies that can be employed include battery power, USB cable, and/or electrical outlet power.
[0033] The type of power supply 110 may depend on the intended use of the system 100 and can potentially enhance the convenience of employing the system 100 , For example, if the system 100 is used only to take absorption measurements versus fluorescent measurements, it can run on battery power for relatively long periods of time (e.g. several days of continuous operation, depending on the battery technology employed). The system 100 can also be powered from the USB port of a personal computer 180 . This is a convenient arrangement when the goal is, for example, to continuously upload readings from the spectrometric assembly 170 over the same USB cable, because it means that the system 100 does not require any extra external power connection. It is also convenient when the system 100 needs to be taken out in the field, because the user can then view the system 100 as a peripheral (much the same way as a USB memory stick is viewed as a peripheral) that simply attaches to the computer 180 . The power supply 110 can run off of wall current if, for example, the goal is to provide continuous monitoring over a long period of time.
[0034] The light source driver control 120 drives one or more excitation light sources 140 , mounted on the source-receiver assembly 130 . Any suitable light source driver can be employed. For example, the light source driver control 120 can be a manual system of switches and potentiometers or an automatic electronic system controlled from the computer 180 in a closed loop configuration.
[0035] In an embodiment, the computer 180 provides continuous monitoring of the sample 150 and adjusts the light source 140 brightness via the automatic electronic system based on how much light is being transmitted through the sample 150 , as well as how much fluorescence is being detected by the receiving optics 160 . In this case, a control loop 185 for controlling the light source can be driven automatically without any manual intervention whatsoever. The source-receiver assembly 130 contains a light source 140 that irradiates the Sample 150 , which in turn transmits both light from the light source 140 and fluoresced light from analytes in the sample 150 . This light is detected by the receiving optics 160 which provides input to a spectrometric assembly 170 .
[0036] In an embodiment, the source-receiver assembly can contain one or more LED light sources 140 . Light from the light source 140 can excite several analytes in the sample 150 and passes a single spectrum via the receiving optics 160 to the spectrometric assembly 170 . The receiving optics 160 may comprise, for example, a collimating lens that connects to the spectrometric assembly 170 via a fiber optic cable 195 .
[0037] In an embodiment, light source 140 can be configured as a set of LEDs clustered together on a single clip arm or a single chip substrate. The LEDs can be turned on and off in sequence, exciting a series of spectrums in the sample 150 that pass through the receiving optics 160 and are transmitted to the spectrometric assembly 170 . In this manner, it is possible to detect multiple components using multiple excitation wavelengths. For example, a sensor head containing both a 425 nm LED and a 346 nm LED can be used to non-invasively detect Zinc Protoporphyrin and Retinol (Vitamin A) simultaneously.
[0038] In one embodiment, the source-receiver assembly 130 can be configured as a sample holding device, illustrated in FIG. 4 , that pinches the sample between the light source 140 and the receiving optics 160 . The decoding and analysis of the set of spectrums can then be done by the computer 180 . The source-receiver assembly can include, for example, a sample holding device 400 having an upper arm 430 and a lower arm 440 . FIG. 4 illustrates a sample holding device 400 in an open position 410 and a closed position 420 . The source-receiver assembly 130 may include a set of sample holding devices 400 , as shown in FIG. 5 , each with a single or multiple LED light source 140 , as described previously. This configuration can be used if, for example, the tester wants to take simultaneous measurements of different parts of the subject 150 at the same time. If the tester wants a narrowed spectrum light, the source-receiver assembly 130 can employ laser diodes as light sources 140 in place of the LEDs. If the tester wants more exact wavelength control, the source-receiver assembly 130 can employ a traditional monochromator as a Light Source 140 .
[0039] The spectrometric assembly 170 can be a single spectrometer, such as an OceanOptics USB2000, which connects to the computer 180 via, for example, a USB port. An alternate embodiment is a spectrometric assembly 170 with a set of photodiode/filter pairs where each pair is tuned to either the excitation wavelength or fluorescent emission peaks of analytes of interest. For high resolution applications, a high sensitivity version of the spectrometric assembly 170 can employ a single photomultiplier tube or charge coupled device (CCD) array, and the filters can be successively passed over the active area of the receiving optics in order make the device sensitive to the wavelengths of interest. In light of the disclosure herein, providing any of the above mentioned spectrometric assemblies is well within the ordinary skill of the art.
[0040] The spectrometric assembly 170 is linked to a computer 180 . The computer 180 can be a “personal computer” running spectrographic analysis algorithms. However, in the event the tester wants to provide continuous monitoring in a small form factor, the computer 180 can be a micro-controller, such as, for example, a member of the Texas Instruments MSP430FG43x: mixed signal microcontroller family. In this case, the computer 180 can, for example, monitor the input spectrum from the spectrometric assembly 170 , control the light source 140 through the light source driver control 120 via the control loop 185 , analyze the spectrum and convert the results to human readable form.
[0041] FIG. 2 illustrates a signal processing functional diagram 200 , according to an embodiment of the present disclosure. A closed-loop control function 210 passes an electric-digital control representation 213 to an electric-digital to electric-analog conversion function 220 . The electric-digital to electric-analog conversion function 220 passes an electric-analog representation 223 to an electric-analog to optical conversion function 230 . The electric-analog to optical conversion function 230 generates an incident optical signal 233 which is directed to a first surface of the sample 150 . An optical signal 238 emerging from a second surface of the sample 150 is received by an optical to electric-analog conversion function 240 . The optical to electric-analog conversion function 240 passes an electric-analog representation 243 to an electric-analog to electric-digital conversion function 250 . The electric-analog to electric-digital conversion function 250 passes an electric-digital representation 253 back to the closed-loop control function 210 . A high level data collection and computing function 260 communicates with the closed-loop control function 210 through an interface function 263 .
[0042] In operation, an embodiment of the dosed loop control function 210 can be configured to provide control instructions for the electric-digital to electric-analog conversion function 220 , the electric-analog to optical conversion function 230 , data gathering for the optical to electric-analog conversion function 240 and the electric-analog to electric-digital conversion function 250 .
[0043] The closed loop control functions can be either manual or automatic. Any suitable closed-loop control function can be employed. A manual control function uses an operator to read feedback parameters such as noise and received light intensity at particular wavelengths and computed functions thereof (e.g. SpO 2 level) and to manually adjust the incident light intensity, duration and physical and temporal point of measurement in order to get a strong signal that does not swamp the receiving optics. An automatic control function is performed automatically in real-time and can be implemented using micro controllers such as, for example, Atmel's AVR or Texas Instrument's MSP430. In one embodiment, the closed loop control function 210 can be a pulse oximeter, which can take, for example, red and infrared light absorption readings every 1 ms using a standard pulse oximetry probe. These readings can be smoothed by the closed loop control function 210 and transmitted to the high level data collection and computing function 260 in order for the system to monitor and record sample data. The closed loop control function 210 may also receive commands from the high level data collection and computing function 260 , allowing it, for example, to take additional readings with other wavelengths, at desired points in time and for desired durations.
[0044] In an embodiment, the electric-digital to electric-analog conversion functions 220 can be used to convert a digital control representation 213 to an analog representation 223 . In one embodiment, the digital control representation 213 may be used to select a desired light source and an associated intensity with which to illuminate the sample. In this case, the electric-digital to electric-analog conversion function 220 may convert the digital control representation 213 to a set of analog signals at various voltage or current levels (including zero) to drive the electric-analog to optical conversion function 230 . The electric-digital to electric-analog conversion function 220 can be performed with a digital to analog converter (DAC). The DAC may be a standalone unit, or integrated with the closed loop control function 210 as in the case of, for example, the MSP430.
[0045] In an embodiment, the electric-analog to optical conversion function 230 can be used to convert the analog electrical representation 223 to the light signal that illuminates the sample. This function can be implemented for example as one or more LEDs or laser diodes mounted on a semiconductor chip, as a bundle of fibers connecting to an array of LEDs or laser diodes mounted on a board, or as a single light source with a switchable set of filters. The electric-analog to optical conversion function 230 may be for example a standalone unit, or integrated with the optical to electric-analog conversion function 240 as in the case of, for example, a Nellcor Pulse Oximeter probe.
[0046] In an embodiment, the optical to electric-analog conversion function 240 is used to convert the light signal that is received from the sample 150 to an electric-analog representation 243 . The optical to electric-analog conversion function 240 can be, for example, a photodiode as used in a pulse oximeter; a diffraction grating and CCD array as used in a spectrometer, such as the OceanOptics USB 2000; or a Photomultiplier tube, such as used in a Fluorimeter. The optical to electric-analog conversion function 240 may be a standalone unit, or integrated with the electric-analog to electric-digital conversion function 250 , as used, for example, in an OceanOptics Spectrometer.
[0047] In an embodiment, the electric-analog to electric-digital conversion function 250 can be used to convert an analog representation 243 to a digital control representation 253 . In an embodiment, this conversion can be an analog to digital converter (ADC). The electric-analog to electric-digital conversion function 250 may be, for example, a standalone unit, or integrated with the closed loop control function 210 as in, for example, the Texas Instrument's MSP430.
[0048] In an embodiment, the high level data collection and computing function 260 can communicate with the closed-loop control function 210 to transmit instructions and receive and store data. The high level data collection and computing function 260 can be any suitable computing device such as, for example, a personal computer, a handheld computer or a laptop computer.
[0049] The functions closed-loop control 210 , electric-digital to electric-analog conversion 220 , electric-analog to electric-digital conversion 250 , and high level data collection and computing 260 , could potentially be performed manually by an operator, but any such embodiments would be of little value compared to automated functions offered by modern technology.
[0050] FIG. 3 illustrates an embodiment of the light source driver control 120 . Current from the power supply 110 flows through power switch 310 , which controls when power is applied to the source-receiver assembly 130 to excite the sample and generate a fluorescent output characteristic of the analytes to be measured. The light source selector switch 320 provides flexibility to select any configuration of light sources 140 that may be appropriate to optimize a particular application. The intensity of each light source 140 can be independently controlled by a light source intensity controller 330 , either manually or automatically. In one embodiment, the light source intensity can be automatically set by a control algorithm running on the computer 180 to a desirable level that optimizes the dynamic range and signal to noise ratios of the detected excitation and/or the analyte spectral signals. In an embodiment, the intensity controllers 330 can be connected to light source connectors 340 , which can provide for a desired connectability to the light source 140 (e.g., LEDs).
[0051] FIG. 4 illustrates an embodiment of the source-receiver assembly 130 in the form of a sample holding device 400 . The sample holding device 400 is illustrated in both an open position 410 and a closed position 420 . The sample 150 to be measured can be held between one or more light sources 140 mounted on the upper arm 430 of the sample holding device 400 and the receiving optics 160 mounted on the lower arm 440 of the sample holding device 400 . Employing appropriate sample thicknesses can allow for the desired transmission of light (e.g., light from the light source 140 and/or fluoresced light) through the sample. For example, sample thicknesses can be consistent with a desired resolution of quantitative measurements of intensity of both excitation light transmitted through the sample and the fluoresced light emitted by blood analytes upon excitation by the light source. Examples of samples for which the clip mechanism is desirable include: a thin film, the webbing between a subject's index finger and thumb, the subjects ear, the subject's nose, the subject's cheek, a section of loose skin on a subject's wrist or elbow joint or any other part of the subjects body where a desired sample thickness can be identified. When applying the sample holding device 400 to a subject for blood testing, the pressure blanches the skin, resulting in a dilution effect of the blood in the sample, which minimizes inner filtering. A light source connection device 450 can provide a connection to light source driver control 120 . A receiving optics connection device 460 can provide a connection to the spectrometric assembly 170 .
[0052] FIG. 4 also shows a “C” clamp 470 to illustrate a mechanism to control the sample thickness by compressing the gap between the upper and lower arm of the sample holding device 400 . Also shown are an adjustment knob 475 and a side view of the “C” clamp 480 . In other embodiments, the mechanism to control the sample thickness can use a variety of modern technologies. Examples of such technologies include: a piezoelectric crystal based system attached to the arm, a hydraulic based system consisting of a pressurized liquid filled cylinder and a pneumatic based system with a pressurized air filled bag. An additional advantage of these modern technologies is the capability to provide a way to control sample thickness without completely blanching the tissue.
[0053] The mechanism to control the sample thickness may improve the results obtained using the system of the present application for cases where the wavelengths of interest are heavily attenuated by the sample. For example, measurements of zinc protoporphyrin (ZPP) at wavelengths in the ranges of 346 to 370 nm, 390 to 400 nm and 420 to 430 nm in a sample of in vivo skin, can be more reliably obtained where the skin can be pinched to a suitable thickness.
[0054] In accordance with the Beer-Lambert law, the attenuation of light within the sample increases exponentially with the sample thickness and analyte concentration. The use of a sample holding device configured to provide controlled reductions of the sample thickness can have two beneficial effects. It can cause a reduction of the sample thickness while at the same time it may also reduce the concentration of analytes by a blanching process. While not intending to be limited by theory, it is believed that a significant increase in detected intensity can be achieved due to one or more of these benefits. For example, a ½″ thick sample of hemoglobin irradiated with 10 lumens of light at 940 nm will produce an output intensity of approximately 0.00263 lumens. For comparison, a comparable output intensity can be obtained with a 1/16″ inch thick sample of hemoglobin that has been diluted by a factor of 32 by blanching and is irradiated with the same 10 lumens of light at 426 nm. These considerations illustrate a potential advantage of the aforementioned sample holding device, which is that it can allow transmission fluorimetry to determine analyte concentration ratios via light absorption and fluorescence at wavelengths outside of the “medical spectral window” of 600-1100 nm. Thus, the systems of the present application can employ wavelengths of less than 600 nm, such as for example, wavelengths in the ranges of 346 to 370 nm, 390 to 400 nm and 420 to 430 nm. Wavelengths outside of these example ranges can also be employed, including wavelengths within the medical spectral window.
[0055] Although FIG. 4 shows a very simple mechanism to control the sample thickness, other implementations can use more desirable systems to achieve the objectives outlined herein, such as reducing sample thickness and/or blanching the sample. In light of the disclosure herein, providing any of the above mentioned thickness control systems is well within the ordinary skill of the art.
[0056] FIG. 6 is a flowchart illustrating a preferred method 600 by which the transmission fluorometry system 100 can collect normalized fluorometry data from a sample. At 601 , the source-receiver assembly 130 is applied to the sample 150 . At 602 , power is applied to the light source 140 . At 603 , the output from the spectrometric assembly 170 is transmitted to the computer 180 . At 604 , a computer program is run. The computer program can compute, for example, the relative concentrations of two or more analytes present in the sample 150 based upon spectral outputs collected by the spectrometric assembly 170 .
[0057] In an embodiment, analyte ratios can be computed by using “absorption only” techniques such as those used by pulse oximeters. For example pulse oximeters compute heart rate and blood O 2 concentration using measurements of the relative absorption of blood and surrounding tissue at two different wavelengths over time.
[0058] In another embodiment, these analytes may be computed by using “fluorescence only” techniques, such as algorithms that look at the ratios of emission heights from the same excitation wavelength. The ratios of the heights of multiple emission peaks can be calculated. Exemplary ratios include the ratio of primary to secondary emission peaks of the analyte Zinc Protoporphyrin when excited at 425 nm or the ratio of the primary emission peak of Zinc Protoporphyrin to Protoporphyrin IX when both are excited at 365 nm. In yet another embodiment, a technique employing a ratio of ratios can used, which compares the ratio of one set of excitation and emission peaks to the ratio of another set of excitation and emission peaks. Calculating a ratio of ratios is generally well known in the art.
[0059] In yet another embodiment, analytes may be computed by using “mixed absorption and fluorescence” techniques, such as one that would look at the ratios of emission heights to absorption ratios which occur when the same tissue is irradiated by two or more light sources that are placed very near each other. An example is the ratio of Hemoglobin absorption to ZPP fluorescence relative to the ratio of their respective irradiation light intensities. These analytes may also be computed by using “time resolved methods” or “frequency resolved methods”. For example, one such method distinguishes between two analytes with similar spectral signatures by measuring their fluorescent lifetimes. Given the present disclosure, one of ordinary skill in the art would be able to employ the systems disclosed herein to detect analytes using absorption only, fluorescence only and mixed absorption and fluorescence techniques.
II. NORMALIZING DATA
[0060] Fluorometry data taken from the sample can be normalized to allow different readings taken independently to be compared. Any suitable method of normalizing the data can be employed. FIG. 7 illustrates an embodiment of a sample normalization algorithm 600 . A spectrometric assembly 170 organizes data in terms of a graph of relative intensity 710 versus wavelength 720 . For illustrative purposes, relative intensity 710 can be an integer that ranges from 0 to a maximum relative intensity 760 of 4095 , as depicted in FIG. 7 . To allow intensity data from different light sources 140 examining the same subject at the same time to be compared to each other, the intensity can be normalized. This is done by first determining the “minimum relative intensity” 730 , which is the smallest intensity recorded by the spectrometric assembly 170 for the sample 150 . Next, the “excitation relative intensity” 740 is determined by looking up the intensity at the excitation wavelength 770 . Finally, a normalized intensity value is calculated at each wavelength by taking the relative intensity reading at that wavelength, subtracting the minimum relative intensity 730 , and dividing this difference by the difference between the excitation relative intensity 740 and the minimum relative intensity 730 . If done for each wavelength, this algorithm will produce a graph of normalized intensities 750 where the intensity at the excitation wavelength 770 will have a value of “1.00” with all other intensities scaled relative to it.
III. CONCLUSION
[0061] Although this invention has been described in terms of certain preferred embodiments, other embodiments that are apparent to those of ordinary skill in the art, including embodiments that do not provide all of the features and advantages set forth herein, are also within the scope of this invention. Therefore, the scope of the present invention is defined only by reference to the appended claims and equivalents thereof. | 1a
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FIELD OF THE INVENTION
The present invention relates to compounds for delivering active agents, such as biologically or chemically active agents, to a target. These compounds are well suited for forming non-covalent mixtures with active agents for oral, intracolonic, pulmonary, or other routes of administration to animals. Methods for the preparation and administration of such compositions are also disclosed.
BACKGROUND OF THE INVENTION
Conventional means for delivering active agents are often severely limited by biological, chemical, and physical barriers. Typically, these barriers are imposed by the environment through which delivery occurs, the environment of the target for delivery, and/or the target itself. Biologically and chemically active agents are particularly vulnerable to such barriers.
In the delivery to animals of biologically active and chemically active pharmacological and therapeutic agents, barriers are imposed by the body. Examples of physical barriers are the skin, lipid bi-layers and various organ membranes that are relatively impermeable to certain active agents but must be traversed before reaching a target, such as the circulatory system. Chemical barriers include, but are not limited to, pH variations in the gastrointestinal (GI) tract and degrading enzymes.
These barriers are of particular significance in the design of oral delivery systems. Oral delivery of many biologically or chemically active agents would be the route of choice for administration to animals if not for biological, chemical, and physical barriers. Among the numerous agents which are not typically amenable to oral administration are biologically or chemically active peptides, such as calcitonin and insulin; polysaccharides, and in particular mucopolysaccharides including, but not limited to, heparin; heparinoids; antibiotics; and other organic substances. These agents may be rapidly rendered ineffective or destroyed in the gastro-intestinal tract by acid hydrolysis, enzymes, and the like. In addition, the size and structure of macromolecular drugs may prohibit absorption.
Earlier methods for orally administering vulnerable pharmacological agents have relied on the co-administration of adjuvants (e.g., resorcinols and non-ionic surfactants such as polyoxyethylene oleyl ether and n-hexadecylpolyethylene ether) to increase artificially the permeability of the intestinal walls, as well as the co-administration of enzymatic inhibitors (e.g., pancreatic trypsin inhibitors, diisopropylfluorophosphate (DFF) and trasylol) to inhibit enzymatic degradation. Liposomes have also been described as drug delivery systems for insulin and heparin. However, broad spectrum use of such drug delivery systems is precluded because: (1) the systems require toxic amounts of adjuvants or inhibitors; (2) suitable low molecular weight cargos, i.e. active agents, are not available; (3) the systems exhibit poor stability and inadequate shelf life; (4) the systems are difficult to manufacture; (5) the systems fail to protect the active agent (cargo); (6) the systems adversely alter the active agent; or (7) the systems fail to allow or promote absorption of the active agent.
More recently, proteinoid microspheres have been used to deliver pharmaceuticals. For example, see U.S. Pat. No. 5,401,516, U.S. Pat. No. 5,443,841 and U.S. Pat. No. RE35,862. In addition, certain modified amino acids have been used to deliver pharmaceuticals. See, e.g., U.S. Pat. No. 5,629,020; U.S. Pat. No. 5,643,957; U.S. Pat. No. 5,766,633; U.S. Pat. No. 5,776,888; and U.S. Pat. No. 5,866,536.
However, there is still a need for simple, inexpensive delivery systems which are easily prepared and which can deliver a broad range of active agents by various routes.
SUMMARY OF THE INVENTION
Compounds and compositions that are useful in the delivery of active agents are provided. The present invention encompasses compounds having the following formula, or salts thereof, or mixtures thereof.
The compositions of the present invention comprise at least one active agent, preferably a biologically or chemically active agent, and at least one of the compounds, or salts thereof, of the present invention. Methods for the preparation and administration of such compositions are also provided.
Also provided are dosage unit forms comprising the compositions. The dosage unit form may be in the form of a solid (such as a tablet, capsule or particle such as a powder or sachet) or a liquid.
Methods for administering a biologically active agent to an animal in need of the agent, especially by the oral, intracolonic or pulmonary routes, with the compositions of the present invention, are also provided, as well as methods of treatment using such compositions. A method of treating a disease in an animal comprising administering a composition of the present invention to the animal in need thereof is provided.
DETAILED DESCRIPTION OF THE INVENTION
Compounds
The compounds may be in the form of the carboxylic acid and/or their salts. Salts include but are not limited to organic and inorganic salts, for example alkali-metal salts, such as sodium, potassium and lithium; alkaline-earth metal salts, such as magnesium, calcium or barium; ammonium salts; basic amino acids such as lysine or arginine; and organic amines, such as dimethylamine or pyridine. Preferably, the salts are sodium salts. The salts may be mono- or multi-valent salts, such as monosodium salts and di-sodium salts. The salts may also be solvates including ethanol solvates.
In addition, poly amino acids and peptides comprising one or more of these compound may be used.
An amino acid is any carboxylic acid having at least one free amine group and includes naturally occurring and synthetic amino acids. Poly amino acids are either peptides (which are two or more amino acids joined by a peptide bond) or are two or more amino acids linked by a bond formed by other groups which can be linked by, e.g., an ester or an anhydride linkage. Peptides can vary in length from dipeptides with two amino acids to polypeptides with several hundred amino acids. One or more of the amino acids or peptide units may be acylated or sulfonated.
The compounds described herein may be derived from amino acids and can be readily prepared from amino acids by methods within the skill of those in the art based upon the present disclosure and the methods described in WO96/30036, WO97/36480, U.S. Pat. No. 5,643,957 and U.S. Pat. No. 5,650,386. For example, the compounds may be prepared by reacting the single amino acid with the appropriate acylating or amine-modifying agent, which reacts with a free amino moiety present in the amino acid to form amides. Protecting groups may be used to avoid unwanted side reactions as would be known to those skilled in the art. With regard to protecting groups, reference is made to T. W. Greene, Protecting Groups in Organic Synthesis , Wiley, N.Y. (1981), the disclosure of which is hereby incorporated herein by reference.
Salts of the present compound may be made by methods known in the art. For example, sodium salts may be made by dissolving the compound in ethanol and adding aqueous sodium hydroxide.
The compound may be purified by recrystallization or by fractionation on one or more solid chromatographic supports, alone or linked in tandem. Suitable recrystallization solvent systems include, but are not limited to, acetonitrile, methanol, and tetrahydrofuran. Fractionation may be performed on a suitable chromatographic support such as alumina, using methanol/n-propanol mixtures as the mobile phase; reverse phase chromatography using trifluoroacetic acid/acetonitrile mixtures as the mobile phase; and ion exchange chromatography using water or an appropriate buffer as the mobile phase. When anion exchange chromatography is performed, preferably a 0-500 mM sodium chloride gradient is employed.
According to one embodiment, the compound is employed in its anhydrous form.
Active Agents
Active agents suitable for use in the present invention include biologically active agents and chemically active agents, including, but not limited to, pesticides, pharmacological agents, and therapeutic agents.
For example, biologically or chemically active agents suitable for use in the present invention include, but are not limited to, proteins; polypeptides; peptides; hormones; polysaccharides, and particularly mixtures of muco-polysaccharides; carbohydrates; lipids; other organic compounds; and particularly compounds which by themselves do not pass (or which pass only a fraction of the administered dose) through the gastro-intestinal mucosa and/or are susceptible to chemical cleavage by acids and enzymes in the gastro-intestinal tract; or any combination thereof.
Further examples include, but are not limited to, the following, including synthetic, natural or recombinant sources thereof: growth hormones, including human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormones, and porcine growth hormones; growth hormone-releasing hormones; interferons, including α, β and γ; interleukin-1; interleukin-2; insulin, including porcine, bovine, human, and human recombinant, optionally having counter ions including sodium, zinc, calcium and ammonium; insulin-like growth factor, including IGF-1; heparin, including unfractionated heparin, heparinoids, dermatans, chondroitins, low molecular weight heparin, very low molecular weight heparin and ultra low molecular weight heparin; calcitonin, including salmon, eel, porcine and human; erythropoietin; atrial naturetic factor; antigens; monoclonal antibodies; somatostatin; protease inhibitors; adrenocorticotropin, gonadotropin releasing hormone; oxytocin; leutinizing-hormone-releasing-hormone; follicle stimulating hormone; glucocerebrosidase; thrombopoietin; filgrastim; prostaglandins; cyclosporin; vasopressin; cromolyn sodium (sodium or disodium chromoglycate); vancomycin; desferrioxamine (DFO); parathyroid hormone (PTH), including its fragments; antimicrobials, including anti-fungal agents; vitamins; analogs, fragments, mimetics or polyethylene glycol (PEG)-modified derivatives of these compounds; or any combination thereof. Other suitable forms of insulin, including, but not limited to, synthetic forms of insulin, are described in U.S. Pat. Nos. 4,421,685, 5,474,978, and 5,534,488, each of which is hereby incorporated by reference in its entirety.
Delivery Systems
The compositions of the present invention comprise a delivery agent and one or more active agents. In one embodiment, one or more of the delivery agent compounds, or salts of these compounds, or poly amino acids or peptides of which these compounds or salts form one or more of the units thereof, may be used as a delivery agent by mixing with the active agent prior to administration.
The administration compositions may be in the form of a liquid. The dosing vehicle may be water (for example, for salmon calcitonin, parathyroid hormone, and erythropoietin), 25% aqueous propylene glycol (for example, for heparin) and phosphate buffer (for example, for rhGH). Other dosing vehicles include polyethylene glycols, sorbitol, maltitol, and sucrose. Dosing solutions may be prepared by mixing a solution of the delivery agent compound with a solution of the active agent, just prior to administration. Alternately, a solution of the delivery agent (or active agent) may be mixed with the solid form of the active agent (or delivery agent). The delivery agent compound and the active agent may also be mixed as dry powders. The delivery agent compound and the active agent can also be admixed during the manufacturing process.
The dosing solutions may optionally contain additives such as phosphate buffer salts, citric acid, glycols, or other dispersing agents. Stabilizing additives may be incorporated into the solution, preferably at a concentration ranging between about 0.1 and 20% (w/v).
The administration compositions may alternately be in the form of a solid, such as a tablet, capsule or particle, such as a powder or sachet. Solid dosage forms may be prepared by mixing the solid form of the compound with the solid form of the active agent. Alternately, a solid may be obtained from a solution of compound and active agent by methods known in the art, such as freeze drying, precipitation, crystallization and solid dispersion.
The administration compositions of the present invention may also include one or more enzyme inhibitors. Such enzyme inhibitors include, but are not limited to, compounds such as actinonin or epiactinonin and derivatives thereof. Other enzyme inhibitors include, but are not limited to, aprotinin (Trasylol) and Bowman-Birk inhibitor.
The amount of active agent used in an administration composition of the present invention is an amount effective to accomplish the purpose of the particular active agent for the target indication. The amount of active agent in the compositions typically is a pharmacologically, biologically, therapeutically, or chemically effective amount. However, the amount can be less than that amount when the composition is used in a dosage unit form because the dosage unit form may contain a plurality of compound/active agent compositions or may contain a divided pharmacologically, biologically, therapeutically, or chemically effective amount. The total effective amount can then be administered in cumulative units containing, in total, an effective amount of the active agent.
The total amount of active agent to be used can be determined by methods known to those skilled in the art. However, because the compositions may deliver active agents more efficiently than prior compositions, lower amounts of biologically or chemically active agents than those used in prior dosage unit forms or delivery systems can be administered to the subject, while still achieving the same blood levels and/or therapeutic effects.
The presently disclosed compounds deliver biologically and chemically active agents, particularly in oral, intranasal, sublingual, intraduodenal, subcutaneous, buccal, intracolonic, rectal, vaginal, mucosal, pulmonary, transdermal, intradermal, parenteral, intravenous, intramuscular and ocular systems, as well as traversing the blood-brain barrier.
Dosage unit forms can also include any one or combination of excipients, diluents, disintegrants, lubricants, plasticizers, colorants, flavorants, taste-masking agents, sugars, sweeteners, salts, and dosing vehicles, including, but not limited to, water, 1,2-propane diol, ethanol, olive oil, or any combination thereof.
The compounds and compositions of the subject invention are useful for administering biologically or chemically active agents to any animals, including but not limited to birds such as chickens; mammals, such as rodents, cows, pigs, dogs, cats, primates, and particularly humans; and insects.
The system is particularly advantageous for delivering chemically or biologically active agents that would otherwise be destroyed or rendered less effective by conditions encountered before the active agent reaches its target zone (i.e. the area in which the active agent of the delivery composition is to be released) and within the body of the animal to which they are administered. Particularly, the compounds and compositions of the present invention are useful in orally administering active agents, especially those that are not ordinarily orally deliverable, or those for which improved delivery is desired.
The compositions comprising the compounds and active agents have utility in the delivery of active agents to selected biological systems and in an increased or improved bioavailability of the active agent compared to administration of the active agent without the delivery agent. Delivery can be improved by delivering more active agent over a period of time, or in delivering active agent in a particular time period (such as to effect quicker or delayed delivery) or over a period of time (such as sustained delivery).
Following administration, the active agent present in the composition or dosage unit form is taken up into the circulation. The bioavailability of the agent is readily assessed by measuring a known pharmacological activity in blood, e.g. an increase in blood clotting time caused by heparin, or a decrease in circulating calcium levels caused by calcitonin. Alternately, the circulating levels of the active agent itself can be measured directly.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The following examples illustrate the invention without limitation. All parts are given by weight unless otherwise indicated.
EXAMPLE 1
Compound Preparation
1a. Preparation of Compound 1.
4-Chlorosalicylic acid (10.0 g, 0.0579 mol) was added to a one-neck 250 ml round-bottomed flask containing about 50 ml methylene chloride. Stirring was begun and continued for the remainder of the reaction. Coupling agent 1,1-carbonyldiimidazole (9.39 g, 0.0579 mol) was added as a solid in portions to the flask. The reaction was stirred at room temperature for approximately 20 minutes after all of the coupling agent had been added and then ethyl-4-aminobutyrate hydrochloride (9.7 g, 0.0579 mol) was added to the flask with stirring. Triethylamine (10.49 ml, 0.0752 mol) was added dropwise from an addition funnel. The addition funnel was rinsed with methylene chloride. The reaction was allowed to stir at room temperature overnight.
The reaction was poured into a separatory funnel and washed with 2N HCl and an emulsion formed. The emulsion was left standing for two days. The emulsion was then filtered through celite in a fritted glass funnel. The filtrate was put back in a separatory funnel to separate the layers. The organic layer was dried over sodium sulfate, which was then filtered off and the filtrate concentrated by rotary evaporation. The resulting solid material was hydrolyzed with 2N NaOH, stored overnight under refrigeration, and then hydrolyzing resumed. The solution was acidified with 2N HCl and the solids that formed were isolated, dried under vacuum, and recrystallized twice using methanol/water. Solids precipitated out overnight and were isolated and dried. The solids were dissolved in 2N NaOH and the pH of the sample was brought to pH 5 with 2N HCl. The solids were collected and HPLC revealed a single peak. These solids were then recrystallized in methanol/water, isolated, and then dried under vacuum, yielding 4.96 g (33.0%) of 4-(4 chloro-2-hydroxybenzoyl)aminobutyric acid. (C 11 H 12 ClNO 4 ; Molecular weight 257.67.) Melting point: 131-133° C. Combustion analysis: % C: 51.27(calc.), 51.27 (found); % H: 4.69 (calc.), 4.55 (found); % N: 5.44 (calc.), 5.30 (found). H NMR Analysis: (d 6 -DMSO): δ 13.0, s, 1H (COOH); δ 12.1, s, 1H (OH); δ 8.9, t, 1H (NH); δ 7.86, d, 1H (H ortho to amide); δ 6.98, d, 1H (H ortho to phenol OH); δ 6.96, d, 1H, (H meta to amide); δ 3.33, m, 2H (CH 2 adjacent to NH); δ 2.28, t, 2H (CH 2 adjacent to COOH); 67 1.80, m, 2H (aliphatic CH 2 beta to NH and CH 2 beta to COOH)
1b. Additional Preparation of Compound 1.
4-Chlorosalicylic acid (25.0 g, 0.1448 mol) was added to a one-neck 250 ml round-bottomed flask containing about 75-100 ml methylene chloride. Stirring was begun and continued to the remainder of the reaction. Coupling agent 1,1-carbonyldiimidazole (23.5 g, 0.1448 mol) was added as a solid in portions to the flask. The reaction was stirred at room temperature for approximately 20 minutes after all of the coupling agent had been added and then ethyl-4-aminobutyrate hydrochloride (24.3 g 0.1448 mol) was added to the flask with stirring. Triethylamine (26.0 ml, 0.18824 mol) was added dropwise from an addition funnel. The addition funnel was rinsed with methylene chloride. The reaction was allowed to stir at room temperature overnight.
The reaction was poured into a separatory funnel and washed with 2N HCl and an emulsion formed. The emulsion was filtered through celite in a fritted glass funnel. The filtrate was put back in a separatory funnel to separate the layers. The organic layer was washed with water and brine, then dried over sodium sulfate, which was then filtered off and the filtrate concentrated by rotary evaporation. The resulting solid material was hydrolyzed with 2N NaOH overnight. The solution was acidified with 2N HCl and the brown solids that formed were recrystallized using methanol/water, hot filtering off insoluble black material. White solids precipitated out and were isolated and dried, yielding 11.68 g (37.0%)of 4-(4 chloro-2-hydroxybenzoyl)aminobutyric acid. (C 11 H 12 ClNO 4 ; Molecular weight 257.67.) Melting point: 129-133° C. Combustion analysis: % C: 51.27(calc.), 51.26 (found); % H: 4.69 (calc.), 4.75 (found); % N: 5.44 (calc.), 5.32 (found). H NMR Analysis: (d 6 -DMSO): δ 13.0, s, 1H (COOH); δ 12.1, s, 1H (OH); δ 8.9, t, 1H (NH); δ 7.86, d, 1H (H ortho to amide); 67 6.98, d, 1H (H ortho to phenol OH); δ 6.96, d, 1H, (H meta to amide); δ 3.33, m, 2H (CH 2 adjacent to NH); δ 2.28, t, 2H (CH 2 adjacent to COOH); δ 1.80, m, 2H (aliphatic CH 2 beta to NH and CH 2 beta to COOH).
1c. Additional Preparation of Compound 1
(4-[(4-Chloro-2-hydroxybenzoyl)amino]butanoic acid)
A 22 L, five neck, round bottom flask was equipped with an overhead stirrer, 1 L Dean-Stark trap with reflux condenser, thermocouple temperature read out, and heating mantle. The following reaction was run under a dry nitrogen atmosphere. Reagent n-butanol (5000 mL) and 4-chlorosalicylic acid (2000 g, 11.59 mol) were charged to the reaction flask. The Dean-Stark trap was filled with n-butanol (1000 mL). Concentrated sulfuric acid (50 g) was added. The reaction mixture was heated to reflux for approximately 120 hours. Approximately 206 mL water was collected in the trap during this time. The heating mantle was removed and the reaction mixture allowed to cool to ambient temperature. The Dean-Stark trap was drained and removed. Deionized water (1000 mL) was charged. The biphasic mixture was stirred for 10 minutes. Stirring was stopped and the phases allowed to separate. The lower aqueous phase was siphoned off and discarded. A 10 wt % aqueous solution of sodium bicarbonate (1000 mL) was charged to the reaction mixture. The mixture was stirred for 10 minutes. The reaction mixture was tested with pH paper to ensure the pH of the solution was greater than 7. Water (500 mL) was added to the reaction mixture. The stirring was stopped and the phases allowed to separate. The lower aqueous layer was siphoned off and discarded. The reaction mixture was washed with another 500 mL portion of deionized water. The reactor was set up for atmospheric distillation into a tared 5 L receiver. The mixture was distilled until the pot temperature rose to between 140 and 150° C. The distillation was switched from atmospheric distillation to vacuum distillation. The pressure in the distillation setup was slowly lowered to 100 mmHg. The pot temperature fell and the remaining n-butanol and n-butyl ether (a reaction byproduct) distilled off. The heating was stopped and the reaction mixture allowed to cool to ambient temperature. The vacuum was broken with dry nitrogen. The crude butyl ester was transferred to a 5 L pot flask of a vacuum distillation setup. The crude butyl ester was distilled at a pressure between 0.2 and 0.5 mmHg. The forerun collected at a head temperature of <40° C. was discarded. The butyl 4-chloro-2-hydroxybenzoate fraction was collected at a head temperature between 104 and 112° C. This fraction had a weight of 2559 g. The yield was 96%.
A 22 L, five neck, round bottom flask was equipped with an overhead stirrer, reflux condenser, thermocouple temperature read out, and a heating mantle. The reactor was purged with nitrogen. Butyl 4-chloro-2-hydroxybenzoate (2559 g, 11.2 moles) and reagent methanol (10,000 mL) were charged to the reaction flask, and the contents were stirred until a solution was obtained. The reaction mixture was filtered through a Buchner funnel and returned to the reactor. The stirring rate was increased, and gaseous ammonia was added rapidly to the headspace of the reactor. The ammonia gas addition was continued until the temperature of the reactor reached 45° C. The addition of the ammonia was suspended and the agitation rate lowered. The reaction was allowed to cool to ambient temperature. Ammonia gas addition, as described above, was repeated until the reaction was complete as indicated by liquid chromatography. Seven ammonia charges over five days were needed to complete the reaction. Approximately half of the solvent was removed by atmospheric distillation. The reaction mixture was cooled to ambient temperature and 5 L of deionized water was added. Concentrated hydrochloric acid (approximately 500 mL) was added slowly to the reactor until the pH of the reaction mixture was between 4 and 5. The resulting precipitate was collected by vacuum filtration through a large sintered glass funnel. The product filter cake was washed with 2000 mL of deionized water, and dried at 50° C. for 32 hours to give 1797 g of 4-chloro-2-hydroxybenzamide. The yield was 94%.
A 22 L, five neck, round bottom flask was equipped with an overhead stirrer, reflux condenser, addition funnel, thermocouple temperature read out, and a heating mantle. The reactor was purged with nitrogen. Acetonitrile (4700 mL) and 4-chloro-2-hydroxybenzamide (1782 g, 10.4 mol) were charged to the reaction flask and the stirring was started. Pyridine (1133 mL, 14.0 mol) was charged to the reactor. The resulting reaction slurry was cooled to less than 10° C. with an ice bath. Ethyl chloroformate (1091 mL, 1237 g, 11.4 mol) was placed in the addition funnel and charged slowly to the stirred reaction mixture such that the temperature of the reaction mixture did not exceed 15° C. during the addition. The temperature of the reaction mixture was held between 10 and 15° C. for 30 minutes after the ethyl chloroformate addition was complete. The ice bath was removed, and the reaction mixture was warmed to ambient temperature. The reaction mixture was then slowly heated to reflux and held at that temperature for 18 hours. Liquid chromatographic analysis of the reaction mixture indicated that the reaction was only 80% complete. Approximately half of the solvent was removed by atmospheric distillation. The reaction mixture was cooled first to ambient temperature and then to <10° C. with an ice bath. Additional pyridine (215 mL, 2.65 mol) was added to the reaction mixture. Ethyl chloroformate (235 g, 2.17 mol) was added slowly via an addition funnel to the cold reaction mixture. The reaction mixture was held between 10 and 15° C. for 30 minutes after the ethyl chloroformate addition was complete. The ice bath was removed, and the reaction mixture was warmed to ambient temperature. The reaction mixture was then slowly heated to reflux and held at that temperature for 18 hours, after which time liquid chromatographic analysis indicated that the reaction was complete. The reaction mixture was cooled first to ambient temperature and then to <10° C. with an ice bath. Water (1600 mL) was added slowly via an addition funnel and the resulting slurry held at <10° C. for 90 minutes. The solid product was collected by vacuum filtration through a large sintered glass funnel. The product filter cake was washed with deionized water and vacuum dried at 50° C. for 18 hours to give 1914 g of 7-chloro-2H-1,3-benzoxazine-2,4(3H)-dione as a tan solid. The yield was 83%.
A 22 L, five neck, round bottom flask was equipped with an overhead stirrer, reflux condenser, thermocouple temperature read out, and heating mantle. The following reaction was run under a dry nitrogen atmosphere. 7-Chloro-2H-1,3-benzoxazine-2,4(3H)-dione (1904 g, 9.64 mol), ethyl 4-bromobutyrate (1313 mL, 9.18 mol), and N,N-dimethylacetamide (4700 mL) were charged under a nitrogen purge. The reaction mixture was heated to 70° C. Sodium carbonate (1119 g, 10.55 mol) was charged to the clear solution in five equal portions over approximately 40 minutes. The reaction mixture was held at 70° C. overnight. The reaction was cooled to 55° C. The inorganic solids were removed by vacuum filtration through a sintered glass funnel. The reaction flask was rinsed with 2B-ethanol (2000 mL) and this rinse used to wash the filter cake. The reaction flask was cleaned with deionized water. The filtrate was returned to the clean reaction flask. The filtrate was cooled in an ice bath. Deionized water (9400 mL) was added slowly with an addition funnel. The chilled mixture was allowed to stir overnight. The resulting solids were recovered by vacuum filtration through a sintered glass funnel. The product cake was washed with deionized water. The ethyl 3-(4-butanoate)-7-chloro-2H-1,3-benzoxazine-2,4-(3H)-dione had a weight of 2476.0 g. The yield was 82.2%.
A 12 L, stainless steel reactor was equipped with an overhead stirrer, reflux condenser, thermocouple temperature read out, addition funnel, and heating mantle. The following reaction was run under a dry nitrogen atmosphere. Water (3 L) and ethyl 3-(4-butanoate)-7-chloro-2H-1,3-benzoxazine-2,4-(3H)-dione (1118 g, 3.58 mol) were charged to the reactor and stirring was started. A solution of sodium hydroxide (574 g, 4.34 mol) in-water (2 L) was added slowly to the reaction slurry. The reaction was heated to 70° C. for 6 hours, and then allowed to cool slowly to ambient temperature. The reaction mixture was filtered through a Buchner funnel.
A 22 L five neck round bottom flask was equipped with an overhead stirrer, reflux condenser, thermocouple temperature read out, and an addition funnel. Deionized water (1880 mL) and concentrated hydrochloric acid (1197 g, 12.04 mol) were charged to the reactor. The hydrolysate from above was added slowly via addition funnel to the acid solution. The pH of the resulting slurry was adjusted to 3 by adding additional hydrochloric acid (160 mL, 1.61 mol) The product solids were collected by filtration through a sintered glass funnel and dried in a vacuum oven at 50° C. for 24 hours to give 1109.3 g of 4-[(4-chloro-2-hydroxy-benzoyl)amino]butanoic acid as an off white solid. The yield was quantitative.
EXAMPLE 1d
Preparation of Anhydrous Sodium 4-[(2-Hydroxybenzoyl)amino]butanoate
A 22 L, five neck round bottom flask, was equipped with an overhead stirrer, reflux condenser, thermocouple temperature read out, and heating mantle. The following reaction was run under a dry nitrogen atmosphere. Reagent acetone (13000 mL) and 4-[(4-chloro-2-hydroxy-benzoyl)amino]butanoic acid (500.0 g, 1.94 mol) were charged to the reactor and stirring was started. The reaction slurry was heated to 50° C. until a hazy brown solution was obtained. The warm solution was pumped through a warm pressure filter dressed with Whatman #1 paper into a clean 22 L reactor. The clear yellow filtrate was heated to 50° C. while stirring. Sodium hydroxide solution (50% aqueous; 155 g, 1.94 mol) was charged to the reactor while maintaining vigorous agitation. After the base addition was complete, the reactor was heated to reflux (60° C.) for 2.5 hours and then allowed to cool slowly to ambient temperature. The product was isolated by vacuum filtration through a sintered glass funnel and dried in a vacuum oven at 50° C. for 24 hours to give 527.3 g of sodium 4-[(2-hydroxybenzoyl)amino]butanoate as an off-white solid. The yield was 97.2%.
EXAMPLE 1e
Preparation of Sodium 4-[(4-chloro-2-Hydroxybenzoyl)amino]butanoate
A 22 L flask was equipped with an overhead stirrer. Deionized water (2000 mL) and 4-[(4-chloro-2-hydroxy-benzoyl)amino]butanoic acid (380.0 g, 1.47 mol) were added and stirring was started. A solution of sodium hydroxide (59.0 g, 1.48 mol) in water (500 mL) was added to the reactor. Water (1500 mL) was added to the reactor, and the resulting slurry was heated until a complete solution was obtained. The reaction mixture was cooled to ambient temperature, and then concentrated to dryness under reduced pressure. The resulting solids were scraped from the flask and vacuum dried at 50° C. to give 401.2 g of sodium 4-[(2-hydroxybenzoyl)amino]butanoate as an off-white solid. The yield was 96.9%.
EXAMPLE 1f
Preparation of Sodium 4-[(2-Hydroxybenzoyl)-amino]butanoate Through the Isopropanol Solvate
A one liter, four neck round bottom flask was equipped with an overhead stirrer, reflux condenser, thermocouple temperature read out, and heating mantle. The following reaction was run under a dry nitrogen atmosphere. Isopropanol (400 mL) and 4-[(4-chloro-2-hydroxy-benzoyl)amino]butanoic acid (25.0 g, 0.09 mol) were charged to the reactor and stirring was started. The reaction slurry was heated to 50° C. until a hazy brown solution was obtained. The warm solution was filtered through a warm pressure filter dressed with Whatman #1 paper into a clean 1 L reactor. The clear yellow filtrate was heated to 62° C. while stirring. Sodium hydroxide solution (50% aqueous; 7.2 g, 0.09 mol) was charged to the reactor while maintaining vigorous agitation. After the base addition was complete, the reactor was heated to reflux (72° C.) and then allowed to cool slowly to ambient temperature. The product was isolated by vacuum filtration through a sintered glass funnel and vacuum dried at 50° C. for 24 hours to give 23.16 g of sodium 4-[(2-hydroxybenzoyl)amino]butanoate as an off-white solid. The yield was 92%.
EXAMPLE 1g
Capsule Preparation
Capsules for primate dosing containing the monosodium salt of compound 1 (as prepared in example 1d) and insulin were prepared as follows. The compound 1 monosodium salt and QA307X zinc insulin crystals human: proinsulin derived (recombinant DNA origin) (available from Eli-Lilly & Co. of Indianapolis, Ind.) were first screened through a 35 mesh Tyler standard sieve and the required amount weighed. Screened compound 1 monosodium salt and insulin were blended using geometric sieving method in a suitably sized glass mortar. The materials in the mortar were mixed well with a glass pestle. A spatula was used for scrapping the sides of the mortar. The resulting formulation was transferred to a plastic weigh boat for capsule filling. The formulation was hand packaged into size #0 Torpac hard gelatin capsules (available from Torpac, Inc. of Fairfield, N.J.). Each capsule fill weight was dependent on the individual animal weight. Capsules doses of compound 1 were 100 mg/kg, 75 mg/kg and 50 mg/kg (as monosodium salt). Capsule doses of insulin were 0.25 to 0.5 mg per kg.
EXAMPLE 2
Insulin—Oral Delivery
A. Rat Studies Oral dosing (PO) compositions of delivery agent compound (prepared as in Example 1a or 1b as indicated below) and zinc human recombinant insulin (available from Calbiochem-Novabiochem Corp., La Jolla, Calif. (Catalog # 407694)) were prepared in deionized water. Typically, 500 mg of delivery agent compound was added to 1.5 ml of water. The free acid of the delivery agent compound was converted to the sodium salt by stirring the resultant solution and adding one equivalent of sodium hydroxide. The solution was vortexed, then heated (about 37° C.) and sonicated. The pH was adjusted to about 7 to 8.5 with NaOH or HCl. Additional NaOH was added, if necessary, to achieve uniform solubility, and the pH re-adjusted. (For example, for compound 1a, a total of 258.5 ml 10N NaOH was added to 501 mg compound in 1.5 ml water, final pH 7.73.) Water was then added to bring the total volume to about 2.4 ml and vortexed. About 1.25 mg insulin from an insulin stock solution (15 mg/ml made from 0.5409 g insulin and 18 ml deionized water, adjusting with HCl and NaOH to pH 8.15 and to obtain a clear solution using 40 ml concentrated HCl, 25 ml 10N NaOH and 50 ml 1N NaOH) was added to the solution and mixed by inverting. The final delivery agent compound dose, insulin dose and dose volume amounts are listed below in Table 1.
The dosing and sampling protocols were as follows. Male Sprague-Dawley rats weighing between about 200-250 g were fasted for 24 hours and administered ketamine (44 mg/kg) and chlorpromazine (1.5 mg/kg) 15 minutes prior to dosing and again as needed to maintain anesthesia. A dosing group of five animals was administered one of the dosing solutions. For oral dosing, an 11 cm Rusch 8 French catheter was adapted to a 1 ml syringe with a pipette tip. The syringe was filled with dosing solution by drawing the solution through the catheter, which was then wiped dry. The catheter was placed down the esophagus leaving 1 cm of tubing past the incisors. Solution was administered by pressing the syringe plunger.
Blood samples were collected serially from the tail artery, typically at time=15, 30, 60, 120 and 180 minutes after administration. Serum insulin levels were determined with an Insulin ELISA Test Kit (Kit # DSL-10-1600 from Diagnostic Systems Laboratories, Inc., Webster, Tex.), modifying the standard protocol in order to optimize the sensitivity and linear range of the standard curve for the volumes and concentrations of the samples used in the present protocol. Serum human insulin concentrations (μU/ml) were measured for each time point for each of the five animals in each dosing group. The five values for each time point were averaged and the results plotted as serum insulin concentration versus time. The maximum (peak) and the area under the curve (AUC) are reported below in Table 1. Previous experiments revealed no measurable levels of human insulin following oral dosing with human insulin alone.
TABLE 1 Insulin-Oral Delivery Mean Peak volume Compound Insulin Serum Human dose Dose Dose Insulin Compound (ml/kg) (mg/kg) (mg/kg) (μU/ml ± SE) AUC 1a 1.0 200 0.5 1457 ± 268 58935 1b 1.0 200 0.5 183 ± 89 8674 1b 1.0 200 0.5 136 ± 52 5533 1b 1.0 200 0.5 205 ± 61 7996 1b 1.0 200 0.5 139 ± 43 5271
B. Monkey Studies
All animal protocols adhered to the “Principles of Laboratory Animal Care” and were Institutional Animal Care and Use Committee (IACUC) approved.
The dosing protocol for administering the capsules to each animal was as follows. Baseline plasma samples were obtained from the animals prior to dosing. Groups of four cynomolgus monkeys, two males and two females, weighing 2-3 kg were fasted for 4 hours prior to dosing and up to 2 hours after dosing. The animals were anesthetized with an intramuscular injection of 10 mg/kg ketamine hydrochloride immediately prior to dosing. Each animal was administered varying doses of compound 1 (25-100 mg/kg) in combination with varying doses of insulin 0.25-0.5 mg/kg insulin as 1 capsule. Water was available throughtout the dosing period and 400 ml of juice was made available to the animal overnight prior to dosing and throughout the dosing period. The animal was restrained in a sling restraint. A capsule was placed into a pill gun, which is a plastic tool with a cocket plunger and split rubber tip to accommodate a capsule. The pill gun was inserted into the espophagus of the animal. The plunger of the pill gun was pressed to push the capsule out of the rubber tip into the espophagus. The pill gun was then retracted. The animals mouth was held closed and approximately 5 ml reverse osmosis water was administered into the mouth from the side to induce a swallowing reflex. The throat of the animal was rubbed further to induce the swallowing reflex.
Citrated blood samples (1 mL each) were collected by venipuncture from an appropriate vein at 1 hour before dosing and at 10, 20, 30, 40, and 50 minutes and 1, 1.5, 2, 3, 4, and 6 hours after dosing. Each harvested plasma sample was divided into two portions. One portion was frozen at −80° C. and shipped to another location for insulin assay. The other portion was used in the blood glucose assay. Four monkeys also received insulin subcutaneously (0.02 mg/kg). Blood samples were collected and analyzed as described above.
Insulin Assays. Serum insulin levels were measured using the Insulin ELISA Test Kit (DSL, Webster, Tex.).
Glucose Assays. Blood glucose measurements were performed using ONETOUCH® Glucose Monitoring System from Live Scan Inc., Newtown, Pa.
The results are shown in Table 1A below.
TABLE 1A
Insulin - Oral Delivery to Monkeys
Mean Peak
Compound
Insulin
Serum Human
Mean Peak Blood
Com-
Dose
Dose
Insulin
Glucose Reduction
pound
(mg/kg)
(mg/kg)
(μU/ml ± SE)
(μU/ml ± SE)
1d
100
0.5
91.4 ± 45
52.3 ± 5.3
1d
50
0.5
124.1 ± 51.95
−61 ± 12.7
1d
25
0.5
87.14 ± 53.85
−28.75 ± 21.59
1d
25
0.25
36.35 ± 32.3
−19 ± 10.21
EXAMPLE 3
Cromolyn—Oral Delivery
Dosing solutions containing a delivery agent compound (prepared as in Example 1b) and cromolyn, disodium salt (cromolyn) (Sigma, Milwaukee, Wis.) were prepared in deionized water. The free acid of the delivery agent compound was converted to the sodium salt with one equivalent of sodium hydroxide. This mixture was vortexed and placed in a sonicator (about 37° C.). The pH was adjusted to about 7-7.5 with aqueous NaOH. Additional NaOH was added, if necessary, to achieve uniform solubility, and the pH re-adjusted. The mixture was vortexed to produce a uniform solution, also using sonication and heat if necessary. The delivery agent compound solution was mixed with cromolyn from a stock solution (175 mg cromolyn/ml in deionized water, pH adjusted, if necessary, with NaOH or HCl to about 7.0, stock solution stored frozen wrapped in foil, then thawed and heated to about 30° C. before using). The mixture was vortexed to produce a uniform solution, also using sonication and heat if necessary. The pH was adjusted to about 7-7.5 with aqueous NaOH. The solution was then diluted with water to the desired volume (usually 2.0 ml) and concentration and stored wrapped in foil before use. The final delivery agent compound and cromolyn doses, and the dose volumes are listed below in Table 2.
The typical dosing and sampling protocols were as follows. Male Sprague-Dawley rats weighing between 200-250 g were fasted for 24 hours and were anesthetized with ketamine (44 mg/kg) and chlorpromazine (1.5 mg/kg) 15 minutes prior to dosing and again as needed to maintain anesthesia. A dosing group of five animals was administered one of the dosing solutions. An 11 cm Rusch 8 French catheter was adapted to a 1 ml syringe with a pipette tip. The syringe was filled with dosing solution by drawing the solution through the catheter, which was then wiped dry. The catheter was placed down the esophagus leaving 1 cm of tubing past the incisors. Solution was administered by pressing the syringe plunger.
Blood samples were collected via the tail artery, typically at 0.25, 0.5, 1.0 and 1.5 hours after dosing. Serum cromolyn concentrations were measured by HPLC. Samples were prepared as follows: 100 μl serum was combined with 100 μl 3N HCl and 300 μl ethyl acetate in an eppendorf tube. The tube was vortexed for 10 minutes and then centrifuged for 10 minutes at 10,000 rpm. 200 μl ethyl acetate layer was transferred to an eppendorf tube containing 67 μl 0.1 M phosphate buffer. The tube was vortexed for 10 minutes and then centrifuged for 10 minutes at 10,000 rpm. The phosphate buffer layer was then transferred to an HPLC vial and injected into the HPLC (column=Keystone Exsil Amino 150×2 mm i.d., 5 μm, 100 Å (Keystone Scientific Products, Inc.); mobile phase=35% buffer(68 mM KH 2 PO 4 adjusted to pH 3.0 with 85% H 3 PO 4 )/65% acetonitrile; injection volume=10 μl; flow rate=0.30 ml/minute; cromolyn retention time=5.5 minutes; absorbance detected at 240 nm). Previous studies indicated baseline values of about zero.
Results from the animals in each group were averaged for each time point and the highest of these averages (i.e., mean peak serum cromolyn concentration) is reported below in Table 2.
TABLE 2
Cromolyn - Oral Delivery
Mean Peak
volume
Compound
Cromolyn
serum
dose
Dose
Dose
[cromolyn] ±
Compound
(ml/kg)
(mg/kg)
(mg/kg)
SD (SE)
1b
1
200
25
0.70 ± 0.36
(0.16)
EXAMPLE 4
Recombinant Human Growth Hormone (rhGH)—Oral Delivery
Oral gavage (PO) dosing solutions of delivery agent compound (prepared as in Example 1a or 1b as indicated in Table 3 below) and rhGH were prepared in phosphate buffer. The free acid of the delivery agent compound was converted to the sodium salt with one equivalent of sodium hydroxide. Typically, a solution of the compound was prepared in phosphate buffer and stirred, adding one equivalent of sodium hydroxide (1.0 N) when making the sodium salt. Additional NaOH was added, if necessary, to achieve uniform solubility, and the pH re-adjusted. The final dosing solutions were prepared by mixing the compound solution with an rhGH stock solution (15 mg rhGH/ml made by mixing as powders 15 mg rhGH, 75 mg D-mannitol, 15 mg glycine and 3.39 mg dibasic sodium phosphate, then diluting with 2% glycerol) and diluting to the desired volume (usually 3.0 ml). The compound and rhGH doses and the dose volumes are listed below in Table 3.
The typical dosing and sampling protocols were as follows. Male Sprague-Dawley rats weighing between 200-250 g were fasted for 24 hours and administered ketamine (44 mg/kg) and chlorpromazine (1.5 mg/kg) 15 minutes prior to dosing and again as needed to maintain anesthesia. A dosing group of five animals was administered one of the dosing solutions. An 11 cm Rusch 8 French catheter was adapted to a 1 ml syringe with a pipette tip. The syringe was filled with dosing solution by drawing the solution through the catheter, which was then wiped dry. The catheter was placed down the esophagus leaving 1 cm of tubing past the incisors. Solution was administered by pressing the syringe plunger.
Blood samples were collected serially from the tail artery, typically at time=15, 30, 45 and 60 minutes after administration. Serum rHGH concentrations were quantified by an rHGH immunoassay test kit (Kit # K1F4015 from Genzyme Corporation Inc., Cambridge, Mass.). Previous studies indicated baseline values of about zero.
Results from the animals in each group were averaged for each time point. The maximum of these averages (i.e., the mean peak serum rhGH concentration) is reported below in Table 3. (In the cases where no standard deviation (SD) or standard error (SE) is given below, the five samples from each time period were pooled prior to assaying.)
TABLE 3
rhGH - Oral Delivery
Volume
Compound
rhGH
Mean Peak
dose
Dose
Dose
Serum [rhGH] ± SD
Compound
(ml/kg)
(mg/kg)
(mg/kg)
(SE) (ng/ml)
1a
1
200
3
99.35
1a
1
200
3
42.62
1b
1
200
3
84.01 ± 73.57
(32.90)
1b
1
200
3
50.44 ± 34.13
(15.26)
EXAMPLE 5
Interferon—Oral Delivery
Dosing solutions of delivery agent compound (prepared as in Example 1b) and human interferon (IFN) were prepared in deionized water. The free acid of the delivery agent compound was converted to the sodium salt with one equivalent of sodium hydroxide. Typically, a solution of the delivery agent compound was prepared in water and stirred, adding one equivalent of sodium hydroxide (1.0 N) when making the sodium salt. This mixture was vortexed and placed in a sonicator (about 37° C.). The pH was adjusted to about 7.0 to 8.5 with aqueous NaOH. The mixture was vortexed to produce a uniform suspension or solution, also using sonication and heat if necessary. Additional NaOH was added, if necessary, to achieve uniform solubility, and the pH re-adjusted. The delivery agent compound solution was mixed with an IFN stock solution (about 22.0 to 27.5 mg/ml in phosphate buffered saline) and diluted to the desired volume (usually 3.0 ml). The final delivery agent compound and IFN doses, and the dose volumes are listed below in Table 4.
The typical dosing and sampling protocols were as follows. Male Sprague-Dawley rats weighing between 200-250 g were fasted for 24 hours and administered ketamine (44 mg/kg) and chlorpromazine (1.5 mg/kg) 15 minutes prior to dosing and again as needed to maintain anesthesia. A dosing group of five animals was administered one of the dosing solutions. An 11 cm Rusch 8 French catheter was adapted to a 1 ml syringe with a pipette tip. The syringe was filled with dosing solution by drawing the solution through the catheter, which was then wiped dry. The catheter was placed down the esophagus leaving 1 cm of tubing past the incisors. Solution was administered by pressing the syringe plunger.
Blood samples were collected serially from the tail artery, typically at time=0, 15, 30, 45, 60 and 90 minutes after administration. Serum IFN concentrations were quantified using Cytoscreen Immunoassay Kit for human IFN-alpha (catalog # KHC4012 from Biosource International, Camarillo, Calif.). Previous studies indicated baseline values of about zero. Results from the animals in each group were averaged for each time point. The maximum of these averages (i.e., the mean peak serum IFN concentration) is reported below in Table 4.
TABLE 4
Interferon - Oral Delivery
Mean Peak
Volume
Compound
IFN
Serum [IFN]
dose
Dose
Dose
(ng/ml) ±
Compound
(ml/kg)
(mg/kg)
(mg/kg)
SD (SE)
1b
1.0
200
1.0
17.80 ± 13.52
(6.05)
The above-mentioned patents, applications, test methods, and publications are hereby incorporated by reference in their entirety.
Many variations of the present invention will suggest themselves to those skilled in the art in light of the above detailed description. All such obvious variations are within the fully intended scope of the appended claims. | 1a
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RELATED APPLICATIONS
[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 61/724,883, the entire contents of which are incorporated herein by reference.
TECHNICAL FIELD
[0002] The subject matter described herein relates to a method of treating inflammatory diseases with Adenosine 2B receptor antagonists in particular with xanthine derived inhibitors.
BACKGROUND
[0003] The methods and compositions to be described relate to Adenosine 2B receptor antagonists and their use to treat inflammatory diseases, disorders, and conditions: Adenosine is a ubiquitous signalling agent in mammalian biology and there are, accordingly, mechanisms that allow spatial and temporal specification of adenosine signals. These include a variety of receptor isoforms (A1, A2A, A2B, A3) with varying functions from the class of purine and pyrimidine receptors. A2B receptors are, in particular, expressed in cells of the immune system such as mast cells and are activated in processes like mast cell degranulation. A2B has a moderate affinity for adenosine in the range of 1 μM which is low enough to provide some scope for displacement by a synthetic ligand, however, adenosine is itself relatively abundant being derived from successive dephosphorylation of ATP which is, itself present at mM intracellular levels. It appears that adenosine is ordinarily an intracellular metabolite and that its release into the extracellular matrix would be indicative of cell injury. Hence its utility as a signal for an extracellular receptor.
BRIEF SUMMARY
[0004] The following aspects and embodiments thereof described and illustrated below are meant to be exemplary and illustrative, not limiting in scope.
[0005] In one aspect, a method for treating an immune disorder is provided, comprising: administering Adenosine 2B receptor antagonists to a subject suffering from an immune disorder in an amount sufficient to modify disease.
[0006] In some embodiments, the immune disorder is an autoimmune disease. In particular embodiments, the immune disorder is rheumatoid arthritis. In other particular embodiments, the immune disorder is multiple sclerosis. In still other particular embodiments, the immune disorder is selected from, psoriasis, psoriatic arthritis, Crohn's disease, systemic lupus erythematosus, pulmonary fibrosis, liver inflammation, myocarditis, transplant rejection and atherosclerosis.
[0007] In some embodiments, the Adenosine 2B receptor antagonists is administered by injection at a dose that achieves blood levels of about 0.02 micromolar or greater. In a preferred embodiment, the Adenosine 2B receptor antagonist is injected in a depot formulation such that it provides adequate blood levels for 1 to 28 days. In some embodiments, Adenosine 2B receptor antagonists are orally administered.
[0008] In some embodiments, the Adenosine 2B receptor antagonists is orally administered at a dose above 500 mg per day to treat acute disease. In other embodiments, the dose is less than 300 mg/day to treat non-acute disease. In certain embodiments, prophylaxis of immune disease is achieved by daily doses below 200 mg, preferably below 100 mg and still more preferably, in the range 10 to 50 mg per day.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 shows a generic structure of the xanthine class of compounds and Adenosine 2B receptor antagonists
[0010] FIG. 2 shows a structure of the prototypic Adenosine 2B receptor antagonist Compound 1
[0011] FIG. 3 illustrates treatment of collagen induced (CIA) arthritis in mice by treatment with Adenosine 2B receptor antagonist Compound 1, at doses of 30 mg/kg (squares) given i.p. once-daily starting when CIA is established. Control mice were treated with saline (circles). Data are the mean arthritis paw thickness, assessed using a calliper in the days following primary immunization and boost.
[0012] FIG. 4A and FIG. 4B illustrate prevention of Experimental Autoimmune Encephalomyelitis (EAE) in mice by treatment with Adenosine 2B receptor antagonists, at doses of 15 mg/kg (circles) given i.p. once-daily starting when EAE is first induced. Control mice were treated with PEG/saline (triangles). FIG. 4A shows the mean weight of animals normalised to weight prior to induction of disease. FIG. 4B shows the mean EAE score, assessed using a visual scoring system from 0 to 5 in which 5 represents full paralysis, and 0, normal activity. Data are the mean plotted with the standard error of the mean.
[0013] FIG. 5 illustrates the pharmacokinetics of Compound 1 in C57BLK6 mice by either the oral or intravenous route. Compound 1 is detectable only via injection.
DETAILED DESCRIPTION
[0014] I. Definitions
[0015] “Treat” or “treating” means any treatment, including, but not limited to, alleviating symptoms of a disease, disorder, or condition.
[0016] “Preventing” refers to inhibiting the initial onset of a pathologic process.
[0017] “Therapeutically effective amount” means an amount of a compound that is effective in treating or preventing a particular disorder or condition.
[0018] “Pharmaceutically acceptable carrier” is a non-toxic solvent, dispersant, excipient, or other material used in formation of a pharmaceutical composition, i.e., a dosage form capable of administration to a subject or patient.
[0019] “Immune disorder” means any disease or pathology that is associated with non-normal function of the immune system such that the immune system is auto reactive, excessively active or otherwise causes a pathological effect on its host that may have an inflammatory component. Examples include rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, graft rejection, myocarditis, atherosclerosis, asthma, chronic bronchitis and psoriasis. A “selective inhibitor of the adenosine 2 B receptor” is a substance that has a Ki for the receptor of 10 μM or lower and for which the Ki on A2B is at least 10-fold lower than for A1, A2A and A3.
[0020] An “adenosine 2 B receptor antagonist” is an inhibitor of the A2B receptor.
[0021] A. Overview
[0022] In various aspects, methods for treating and preventing inflammatory diseases are described. Such methods include those for inhibiting the initiation of inflammation, inhibiting inflammatory diseases related to mast cells, inhibiting inflammatory diseases involving activated macrophage, and inhibiting inflammatory diseases involving osteoclasts. The methods include administering Adenosine 2B receptor antagonists at a dosage sufficient to selectively inhibit the A2B receptor, thereby modulating the downstream signalling effects of the receptors, causing a beneficial therapeutic affect on a subject/patient.
[0023] Adenosine 2B receptor antagonists include inhibitors described in the following publications:
[0024] Bormann et al., J. Med. Chem. 2009, 52, 3994-4006, Yan et al., J. Med. Chem. 2006, 49, 4384 4391, Yan and Müller J. Med. Chem. 2004, 47, 1031 1043
[0025] Hayella et al., J. Med. Chem. 2002, 45, 1500 1510 along with other analogs of similar activity, all of which are hereby incorporated by reference.
[0026] Adenosine 2B receptor antagonists of utility include structures related to the 8-aryl-xanthines substituted with piperidyl-sulfonamides as indicated in the following generic structure.
[0000]
[0027] Where R1 and R2 are independently selected from H, Alkyl, branched alkyl, 1-Propin-3-yl, amino alkyl
[0028] n is independently selected from 0, 1, 2 or 3,
[0029] R3 and R4 are independently selected from H, halogen (F, Cl, Br, I), trifluoromethyl, hydroxyl or alkoxy, methylendioxy.
[0030] In a preferred embodiment, R2 is H and R1 is an alkyl group and n is 0, 1 or 2.
[0031] In a more preferred embodiment, R2 is H and R1 is propyl, and n is 0
[0032] Additional adenosine 2B receptor antagonists of utility include structures related to the 8-aryl-xanthines substituted with piperidyl-sulfonamides as indicated in the following generic structure.
[0000]
[0033] Where R1 and R2 are independently selected from H, Alkyl, branched alkyl, 1-Propin-3-yl, amino alkyl
[0034] R3 is selected from H, piperdinyl, pyridinyl, cyclohexyl, cycloheptyl,
[0035] Further adenosine 2B receptor antagonists of utility include structures related to the 8-aryl-xanthines substituted with piperidyl-sulfonamides as indicated in the following generic structure.
[0000]
[0036] Where R1 and R2 are independently selected from H, Alkyl, branched alkyl, 1-Propin-3-yl, amino alkyl
[0037] R3 and R4 are independently selected from H, alkylphenyl, alkyl, branched alkyl, hydroxyalkly, carboxyalkyl and alkylarylether, halo aryl, pyridinyl
[0038] In a preferred embodiment, R2 is H and R1 is an alkyl group and n is 0, 1 or 2.
[0039] In a more preferred embodiment, R2 is H and R1 is propyl,
[0040] The selectivity of these substances at various adenosine receptors is illustrated as follows:
[0000]
rA1
rA2A
hA2B
hA3
Ki ± SEM
Ki ± SEM
IC50 ± SEM
Ki ± SEM
Comp. #
R1
R2
[nM]
[nM]
[nM]
[nM]
Propyl-
3,4-(Methylen-
79 ± 5
590 ± 29
24 ± 10
4150
dioxy)benzyl-
Propyl-
p-Methoxybenzyl-
84 ± 19
1020 ± 561
16 ± 6
>10000
Propyl-
p-Chlorbenzyl-
386 ± 98
1730 ± 790
4 ± 1
−10000
Propyl-
m-Trifluormethylbenzyl-
273 ± 47
1700 ± 217
4 ± 0.2
−10000
2
Propyl-
p-Trifluormethylbenzyl-
463 ± 122
1540 ± 271
2 ± 1
>10000
4
Propyl-
m-Chlorbenzyl-
178 ± 38
799 ± 358
2 ± 0.1
−10000
5
Propyl-
m-Fluorbenzyl-
111 ± 43
782 ± 236
3 ± 0.2
−10000
Propyl-
Benzyl-
151 ± 38
848 ± 433
10 ± 2
>10000
1
Propyl-
p-Chlorphenyl-
>10000
>10000
1 ± 0.4
>10000
Propyl-
2-(Phenyl)ethyl-
>10000
154 ± 44.9
11 ± 3
<10000
Ethyl-
Phenyl-
142 ± 6
514 ± 41
4 ± 3
>10000
Ethyl-
3,4-(Methylen-
54 ± 5
332 ± 129
5 ± 2
<10000
dioxy)benzyl-
Ethyl-
p-Methoxybenzyl-
129 ± 41
630 ± 305
5 ± 1
<10000
3
Ethyl-
m-Trifluormethylbenzyl-
509 ± 155
499 ± 129
2 ± 1
>10000
[0041] The methods for synthesising the foregoing compounds are recorded in Bormann et al., J. Med. Chem. 2009, 52, 3994-4006.
[0042] Adenosine 2B receptor antagonists for treating rheumatoid arthritis
[0043] In studies described herein, it is shown that Adenosine 2B receptor antagonists prevent and treat inflammatory diseases by selectively inhibiting a spectrum of signal transduction pathways central to the pathogenesis of the inflammatory disease. Using collagen-induced arthritis (CIA) in mice as a model of an exemplary inflammatory disease, rheumatoid arthritis (RA), i.p. administration of Adenosine 2B receptor antagonists to mice was shown to be effective in treating the progression of CIA (e.g., Example 1 and FIG. 3 ) in mice with established clinical arthritis. After the end of treatment, the inhibitory effect was maintained for a period of 2-3 days after which signs began to re-emerge. These data suggest that the activity of the A2B receptor is required for the maintenance of inflammation. Perhaps more importantly, these data suggest that it is possible to rapidly suppress established arthritis in the course of the peak inflammatory potential, a period of CIA that resembles the conditions of an acute arthritic flair.
[0044] In further experiments performed in support of the present compositions and methods, the ability of Adenosine 2B receptor antagonists to treat and/or prevent another exemplary inflammatory condition, experimental autoimmune encephalomyelitis (EAE), was evaluated. EAE is a widely used animal model for multiple sclerosis (MS). Mice in which EAE had been induced were treated with Adenosine 2B receptor antagonists once daily i.p. and the severity of the disease was determined using a standard scoring system, described in Example 2. Animals treated with Adenosine 2B receptor antagonist Compound 1 once daily at 15 mg/kg i.p. demonstrated delayed onset such that there were no signs of EAE compared to control mice. Adenosine 2B receptor antagonists likely provided a beneficial therapeutic effect by inhibiting the signalling required to initiate inflammation. While the EAE model is not necessarily able to replicate all aspects of human forms or multiple sclerosis, these data suggest that the Adenosine 2B receptor antagonists are able to exert a general anti-inflammatory action irrespective of the inflamed organ.
[0045] Delivery and Formulations
[0046] The inhibitors described herein are suitable for once daily injection, however, they are relatively quickly eliminated and thus they are suitable for use in depot and modified release forms as a means to extend their duration of action.
[0047] In certain applications, rapid elimination is an advantage in that it provides a reduction in toxicological risk. In this respect, in a preferred embodiment, the inhibitor has a plasma half-life following subcutaneous injection of 8 hours or less in human subjects.
[0048] Administration less than every day is also contemplated, for example administration every other day or several times per week or once per week or once every 14 days using formulations designed to have some depot effect. Additionally, intermittent courses of therapy with Adenosine 2B receptor antagonists or are contemplated, for example, treatment for one week then off drug for one week, or treatment for one week then off drug for three weeks, or treatment only during periods of disease flare.
[0049] In a preferred embodiment, the Adenosine 2B receptor antagonists is administered parenterally. In one embodiment, substance is provided in a simple propylene glycol suspension for subcutaneous administration. In a further embodiment, the suspension may be incorporated in a matrix such as a poly-lactide or similar biocompatible polymers.
[0050] For treatment of disease of the digestive system and the liver, oral administration is contemplated. In inflammatory bowel disease, oral formulations including enterically coated materials are suitable.
[0051] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically-acceptable excipient or carrier, such as sodium citrate or dicalcium phosphate and/or (a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia, (c) humectants such as glycerol, (d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, (e) solution retarding agents such as paraffin, (f) absorption accelerators such as quaternary ammonium compounds, (g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, (h) absorbents such as kaolin and bentonite clay, and (i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.
[0052] The solid dosage forms of tablets, dragees, capsules, pills, and granules may be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. The active compound can also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned excipients.
[0053] Liquid dosage forms for oral administration include pharmaceutically-acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof.
[0054] Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. Suspensions may contain, in addition to the active compounds, suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, and tragacanth, and mixtures thereof. From the foregoing, various additional aspects and embodiments of the present compositions and methods will become apparent. The following Examples are provided to illustrate the compositions and methods but are not intended as limiting.
EXAMPLES
[0055] The following examples are illustrative in nature and are in no way intended to be limiting.
Example 1
[0056] Treatment of rheumatoid arthritis using Collagen Induced Arthritis as a model Collagen-induced arthritis studies. CIA in DBA/1 mice was induced by injecting DBA/1 mice with bovine type Il collagen (CII) emulsified in CFA1 followed by boosting 21 days later with CII emulsified in incomplete Freund's adjuvant (IFA). Technical Adenosine 2B receptor antagonist (Compound 1) was suspended in warm PEG 400 at a concentration of 60 mg/mL and diluted 1 in 10 in saline to form an injectable suspension. 30 mg/kg was delivered by i.p. injection once daily, starting following the development of clinical arthritis in treatment experiments. Animals were monitored daily following boost of arthritis, following the emergence of clear signs of disease observed on two consecutive days, animals were allocated randomly to treatment groups. Signs monitored included weight loss, paw thickness, and observed clinical score. Scoring is according to the presence of inflamed joints: 1 point for an inflamed digit, 1 point for a inflamed metatarsus, and 1 point for an inflamed joint above the metatarsus.
[0057] Mice treated with Adenosine 2B receptor antagonists displayed significant reductions in the severity of CIA based on reduced paw swelling, erythema and joint rigidity as assessed by the mean visual arthritis score, as shown in FIG. 3 . Of particular clinical importance in these data is the fact that the adenosine 2B receptor antagonist was able to reduce an existing inflammation to a normal state. This is in contrast to substances such as methotrexate that function only in prophylaxis.
Example 2
Method of Treating Multiple Sclerosis, the Effect of Adenosine 2B Receptor Antagonists in EAE
[0058] Adenosine 2B receptor antagonist compound 1 was tested for its ability to prevent and treat experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). EAE was induced in C57B/6 mice by subcutaneous immunization with 100 ug/mouse myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 emulsified in compete Freund's adjuvant (CFA) containing 2 mg/ml heat-killed mycobacterium tuberculosis H37Ra (Hooke Laboratories). As part of the induction protocol, mice were also injected intraperitoneally on the day of immunization and 48 hours later with 0.1 ml of 4 [mu]g/mL Bordetella pertusis toxin. Severity of EAE was determined daily based on a standard scoring system: 1, tail weakness or paralysis; 2, hind leg weakness; 3, hind limb paralysis; 4, forelimb weakness; and 5, moribund animals or death. Mice treated with 15 mg/kg Adenosine 2B receptor antagonists once daily demonstrated a delay in the onset of EAE compared to the vehicle control mice.
[0059] These data demonstrate that the Adenosine 2B receptor antagonists are also efficacious in treating a rodent model of multiple sclerosis.
Example 3
Method of Preparing an Injectable Formulation of an Adenosine 2B Receptor Antagonist
[0060] Adenosine 2B receptor antagonist compound 1 (30 mg) was suspended in 1 mL of warm (50 C) propylene glycol and vigourously ground using either a mortar (prewarmed) or a bead mill The resulting homogenate was further mixed with 1 mL of saline containing 1 w/V Tween 80 and vigorously mixed. The resulting suspension was then diluted to 10 mL in saline.
Example 4
Method of Preparing an Injectable Formulation of an Adenosine 2B Receptor Antagonist
[0061] Polylactide co-glycolide was dissolved in N-methyl pyrollidone triacetin to a concentration of 15% W/V according to Madhu et al, 2009. Adenosine 2B receptor antagonist compound 1 (100 mg) was suspended in 1 mL of warm (60 C) polylactideglycolide and homogenised using a bead mill The preparation is tested for its ability to prevent and treat disease as in the earlier examples.
Example 5
Pharmacokinetics of Compound 1
[0062] Adenosine 2B receptor antagonist compound 1 was prepared in either the 1% methyl cellulose in water, 0.2% Tween 80 at 5 mg/ml, or in mouse serum 0.8 mg/mL. The cellulose formulation was administered to C57BLK6 mice orally. The serum suspension/solution was administered intravenously. At various times after administration, small samples of blood ca. 20 μL were taken and analysed for compound 1. The results are recorded in FIG. 5 . These data show that compound 1 is not orally available, but is has a terminal half life in the range of 1 to 2 h after i.v. application.
[0063] While a number of exemplary aspects and embodiments have been discussed above, those of skill in the art will recognize certain modifications, permutations, additions and sub-combinations thereof. It is therefore intended that the following appended claims and claims hereafter introduced are interpreted to include all such modifications, permutations, additions and sub-combinations as are within their true spirit and scope.
CITED NON-PATENT DOCUMENTS
[0064] Bormann et al., J. Med. Chem. 2009, 52, 3994-4006
[0065] Yan et al., J. Med. Chem. 2006, 49, 4384 4391
[0066] Yan and Müller J. Med. Chem. 2004, 47, 1031 1043
[0067] Hayella et al., J. Med. Chem. 2002, 45, 1500 1510
[0068] Madhu et al., International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 1 Supp. 1, November-December 2009 | 1a
|
BACKGROUND OF THE INVENTION
Carotenoids such as carotene, lycopene, bixin, zeaxanthin, cryptoxanthin, lutein, canthaxanthin, β-apo-8'-carotenal, β-apo-12'-carotenal and esters of hydroxy- or carboxy-containing members of this group have attained considerable importance as coloring agents. This importance has increased due to possible governmental regulations withdrawing or limiting the use of certain previously certified coloring agents.
Carotenoids are yellow to red pigments either identical with or related to pigments occurring in the plant and animal kingdom. Because of this relationship to naturally occurring pigments, carotenoids possess considerable interest as replacements for the synthetic coloring agents for use as coloring materials, e.g., for foodstuffs and pharmaceutical or cosmetic properties. In addition, the carotenoids are used in animal feedstuffs to provide, for example, enhanced egg yolk or skin pigmentation as well as a source of vitamin A activity.
Carotenoids are substances which are insoluble in water and which have relatively high melting points. Moreover, carotenoids are substances which are very sensitive to oxidation. These characteristics militate against direct employment of the crystalline materials for coloration of aqueous foodstuffs or feedstuffs or for use as a source of vitamin A since in this form, the materials are poorly absorbed or give poor coloring effects. The above-mentioned characteristics of carotenoids are especially disadvantageous in the coloring of aqueous media; since, as a result of the water-insolubility of carotenoids, it is quite difficult to obtain a homogeneous or sufficiently intense color effect. Hence, the water insolubility of the carotenoids prevents their direct use as coloring agents for coloring foodstuffs having an aqueous base such as fruit juices, mineral water with fruit juices or with fruit juice flavors, ice-cream, etc. and dry products which are to be added to water in their original form or first prepared with water prior to use such as, for example, pudding powders, soup powders, powdered eggs, tomato concentrates and dry beverage bases such as lemonade powder.
SUMMARY OF THE INVENTION
This invention relates to carotenoid powder compositions which are dispersible in aqueous solutions to form optically clear aqueous compositions and which color these aqueous solutions to a desired uniform color. The carotenoid compositions can be prepared by forming a solution of a carotenoid in a volatile organic carotenoid solvent and emulsifying this solution with an aqueous solution containing sodium lauryl sulfate (SLS) using high speed mixing with high shear. The volatile solvent is then removed from the resulting emulsion by heating the emulsion while maintaining the high speed mixing with high shear until complete removal of the volatile solvent occurs. This emulsion can be used as is or it can be subsequently dried to yield carotenoid-containing powder compositons. For example, water-dispersible powders are formed by spray drying while beadlets suitable for use in animal feedstuffs are prepared by spraying droplets of the emulsion into collecting powders, e.g. starch.
DETAILED DESCRIPTION OF THE INVENTION
The carotenoids which can be used in the practice of this invention are the known natural or synthetic available representatives of this class of compounds useful as coloring agents, e.g. carotene, lycopene, bixin, zeaxanthin, cryptoxanthin, lutein, canthaxanthin, β-apo-8'-carotenal, β-apo-12'-carotenal, β-apo-8'-carotenoic acid, and esters of hydroxy- or carboxy-containing members of this group, such as lower alkyl esters and, preferably, methyl and ethyl esters. The above carotenoids can be employed singly or in admixtures, depending on the color desired. Especially preferred is canthaxanthin which either can be obtained from natural sources or prepared synthetically.
Water-dispersible powders containing from 2.5 to 15% by weight of canthaxanthin can be prepared by the process of this invention. The clarity of aqueous compositions containing these powders dispersed therein is excellent. These aqueous canthaxanthin compositions are red in color, optically clear and have marked coloring ability which is useful for the coloring of products where optical clarity is important, i.e., fruit juices, syrups, confections and the like.
Beadlets containing 1% zeaxanthin, prepared by the process of this invention, when fed to hens cause marked improvement in egg yolk pigmentation as compared to egg yolk pigmentation using a zeaxanthin of large particle size.
The quantity of sodium lauryl sulfate which is used in the emulsification process to provide optimum emulsification of the ingredients of the oil phase may vary from about 1 percent to about 6 percent by weight based on the weight of the powder composition. Higher amounts of sodium lauryl sulfate may be used without deleterious effects on the final powders but no particular advantage is achieved by the use of such higher amounts.
The carotenoid powder compositions of this invention contain, in addition to the carotenoid and sodium lauryl sulfate, from about 75% by weight to about 90 % by weight, based on the weight of the powder composition, of an edible, pharmaceutically acceptable, water-soluble carrier composition which comprises a carbohydrate, e.g., sucrose, fructose, lactose, invert sugar and the like, and a water-soluble protective colloid, e.g. gelatin, modified food starch and the like, wherein the weight ratio of water-soluble protective colloid to carbohydrate ranges from about 1/1 to about 2/1. The modified food starches are the products of the treatment of any of several grain- or root-based native starches (e.g., corn, sorghum, wheat, potato, tapioca, sago, etc.) with small amounts of certain chemical agents which modify the physical characteristics of the native starches to produce desirable properties. A preferred modified food starch for use in compositions of this invention is a starch ester--starch sodium octenyl succinate.
In addition, the carotenoid powder compositions contain from about 0.01% by weight, based on the weight of the powder composition, of an edible, pharmaceutically acceptable preservative, e.g. one or more of the following: benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, methyl p-hydroxybenzoate (methylparaben), propyl p-hydroxybenzoate (propylparaben) and the like.
From about 0.05% by weight to about 0.3% by weight, based on the weight of the carotenoid powder composition, of an edible, pharmaceutically acceptable stabilizing agent, e.g. ethylene diamine tetraacetic acid (EDTA) can be used to stabilize the emulsion against the effects of trace metals.
The compositions of this invention also include from about 1% by weight to about 10% by weight, based on the weight of the carotenoid powder composition preferably from about 6% to about 7% by weight, of an edible, pharmaceutically acceptable antioxidant comprising one or more of such conventional substances as, for example, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ascorbic acid and the tocoperhols. Preferred is a blend of butylated hydroxytoluene and dl-α-tocopherol used at an optimal level of about 1 part of an equal quantity of each antioxidant for 1 to 2 parts of the carotenoid.
The pH of the aqueous phase precursor of the emulsion is a critical factor since both sodium lauryl sulfate and the resulting emulsion are unstable at a pH of 7.0 or lower. In addition, spray dried carotenoid powders prepared from emulsions having these pH values of 7.0 or lower are also unstable and adversely affect the clarity of solutions prepared therefrom. Preferably, the aqueous phase emulsion precursor should be within the pH range of 10-11 with a pH of 10.4 ± 0.2 optimal. Using this aqueous phase pH range, the resulting emulsion pH after removal of chloroform and prior to spray drying can vary from about 9 to about 10. The carotenoid powders prepared from such emulsions have improved stability and form, when dispersed in aqueous food preparations or solutions, products having the optical clarity of the original uncolored products.
The modified emulsification technique employed in this invention involves the use of high-speed mixing (i.e. from about 3,000 to 12,000 rpm) coupled with a high shear force. The high shear force is essential to obtaining a small particle size for the carotenoid in the dispersed phase of the emulsion and a consequent small particle size for the carotenoid in the resulting dried carotenoid-containing powder compositions.
High shear force relates to the applied forces which cause two contiguous parts of a body to slide relative to each other in a direction parallel to their plane of contact. The effective shear force is dependent on the solids content and the viscosity of the medium being mixed, the speed of mixing and the geometry of the mixer and the mixing vessel. A type of mixer which achieves this dual function of high speed mixing and high shear force is, for example, one employing a single shaft mixer with two separated, serrated circular horizonal shear plates set between two inverted feed cones on a single shaft. Using a mixer of this type, as, for example, a Lee Turbon mixer, both high speed mixing and high shear force are rapidly achieved.
What is important in achieving the water-dispersible carotenoid powders of this invention is the obtention of a shear force high enough to keep the particle size range of the droplets of the dispersed phase below 0.1 micron in diameter. Thus, critical to the practice of this invention is the maintenance of both high speed mixing and high shear force during the removal of the volatile solvent.
The combination of both the modified emulsification technique and the use of controlled pH in conjunction with the sodium lauryl sulfate emulsifier results in a significant decrease in the particle size of the carotenoid in the dispersed oil-phase of the emulsion to below 0.1 micron and a particle size range of less than 0.1 micron for the carotenoid in the resulting dried carotenoid-containing powder compositions. This carotenoid particle size is the major factor in obtaining the optically clear, aqueous compositions upon dispersal of the carotenoid-containing powder compositions in aqueous solutions and in providing enhanced bioavailability of the carotenoid particles when used in animal feedstuffs. The particle size of the dry carotenoid-containing powder compositions is, thus, not a critical factor per se.
Thus, water-dispersible powders containing from about 2.5 to about 15% carotenoid can be prepared when sodium lauryl sulfate is used as the emulsifying agent. Clarity of the aqueous compositons prepared from these carotenoid powder compositions containing the various percentages of the carotenoids is excellent.
The volatile organic solvents suitable for use herein are those which are known solvents for the carotenoids. Such solvents include halogenated aliphatic hydrocarbons, preferably polyhalogenated methane, e.g. chloroform, carbon tetrachloride and methylene chloride. However, other volatile solvents can also be used, such as benzene or carbon disulfide. Chloroform is the preferred solvent.
In a preferred process of this invention, the aqueous phase emulsion precursor containing sodium lauryl sulfate emulsifier, a water-soluble carrier composition (gelatin, modified food starch and a sugar), preservatives (ascorbic acid, sorbic acid and sodium benzoate) and a stabilizing agent (EDTA) is prepared and the pH is adjusted to between 10-11 with a base, e.g. sodium hydroxide.
The oil phase emulsion precursor is prepared by dissolving the carotenoid and antioxidants, i.e., BHT and dl-α-tocopherol in chloroform or other suitable organic solvents. Such other suitable solvents are, as noted earlier, halogenated aliphatic hydrocarbons, benzene or carbon disulfide.
The carotenoid-containing oil phase is added to the aqueous phase using both high speed mixing and a high shear force. The high speed mixing and high shear force are continued after emulsification until all the volatile organic solvent has been removed by evaporation.
The resulting emulsion is amenable to spray drying operations using a standard spray drying tower, to drying in beadlet form by double dispersion techniques or by spraying droplets into a collecting powder, to casting of the emulsion followed by drying and comminuting, to drum drying and to lyophilization techniques.
Using the above formulations, water-dispersible carotenoid-containing powder compositions containing from 2 to about 15 % by weight of the carotenoid can be prepared. The carotenoid constituent of such powder compositions have a particle size of less than 0.1 micron. The ability to form carotenoid-containing powder compositions having such a range of carotenoid concentration means, for example that quite a broad color range can be obtained in solution depending on the concentration of carotenoid in the powder.
The following examples illustrate the invention.
EXAMPLE 1
2.5% Canthaxanthin Spray-Dried Powder
330 Grams of gelatin, 279 grams of sucrose, 0.75 grams of sorbic acid and 1.50 grams of sodium benzoate are added to 330 grams of distilled water. The gelatin mixture is solubilized by hydrating overnight at about 50° C.
The following solution is prepared:
______________________________________Ascorbic acid 2.25 gramsEDTA 0.75 gramsSodium laurylsulfate 12.0 gramsDistilled water 105.0 grams______________________________________
This solution is then added to the gelatin-sugar solution to form the aqueous phase of the emulsion. The pH of this solution is adjusted to 10.4 ± 0.2 using a 20% w/w sodium hydroxide solution.
The oil phase comprising:
______________________________________Canthaxanthin 23.3 gramsButylated hydroxy-toluene (BHT) 22.5 gramsdl-α-tocopherol 22.5 gramsChloroform 525 grams,______________________________________
is prepared by first dissolving the BHT in dl-α-tocopherol by heating the mixture to 80° C. The solution is cooled to 55° C. and then mixed with the chloroform until a clear solution results. Canthaxanthin is added to this solution under nitrogen atmosphere and dissolved.
Both the aqueous and oil phases are heated to about 50°-55° C. The oil phase is added slowly to the aqueous phase using both a high rate of mixing and a high shear force mixer. After the addition is completed, the emulsion temperature is maintained at 55° C. while high speed shear mixing is continued for 15 minutes. The temperature is gradually raised and mixing is continued until all the chloroform has been evaporated. This evaporation is usually completed when the temperature of the emulsion reaches about 75° C.
During the evaporation procedure, distilled water is added to the emulsion to maintain a suitable viscosity.
After all the chloroform has been removed sufficient distilled water is added to and thoroughly admixed with the emulsion to achieve an emulsion solids content and viscosity suitable for spray-drying.
The emulsion is spray-dried under standard spray drying conditions using a spray drying tower.
The carotenoid constituent of the resulting powder composition has a particle size which is below 0.1 micron.
The spray-dried powder is free-flowing and dissolves in water to form very clear dispersions. When used in preparations intended to be reconstituted as clear fruit flavored gelatin-type desserts and in flavored aqueous beverages, the resulting products have excellent clarity and color.
Stability, i.e. the retention of the carotenoid in the water-dispersible powder, was measured both at room temperature and at 45° C. Results are tabulated below.
______________________________________Temperature, Time, %° C. Months Container Retention______________________________________Room 3 Closed 10045 1 Open 9745 1 Closed 10045 2 Open 9745 2 Closed 10045 3 Open 9445 3 Closed 100______________________________________
EXAMPLE 2
The following spray-dried water-dispersible carotenoid-containing powders were formed from emulsions prepared as described in Example 1 and containing 5.0, 7.5 and 10%, of canthaxanthin:
__________________________________________________________________________ 5.0% 7.5% 10%__________________________________________________________________________Canthaxanthin 46.6 grams 70 grams 93 gramsBHT 22.5 grams 22.5 grams 22.5 gramsdl-α-tocopherol 22.5 grams 22.5 grams 22.5 gramsSucrose 279 grams 279 grams 279 gramsGelatin 330 grams 330 grams 330 gramsAscorbic acid 2.25 grams 2.25 grams 2.25 gramsSodium benzoate 1.5 grams 1.5 grams 1.5 gramsSorbic acid 0.75 grams 0.75 grams 0.75 gramsEDTA 0.75 grams 0.75 grams 0.75 gramsSodium lauryl sulfate 22 grams 30 grams 40 gramsSodium hydroxide (20%w/w solution) to adjustpH of aqueous phase to 10.35 10.4 10.5Final pH of emulsion 9.65 9.4 9.4Spray dried powder,solution clarity Very Clear Clear ClearGelatin dessert test* Very Clear Clear ClearLiquid beverage test* Very Clear Clear Clear with Sl. Opalescence__________________________________________________________________________ *Reconstituted
Stability data are reported below:
______________________________________ Temperature, Time, %Sample ° C. Months Container Retention______________________________________5% Room 3 Closed 1005% 45 1 Open 1025% 45 1 Closed 1035% 45 2 Open 1005% 45 2 Closed 1035% 45 3 Open 945% 45 3 Closed 100 7.5% 45 1 Open 100 7.5% 45 1 Closed 10010% 45 1 Open 9810% 45 1 Closed 94______________________________________
EXAMPLE 3
A water-dispersible spray-dried β-apo-8'-carotenal powder containing 5% β-apo-8'-carotenal and having the composition as listed below was prepared by spray-drying an emulsion prepared as described in Example 1.
______________________________________Apocartenal 31.0 gramsBHT 15.0 gramsdl-α-tocopherol 15.0 gramsGelatin 135.0 gramsModified Food Starch 135.0 gramsSucrose 135.0 gramsAscorbic acid 1.5 gramsSorbic acid 0.5 gramsSodium benzoate 1.0 gramsEDTA 0.5 gramsSodium lauryl sulfate 15.0 gramsSodium hydroxide q.s. to aqueous(20% w/w/Solution) phase pH of 10.4______________________________________
EXAMPLE 4
Beadlets containing 1% zeaxanthin and having the composition listed below were prepared from an emulsion prepared as described in Example 1.
______________________________________Zeaxanthin 17.1 gramsBHT 22.5 gramsdl-α-tocopherol 22.5 gramsSucrose 279 gramsGelatin 330 gramsAscorbic acid 2.25 gramsSodium benzoate 1.5 gramsSorbic acid 0.75 gramsEDTA 0.75 gramsSodium lauryl sulfate 7.4 gramsSodium hydroxide q.s. to pH 10.4(20% w/w solution)______________________________________
An apparatus provided with a revolving spray head and a counter-rotating drum was used to prepare the beadlets. In this apparatus the emulsion is forced through tiny orifices of the revolving spray head. The resulting droplets contact the powdery starch material which is suspended in air in the rotating drum. The drum and the spray head are rotated in opposite directions so that the suspension of the starchy powder in air is swirled in a direction of rotation opposite to the entering droplets of the emulsion spray.
The emulsion obtained was loaded into the revolving spray head. The drum was loaded with 2 kg. of "Dry-Flo", previously dried to a moisture content of about 3 percent. After all the emulsion had been collected in the "Dry-Flo", the mixture of starch and beadlets was allowed to stand for about an hour and then screened through a 150 mesh screen. The carotenoid-containing particles retained upon the screen were collected, spread out on drying trays and then dried in an oven.
The dry, free-flowing beadlets are suitable for use in animal feedstuff. When fed to hens, the small particle size of the zeaxanthin contained therein enhanced the yolk pigmenting effect. | 1a
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RELATED APPLICATIONS
This application is a divisional application of U.S. patent application Ser. No. 10/864,610 filed Jun. 9, 2004, now abandoned, which is a continuation of U.S. patent application Ser. No. 09/928,007 filed Aug. 10, 2001, now U.S. Pat. No. 6,813,868, which claims priority under 35 U.S.C. § 119 to U.S. Provisional Patent Application Ser. No. 60/224,136, filed Aug. 10, 2000. Each of the above-identified patent applications is hereby incorporated by reference in its entirety.
FIELD OF THE INVENTION
The present invention generally relates to the handling of syringes, and is particularly apt for use in automated syringe handling operations, such as syringe filling, labeling and capping operations.
BACKGROUND OF THE INVENTION
Each year countless syringes are used throughout the world by the healthcare industry for the administration of liquid medications to humans and animals with hypodermic needles or infusion catheters, as well as for delivery of oral and topical medications. Some medications provided by pharmaceutical manufacturers are prepared, stored, and shipped as powders, crystals, or some other solid form due to the lack of stability in solution. These medications are then reconstituted with liquid, such as water or some other suitable liquid solvent. For one or several administrations of a medication, the manual filling of the syringes with reconstituted liquid medication is a small chore. However, larger health care institutions often administer medications in syringes to hundreds of patients per day, thus requiring the rather large chore of filling hundreds of syringes with medications and labeling each filled syringe to show the contents, strength, and fill dates, usually under the direction of a qualified pharmacist. Healthcare providers have found that preparing (e.g. filling and labeling) the quantities of syringes needed has many efficiencies and other advantages when it is done in batches.
In the later regard, batch preparation may be particularly preferred for syringes carrying medications that are not stable in liquid form and are therefore frozen after preparation to maintain acceptable stability. Further, the task of maintaining sterility in the transfer of liquid from containers provided by pharmaceutical manufacturers to pre-sterilized syringes may be enhanced by batch completion in controlled environments. Also, safety and overall reliability may improve when syringes are prepared in batches by pharmacy personnel or others who are dedicated to and well-trained for the task.
Currently, syringe preparation typically entails a number of separate operations with individual syringe handling. For example, systems used today fill syringes with dispensing pumps that are capable of delivering exact quantities of fluids but that require individual handling of each syringe. Peristaltic pumps that can be accurately calibrated, such as that described in U.S. Pat. No. 5,024,347, are often used. In such arrangements, the syringe caps are packaged so that sterility can be maintained in the capping procedure. The caps are located in trays where each cap is positioned so that the person doing the filling can manually place the tip of the syringe into the cap without touching or holding the cap. Labeling of the syringes has been done using a label dispenser similar to those used for applying pricing labels to grocery or other similar products.
With smaller syringes there are sometimes problems with getting sufficient label information on the syringe without covering over the syringe graduations or blocking the view of the medication. To overcome this, the labels are often applied by hand with the label wrapped around the syringe with most of the label extending from the syringe to form a flag.
Silicone lubricants are used in syringe manufacturing to provide lubrication for lowering the frictional force in movement of the syringe plunger. These silicone lubricants have a characteristic of migrating over all surfaces. Often, this migration causes difficulties in getting pressure sensitive labels to stay in place. This has caused users to use a clear plastic tape to wrap completely around the syringe and the label.
Efforts to automate hospital or clinic-based syringe preparation have been made, but most systems have automated only portions of the process and still require human intervention during critical stages of the process. In one such system, caps are pre-positioned in a cartridge holder. The syringes are also provided in a cartridge where each syringe is oriented. The machine to perform the filling and capping function requires an operator to load the cartridges of caps and syringes. The filling is done with a calibrated peristaltic pump. The machine fills each syringe and places a cap. The labeling is done separately by a labeling machine that is commercially available.
SUMMARY OF THE INVENTION
In view of the foregoing, a broad objective of the present invention is to provide a method, system and apparatus for enhanced syringe handling. A closely related objective is to facilitate automated syringe handling for various operations, such as syringe filling, labeling and capping.
Another objective of the present invention is to provide a syringe handling approach that facilitates the maintenance of sterility.
An additional objective of the present invention is to provide an improved syringe filling and capping approach.
Yet another objective of the present invention is to provide an improved approach for syringe labeling.
In addressing one or more of the above objectives, the present inventors have recognized that significant benefits may be realized by interconnecting multiple syringe bodies to facilitate handling of the same. More particularly, such interconnection allows multiple syringes to be commonly oriented for packaging and/or automated preparation operations.
In one aspect of the invention, an apparatus is provided that includes a plurality of syringe bodies, e.g. each comprising a barrel, and a belt fixedly connected to (e.g. adhered to or shrink-wrapped upon) each of the syringe bodies. Each syringe body may further include a plunger at least partially disposed in an open end of the barrel and a removable cap disposed on a dispensing end of the barrel. Of importance, the belt is provided to both interconnect the plurality of syringe bodies and position the same in a predetermined orientation.
In the later regard, and by way of primary example, the dispensing ends of the syringe body barrels may be oriented to extend in a common direction. In addition, the barrels of adjacent ones of the plurality of syringe bodies may be disposed in side-by-side, series relation. Further, the belt may be provided to define a predetermined spacing between adjacent ones of the syringe bodies, such spacing preferably being equidistance throughout a given assembly to accommodate ready positioning in holders adapted for automated operations, as will be further described.
To facilitate handling, production and packaging, the belt may be of a pliable construction. Further, the belt may be advantageously constructed for ready separation in automated labeling operations, as described hereinbelow. In this regard, it is advantageous for the belt to be of a predetermined length between adjacent ones of the plurality of syringe bodies, such predetermined length defining belt segments that are sufficient for the placement of contents information thereupon (e.g. via the application of a label thereto or direct printing thereupon).
Preferably, the belt is interconnected to each of the syringe body barrels. In this regard, the barrels maybe of a common length, wherein the belt is fixedly connected to the barrels along a common portion of the length of each. In addition, the belt may advantageously be of a width that exceeds a majority of a length of each of the barrels. Further, the belt may comprise a first portion that extends between adjacent ones of the plurality of syringe bodies, and a second portion that extends about at least a portion of each of the syringe body barrels. Preferably, the second portion adhesively engages the syringe body barrels and may be substantially transparent to facilitate observation of the volumetric contents within and markings on the syringe barrels.
In one approach, the belt may be defined by opposing layers adjoined in face-to-face relation between adjacent ones of the plurality of syringe bodies and wrapped about opposing sides of the barrels of each of the syringe bodies. At least one of the opposing layers may be substantially transparent to allow for visual determination of volumetric contents and amount. As may be appreciated, a clear pliable plastic material may be utilized for easy and low-cost construction of the belt.
As noted, each syringe body of the inventive apparatus may typically include a plunger and cap. In this regard, the barrel, inserted plunger and applied cap may preferably be assembled under low bioburden environment conditions, such as a class 100,000 or lower clean room. Further, and of importance, the plurality of interconnected syringe bodies should preferably be packaged (e.g. in a shipment container) and thereafter sterilized (e.g. via gamma radiation) to achieve terminal sterilization.
To facilitate the maintenance of a clean internal volume, yet allow for syringe filling, the caps utilized on syringe bodies should preferably engage dispensing ends of the barrels in a mating fashion. By way of primary example, each cap may include an inner member matingly positionable within or about a fluid port of the barrel dispensing end, and an outer member matingly positionable about an outer flange of the barrel dispensing end.
In another aspect of the present invention, a method is provided for producing an assembly of syringe bodies. The inventive method includes the steps of positioning a plurality of syringe bodies in a predetermined relative orientation, and disposing opposing layers of material about opposing sides of the syringe bodies and in face-to-face relation between adjacent ones of the syringe bodies. As may be appreciated, the inventive method defines an assembly comprising a belt that interconnects and orients a plurality of syringe bodies to facilitate handling as previously described.
In an additional more general aspect of the present invention, an overall method and apparatus for handling a plurality of syringe bodies is provided. Such method comprises the steps of positioning a plurality of syringe bodies in a predetermined orientation, and interconnecting a belt to each of the plurality of syringe bodies in said predetermined orientation. The method may further comprise the step of positioning the plurality of syringe bodies into a plurality of holders for at least one production operation. To facilitate such positioning, the belt may advantageously define a predetermined spacing between adjacent ones of the syringe bodies, wherein the holders are separated by a distance that corresponds with the predetermined spacing between adjacent ones of the syringe bodies. Further, where the belt is constructed of a pliable material, the method may include the step of successively suspending, or hanging, adjacent ones of the syringe bodies so as to position the same for receipt by a holder.
Numerous automated production operations may be facilitated by the disclosed handling method, wherein the holders may be moved along a predetermined path during such operations. Of particular note, one or all of the following production operations may be automated utilizing the invention:
filling the plurality of syringe bodies with a predetermined fluid (e.g. reconstituted medication); uncapping and/or recapping the plurality of syringe bodies in conjunction with filling; and labeling the plurality of the syringe bodies to indicate the contents thereof.
Each of these production operations will be further described hereinbelow.
In relation to the inventive apparatus for handling a plurality of syringe bodies, it should be appreciated that it is particularly advantageous for the syringe bodies to be interconnected in series by a belt in a predetermined orientation and with a predetermined spacing therebetween. In the latter regard, the inventive apparatus may comprise a plurality of holders for holding the of syringe bodies, such holders being separated by a distance corresponding with the predetermined spacing.
The apparatus may further include a drive for moving the holders along a predetermined path. In this regard, the holders may be oriented so as to locate adjacent ones of the plurality of syringe bodies in substantial parallel relation, wherein the dispensing and opposing ends of the syringe bodies extend outwardly from and in a common orientation relative to the predetermined path. In turn, at least one workstation may be provided having a support member disposed to move towards and away from the dispensing ends of the syringe bodies. By way of primary example, such workstations may be provided for automated filling and/or automated cap removal/replacement, free from manual handling requirements.
Further, one or more workstations may be provided with a support member disposed to move towards and away from an outward facing surface of the belt at locations between adjacent ones of the syringe bodies. Such workstations may provide for automated separation of the belt between adjacent ones of the syringe bodies and/or automated printing of contents information on belt segments located between adjacent ones of the syringe bodies.
In a further aspect of the present invention a method and apparatus is provided for filling syringe bodies. In the inventive method, the filling of each syringe body entails the step of holding the syringe body in at least one holder and the further steps of removing a cap from, filling and replacing the cap back on the syringe body during the holding step. As may be appreciated, completion of the removing, filling and replacing steps while the syringe body is being held by at least one holder yields a significant handling advantage in that manual manipulation of a syringe body may be avoided.
The filling method may further include, for each syringe body, the steps of placing the cap on the dispensing end of the syringe body prior to the holding step, and packaging the syringe body in a container (e.g. for bulk shipment with other syringe bodies) and unpackaging the syringe body from the container after the placing step and prior to the holding step. Such sequencing allows for cap placement and packaging in a production location, followed by shipment to a remote location for unpackaging and completion of the filling method. Further in this regard, the method may include the important step of sterilizing syringe bodies after packaging (e.g. at the production facility prior to shipment).
Additionally, the method may comprise the step of interconnecting a belt to the plurality of syringe bodies in a predetermined orientation. Preferably, such interconnection occurs prior to the packaging and sterilization steps.
In conjunction with the removal and replacement of each of the caps, such steps may include, for each of the syringe bodies, the further steps of retainably engaging the cap in a retainer and moving at least one of the retainer and the holder to affect relative movement between the cap and the dispensing end of the syringe body. Further in this regard, such retainable engagement may be completed by moving the holder for a syringe along a predetermined path so as to insert the cap in the retainer.
In conjunction with noted filling step, the method may further provide for the interconnection of a fluid supply member with a dispensing end of the syringe body and for the flow of fluid into the syringe body through the interconnected fluid supply member. In one embodiment, such steps as well as the cap removal and cap replacement steps, may be completed with the syringe body held at a single location. In such embodiment the retainer, and fluid supply member may be interconnected for tandem forward/rearward and sideways movement. In another embodiment, the cap removal and cap replacement steps may be completed with a syringe body held at a first location, while the filling step may be completed at a second location. Such an approach only requires forward/rearward tandem movement of the retainer and fluid supply member.
Of note, the inventive filling method and apparatus may also provide for sensing of the position of a syringe body plunger during fluid filling. In this regard, optical sensing, pressure sensing or the like may be utilized, wherein a sense signal may be provided that reflects the fluid volume within a syringe as it is filled. In turn, the sense signal may be employed to terminate the flow of fluid at a predetermined amount. In another approach, a predetermined amount of fluid may be drawn into each syringe body via controlled retraction of the associated plunger.
As may be appreciated, the inventive apparatus for filling a plurality of syringe bodies may include at least one, and preferably a plurality of holders for holding a plurality of syringe bodies in a predetermined orientation. Further, the apparatus may include a retainer for retainably engaging the cap of a syringe body, wherein the cap may be selectively removed and replaced by the retainer. Additionally, the apparatus may include a fluid supply member disposed for selective fluid interconnection with a dispensing end of the syringe body.
To facilitate automated operations, the inventive apparatus may further comprise a driven support member for moving the holder(s) along a predetermined path. Additionally, one or more driven support members may be provided for moving the retainer towards/away from the dispensing end(s) of each syringe body and/or for moving the fluid supply member towards and away from the dispensing end(s) of each syringe body.
In yet additional aspect of the present invention, an inventive method and apparatus are provided for labeling a plurality of syringe bodies. The inventive method includes the steps of interconnecting a belt to a plurality of syringe bodies in a predetermined orientation, and placing contents-related information on belt segments interconnected to each of the syringe bodies. The method further includes the step of separating the belt between each of said plurality of syringe bodies to define an interconnected flap (e.g. corresponding with the belt segments) on each of the syringe bodies.
In conjunction with the inventive labeling method, the separating step may provide for severing, or cutting the belt between adjacent ones of the plurality of syringe bodies. Alternatively, the separating step may entail relative displacement of adjacent ones of the syringe bodies so as to achieve separation along perforation lines or the like.
With respect to the step of placing contents-related information on each given belt segment, such step may entail the printing of information on a label and fixation of such label to a belt segment. Alternatively, this step may simply be completed via printing of the contents-related information directly on a given belt segment.
In either case, the contents-related information may comprise one or more of the following types of information:
information regarding the fluid contained in a given syringe body; information regarding fluid fill date for each given syringe body; information regarding the volumetric fluid content of each given syringe body; information comprising a product code corresponding with the contents of a given syringe body; information regarding the lot or batch number corresponding with each given syringe body; and information regarding storage and/or handling instructions for each given syringe body.
As may be appreciated, such information may be provided in an alphanumeric or coded fashion. In the later regard, at least some of the information may be embodied in a bar code format to allow for optical scanning.
In further relation to the inventive labeling method, the interconnected syringe bodies may be packaged in a container, sterilized and unpackaged from the container prior to the separating and contents-information placement steps. As may be appreciated, such sequencing provides for the interconnection, packaging and sterilization of syringe bodies at a production location, and the unpackaging, separation and labeling of the syringe bodies at another location (e.g. at a location where the syringe bodies are filled with liquid medication).
The inventive labeling apparatus is particularly adapted for use with a plurality of syringe bodies interconnected by belt, as described above, and may include a plurality of holders and a labeling member for placing contents-related information on belt segments extending between the syringe bodies. The apparatus may further include a separation member for separating the belt between adjacent ones of the plurality of syringe bodies, wherein a different belt segment in the form of a flap is interconnected with each one of the plurality of syringe bodies. To facilitate operation of the separation member and labeling member, each of such members may be provided with driven support members that may be selectively actuated to such members towards and away from the belt segments.
As may be appreciated, various ones of the inventive aspects noted hereinabove may be combined to yield an inventive system for handling a plurality of syringe bodies, including a system that facilitates automated labeling and filling operations. The automated filling operations may further provide for automated cap removal and replacement.
These and other aspects, advantages, and novel features of the invention are set forth in part in the description that follows and will become apparent to those skilled in the art upon examination of the following description and figures or may be learned by practicing the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings, which are incorporated in and form a part of the specification, illustrate embodiments of the present invention, and together with the descriptions serve to explain the principles of the invention.
FIG. 1 is an isometric view of a labeled, filled, and capped syringe with a label substrate and label attached according to one embodiment of the present invention;
FIG. 2 is an isometric view of a plurality of sterile capped syringes mounted in a belt or band for automated labeling and/or cap removal, fluid filling, and cap replacement according to one embodiment of this invention;
FIG. 3 is a diagrammatic elevation view of an apparatus and process for mounting syringes in a tape band or belt according to one embodiment of this invention;
FIG. 4 is diagrammatic elevation view of an apparatus and process for mounting syringes in a tape band or belt according to another embodiment of this invention;
FIG. 5 is a diagrammatic elevation view of a labeling and filling apparatus of one embodiment of this invention;
FIGS. 6 a through 6 e comprise diagrammatic plan views of the syringe-filling station on the apparatus embodiment of FIG. 5 wherein a sequence of component positions are shown that correspond to and illustrate sequential steps of cap removal, fluid filling, and cap replacement operation.
FIGS. 7 a and 7 b comprise isometric assembly and exploded views, respectively, of a labeling and filling apparatus of the embodiment corresponding with FIGS. 5 and 6 a–e;
FIGS. 8 a – 8 d comprise isometric views of the syringe-filling station of the apparatus embodiment of FIG. 7 , wherein a sequence of component positions are shown that correspond with and illustrate the sequential steps of cap removal, fluid filling, and cap replacement operations.
FIG. 9 is a schematic elevation view of a labeling and filling apparatus according to another embodiment of this invention;
FIG. 10 is an isometric view of a syringe-filling station of the apparatus embodiment of FIG. 9 ; and
FIGS. 11 a – 11 h are flat, diagrammatic views of syringe handling operations at the filling-station of the apparatus embodiment of FIGS. 9 and 10 .
FIGS. 12 a – 12 c are isometric, end and cross-sectional views of a syringe cap employable in one embodiment of the syringe shown in FIG. 1 .
FIGS. 13 a – 13 c are isometric, end and cross-sectional views of a syringe cap employable in another embodiment of the syringe shown in FIG. 1 .
DETAILED DESCRIPTION OF THE INVENTION
A capped syringe S that has been labeled and filled according to one embodiment of this invention is shown in FIG. 1 . A cap C covers and protects the sterility of the dispensing luer tip (concealed from view in FIG. 1 by the cap C). Since the barrel B of the syringe S is full in FIG. 1 , the plunger P is extended longitudinally. A flap or substrate 10 for a label 12 is provided by two strips of adhesive tape 14 , 16 , both of which are wrapped around and adhered to respectively opposite sides of the barrel B and adhered to each other in face-to-face relation in extensions 18 , 20 of the adhesive tape 14 , 16 that extend in diametrically opposite directions from the barrel B. It is preferred, but not necessary, that at least one of the adhesive tapes 14 , 16 be transparent so that the graduation marks G that are on most conventional syringes as well as the plunger piston (not shown) in FIG. 1 ) can be seen through the adhesive tape.
In the embodiment shown in FIG. 1 , the label 12 is a printed sheet that has been adhered to the panel extension 20 of the substrate 10 . However, the label could also be provided in other ways according to this invention. For example, but not for limitation, the printed information could be printed directly on one or both of the adhesive tapes 14 , 16 . Such printing, if placed on a transparent tape 14 , 16 would preferably not be enough to mask the graduation marks G. Another option could be to make one of the tapes, such as tape 14 opaque, perhaps with label information on it, but make the other tape 16 transparent so as not to mask or hide the graduation marks G. For another possibility, a sheet label similar to label 12 could be sandwiched between the two adhesive tapes 14 , 16 .
As mentioned above, a significant feature of this invention is having a plurality of sterile, capped syringes S mounted in spaced apart relation to each other in a band or belt 30 , as shown in FIG. 2 , for handling the syringes S in automated preparation operations. For example, belt 30 may be employed for pulling the syringes S into and preferably at least partially through a labeling and/or filling apparatus and process, as will be described in more detail below. The band or belt 30 can be made with the two elongated adhesive tapes 14 , 16 that were described above and which can be cut to separate the syringes S into individual syringes S with the label substrate 10 as shown in FIG. 1 and as will be described in more detail below.
Before proceeding, reference is now made to FIGS. 12 a – 12 c and FIGS. 13 a – 13 c which illustrate alternate embodiments of caps C employable with syringes S of the type shown in FIGS. 1 and 2 . As shown, the caps C of the two embodiments each include a cylindrical outer member 500 for matingly engaging the outer flange provided at the dispensing end of the barrel B of the syringe S. In the FIG. 12 a – 12 c embodiment, a cylindrical inner member 502 is also provided for matingly receiving the fluid port provided at the dispensing end of barrel B of syringe S. In the case of the embodiment shown in FIGS. 13 a – 13 c a central pin-like inner member 504 is provided for mating insertion into the fluid port provided at the dispensing end of the barrel B of syringe S. Of further note, internal locating legs 506 are provided in the embodiment of FIG. 13 a – 13 c for retentively engaging the fluid port of barrel B. As may be appreciated, the embodiments of FIG. 12 a – 12 c and FIG. 13 a – 13 c both provide for isolation of the contents of syringe S.
There are many ways by which the plurality of syringes S can be mounted in the band or belt 30 shown in FIG. 2 , and this invention is not limited to any one of such ways of doing so. However, for purposes of example, but not for limitation, one method and apparatus for mounting multiple syringes S into a band or belt 30 is shown in FIG. 3 . As one tape strip, e.g., tape strip 16 , is unwound from a roll 32 , as indicated by arrows 34 , 36 , it is threaded around the periphery 38 of a syringe mounting wheel 40 , which rotates as indicated by arrow 42 . A pair of rims (only one rim 44 of the pair can be seen in the elevation view of FIG. 2 ) extend radially outward beyond each side of the periphery 38 , and each of the rims 44 has a plurality of notches 46 in equal, angularly spaced relation to each other around the periphery 38 . As the wheel 40 rotates, preferably capped, empty syringes S are placed serially into the notches 46 , as indicated by arrows 48 , where they contact the adhesive side of the tape strip 16 .
As the wheel 40 rotates, as indicated by the arrow 42 , it carries the syringes S in the notches 46 and in contact with the tape strip 16 to a position where the syringes S come into contact with the adhesive side of the other tape strip 14 , which is simultaneously being unwound from a roll 50 as indicated by arrows 52 , 54 , 56 . An idler wheel 58 positions the tape strip 14 in relation to the wheel 40 so that it contacts the syringes S mounted in the notches 46 . Therefore, the tapes strips 14 , 16 get adhered to diametrically opposite sides of the syringes S. In this regard, a contact plate 67 may also be provided to insure engagement between tape strip 14 and syringes.
As the syringes S, which are adhered to tape strips 14 , 16 emerge from the wheel 40 , they are captured by notches 60 in a press wheel 62 that rotates, as indicated by arrow 64 , to press the tape strips 14 , 16 to each other between the syringes S. Press wheel 62 may be provided for driven rotation, wherein such driven rotation effects rotation of the tape rolls 32 and 50 , as well as rotation of syringe mounting wheel 40 as the tape strips 14 , 16 are pulled around press wheel 62 with syringes S secured therebetween. A rotatable pressing block 63 is juxtaposed to the press wheel 62 so that the tape strips 14 , 16 run between the press wheel 62 and the rotatable pressing block 63 . The pressing block 63 may be configured to present a plurality of semicircular surfaces that are spaced to be in opposing relation to notches 60 . Thus, the press wheel 62 and the pressing block 63 cooperate to press and adhere the tape strips 14 , 16 tightly together and around the circumference of each syringe S. The pressing block 63 is preferably yieldably biased by a spring-loaded pivot arm 65 or some other bias system to press the pressing block 63 toward the press wheel 62 .
After disengaging from press wheel 62 , the belt 30 with the syringes S mounted therein are fed as indicated by arrow 66 into a bin or bag 68 . Alternatively, the belt 30 with syringes S could be fed directly into a labeling and/or filling apparatus, which will be described below.
In general, the syringes S are positioned in the band or belt 30 in a common orientation, i.e., with luers of all the syringes S on the same side of the band 30 . The notches 46 in the wheel 40 are spaced uniformly around the rim 44 , so the syringes S in the resulting band 30 are spaced equidistantly apart. The caps C can be placed on the syringes S either before, while, or after the syringes S are mounted in the band 30 . The band 30 of syringes S can then be fan folded or rolled and placed in the plastic bag 68 , which can be closed and/or sealed to protect sterility. The package or bag 68 of banded syringes 30 can then be sterilized by any of a variety of standard sterilization processes, for example by gamma radiation. The sterilized packages 68 of sterilized, banded syringes S, usually in quantities of about 200 to 1,000 syringes S per package 68 , are shipped to users, such as hospitals or other health care institutions, who will label and/or fill and re-cap the syringes S for use within an acceptable time after filling.
FIG. 4 illustrates another method and apparatus embodiment for mounting multiple syringes S into a band or belt 30 . In this embodiment a syringe feed-wheel 203 is driven synchronously with tape feed wheels 240 and 262 to form a band 30 of interconnected syringes S. More particularly, tape feed wheels 240 and 262 are driven to pull adhesive tapes 16 and 14 about idler wheels 215 and 258 from tape rolls 232 and 250 , respectively. Tensioning devices 211 and 213 are provided to establish a desired amount of tension along tape strips 16 and 14 as they are fed to tape feed wheels 240 and 262 , respectively.
As shown by FIG. 4 , a vibrating track 201 is provided to advance syringes S for sequential loading into notches 205 of the syringe feed wheel 203 . In turn, the syringe feed-wheel 203 is located immediately adjacent to the tape feed-wheel 240 so that notches 246 of the tape feed-wheel and notches 205 of the syringe feed-wheel 203 are disposed in opposing relation. As such, it can be seen that tape 16 will be pressed into notches 246 on one side of syringes S to achieve conformal interconnection therewith. Further in this regard, a pneumatic position and tension control device 207 is provided to enhance the interconnection between syringes S and tape 16 . Device 207 includes a mount lever arm 207 a interconnected to the syringe feed-wheel 203 , and a pneumatic cylinder 207 b for locating the arm 207 a and syringe feed-wheel 203 as appropriate so that syringes S apply a predetermined, desired amount of force against tape 16 .
After interconnection of one side of syringes S to adhesive tape 16 , the FIG. 4 embodiment provides for the interconnection of adhesive tape 14 to the other side of syringes S. More particularly, tape feed-wheel 262 is driven synchronously with and positioned relative to tape feed-wheel 240 so that notches 260 are in aligned relation with notches 246 to capture syringes S between adhesive tape strips 14 and 16 . Concomitantly, tape 14 is pressed about the syringes S to complete band 30 .
As further shown in FIG. 4 , a pneumatic position and tension control device 209 is provided at the tape feed-wheel 262 . Device 209 includes a mount lever arm 209 a and a pneumatic cylinder 209 b for locating the tape feed-wheel 262 as appropriate to establish the desired amount of force applied by syringes S to tape strip 16 .
Referring now to the diagrammatic elevation view of the labeling and filling apparatus 70 in FIG. 5 , a band 30 of syringes S is pulled from the bag 68 by a sprocket wheel or drum 72 and rotated to positions where the band 30 is cut to form the label substrates 10 (see FIG. 1 ), and, if the substrates are not already labeled, to attach labels 12 to the substrates 10 , and to remove the caps C, fill the syringes S with the desired medication, and replace the caps C.
In FIG. 5 , if the bands 30 do not already have labels, the user will prepare a quantity of labels 12 and mount them to feed into a labeling station 80 . The labels can be prepared in any suitable manner, for example, using a standard computer label printer, and the quantity of labels 12 prepared can correspond to the number of syringes S to be filled with medication that matches the labels 12 . The user also prepares the liquid medication 91 in a container 92 , which the user connects to a suitable fluid control system, such as conventional peristaltic pump 93 or other suitable syringe filling, fluid metering, or handling system. The medication will be conveyed via a suitable tube 94 or other conduit to the syringe filling station 90 , which will be explained in more detail below. The volume of medication to be pumped into each syringe S can be set and controlled in any of a variety of ways. For example, the pump 93 can be actuated to initiate a fill and deactuated when the syringe has been filled with the desired volume of medication, as will be described in more detail below.
With continuing reference primarily to FIG. 5 , the sprocket drum 72 has a plurality of notches 74 in equal, angularly-spaced relation to each other around the circumference of the drum 72 . The notches 74 are large enough to receive and retain a syringe S, and they are spaced apart from each other the same distance as the spacing between the syringes S in the band 30 . Therefore, when at least one of the syringes S in the band 30 is positioned in an appropriate notch 74 , rotation of the drum 72 , as indicated by arrow 75 , will cause the band 30 to pull successive syringes S in the band 30 out of the bag 68 and into the labeling and filling apparatus 70 . Suitable guides, for example, guides 76 , 77 , 78 , can be used to hold the syringes S in the notches 74 as the drum 72 rotates and carries the syringes S through the cutting station 100 , labeling station 80 , and filling station 90 .
It is appropriate to mention at this point that the sequential order of cutting, labeling, and filling is not critical to the invention, and these operations can be performed in any sequential order or even simultaneously, depending on how one wishes to mount the appropriate equipment, as would be within the capabilities of persons skilled in the art once the principles of this invention are understood. However, the convenient sequence of cutting, labeling, and filling will be used for purposes of this description of the invention. The drum 72 can be driven to rotate, as indicated by arrow 75 , and to stop with syringes S positioned appropriately for the cutting, labeling, and filling operations at the respective stations 100 , 80 , 90 by any appropriate drive and control system as is well within the capability of persons skilled in the art, such as, for example, with a stepper motor (not shown) connected to appropriate motor control devices (not shown). A control panel (not shown) connected to the stepper motor can be set up for use by an operator to either jog the drum 72 through incremental steps and/or jog the cutting station 100 , labeling station 80 , or filling station 90 through their respective operations or to initiate continuous automatic operation.
At the cutting station 100 , an actuator 101 drives a knife blade 102 as indicated by arrow 103 to cut and sever the band 30 to disconnect the syringes S from each other and to leave the resulting band segments or flaps connected to each syringe S to form individual label substrates 10 for each syringe S. The knife blade 102 is preferably serrated and a slot 104 in the drum in alignment with the knife blade 102 facilitate sure, complete cuts. Any suitable actuator 101 can be used, such as a rotary drive motor, solenoid, or the like. A sheath (not shown) can be provided to cover the blade 102 when it is not cutting. An optical or other sensor (not shown) can be positioned adjacent the drum 72 where the syringes S are first engaged by notches 74 to detect whether any syringes S have missing caps. A signal from the sensor in response to a missing cap could actuate and alarm and/or shut down the apparatus to prevent an uncapped syringe S from being labeled and filled.
For the syringe S that has advanced to the labeling station 80 , a labeler device 81 , moving as indicated by arrow 82 , affixes a label 12 to the substrate 10 . The labeler device 81 can be any of a variety of known label apparatus that transfer labels 12 from a strip 83 to an object, or it could be some other device, such as printer apparatus that prints the label directly onto the flap substrate 10 , or some combination of such apparatus, as would be within the capabilities of persons skilled in the art once they understand the principles of this invention. An optical sensor (not shown) is used to detect whether a label has been affixed to the substrate 10 at the label station 80 . A microprocessor (not shown) can be used to keep count of labels properly affixed and/or activate an alarm and/or shut down the apparatus 70 if a label is not detected on a substrate where a label is supposed to be affixed.
For a syringe S that has advanced to the fill station 90 , the cap C (not shown in FIG. 5 ) is removed by a cap handling apparatus 110 , then a liquid dispensing apparatus 120 is connected to the luer L (not shown in FIG. 5 ) of the syringe S to dispense liquid medication into the syringe S, and the pump 93 (or other suitable liquid metering or control apparatus) is actuated to move the medication 91 from the container 92 into the syringe S. When the syringe S is filled with the desired volume of fluid, as sensed, for example, by a proximity sensor that senses the corresponding desired position of the plunger P (not shown in FIG. 4 ) of the syringe S, the pump 93 (or other suitable liquid metering or control apparatus) is deactuated. Then, the liquid dispensing apparatus 120 is disconnected from the syringe S, and the cap handling apparatus 110 is moved into position to replace the cap C (not shown in FIG. 5 ) onto the luer (not shown in FIG. 4 ) of the syringe S. The cap handling apparatus 110 and the liquid dispensing apparatus 120 are mounted on a cammed shuttle 130 , which moves laterally in two axes, as indicated by arrow 131 in the plane of the paper and by arrow 132 perpendicular to the plane of the paper, to accomplish the cap removal, fill, and cap replacement functions described above. While these functions could be performed by myriad other devices and combinations of devices, as would be within the capabilities of persons skilled in the art once they understand the principles of this invention, an example cammed shuttle 130 , cap handling apparatus 110 , and liquid dispensing apparatus 120 shown diagrammatically in FIG. 4 will be described in more detail below.
After the syringes S leave the fill station 90 , they are allowed to drop individually out of the sprocket drum 72 and, for example, into a basket 115 or other receptacle. At this stage, the syringes S are labeled, filled, and ready for use, as shown in FIG. 1 .
Referring now to FIGS. 6 a , 6 b , 6 c , 6 d , and 6 e in combination with FIG. 5 , the cammed shuttle 130 is driven by a motor, such as a stepper motor 133 , which rotates a slotted cam lever or crank arm 134 mounted on the drive shaft 135 of the motor 133 . A driver block 136 has a slide pin or a cam roll (concealed from view) extending in one direction into the slotted race groove 137 of the cam lever or crank arm 134 and another cam follow pin or cam roll 138 extending in the opposite direction into a U-shaped cam slot 139 in a stationary cam block 140 . Therefore, as the stepper motor 133 rotates, for example as shown by arrow 141 in FIGS. 6 b and 6 c , the cam lever 134 causes the cam follower pin or cam roll 138 extending from the driver block 136 to follow the U-shaped path of the cam slot 139 , which moves the two slide shafts 142 , 143 extending laterally from driver block 136 as well as the connecting block 144 at the distal ends of slide shafts 142 , 143 to move simultaneously in the same U-shaped motion pattern. The two slide shafts 142 , 143 extend slidably through two holes 145 , 146 in a pillow block 147 , which is mounted slidably on two support rods 148 , 149 . The support rods 148 , 149 are mounted in two stationary anchor blocks 150 , 151 and extend slidably through two holes 152 , 153 in pillow block 147 , which are perpendicular to, but vertically offset from, holes 145 , 146 . Thus, as the stepper motor 133 drives the driver block 136 through the U-shaped pattern of cam slot 139 , the pillow block 147 slides laterally on support rods 148 , 149 as indicated by arrow 154 , while the slide shafts 142 , 143 slide longitudinally in pillow block 147 as indicated by arrow 155 . As a result, the connector block 144 and cammed shuttle 130 also move both laterally and longitudinally as indicated by arrows 131 , 132 in the same U-shape pattern as the U-shaped cam slot 139 to remove the cap C from the syringe S, connect the syringe S to a nozzle 121 in the liquid dispensing apparatus 120 to fill the syringe S, disconnect the nozzle 121 , and replace the cap C, as will be described in more detail below. Suitable bushing or bearings can be used to enhance the sliding movement of the shafts 142 , 143 and support rods 148 , 149 in the pillow block 147 .
Referring now to FIG. 6 a in combination with FIG. 4 , the drum 72 has moved a syringe S to the filling station 90 , where it stops for the cap removal, fill, and cap replacement operation. The syringe S is shown in FIG. 6 a positioned in a notch 74 with a label 12 affixed to the substrate 10 . As the drum 72 moved the syringe S to the position shown in FIG. 6 a , the cap C was moved into a set of jaws 160 , which is aligned longitudinally with the syringe S when the slotted cam lever 134 is stopped in the position shown in FIG. 6 a and the drum 72 stops the syringe S in the filling station 90 . A cap gripper 161 , such as resilient spring steel, presses against the cap C in jaws 160 to capture and retain the cap C in the jaws 160 . Again, optical sensors (not shown) or other suitable sensors and/or control devices or methods can be used to stop the drum 72 when the syringe S is positioned with the cap C captured in the jaws 160 as would be understood by persons skilled in the art once they understand the principles of this invention. Then, the motor 133 is actuated to rotate the slotted cam lever 134 as indicated by arrow 141 in FIG. 6 b , which extends the slide shafts 142 , 143 , as indicated by arrow 156 , as the pillow block 147 slides to the right on support rods 148 , 149 , as indicated by arrow 157 . As a result, the cammed shuttle 130 moves the jaws 160 with the cap C away from the syringe S, thereby removing the cap C from the syringe S and leaving the luer L of the syringe S exposed and open, as shown in FIG. 6 b . Again, the gripper 161 described above retains the cap C in the jaws 160 when the cap C is removed from the luer L.
Continued rotation of the cam lever 134 as indicated by the arrow 141 in FIG. 6 c translates the pillow block 147 still farther to the right on support rods 148 , 149 , as indicated by arrow 157 in FIG. 6 c , until the longitudinal axis 122 of the fill connector or nozzle 121 aligns with the longitudinal axis 123 of syringe S, then retracts the slide shafts 142 , 143 , as indicated by arrow 158 , to position the nozzle 121 on luer L of the syringe S. At that position of the cammed shuttle 130 , the motor 133 is deactuated, so the nozzle 121 stays on the luer L while the pump 93 ( FIG. 5 ) is actuated to pump liquid medication 91 from the container 92 to fill the syringe S. The fill connector or nozzle 121 is preferably mounted on the cammed shuttle 130 by a spring-loaded slide (not shown) or similar yieldable, resilient mounting to apply an appropriate, uniform force to the nozzle 121 as it is being forced by the cammed shuttle 130 onto the luer L of the syringe S. This motion to remove the cap C and place the fill connector or nozzle 121 on the syringe S can be accomplished in approximately 250 milliseconds with this mechanism. The U-shaped cam slot 139 provides a straight, longitudinal pull of the cap C in alignment with the longitudinal axis 123 of the syringe S and a corresponding straight, longitudinal push to attach the nozzle 121 to the luer L.
As best seen in FIG. 6 d , the plunger P of the syringe S is pushed outwardly by the liquid medication that is pumped into the syringe S. When the syringe S has been filled with the desired volume of liquid medication, the flow of liquid medication into the syringe S is stopped. The flow can be measured and stopped in a variety of ways, such as flow meters, valves, known pump displacement, and the like, as would be within the knowledge and capabilities of persons skilled in the art once they understand the principles of this invention. However, a particularly novel and innovative way of controlling the fill volume according to this invention is to use a sensor 124 to detect when the plunger P has been pushed out to a predetermined extent that corresponds to the fill volume desired, as illustrated in FIG. 6 d . A myriad of sensors could be used for this function, such as a capacitive proximity sensor, optical sensor, microswitch, and the like. Upon sensing the desired extension of the plunger P, a signal from the sensor 124 can be used to shut off the flow of liquid medication into the syringe S. A suitable signal control circuit, for example, a microprocessor and/or relay, (not shown) to shut off the pump 93 or to close some control valve (not shown) is well within the capabilities of persons skilled in the art once they understand the principles of this invention. As shown in FIG. 6 d , the sensor 124 can be mounted on an adjustable base 125 with a scale 126 and pointer 127 to correlate adjustable physical position of the sensor with the desired fill volume.
When the desired fill volume has been reached and detected, as explained above, a signal from the sensor 124 is used to deactuate the pump 93 . A preferred, albeit not essential, pump 93 is a peristaltic pump, such as, for example, a model 099 Repeater Pump, manufactured by Baxa Corporation, of Englewood, Colo., which can be reversed momentarily to take the fluid pressure off the tubing 94 and syringe S to minimize, if not prevent, dripping of the liquid medication when the nozzle 121 is detached from the luer L. Then, the motor 133 is actuated to rotate the cam lever 134 in the opposite direction, as indicated by the arrow 159 in FIG. 6 e , to detach the nozzle 121 from the luer L of the syringe S and move the jaws 160 and cap C back into longitudinal alignment with the axis 123 of the syringe S for replacing the cap C on the syringe S. Specifically, as the cam lever 134 rotates, as shown by arrow 159 , the cammed shuttle 130 moves back through the U-shaped pattern defined by the U-shaped cam slot 139 . First, the slide shafts 142 , 143 are extended as indicated by arrow 171 to detach the nozzle 121 from the luer L of syringe S. Then the cammed shuttle is moved in an arc as indicated by arrow 172 to align the cap C in jaws 160 with the longitudinal axis 123 of the syringe S. Finally, the slide shafts 142 , 143 are retracted again, as indicated by arrow 173 , to push the cap C back onto the syringe S. The cap handling apparatus 110 can be mounted by a spring-loaded slide (not shown) or some other yieldable, resilient structure, if desired, to ensure a uniform pressure application to the cap C as it is being pushed by the cammed shuttle 130 back onto the syringe S.
At this position, shown in FIG. 6 e , the fill is completed, and the drum 72 can be rotated again to move the cap C out of the jaws 160 and to move the next syringe S in the sequence into the jaws 160 for a repeat of the cap removal, fill, and cap replacement sequence described above on the next syringe S in the drum 72 . At the next position after the filling station 90 , a sensor (not shown), such as an optical sensor, is used to determine if the cap C is placed correctly back on the syringe S. If it is not placed correctly, the apparatus is stopped and/or an alarm is sounded in response to a signal from the sensor indicating that the cap C is not replaced. After that cap-check position, the drum moves the syringe to a point where hold down or guide tracks end, thereby freeing the syringe S to drop out of the drum 72 and into a chute (not shown) that guides the labeled, filled, and recapped syringe S into the holding basket 115 .
The control system (not shown) can utilize signals from the sensors to record number of syringes S filled, program the number of doses desired and automatically stop when that number of syringes S are filled, record the number of doses actually pumped, record the number of doses or syringes in the basket 115 and keep track of rejected labels or syringes. Other functions can also be provided.
Referring now to FIGS. 7 a and 7 b , the labeling and filling apparatus embodiment of FIG. 5 and FIG. 6 a – 6 e is further illustrated in a production implementation. Of note, the labeling and filling apparatus 70 is shown in a compact table top arrangement that may be readily positioned in a sterile environment, e.g. within a sterile area having an appropriate exhaust hood. As will be recognized, the apparatus 70 includes a cutting station 100 , labeling station 80 and filling station 90 .
The drum 72 may be driven in a clockwise direction by a step motor 301 , wherein syringes S are positioned into the notches 74 for sequential feeding to the work stations 80 , 90 and 100 . At cutting station 100 , an actuator 101 in the form of a stepper motor may be utilized. In particular, the actuator 101 may be controlled to turn a crank 303 having a cam follower 305 that is located in a slot 307 on a mount block 309 for cutting blade 102 . The block 309 is supported on rails 313 , wherein driven rotation of the crank 303 effects linear travel of the cutting blade 102 towards and away from the drum 72 and a belt 30 with syringes S carried thereby. The operation of actuator 101 may be timed in relation to the stepped movement of drum 72 so that belt 30 is cut into belt segments 10 of a consistent width by cutting blade 102 .
At labeling station 80 , the labeling device 81 may include a stepper motor (not illustrated) to which a shaft (not illustrated) is interconnected for driven eccentric motion. That is, upon actuation stepper motor may drive shaft through an arc from a first position to a second position. By way of example, the first position may be as illustrated in FIGS. 7 a and 7 b , wherein the labeling device 81 is located in a down position for label placement. Upon eccentric motion of the shaft to a second position, shaft will engage the labeling device 81 causing the cantilevered end thereof to cock upwards about a stationary shaft (not illustrated). As may be appreciated, the operation of stepper motor is timed in relation to the stepped movement of drum 72 to affect label placement on the belt segments 10 between adjacent syringes S.
Referring now to FIGS. 8 a – 8 d , operation of the filling station 80 shown in FIGS. 7 a and 7 b will be further described. In FIG. 8 a a syringe S has advanced to the filling station 90 with a cap C inserted into cap handling apparatus 110 . As illustrated, syringe S has an interconnected belt segment on flap 10 with a label 12 adhered thereto.
As next shown in FIG. 8 b , it can be seen that filling station 90 has retracted away from drum 72 so as to remove cap C from the dispensing end of the syringe S. As previously noted, such retraction is achieved by activating stepper motor 133 to rotate cam lever 134 , thereby causing driver block 136 , slide shafts 142 , 143 , connecting block 144 and shuttle 130 to move along a first straight leg portion of U-shaped motion pattern.
In the later regard, FIG. 8 c shows the filling station 90 immediately after cam lever 134 has moved through the curved portion of the U-shaped motion pattern. In this position it can be seen that the nozzle 121 of the liquid dispensing apparatus 120 is aligned with the dispensing end of the syringe S. As such, and as seen in FIG. 8 d , further movement of the filling station 90 along the second straight leg portion of the U-shaped motion pattern causes the liquid dispensing apparatus 120 to linearly advance towards syringe S, wherein the nozzle 121 engages and fluidly interconnects with the dispensing end of the syringe S. Upon reaching the FIG. 8 d position, filling station 90 may be controlled so that fluid is injected through nozzle 121 into the syringe S. As further shown in FIG. 8 d , fluid has filled the syringe S to displace the plunger P into contact with the sensor 124 . At this point, a sensor signal is transmitted to terminate the filling of syringe S. Thereafter, stepper motor 133 may again rotate cam lever 134 through the U-shaped motion pattern to reposition cap C back onto the dispensing end of the syringe S.
As noted above, the filling and labeling apparatus 70 is only one embodiment of the present invention. Numerous other embodiments will be apparent to those skilled in the art. By way of example, reference is now made to FIGS. 9 , 10 and 11 a – 11 f , which illustrate an alternate embodiment.
In this embodiment a drum 472 is driven in a counter-clock wise direction, wherein a band 430 of syringes S pulled in series into the notches 474 for preparation operations. In the later regard, the band 430 is suspended from the drum 472 to facilitate aligned, side-by-side positioning of the syringes S in notches 474 . As schematically shown in FIG. 9 , the syringes S are sequentially advanced through filling station 490 , labeling station 480 and cutting station 400 . Thereafter, the separated syringes S may be directed into a container (not shown) via a chute 451 . The operation of labeling station 480 and cutting station 400 may be analogous to the operations of the labeling station 80 and cutting station 100 described above in relation to FIG. 5 and FIGS. 6 a – 6 b . In contrast to that embodiment, however, the embodiment shown in FIGS. 9 , 10 and 11 a – 11 h may implement a different approach at filling station 490 .
In the modified operation shown in FIG. 9 , a syringe is first positioned at location I for cap removal, then located at a second position II for filling, followed by location back at work location I for cap replacement. To facilitate an understanding of such approach, the labeling station 480 and cutting station 400 are not presented in FIG. 10 . As best shown by FIG. 10 , filling station 490 includes a cap handling apparatus 410 and liquid dispensing apparatus 420 . As will be appreciated, liquid dispensing apparatus 420 is interconnectable to a reservoir (not shown) containing a fluid for filling syringes S. Of note, both the cap handling apparatus 410 and liquid dispensing apparatus 420 are mounted on a common support member 431 . Support member 431 may be interconnected to a stepper motor (not shown) acutatable to affect linear travel of the cap handling apparatus 410 and liquid dispensing apparatus 420 towards and away from the drum 472 . Such linear travel, together with the rotation of drum 472 are the only required motions for cap removal, filling and cap replacement. Such operations will now be further described with reference to FIGS. 11 a – 11 h.
FIGS. 11 a – 11 h are flat, diagrammatic views of filling station 490 from a rearward perspective relative to the isometric front view shown in FIG. 10 . Before proceeding, it should be noted that the filling station 490 shown in FIGS. 11 a – 11 h further includes a syringe flange retention track 492 and a plunger flange retention member 494 . As will be further described, the plunger flange retention number 494 is selectively retractable relative to retention track 492 so that fluid may be drawn from liquid dispensing apparatus 420 to fill syringes S. In this regard, liquid dispensing apparatus 420 may include a valve to control the passage/stoppage of fluid therethrough. By way of example, such valve may comprise an actuatable roller.
With particular reference to FIG. 11 a , a syringe S is shown in the first location I shown in FIG. 9 wherein cap C has been inserted in the cap handling apparatus 410 for retention thereby. Concomitantly, a flange on syringe S has been inserted and advanced within the retention track 492 . Next, and as shown in FIG. 11 b , cap handling apparatus 410 has been retracted from the syringe S with cap C retained thereby. As will be appreciated, such retraction may be affected via linear driven travel of the support member 431 shown in FIG. 10 .
FIG. 11 c shows the syringe S moved to the location II shown in FIG. 9 . More particularly, drum 472 may be rotated clockwise to affect such positioning, wherein the liquid dispensing apparatus 420 is aligned with the dispensing end of the syringe S. Then, liquid dispensing apparatus 420 may be advanced into engagement with the dispensing end of syringe S as shown in FIG. 11 d . Again, such linear travel may be affected via movement of support member 431 . Of note, both FIGS. 11 c and lid show the plunger P being positioned in the retention member 494 .
In this regard, and referring now to FIG. 11 e , retention member 494 may be provided for driven retraction away from syringe S (e.g. via an unshown stepper motor), with the valve of liquid dispensing apparatus 420 opened so as to draw fluid through liquid dispensing apparatus 420 into the syringe S. As may be appreciated, the amount, or length, of retraction of retention member 494 may be precisely controlled to achieve a preset filling volume. When the desired volume has been reached, the valve of liquid dispensing apparatus 420 may be closed. Where an actuatable roller is utilized, the roller may be positioned to pinch off a fluid conduit to back up the fluid a desired amount, thereby bringing the fluid pressure slightly below atmospheric pressure. After filling, the liquid dispensing apparatus 420 may be withdrawn from the dispensing end of the syringe S as shown in FIG. 11 f . Again, such linear travel may be affected by controlled retraction of the support member 431 .
Thereafter, syringe S may return to location I via counter-clockwise rotation of drum 472 , as shown in FIG. 11 g . Finally, cap C may be replaced onto the dispensing end of the syringe S via advancement of the cap handling apparatus 410 on support member 431 . The syringe S may then be advanced for further operations at the labeling station 480 and cutting station 400 shown in FIG. 9 .
The foregoing description is considered as illustrative only of the principles of the invention. Furthermore, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired limit the invention to the exact construction and process shown and described above. Accordingly, resort may be made to all suitable modifications and equivalents that fall within a scope of the invention as defined by the claims which follow. The words “comprise,” “comprises,” “comprising,” “include,” “including,” and “includes” when used in this specification are intended to specify the presence of stated features, integers, components, or steps, but they do not preclude the presence or addition of one or more other features, integers, components, steps, or groups thereof. | 1a
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PRIORITY CLAIM
[0001] This application claims priority to U.S. Provisional Application Ser. No. 62/189,501 filed Jul. 7, 2015, the entire contends of which is hereby incorporated by reference herein.
FIELD OF INVENTION
[0002] This invention relates to an exercise apparatus, and more particularly, it relates to a weight-lifting apparatus that simulates dumbbell exercises.
BACKGROUND INFORMATION
[0003] Fitness is increasingly popular among people of all ages and professions. The common approach for an exerciser who wishes to develop his physique is to practice strength training exercises that develop muscle strength, hypertrophy and endurance.
[0004] Free-weight versions of these exercises may involve dumbbells and barbells which pose a certain degree of danger to beginner and veteran exercisers. For example, when performing an exercise (e.g., a bench press, an overhead shoulder press, etc.), the exerciser is required to lift the dumbbell/barbell above his head or chest. In the case of failure to properly complete the exercise, the dumbbell/barbell may pose serious threat to the exerciser.
[0005] Several conventional barbell-simulating machines have attempted to solve these safety issues by adding guide rails to plate-loaded assemblies. However, the adding of the guide rails has led to restricted movements which limit the development of small muscle groups known as stabilizing muscles. Some of such machines have focused on safety associated with barbell use [e.g., U.S. Pat. Nos. 8,500,608 and 4,527,797]. In particular, the Smith Machine [e.g., U.S. Patent Publication Application No. 2006/0252615] adds one pair of vertical rails restricting a barbell to two vertical guides and ultimately allowing only linear movements in one direction. The Dual Action Machine [e.g., U.S. Pat. No. 7,909,743] adds one more pair of guide rails perpendicular to the vertical guide rails and parallel to the sidetrack, thus allowing a greater variety of exercises, but still limiting movements to two degrees of freedom (e.g., up & down, back & forth).
[0006] The dangers of free-weight exercises become more prominent when the exercises are performed with dumbbells rather than barbells. In the past, there have been attempts to design machines that simulate dumbbell exercises. However, the achievement of exerciser safety still led to restricted freedoms of movement. The Exercise Apparatus Providing Simulated Free Weight Exercises and Compact Stowage [e.g., U.S. Pat. No. 5,725,459] uses cables that transmit the weight stack resistance; thus, allowing for greater degrees of freedom. However, it requires the entire weight stack to move accordingly during the exercise. The inertia of the entire weight stack makes it difficult to horizontally move back-and-forth. The Free Weight Training Simulation Apparatus [e.g., U.S. Publication Application No. 2010/0216610] applies two sets of rollers to enable horizontal back-and-forth movement. However, its lever arms, connected to the main frame, have a preset radius and thus restrict the freedom of movement to an arc with fixed radius.
SUMMARY OF THE INVENTION
[0007] According to an aspect of the present disclosure, an exercise apparatus comprises first and second guide rails and first and second handles. The first handle is mounted on the first guide rail and configured to be moveable up and down the first guide rail. The second handle is mounted on the second guide rail and configured to be moveable up and down the second guide rail. The exercise apparatus further comprises a first transverse support system on which the first and second guide rails are movably mounted so that each of the first and second guide rails are movable over the first transverse support system along a first axis toward and away from the other of the first and second guide rails. Additionally, a second transverse support system on which the first transverse support system is movably mounted is configured to be moveable along a second axis perpendicular to the first axis.
[0008] In another aspect, the first and second guide rails include sliding joints that enable the first and second guide rails to move over the first transverse support system.
[0009] In another aspect, the first and second guide rails include rollers that enable the first and second guide rails to move over the first transverse support system.
[0010] In another aspect, the first and second guide rails are movable independent of each other along first axis and the second axis.
[0011] In another aspect, the first transverse support system includes a first and a second horizontal guide rail on which the first guide rail is configured to be moveably mounted, and a third and forth horizontal guide rail on which the second guide rail is configured to be moveably mounted.
[0012] In another aspect, the first and second guide rails include at least one hole configured to receive a pin.
[0013] In another aspect, the first transverse support system includes sliding joints that enable the first transverse to move over the second transverse support system.
[0014] In another aspect, the first transverse support system includes rollers that enable the first transverse to move over the second transverse support system.
[0015] In another aspect, the first handle is joined to a first plate hanger and the second handle is joined to a second plate hanger.
[0016] In another aspect, a bench is situated in a lower middle plane of the exercise apparatus.
BRIEF DESCRIPTION OF THE FIGURES
[0017] FIG. 1 is a perspective view of an exercise apparatus according to an exemplary embodiment of the present invention.
[0018] FIG. 2 is a perspective view of the exercise apparatus of FIG. 1 , showing detailed labeling of the components.
[0019] FIG. 3 shows a detailed view of an upper structure of the exercise apparatus of FIG. 1 .
[0020] FIG. 4 shows an alternate exemplary embodiment of the exercise apparatus, according to the present invention.
[0021] FIG. 5 shows a detailed view of an upper structure of the exercise apparatus of FIG. 4 .
[0022] FIG. 6 shows a detailed view of the upper structure of the exercise apparatus of FIG. 4 .
[0023] FIG. 7 shows a detailed view of the upper structure of the exercise apparatus of FIG. 4 .
[0024] FIG. 8 shows a detailed view of the upper structure of the exercise apparatus of FIG. 4 .
[0025] FIG. 9 shows the exercise apparatus, according to an exemplary embodiment of the present invention, being utilized as a flat bench press with an exerciser in the starting position.
[0026] FIG. 10 shows the exercise apparatus, according to an exemplary embodiment of the present invention, being utilized as a flat bench press with the exerciser in the ending position.
[0027] FIG. 11 shows the exercise apparatus, according to an exemplary embodiment of the present invention, being utilized as a shoulder press with the exerciser in the starting position.
[0028] FIG. 12 shows the exercise apparatus, according to an exemplary embodiment of the present invention, being utilized as a shoulder press with the exerciser in the ending position.
[0029] FIG. 13 shows the exercise apparatus, according to an exemplary embodiment of the present invention, being utilized as an incline bench press with the exerciser in the starting position.
[0030] FIG. 14 shows the exercise apparatus, according to an exemplary embodiment of the present invention, being utilized as an incline bench press with the exerciser in the ending position.
[0031] FIG. 15 shows the exercise apparatus, according to an exemplary embodiment of the present invention, being utilized as a squat lunge with the exerciser in the starting position.
[0032] FIG. 16 shows the exercise apparatus, according to an exemplary embodiment of the present invention, being utilized as a squat lunge with the exerciser in the ending position.
DETAILED DESCRIPTION
[0033] The exemplary embodiments may be further understood with reference to the following description of the exemplary embodiments and the related appended drawings, wherein like elements are provided with the same reference numerals. The exemplary embodiments are related to an exercise apparatus.
[0034] The exercise apparatus according to the present invention enables three degrees of freedom of movement of plate-loaded assemblies for upper and lower-body dumbbell pressing exercises including, but not limited to, flat/incline/decline bench press exercise, dumbbell overhead press exercise, squat lunge exercise, deadlift exercise, all whilst ensuring the safety of an exerciser.
[0035] FIGS. 1 and 2 show an exemplary embodiment of an exercise apparatus 100 according to the present invention. The exercise apparatus 100 includes a first base member 1 and a second base member 2 . The first base member 1 is joined to a first vertical strut 3 and a second vertical strut 6 . The second base member 2 is joined to a third vertical strut 4 and a fourth vertical strut 5 . Upper ends of the first vertical strut 3 and the second vertical strut 6 are joined to a first cross strut 7 . Similarly, Upper ends of the third vertical strut 4 and the fourth vertical strut 5 are joined to a second cross strut 8 . The first cross strut 7 and the second cross strut 8 extend towards a center of the exercise apparatus 100 , where they are joined. A first lateral horizontal back-and-forth rail 9 extends between the first vertical strut 3 and the second vertical strut 6 . Similarly, a second lateral horizontal back-and-forth rail 10 extends between the third strut 4 and the fourth strut 5 .
[0036] A first handle 29 and a second handle 30 are slidably mounted on a first guide rail 31 and a second guide rail 32 , respectively, thus allowing a vertical movement up and down. Immediately above the first handle 29 is a first plate hanger 27 , while a second plate hanger 28 is immediately above the second handle 30 . Weight plates (not shown) may be slid onto the plate hangers 27 , 28 . A bench 50 (optional) may be situated in a lower middle of the exercise apparatus 100 . Furthermore, rest plate hangers 21 , 22 , 23 , 24 , 25 , 26 may be attached to any of the vertical struts 3 , 4 , 5 , 6 to hold a variety of different weight plates. In an alternate exemplary embodiment of the present invention, the plate hangers 27 , 28 may be positioned below the handles 29 , 30 or, alternately, the plate hangers 27 , 28 and the handles 29 , 30 may be on the same horizontal plane. Those skilled in the art would understand that the plate hangers 27 , 28 and the handles 29 , 30 may be composed of a single body or two joined bodies.
[0037] Referring to FIGS. 2 and 3 , the top of the first guide rail 31 is connected to a first horizontal left-and-right slider 17 and the top of the second guide rail 32 is connected to a second horizontal left-and-right slider 18 . As will be understood by those skilled in the art, each of the first and second guide rails 31 , 32 and each of the first and second sliders 17 , 18 may be formed as a single body or as multiple bodies. The first slider 17 is slidably mounted on a first pair of horizontal left-to-right guide rails 15 , 16 and the second slider 18 is slidably mounted on a second pair of horizontal left-to-right guide rails 13 , 14 ; thus, allowing horizontal movement left-and-right of each of the guide rails 31 , 32 . In an alternative exemplary embodiment, a first single horizontal guide rail may be used instead of the first pair of horizontal guide rails 15 , 16 and a second single horizontal guide rail may be used instead of the second pair of horizontal guide rails 13 , 14 .
[0038] Those skilled in the art would understand that the shape of the first and second single horizontal guide rails would determine whether the first and second sliders 17 , 18 may rotate in addition to sliding. It should be noted that while the first pair of horizontal guide rails 15 , 16 and the second pair of horizontal guide rails 13 , 14 are is set as being substantially parallel to a horizontal plane, those skilled in the art would understand that circumstances may require for the first pair of horizontal guide rails 15 , 16 and the second pair of horizontal guide rails 13 , 14 to deviate from the horizontal plane.
[0039] The ends of the first pair of guide rails 15 , 16 are connected to a first traveling member 11 , while the opposite ends of the first pair of guide rails 15 , 16 are connected to a second traveling member 20 . Similarly, the ends of the second pair of guide rails 13 , 14 are connected to a third traveling member 12 , while the opposite ends of the second pair of guide rails 13 , 14 are connected to a fourth traveling member 19 . This forms a first transverse support system.
[0040] The first member 11 is slidably mounted on the first lateral rail 9 . The second member 20 is slidably mounted on the rail formed by the first cross strut 7 . The third member 12 is slidably mounted on the second lateral rail 10 . The fourth member 19 is slidably mounted on the rail formed by the second cross strut 8 . The first lateral rail 9 , the second lateral rail 10 , the rail formed by the first cross strut 7 , and the rail formed by the second cross strut 8 form a second transverse support system. This allows for independent lateral back-and-forth movement of each of the guide rails 31 , 32 . Those skilled in the art would understand that alternate configurations may be used to form the second transverse support system.
[0041] FIG. 4 shows an alternative exemplary embodiment of an exercise apparatus 200 according to the present invention. The exercise apparatus 200 utilizes rollers instead of sliding joints. FIG. 5 shows a detailed view of an upper structure of the exercise apparatus 200 . A first roller 39 connects the first member 11 to the first lateral rail 9 . A second roller 40 connects the third member 12 to the second lateral rail 10 . A third roller 33 connects the second member 20 to the rail formed by the first cross strut 7 . A fourth roller 34 connects the fourth member 19 to the rail formed by the second cross strut 8 . This allows for independent lateral back-and-forth movement of each of the guide rails 31 , 32 .
[0042] A fifth roller 35 and a sixth roller 36 connect the first slider 17 to the first pair of horizontal guide rails 15 , 16 . A seventh roller 37 and an eighth roller 38 connect the second slider 18 to the second pair of horizontal guide rails 13 , 14 . This allows for independent horizontal left-and-right movement of each of the guide rails 31 , 32 . The fifth roller 35 and the sixth roller 36 are situated inside first slider 17 , while the seventh roller 37 and the eighth roller 38 are situated inside second slider 18 . While FIGS. 4 and 5 show a single roller on each guide rail, those skilled in the art would understand that multiple rollers per guide rail may be used instead.
[0043] Referring to FIG. 4 , each of the guide rails 31 , 32 may have multiple holes 43 spanning a portion of the length of each of the guide rails 31 , 32 . The holes 43 may be used for inserting a pin (not shown). The pin may prevent the handles 29 , 30 from sliding below a predetermined height set by the pin. The holes 43 may be of any shape, including, but not limited to, circular, triangular or rectangular.
[0044] FIG. 6 shows a detailed view of the first roller 39 connecting to the first member 11 to the first lateral rail 9 . As mentioned above, this allows for independent lateral back-and-forth movement of each of the guide rails 31 , 32 .
[0045] FIG. 7 shows a detailed view of the third roller 33 connecting the second member 20 to the rail formed by the first cross strut 7 and the fourth roller 34 connecting the fourth member 19 to the rail formed by the second cross strut 8 . As previously mentioned, this allows for independent lateral back-and-forth movement of each of the guide rails 31 , 32 .
[0046] FIG. 8 shows a detailed view of the fifth roller 37 and sixth roller 38 connecting the second horizontal slider 18 to the second pair of horizontal guide rails 13 , 14 . As previously mentioned, this allows for independent horizontal left-and-right movement of each of the guide rails 31 , 32 . In addition, a detailed view of the second roller 40 connecting the third member 12 to the second lateral rail 10 is shown.
[0047] FIGS. 9 and 10 show an exemplary utilization of the exercise apparatus 100 according to the present invention. In particular, FIGS. 9 and 10 demonstrate starting and ending positions of the dumbbell bench press exercise. During a concentric phase (i.e., a pushing phase) of the dumbbell bench pressing exercise, ergonomics require for the exerciser to bring his palms toward a center of the body. This requires the horizontal left-and-right movement of the first handle 29 and the second handle 30 . When performing a flat bench press exercise, the exerciser may choose to place a flat bench in the center of the exercise apparatus 100 , and load desirable amount of weight plates onto the first plate hanger 27 and the second plate hanger 28 . The exerciser may start pushing the dumbbells upward, with the plate assembly sliding along the first and second guide rails 31 , 32 . Throughout the pressing movement, the first pair of guide rails 13 , 14 and the second pair of guide rails 15 , 16 will allow the exerciser to bring his palms close together. Meanwhile, each one of the lateral rails 9 , 10 and each one of the travelling members 11 , 12 add to the freedom of movements, allowing the exerciser to work out the surrounding small muscle groups called stabilizing muscles. The iso-lateral design (i.e., the separation of the left weight load from the right), allows the exerciser to move either arm independently, prompting the exerciser to develop a balanced physique and muscularity.
[0048] FIGS. 11 and 12 show another exemplary utilization of the exercise apparatus 100 according to the present invention. In particular, FIGS. 11 and 12 demonstrate starting and ending positions of the shoulder press exercise. Similar to the dumbbell bench pressing exercise shown in FIGS. 9 and 10 , during a concentric phase of the exercise, ergonomics require that the exerciser bring his palms toward the center of the body. This requires the horizontal left-and-right movement of the first handle 29 and the second handle 30 . When performing the shoulder press exercise, the exerciser may choose to place an upright bench in the center of the exercise apparatus 100 , and load desirable amount of weight plates onto the plate hangers 27 , 28 . The exerciser may start pushing the dumbbells upward, with the plate assembly sliding along the first and second guide rails 31 , 32 . Throughout the pressing movement, the first pair of guide rails 13 , 14 and the second pair of guide rails 15 , 16 will allow the exerciser to bring his palms closer together. Meanwhile, each one of the rails 9 , 10 and each one of the travelling members 11 , 12 add to the freedom of movements, allowing the exerciser to work out the stabilizing muscles. Again, the iso-lateral design allows the exerciser to move either arm independently.
[0049] FIGS. 13 and 14 show yet another exemplary utilization of the exercise apparatus 200 according to the present invention. In particular, FIGS. 13 and 14 demonstrate the starting and ending positions of the incline bench press exercise. Similar to the dumbbell bench pressing exercise shown in FIGS. 9 and 10 , during a concentric phase of the exercise, the exerciser brings his palms toward the center of the body. This requires the horizontal left-and-right movement of the first handle 29 and the second handle 30 . When performing the incline bench press, the exerciser may choose to place an incline bench in the center of the exercise apparatus 200 , and load desirable amount of weight plates onto the plate hangers 27 , 28 . The exerciser may start pushing the dumbbells upward, with the plate assembly sliding along the first and second guide rails 31 , 32 . Throughout the pressing movement, the first pair of guide rails 13 , 14 and the second pair of guide rails 15 , 16 will allow the exerciser to bring his palms closer together. Meanwhile, each one of the rails 9 , 10 and each one of the travelling members 11 , 12 add to the freedom of movements, allowing the exerciser to work out the stabilizing muscles. Again, the iso-lateral design allows the exerciser to move either arm independently.
[0050] FIGS. 15 and 16 show a further exemplary utilization of the exercise apparatus 100 according to the present invention. In particular, FIGS. 15 and 16 demonstrate the starting and ending positions of the squat lunge exercise, which requires back-and-forth movement as the exerciser alternatingly lunges forward on each leg. The first and second lateral guide rails 9 , 10 and first and second members 11 , 12 allow the exerciser to move in a back-and-forth direction. In contrast to the exercises described above, it is the first pair of guide rails 13 , 14 and the second pair of guide rails 15 , 16 which add the freedom of movement during the squat lunge exercise, allowing the exerciser to work out the surrounding small muscle groups called stabilizing muscles. As can be seen in FIGS. 15 and 16 , this exercise does not require the optional bench 50 ; thus, the bench 50 is removed or is not placed prior to the squat lunge exercise.
[0051] One of the advantages of the present invention is that an exemplary embodiment achieves a safe simulation of heavy dumbbells exercise with three degrees of freedom of movement can be achieved. This is advantageous over the Smith machine, which offers only one degree of freedom, and the Dual Action Machine, which offers only two degrees of freedom. Further, if an exerciser is having difficulty completing an exercise, the present invention prevents injury to the exerciser because the first guide rail 31 and second guide rail 32 can be adjusted to a suitable length so that weight plate assemblies will stop once they reach the bottom of the guide rails 31 , 32 . Alternatively, if the pins and the holes 43 along the first guide rail 31 and the second guide rail 32 are utilized, each of the pins will prevent each of the handles 29 , 30 from sliding below a predetermined height.
[0052] Another one of the advantages of the present invention is the capability to develop smaller muscles groups (i.e., stabilizing muscles) while ensuring safety as described above. The development of the stabilizing muscles is achieved by utilizing the three degrees of freedom of the present invention and permits either arm to exercise independently of the other while preventing each of the handles 29 , 30 from sliding below a predetermined height.
[0053] Yet another one of the advantages of the present invention is that each one of the rollers 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 may reduce friction and increase the lifespan of the 100/200.
[0054] It will be apparent to those skilled in the art that various modifications may be made to the exemplary embodiments, without departing from the spirit or the scope of the invention. Thus, it is intended that the present invention cover modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents. | 1a
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CROSS REFERENCE TO RELATED APPLICATIONS
Not Applicable
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not Applicable
REFERENCE TO SEQUENCE LISTING, A TABLE, OR A COMPUTER PROGRAM LISTING COMPACT DISK APPENDIX
Not Applicable
BACKGROUND OF THE INVENTION
Non-rigid containers such as bags, usually made of plastic, are cheap, disposable, and universally employed for the collection and disposal of refuse. An example is the use by highway crew members, often volunteers, who employ them to collect discarded highway refuse. Highway cleanup collectors may be required to carry these containers over long distances while picking up discarded items.
Users of non-rigid containers have two significant problems. First, it is awkward to keep them open, especially outdoors in windy conditions. Second, it is difficult to carry them when weighted down with contents, resulting in containers being dragged on the ground rather than carried. Highway trash collectors need a small, easily portable device that overcomes these two problems.
Many inventions have been described for opening and supporting non-rigid containers. However, no prior art is satisfactory as a carrier for roadway refuse collection. (See International Classification search number 665667/12, sack holders, i.e. stands or frames with means for supporting sacks in the open condition to facilitate filling with articles or materials.) Emphasis of prior art has been to support non-rigid containers in their fully open configuration with less emphasis on portability. As examples O. Hanks (U.S. Pat. No. 63,383), H. W. Hildreth (U.S. Pat. No. 1,057,240), E. B. Bannsen (U.S. Pat. No. 3,161,391), S. T. Stoltze U.S. Pat. No. 3,313,504), O'Donnell (U.S. Pat. No. 3,826,455), Elmer (U.S. Pat. No. 4,157,801), Lake (U.S. Pat. No. 3,687,408), Vandermast (U.S. Pat. No. 3,627,242), E. E. Burroughs et al. (U.S. Pat. No. 3,388,882), Hambleton (U.S. Pat. No. 4,437,634), describe framed stands that support and keep open a non-rigid container. These devices are useful at a fixed location or in a limited area but are awkward to carry over a long distance.
Washington (U.S. Pat. No. 4,287,701) describes a ring device for keeping a non-rigid container open, but this device lacks a handle.
F. W. Cerny (U.S. Pat. No. 1,265,996) and Linn (U.S. Pat. No. 9,038,248) describe, a handle for a non-rigid container that is suitable for small, light containers but is not suitable for carrying heavy ones.
Other handles have been described for carrying non-rigid containers having strings, straps, ropes, or other attachment points. None of these devices is suitable as a handle for a typical plastic trash bag devoid of attachment points. Examples are the devices described by Startzell (U.S. Pat. No. 8,020,910), Palmer (U.S. Pat. No. 7,302,735), Bradford (U.S. Pat. No. 7,097,223), Novakovich et al. (U.S. Pat. No. 7,090,272), Shin (U.S. Pat. No. 6,199,690), Tipp (U.S. Pat. No. 5,865,494), Lisbon (U.S. Pat. No. 5,803,522), Kosteniuk (U.S. Pat. No. 5,645,306), and Randels (U.S. Pat. No. 5,527,076).
This application introduces new art that can satisfy the utility, portability, and simplicity requirements of a carrier for non-rigid containers used by crews for highway refuse collection.
BRIEF SUMMARY OF THE INVENTION
A handle that attaches to a non-rigid container by means of friction is described. The device comprises three components: a rigid member having 2 ends such as a rod or tube, an end cap for each end of the rigid member, and a retaining band such as an elastic band for detachably securing each end cap from its associated end of the rigid member. To attach a container the end caps are first removed, the periphery of the open edge of a container is draped across the uncovered ends of the rigid member and the end caps are replaced over each end of the rigid member entrapping the open edge of the container. The edge of the container is held in place by the combined action of the friction of the entrapment and the action of the retaining band. The rigid member serves as a handle for carrying the container as well as a means for maintaining an opening for insertion of articles or material.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
Drawing Sheet 1/3:
FIG. 1 is a front elevational view of one embodiment of the invention with the end caps in place.
FIG. 2 is a front elevational view of the embodiment of the invention shown in FIG. 1 with the end caps removed.
FIG. 3 is a side perspective view of the embodiment of the invention shown in FIG. 1 with the end caps in place.
FIG. 4 is a side perspective view of the embodiment of the invention shown in FIG. 1 with the end caps removed.
Drawing Sheet 2/3:
FIG. 5 is a front elevational view of a second embodiment of the invention with the end caps in place.
FIG. 6 is a front elevational view of a second embodiment of the invention shown in FIG. 5 with the end caps removed.
FIG. 7 is a side perspective view of a second embodiment of the invention shown in FIG. 5 with the end caps in place.
FIG. 8 is a side perspective view of a second embodiment of the invention shown in FIG. 5 with the end caps removed.
Drawing Sheet 3/3:
FIG. 9 is a sketch of an embodiment of the invention with an attached container (plastic bag) illustrating the carrier components, the entrapments of the margin of the container's opening, and the manner in which the container's opening is maintained and the container is carried.
DETAILED DESCRIPTION OF THE INVENTION
Referring to the drawings wherein like numerals represent like elements throughout the several views, there is shown a portable non-rigid container carrier comprising three components: a rigid member ( 1 ) preferably a straight rod or tube having opposed ends, end caps ( 2 ) carefully fitted to the dimensions of the ends of rigid member ( 1 ) preferably composed of a rubber-like material, and a retaining bands ( 3 ) preferably composed of an elastic material.
Component 1 . The preferred embodiment of the rod ( 1 ) is a hollow rod or tube composed of any suitable material such as metal (e.g. aluminum), plastic (e.g. polyvinyl chloride), or composite (e.g. carbon fiber). The strength of the rod ( 1 ) should be sufficient to resist bending under the maximum expected load. The optimum length of the rod ( 1 ) is dependent on the size of the opening of the container, such as a plastic bag ( 4 ), for which it is to serve as a handle. If the rod ( 1 ) is too short, the handle will not keep the container ( 4 ) open to a convenient width; if the rod ( 1 ) is too long, the tension along the opening is likely to tear the container ( 4 ). The optimum length is approximately ¼th of the circumference of the container's opening ( 7 ). A rod ( 1 ) intended for use with different sized containers must have a length that is adjustable. The cross-sectional area of the rod ( 1 ) preferably allows it to fit comfortably in the hand. The cross-sectional dimensions of the ends of the rod ( 1 ) are such as to allow an entrapment area ( 5 ) sufficient to prevent slippage of or perforation of the container ( 4 ).
Component 2 . Caps ( 2 ) are used at each end of the rigid member ( 1 ) in order to entrap the container ( 4 ). If the caps ( 2 ) are to be fitted on the outside of the rigid member ( 1 ), they should have an inside diameter that is determined by the outside diameter of the corresponding end of rigid member ( 1 ) and the thickness of the material of the container ( 4 ). The inside diameter of the caps ( 2 ) should be small enough to hold the edge ( 6 ) of an entrapped container ( 4 ) by friction but not so small that it cannot be inserted over and removed from the end of the rod ( 1 ) by hand. The length of the overlap between the rod ( 1 ) and the cap ( 2 ) is important. If the length of the overlap is too short, the cap ( 2 ) is likely to be pulled off by a loaded container ( 4 ); if the length of the overlap is too long, the cap may be difficult to insert or the container ( 4 ) may tear along the length of the entrapment ( 5 ). The outside diameter and shape of the cap ( 2 ) should make it easy to grasp, pull, and twist by hand. The cap ( 2 ) can be made of any suitable material, but a flexible material, such as rubber, is preferable. The flexibility of a rubber cap ( 2 ) allows it to accommodate to various container thicknesses and is easy to grip by hand. The wall thickness of the overlapping portion of the cap ( 2 ) is determined by the physical properties of the cap material: the more flexible the material, the thicker the wall must be; the less flexible, the thinner the wall must be. The material must be strong enough not to tear under load yet flexible enough not to cause the container ( 4 ) to tear. If a hollow rod (tube) is chosen for the rigid member ( 1 ), end caps ( 2 ) can be configured to fit inside (rather than outside) the rod ( 1 ). Also, end caps ( 2 ) can be configured to fit both inside and outside the rod ( 1 ) to maximize the area of frictional contact between the container ( 4 ), the caps ( 2 ), and the rod ( 1 ).
Component 3 . The third component of the carrier is means for detachably securing the caps ( 2 ) to the ends of the rod ( 1 ). In the embodiments shown in the drawings, the retaining means comprise an elastic band ( 3 ) attached at one end to each of the caps ( 2 ) and at the other end to the rod ( 1 ) ( FIGS. 1-4 ) or a single elastic band ( 3 ) extending within the hollow rod ( 1 ) and attached at either end to one of the caps ( 2 ) ( FIGS. 5-8 ). The retaining band ( 3 ) serves three purposes. First, it holds the caps ( 2 ) in place when the carrier is not in use preventing their loss. Second, it allows the caps ( 2 ) to be removed temporarily while the edge ( 6 ) of the container ( 4 ) is draped over the end of the rod ( 1 ). Third, the retaining band ( 3 ) helps keep the caps ( 2 ) in place while the carrier is in use. The retaining band ( 3 ) should be strong enough to hold the cap ( 2 ) in place but elastic enough to allow the cap ( 2 ) to be removed from the end of the rod ( 1 ) with minimal effort. The retaining band ( 3 ) should be attached to the cap ( 2 ) and the rod ( 1 ) in such a way not to interfere with the procedure of entrapment nor should its placement interfere with the use of the rod ( 1 ) as a handle. One method of attaching the retaining band ( 3 ) is to place it externally near each end of the rod ( 1 ) ( FIGS. 1-4 ); another method is to place it in the cavity of a hollow rod ( FIGS. 5-8 ).
Directions for use:
Step 1. Remove one end cap ( 2 ) from the rod ( 1 ).
Step 2. Drape a portion of the open edge of the container ( 6 ) over one end of the rod ( 1 ).
Step 3. Press the end cap ( 2 ) into place with a twisting motion, entrapping a portion ( 5 ) between the inside of the cap ( 2 ) and the outside of the rod ( 1 ).
Step 4. Remove the other end cap ( 2 ).
Step 5. Pull the edge of the container ( 6 ) along the length of the rod ( 1 ) and over its other end.
Step 6. Press the other end cap ( 2 ) into place with a twisting motion, entrapping another portion ( 5 ) the container's edge ( 6 ) at the other end of the rod ( 1 ).
The rod ( 1 ) is now the handle for carrying the container ( 4 ). The non-rigid container ( 4 ) will drape downward from either side of the rod ( 1 ) keeping the container ( 4 ) open ( 7 ) for insertion of articles or material. Once the container ( 4 ) is filled, both end caps ( 2 ) are removed with a twisting motion to release the container. Steps 1-6 can be repeated for additional containers. | 1a
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FIELD OF THE INVENTION
[0001] The invention relates to methods and apparatus for the provision of ventilatory assistance matched to a subject's respiratory need. The ventilatory assistance can be for a subject who is either spontaneously or non-spontaneously breathing, or moves between these breathing states. The invention is especially suitable for, but not limited to, spontaneously breathing human subjects requiring longterm ventilatory assistance, particularly during sleep.
BACKGROUND OF THE INVENTION
[0002] Subjects with severe lung disease, chest wall disease, neuromuscular disease, or diseases of respiratory control may require in-hospital mechanical ventilatory assistance, followed by longterm home mechanical ventilatory assistance, particularly during sleep. The ventilator delivers air or air enriched with oxygen to the subject, via an interface such as a nosemask, at a pressure that is higher during inspiration and lower during expiration.
[0003] In the awake state, and while waiting to go to sleep, the subject's ventilatory pattern is variable in rate and depth. Most known ventilatory devices do not accurately match the amplitude and phase of mask pressure to the subject's spontaneous efforts, leading to discomfort or panic. Larger amounts of asynchrony also reduce the efficiency of the device. During sleep, there are changes in the neural control of breathing as well as the mechanics of the subject's airways, respiratory muscles and chest wall, leading to a need for substantially increased ventilatory support. Therefore, unless the device can automatically adjust the degree of support, the amplitude of delivered pressure will either be inadequate during sleep, or must be excessive in the awake state. This is particularly important in subjects with abnormalities of respiratory control, for example central hypoventilation syndromes, such as Obesity Hypoventilation Syndrome, where there is inadequate chemoreceptor drive, or Cheyne Stokes breathing such as in patients with severe cardiac failure or after a stroke, where there is excessive or unstable chemoreceptor drive.
[0004] Furthermore, during sleep there are inevitably large leaks between mask and subject, or at the subject's mouth if this is left free. Such leaks worsen the error in matching the phase and magnitude of the machine's effort to the subject's needs, and, in the case of mouth leak, reduce the effectiveness of the ventilatory support.
[0005] Ideally a ventilatory assistance device should simultaneously address the following goals:
[0000] (i) While the subject is awake and making substantial ventilatory efforts, the delivered assistance should be closely matched in phase with the patient's efforts.
(ii) The machine should automatically adjust the degree of assistance to maintain at least a specified minimum ventilation, without relying on the integrity of the subject's chemoreflexes.
(iii) It should continue to work correctly in the presence of large leaks.
[0006] Most simple home ventilators either deliver a fixed volume, or cycle between two fixed pressures. They do so either at a fixed rate, or are triggered by the patient's spontaneous efforts, or both. All such simple devices fail to meet goal (ii) of adjusting the degree of assistance to maintain at least a given ventilation. They also largely fail to meet goal (i) of closely matching the subjects respiratory phase: timed devices make no attempt to synchronize with the subject's efforts; triggered devices attempt to synchronize the start and end of the breath with the subject's efforts, but make no attempt to tailor the instantaneous pressure during a breath to the subject's efforts. Furthermore, the triggering tends to fail in the presence of leaks, thus failing goal (iii).
[0007] The broad family of servo-ventilators known for at least 20 years measure ventilation and adjust the degree of assistance to maintain ventilation at or above a specified level, thus meeting goal (ii), but they still fail to meet goal (i) of closely matching the phase of the subject's spontaneous efforts, for the reasons given above. No attempt is made to meet goal (iii).
[0008] Proportional assistist ventilation (PAV), as taught by Dr Magdy Younes, for example in Principles and Practice of Mechanical Ventilation , chapter 15, aims to tailor the pressure vs time profile within a breath to partially or completely unload the subject's resistive and elastic work, while minimizing the airway pressure required to achieve the desired ventilation. During the inspiratory half-cycle, the administered pressure takes the form:
[0000] P ( t )= P 0 +R·f RESP ( t )+ E·V ( t )
[0000] where R is a percentage of the resistance of the airway, f RESP (t) is the instantaneous respiratory airflow at time t, E is a percentage of the elastance of lung and chest wall, and V(t) is the volume inspired since the start of inspiration to the present moment. During the expiratory half-cycle, V(t) is taken as zero, to produce passive expiration.
[0009] An advantage of proportional assist ventilation during spontaneous breathing is that the degree of assistance is automatically adjusted to suit the subject's immediate needs and their pattern of breathing, and is therefore comfortable in the spontaneously breathing subject. However, there are at least two important disadvantages. Firstly, V(t) is calculated as the integral of flow with respect to time since the start of inspiration. A disadvantage of calculating V(t) in this way is that, in the presence of leaks, the integral of the flow through the leak will be included in V(t), resulting in an overestimation of V(t), in turn resulting in a runaway increase in the administered pressure. This can be distressing to the subject. Secondly, PAV relies on the subject's chemoreceptor reflexes to monitor the composition of the arterial blood, and thereby set the level of spontaneous effort. The PAV device then amplifies this spontaneous effort. In subjects with abnormal chemoreceptor reflexes, the spontaneous efforts may either cease entirely, or become unrelated to the composition of the arterial blood, and amplification of these efforts will yield inadequate ventilation. In patients with existing Cheyne Stokes breathing during sleep, PAV will by design amplify the subject's waxing and waning breathing efforts, and actually make matters worse by exaggerating the disturbance. Thus PAV substantially meets goal (i) of providing assistance in phase with the subject's spontaneous ventilation, but cannot meet goal (ii) of adjusting the depth of assistance if the subject has inadequate chemoreflexes, and does not satisfactorily meet goal (iii).
[0010] Thus there are known devices that meet each of the above goals, but there is no device that meets all the goals simultaneously. Additionally, it is desirable to provide improvements over the prior art directed to any one of the stated goals.
[0011] Therefore, the present invention seeks to achieve, at least partially, one or more of the following:
[0000] (i) to match the phase and degree of assistance to the subject's spontaneous efforts when ventilation is well above a target ventilation,
(ii) to automatically adjust the degree of assistance to maintain at least a specified minimum average ventilation without relying on the integrity of the subject's chemoreflexes and to damp out instabilities in the spontaneous ventilatory efforts, such as Cheyne Stokes breathing.
(iii) to provide some immunity to the effects of sudden leaks.
DISCLOSURE OF THE INVENTION
[0012] In what follows, a fuzzy membership function is taken as returning a value between zero and unity, fuzzy intersection A AND B is the smaller of A and B , fuzzy union A OR B is the larger of A and B , and fuzzy negation NOT A is 1− A .
[0013] The invention discloses the determination of the instantaneous phase in the respiratory cycle as a continuous variable.
[0014] The invention further discloses a method for calculating the instantaneous phase in the respiratory cycle including at least the steps of determining that if the instantaneous airflow is small and increasing fast, then it is close to start of inspiration, if the instantaneous airflow is large and steady, then it is close to mid-inspiration, if the instantaneous airflow is small and decreasing fast, then it is close to mid-expiration, if the instantaneous airflow is zero and steady, then it is during an end-expiratory pause, and airflow conditions intermediate between the above are associated with correspondingly intermediate phases.
[0015] The invention further discloses a method for determining the instantaneous phase in the respiratory cycle as a continuous variable from 0 to 1 revolution, the method comprising the steps of:
selecting at least two identifiable features F N of a prototype flow-vs-time waveform f(t) similar to an expected respiratory flow-vs-time waveform, and for each said feature: determining by inspection the phase φ N in the respiratory cycle for said feature, assigning a weight W N to said phase, defining a “magnitude” fuzzy set M N whose membership function is a function of respiratory airflow, and a “rate of change” fuzzy set C N , whose membership function is a function of the time derivative of respiratory airflow, chosen such that the fuzzy intersection M N AND C N will be larger for points on the generalized prototype respiratory waveform whose phase is closer to the said feature F N than for points closer to all other selected features, setting the fuzzy inference rule R N for the selected feature F N to be: If flow is M N and rate of change of flow is C N then phase=φ N , with weight W N . measuring leak-corrected respiratory airflow, for each feature F N calculating fuzzy membership in fuzzy sets M N and C N , for each feature F N applying fuzzy inference rule R N to determine the fuzzy extent Y N =M N AND C N to which the phase is φ N , and applying a defuzzification procedure using Y N at phases φ N and weights W N to determine the instantaneous phase φ.
[0024] Preferably, the identifiable features include zero crossings, peaks, inflection points or plateaus of the prototype flow-vs-time waveform. Furthermore, said weights can be unity, or chosen to reflect the anticipated reliability of deduction of the particular feature.
[0025] The invention further discloses a method for calculating instantaneous phase in the respiratory cycle as a continuous variable, as described above, in which the step of calculating respiratory airflow includes a low pass filtering step to reduce non-respiratory noise, in which the time constant of the low pass filter is an increasing function of an estimate of the length of the respiratory cycle.
[0026] The invention further discloses a method for measuring the instantaneous phase in the respiratory cycle as a continuous variable as described above, in which the defuzzification step includes a correction for any phase delay introduced in the step of low pass filtering respiratory airflow.
[0027] The invention further discloses a method for measuring the average respiratory rate, comprising the steps of:
[0028] measuring leak-corrected respiratory airflow,
[0029] from the respiratory airflow, calculating the instantaneous phase (I) in the respiratory cycle as a continuous variable from 0 to 1 revolution, calculating the instantaneous rate of change of phase dφ/dt, and
[0030] calculating the average respiratory rate by low pass filtering said instantaneous rate of change of phase dφ/dt.
[0031] Preferably, the instantaneous phase is calculated by the methods described above.
[0032] The invention further discloses a method for providing ventilatory assistance in a spontaneously breathing subject, comprising the steps, performed at repeated sampling intervals, of:
[0033] ascribing a desired waveform template function π(φ), with domain 0 to 1 revolution and range 0 to 1,
[0034] calculating the instantaneous phase φ in the respiratory cycle as a continuous variable from 0 to 1 revolution,
[0035] selecting a desired pressure modulation amplitude A,
[0036] calculating a desired instantaneous delivery pressure as an end expiratory pressure plus the desired pressure modulation amplitude A multiplied by the value of the waveform template function π(φ) at the said calculated phase φ, and
[0037] setting delivered pressure to subject to the desired delivery pressure.
[0038] The invention further discloses a method for providing ventilatory assistance in a spontaneously breathing subject as described above, in which the step of selecting a desired pressure modulation amplitude is a fixed amplitude.
[0039] The invention further discloses a method for providing ventilatory assistance in a spontaneously breathing subject as described above, in which the step of selecting a desired pressure modulation amplitude in which said amplitude is equal to an elastance multiplied by an estimate of the subject's tidal volume.
[0040] The invention further discloses a method for providing ventilatory assistance in a spontaneously breathing subject as described above, in which the step of selecting a desired pressure modulation amplitude comprises the substeps of:
specifying a typical respiratory rate giving a typical cycle time, specifying a preset pressure modulation amplitude to apply at said typical respiratory rate, calculating the observed respiratory rate giving an observed cycle time, and calculating the desired amplitude of pressure modulation as said preset pressure modulation amplitude multiplied by said observed cycle time divided by the said specified cycle time.
[0045] The invention further discloses a method for providing ventilatory assistance in a spontaneously breathing subject, including at least the step of determining the extent that the subject is adequately ventilated, to said extent the phase in the respiratory cycle is determined from the subject's respiratory airflow, but to the extent that the subject's ventilation is inadequate, the phase in the respiratory cycle is assumed to increase at a pre-set rate, and setting mask pressure as a function of said phase.
[0046] The invention further discloses a method for providing ventilatory assistance in a spontaneously breathing subject, comprising the steps of: measuring respiratory airflow, determining the extent to which the instantaneous phase in the respiratory cycle can be determined from said airflow, to said extent determining said phase from said airflow but to the extent that the phase in the respiratory cycle cannot be accurately determined, the phase is assumed to increase at a preset rate, and delivering pressure as a function of said phase.
[0047] The invention further discloses a method for calculating the instantaneous inspired volume of a subject, operable substantially without run-away under conditions of suddenly changing leak, the method comprising the steps of:
[0048] determining respiratory airflow approximately corrected for leak,
[0049] calculating an index J varying from 0 to 1 equal to the fuzzy extent to which said corrected respiratory airflow is large positive for longer than expected, or large negative for longer than expected,
[0050] identifying the start of inspiration, and
[0051] calculating the instantaneous inspired volume as the integral of said corrected respiratory airflow multiplied by the fuzzy negation of said index J with respect to time, from start of inspiration.
[0052] The invention further discloses a method “A” for providing ventilatory assistance in a spontaneously breathing subject, the method comprising the steps, performed at repeated sampling intervals, of:
[0053] determining respiratory airflow approximately corrected for leak,
[0054] calculating an index J varying from 0 to 1 equal to the fuzzy extent to which said respiratory airflow is large positive for longer than expected, or large negative for longer than expected,
[0055] calculating a modified airflow equal to said respiratory airflow multiplied by the fuzzy negation of said index J,
[0056] identifying the phase in the respiratory cycle,
[0057] calculating the instantaneous inspired volume as the integral of said modified airflow with respect to time, with the integral held at zero during the expiratory portion of the respiratory cycle,
[0058] calculating a desired instantaneous delivery pressure as a function at least of the said instantaneous inspired volume, and
[0059] setting delivered pressure to subject to the desired delivery pressure.
[0060] The invention further discloses a method “B” for providing ventilatory assistance in a spontaneously breathing subject, comprising the steps of:
[0061] determining respiratory airflow approximately corrected for leak,
[0062] calculating an index J varying from 0 to 1 equal to the fuzzy extent to which the respiratory airflow is large positive for longer than expected, or large negative for longer than expected,
[0063] identifying the phase in the respiratory cycle,
[0064] calculating a modified respiratory airflow equal to the respiratory airflow multiplied by the fuzzy negation of said index J,
[0065] calculating the instantaneous inspired volume as the integral of the modified airflow with respect to time, with the integral held at zero during the expiratory portion of the respiratory cycle,
[0066] calculating the desired instantaneous delivery pressure as an expiratory pressure plus a resistance multiplied by the instantaneous respiratory airflow plus a nonlinear resistance multiplied by the respiratory airflow multiplied by the absolute value of the respiratory airflow plus an elastance multiplied by the said adjusted instantaneous inspired volume, and
[0067] setting delivered pressure to subject to the desired delivery pressure.
[0068] The invention yet further discloses a method “C” for providing assisted ventilation to match the subject's need, comprising the steps of:
[0069] describing a desired waveform template function π(φ), with domain 0 to 1 revolution and range 0 to 1,
[0070] determining respiratory airflow approximately corrected for leak,
[0071] calculating an index J varying from 0 to 1 equal to the fuzzy extent to which the respiratory airflow is large positive for longer than expected, or large negative for longer than expected,
[0072] calculating J PEAK equal to the recent peak of the index J,
[0073] calculating the instantaneous phase in the respiratory cycle,
[0074] calculating a desired amplitude of pressure modulation, chosen to servo-control the degree of ventilation to at least exceed a specified ventilation,
[0075] calculating a desired delivery pressure as an end expiratory pressure plus the calculated pressure modulation amplitude A multiplied by the value of the waveform template function π(φ) at the said calculated phase φ, and
[0076] setting delivered pressure to subject to said desired instantaneous delivered pressure.
[0077] The invention yet further discloses a method for providing assisted ventilation to match the subject's need, as described above, in which the step of calculating a desired amplitude of pressure modulation, chosen to servo-control the degree of ventilation to at least exceed a specified ventilation, comprises the steps of:
[0078] calculating a target airflow equal to twice the target ventilation divided by the target respiratory rate,
[0079] deriving an error term equal to the absolute value of the instantaneous low pass filtered respiratory airflow minus the target airflow, and
[0080] calculating the amplitude of pressure modulation as the integral of the error term multiplied by a gain, with the integral clipped to lie between zero and a maximum.
[0081] The invention yet further discloses a method for providing assisted ventilation to match the subject's need, as described above, in which the step of calculating a desired amplitude of pressure modulation, chosen to servo-control the degree of ventilation to at least exceed a specified ventilation, comprises the following steps:
calculating a target airflow equal to twice the target ventilation divided by the target respiratory rate, deriving an error term equal to the absolute value of the instantaneous low pass filtered respiratory airflow minus the target airflow, calculating an uncorrected amplitude of pressure modulation as the integral of the error term multiplied by a gain, with the integral clipped to lie between zero and a maximum, calculating the recent average of said amplitude as the low pass filtered amplitude, with a time constant of several times the length of a respiratory cycle, and setting the actual amplitude of pressure modulation to equal the said low pass filtered amplitude multiplied by the recent peak jamming index J PEAK plus the uncorrected amplitude multiplied by the fuzzy negation of J PEAK .
[0087] The invention yet further discloses a method for providing assisted ventilation to match the subject's need, and with particular application to subjects with varying respiratory mechanics, insufficient respiratory drive, abnormal chemoreceptor reflexes, hypoventilation syndromes, or Cheyne Stokes breathing, combined with the advantages of proportional assist ventilation adjusted for sudden changes in leak, comprising the steps, performed at repeated sampling intervals, of:
calculating the instantaneous mask pressure as described for methods “A” or “B” above, calculating the instantaneous mask pressure as described for method “C” above, calculating a weighted average of the above two pressures, and setting the mask pressure to the said weighted average.
[0092] The invention yet further discloses apparatus to give effect to each one of the methods defined, including one or more transducers to measure flow and/or pressure, processor means to perform calculations and procedures, flow generators for the supply of breathable gas at a pressure above atmospheric pressure and gas delivery means to deliver the breathable gas to a subject's airways.
[0093] The apparatus can include ventilators, ventilatory assist devices, and CPAP devices including constant level, bi-level or autosetting level devices.
[0094] It is to be understood that while the algorithms embodying the invention are explained in terms of fuzzy logic, approximations to these algorithms can be constructed without the use of the fuzzy logic formalism.
BRIEF DESCRIPTION OF THE DRAWINGS
[0095] A number of embodiments will now be described with reference to the accompanying drawings in which:
[0096] FIGS. 1 a and 1 b show apparatus for first and second embodiments of the invention respectively;
[0097] FIG. 2 is a pressure waveform function π(φ) used in the calculation of the desired instantaneous delivery pressure as a function of the instantaneous phase φ in the respiratory cycle for a first embodiment of the invention;
[0098] FIG. 3 shows fuzzy membership functions for calculating the degree of membership in each of five magnitude fuzzy sets (“large negative”, “small negative”, “zero”, “small positive”, and “large positive”) from the normalized respiratory airflow according to the first embodiment of the invention; and
[0099] FIG. 4 shows fuzzy membership functions for calculating the degree of membership in each of five rate of change fuzzy sets (“rising fast”, “rising slowly”, “steady”, “falling slowly”, and “falling fast”) from the normalized rate of change of airflow according to the first embodiment of the invention;
[0100] FIG. 5 is a pressure waveform function π(φ) used in the calculation of the desired instantaneous delivery pressure as a function of the instantaneous phase φ in the respiratory cycle for a second embodiment of the invention;
[0101] FIG. 6 shows calculation of a quantity “lead-in” as a function of time since the most recent mask off-on transition;
[0102] FIG. 7 shows a fuzzy membership function for fuzzy set A I as a function of time since the most recent expiratory-to-inspiratory (negative-to-positive) zero crossing of the respiratory airflow signal, such that the membership function measures the extent to which the respiratory airflow has been positive for longer than expected;
[0103] FIG. 8 shows a membership function for fuzzy set B I as a function of respiratory airflow, such that the membership function measures the extent to which respiratory airflow is large positive;
[0104] FIG. 9 shows an electrical analog of the calculation of a recent peak jamming index J PEAK from the instantaneous jamming index J;
[0105] FIG. 10 shows the calculation of the time constant τ used in low pass filtering steps in the calculation of the conductance of a leak, as a function of the recent peak jamming index J PEAK .
[0106] FIG. 11 shows a prototypical respiratory flow-time curve, with time on the x-axis, marking nine features;
[0107] FIG. 12 shows membership functions for fuzzy sets “large negative”, “small negative”, “zero”, “small positive”, and “large positive” as functions of normalized respiratory airflow according to a second embodiment of the invention;
[0108] FIG. 13 shows membership functions for fuzzy sets “falling”, “steady”, and “rising” as functions of normalized rate of change of respiratory airflow df/dt according to a second embodiment of the invention;
[0109] FIG. 14 shows the membership function for fuzzy set “hypopnea”;
[0110] FIG. 15 shows the calculation of the time constant τ for calculation of normalized recent ventilation, as a function of “servo gain” being the gain used for servo-control of minute ventilation to at least exceed a specified target ventilation;
[0111] FIG. 16 shows the membership function for fuzzy set “hyperpnea” as a function of normalized recent ventilation;
[0112] FIG. 17 shows the membership function for fuzzy set “big leak” as a function of leak;
[0113] FIG. 18 shows the membership functions for fuzzy sets “switch negative” and “switch positive” as a function of normalized respiratory airflow;
[0114] FIG. 19 shows the membership functions for fuzzy sets “insp_phase” and “exp_phase” as functions of the instantaneous phase in the respiratory cycle φ;
[0115] FIG. 20 shows schematically how function W(y), used in defuzzification, calculates the area (shaded) of an isosceles triangle of unit base and height cut off below height y;
[0116] FIGS. 21-26 show actual 60 second flow and pressure tracings from the second embodiment of the invention during operation; the vertical scale for flow (heavy trace) is ±1 L/sec, inspiration upwards and the vertical scale for the pressure (light trace) is 0-25 cmH 2 O; where:
[0117] FIG. 21 shows that a short central apnea (b) is permitted when effort ceases at point (c) after a preceding deep breath (a);
[0118] FIG. 22 shows that a central apnea is not permitted when effort ceases at arrow (a) without a preceeding deep breath;
[0119] FIG. 23 is recorded with servo gain set high, and shows that a central apnea is no longer permitted when effort ceases at arrow (a) despite preceding deep breathing;
[0120] FIG. 24 shows automatically increasing end-inspiratory pressure as the subject makes voluntarily deeper inspiratory efforts;
[0121] FIG. 25 is recorded with a somewhat more square waveform selected, and shows automatically increasing pressure support when the subject voluntarily attempts to resist by stiffening the chest wall at point (a);
[0122] FIG. 26 shows that with sudden onset of a sever 1.4 L/sec leak at (a), the flow signal returns to baseline (b) within the span of a single breath, and pressure continues to cycle correctly throughout; and
[0123] FIG. 27 shows an actual 60 second tracing showing respiratory airflow (heavy trace, ±1 L/sec full scale) and instantaneous phase (light trace, 0-1 revolution full scale).
DESCRIPTION OF PREFERRED EMBODIMENTS
[0124] The two embodiments to be described are ventilators that operate in a manner that seeks to simultaneously achieve the three goals stated above.
First Embodiment
[0125] Apparatus to give effect to a first embodiment of the apparatus is shown in FIG. 1 a . A blower 10 supplies a breathable gas to mask 11 in communication with the subject's airway via a delivery tube 12 and exhausted via a exhaust diffuser 13 . Airflow to the mask 11 is measured using a pneumotachograph 14 and a differential pressure transducer 15 . The mask flow signal from the transducer 15 is then sampled by a microprocessor 16 . Mask pressure is measured at the port 17 using a pressure transducer 18 . The pressure signal from the transducer 18 is then sampled by the microprocessor 16 . The microprocessor 16 sends an instantaneous mask pressure request signal to the servo 19 , which compares said pressure request signal with actual pressure signal from the transducer 18 to the control fan motor 20 . The microprocessor settings can be adjusted via a serial port 21 .
[0126] It is to be understood that the mask could equally be replaced with a tracheotomy tube, endotracheal tube, nasal pillows, or other means of making a sealed connection between the air delivery means and the subject's airway.
[0127] The microprocessor 16 is programmed to perform the following steps, to be considered in conjunction with Tables 1 and 2.
[0000]
TABLE 1
Fuzzy Inference Rules for a first embodiment
N
Fuzzy Interference Rule
Fuzzy Phase
1
if size is
Zero
and rate of
Increasing
then phase is
Start Inspiration
2
if size is
Small
and rate of
Increasing
then phase is
Early Inspiration
Positive
change is
Slowly
3
if size is
Large
and rate of
Steady
then phase is
Peak Inspiration
Positive
change is
4
if size is
Small
and rate of
Decreasing
then phase is
Late Inspiration
Positive
change is
Slowly
5
if size is
Zero
and rate of
Decreasing
then phase is
Start Expiration
change is
Fast
6
if size is
Small
and rate of
Decreasing
then phase is
Early Expiration
Negative
change is
Slowly
7
if size is
Large
and rate of
Steady
then phase is
Peak Expiration
Negative
change is
8
if size is
Small
and rate of
Increasing
then phase is
Late Expiration
Negative
change is
Slowly
9
if size is
Zero
and rate of
Steady
then phase is
Expiratory Pause
change is
10
always
phase is
Unchanged
[0000]
TABLE 2
Association of phases with fuzzy rules for a first embodiment.
N
Phase
Φ N
1
Start Inspiration
0.0
2
Early Inspiration
values
3
Peak Inspiration
intermediate between
4
Late Inspiration
0.0 and 0.5
5
Start Expiration
0.50
6
Early Expiration
values
7
Peak Expiration
intermediate between
8
Late Expiration
0.5 and 1.0
9
Expiratory Pause
10
Unchanged
Φ
1. Set desired target values for the duration of inspiration TI TGT , duration of expiration TE TGT , and minute ventilation V TGT . Choose suitable constants P 0 and A STD where P 0 is the desired end expiratory pressure, and A STD is the desired increase in pressure above P 0 at end inspiration for a breath of duration TT TGT =TI TGT +TE TGT .
2. Choose a suitable pressure waveform function π(Φ), such as that shown in FIG. 2 , such that the desired delivery pressure at phase Φ will be given by:
[0000] P=P 0 +A π(Φ)
where the amplitude A equals the difference between the end inspiratory pressure and end expiratory pressure. However, other waveforms may be suitable for subjects with particular needs. 3. Initialize the phase Φ in the respiratory cycle to zero, and initialize the current estimates of actual inspiratory and expiratory duration TI and TE to TI TGT and TE TGT respectively. 4. Initialize the rate of change of phase during inspiration ΔΦ I between sampling intervals of length T to:
[0000] ΔΦ+=0.5 T/TI TGT
5. Initialize the rate of change of phase during expiration ΔΦ E to:
[0000] ΔΦ E =0.5 T/TE TGT
6. Measure the instantaneous respiratory airflow f RESP . 7. Calculate the average total breath duration TT=TI+TE 8. Low pass filter the respiratory airflow with an adjustable time constant τf, where τf is a fixed small fraction of TT. 9. Calculate the instantaneous ventilation V, as half the absolute value of the respiratory airflow:
[0000] V= 0.5 |f RESP | 10. From the target ventilation V TGT and the measured minute ventilation V, derive an error term V ERR , such that large values of V ERR indicate inadequate ventilation:
[0000] V ERR =∫( V TGT −V ) dt
11. TakeV BAR as the result of low pass filtering V with a time constant τV BAR which is long compared with TT. 12. Calculate a normalized airflow f NORM , where
[0000] f NORM =f RESP /V BAR . 13. From f NORM , calculate the degree of membership in each of the fuzzy sets whose membership functions are shown in FIG. 3 . 14. Calculate a normalized rate of change df NORM /dΦ, equal to df NORM /dt divided by the current estimate of the average respiratory cycle time TT. 15. From the normalized rate of change, calculate the degree of membership in each of the fuzzy sets shown in FIG. 4 . 16. For each row N in Table 1, calculate the degree of membership g N in the fuzzy set shown in the column labelled Fuzzy Phase, by applying the fuzzy inference rules shown. 17. Associate with the result of each of the N rules a phase Φ N as shown in Table 2, noting that Φ 10 is the current phase Φ. 18. Increase each of the Φ N excepting Φ 10 by 0.89 τ/TT, to compensate for the previous low pass filtering step. 19. Calculate a new instantaneous phase Φ INST as the angle to the center of gravity of N unit masses at polar coordinates of radius g N and angle Φ N revolutions. 20. Calculate the smallest signed difference ΔΦ INsT between the phase estimated in the previous step and the current phase.
[0000] ΔΦ INST =1−(ΔΦ INST −Φ)(Φ INST −Φ>0.5)
[0000] ΔΦ INST =Φ INST −Φ++1(Φ INST −Φ<−0.5)
[0000] ΔΦ INST=Φ INST −Φ(otherwise)
21. Derive a revised estimate ΔΦ REV equal to a weighted mean of the value calculated in the previous step and the average value (ΔΦ I or ΔΦ E as appropriate).
[0000] ΔΦ=(1 −W )ΔΦ I +WΔΦ INST (0<Φ<0.5)
[0000] ΔΦ=(1 −W )ΔΦ I +WΔΦ INST (otherwise)
Smaller values of W will cause better tracking of phase if the subject is breathing regularly, and larger values will cause better tracking of phase if the subject is breathing irregularly. 22. Derive a blending fraction B, such that the blending fraction is unity if the subject's ventilation is well above V TGT , zero if the subject is breathing near or below V TGT , and increasing proportionally from zero to unity as the subject's ventilation increases through an intermediate range. 23. Calculate ΔΦ BLEND influenced chiefly by ΔΦ calculated in step 21 from the subject's respiratory activity if the subject's ventilation is well above V TGT ; influenced chiefly by the target respiratory duration if the subject is breathing near or below V TGT ; and proportionally between these two amounts if ventilation is in an intermediate range:
[0000] ΔΦ BLEND =BΔΦ+ 0.5(1 −B ) T/TI TGT (0<Φ<0.5)
[0000] ΔΦ BLEND =BΔΦ+ 0.5(1 −B ) T/TE TGT (otherwise)
24. Increment Φ by ΔΦ BLEND 25. Update the average rate of change of phase (ΔΦ I or ΔΦ E as appropriate).
[0000] ΔΦ I =T/τV BAR (ΔΦ BLEND −ΔΦ I )(0<Φ<0.5)
[0000] ΔΦ E =T/τ BAR (ΔΦ BLEND −ΔΦ E )(otherwise)
26. Recalculate the approximate duration of inspiration TI and expiration TE:
[0000] TI= 0.5 T/ΔΦ I
[0000] TE= 0.5 T/ΔΦ E 27. Calculate the desired mask pressure modulation amplitude A D :
[0000] A D =A STD /2( TT<TT STD /2)
[0000] A D =2 ·A STD ( TT> 2 ·TT STD )
[0000] A D =A STD ·TT/TT STD (otherwise) 28. From the error term V ERR , calculate an additional mask pressure modulation amplitude A E :
[0000] A E =K·V ERR ( for V ERR >0)
[0000] A E =0(otherwise)
[0000] where larger values of K will produce a faster but less stable control of the degree of assistance, and smaller values of K will produce slower but more stable control of the degree of assistance.
29. Set the mask pressure P MASK to:
[0000] P MASK =P 0 +( A D +A E )π(Φ)
30. Wait for a sampling interval T, short compared with the duration of a respiratory cycle, and then continue at the step of measuring respiratory airflow.
Measurement of Respiratory Airflow
[0160] As follows from above, it is necessary to respiratory airflow, which is a standard procedure to one skilled in the art. In the absence of leak, respiratory airflow can be measured directly with a pneumotachograph placed between the mask and the exhaust. In the presence of a possible leak, one method disclosed in European Publication No 0 651 971 incorporated herein by cross-reference is to calculate the mean flow through the leak, and thence calculate the amount of modulation of the pneumotachograph flow signal due to modulation of the flow through the leak induced by changing mask pressure, using the following steps:
1. Measure the airflow at the mask f MASK using a pneumotachograph 2. Measure the pressure at the mask P MASK 3. Calculate the mean leak as the low pass filtered airflow, with a time constant long compared with a breath. 4. Calculate the mean mask pressure as the low pass filtered mask pressure, with a time constant long compared with a breath. 5. Calculate the modulation of the flow through the leak as:
[0000] δ(leak)=0.5 times the mean leak times the inducing pressure,
[0000] where the inducing pressure is P MASK −mean mask pressure.
Thence the instantaneous respiratory airflow can be calculated as:
[0000] f RESP =f MASK −mean leak−δ(leak)
[0000] A convenient extension as further disclosed in EP 0 651 971 (incorporated herein by cross-reference) is to measure airflow f TURBINE and pressure P TURBINE at the outlet of the turbine, and thence calculate P MASK and f MASK by allowing for the pressure drop down the air delivery hose, and the airflow lost via the exhaust:
[0000] Δ P HOS E=K 1 ( F TURBINE )− K 2 ( F TURBINE ) 2 1.
[0000] P MASK =P TURBINE −ΔP HOSE 2.
[0000] F EXHAUST =K 3 √P MASK 3.
[0000] F MASK =F TURBINE −F EXHAUST 4.
Alternative Embodiment
[0166] The following embodiment is particularly applicable to subjects with varying respiratory mechanics, insufficient respiratory drive, abnormal chemoreceptor reflexes, hypoventilation syndromes, or Cheyne Stokes breathing, or to subjects with abnormalities of the upper or lower airways, lungs, chest wall, or neuromuscular system.
[0167] Many patients with severe lung disease cannot easily be treated using a smooth physiological pressure waveform, because the peak pressure required is unacceptably high, or unachievable with for example a nose-mask. Such patients may prefer a square pressure waveform, in which pressure rises explosively fast at the moment of commencement of inspiratory effort. This may be particularly important in patients with high intrinsic PEEP, in which it is not practicable to overcome the intrinsic PEEP by the use of high levels of extrinsic PEEP or CPAP, due to the risk of hyperinflation. In such subjects, any delay in triggering is perceived as very distressing, because of the enormous mis-match between expected and observed support. Smooth waveforms exaggerate the perceived delay, because of the time taken for the administered pressure to exceed the intrinsic PEEP. This embodiment permits the use of waveforms varying continuously from square (suitable for patients with for example severe lung or chest wall disease or high intrinsic PEEP) to very smooth, suitable for patients with normal lungs and chest wall, but abnormal respiratory control, or neuromuscular abnormalities. This waveform is combined either with or without elements of proportional assist ventilation (corrected for sudden changes in leak), with servo-control of the minute ventilation to equal or exceed a target ventilation. The latter servo-control has an adjustable gain, so that subjects with for example Cheyne Stokes breathing can be treated using a very high servo gain to over-ride their own waxing and waning patterns; subjects with various central hypoventilation syndromes can be treated with a low servo gain, so that short central apneas are permitted, for example to cough, clear the throat, talk, or roll over in bed, but only if they follow a previous period of high ventilation; and normal subjects are treated with an intermediate gain.
[0000] Restating the above in other words:
The integral gain of the servo-control of the degree of assistance is adjustable from very fast (0.3 cmH 2 O/L/sec/sec) to very slow. Patients with Cheyne-Stokes breathing have a very high ventilatory control loop gain, but a long control loop delay, leading to hunting. By setting the loop gain even higher, the patient's controller is stabilized. This prevents the extreme breathlessness that normally occurs during each cycle of Cheyne-Stokes breathing, and this is very reassuring to the patient. It is impossible for them to have a central apnea. Conversely, subjects with obesity-hypoventilation syndrome have low or zero loop gain. They will not feel breathless during a central apnea. However, they have much mucus and need to cough, and are also often very fidgety, needing to roll about in bed. This requires that they have central apneas which the machine does not attempt to treat. By setting the loop gain very low, the patient is permitted to take a couple of deep breaths and then have a moderate-length central apnea while coughing, rolling to over, etc, but prolonged sustained apneas or hypopneas are prevented. Sudden changes in leakage flow are detected and handled using a fuzzy logic algorithm. The principle of the algorithm is that the leak filter time constant is reduced dynamically to the fuzzy extent that the apparent respiratory airflow is a long way from zero for a long time compared with the patient's expected respiratory cycle length. Rather than simply triggering between two states (IPAP, EPAP), the device uses a fuzzy logic algorithm to estimate the position in the respiratory cycle as a continuous variable. The algorithm permits the smooth pressure waveform to adjust it's rise time automatically to the patient's instantaneous respiratory pattern. The fuzzy phase detection algorithm under normal conditions closely tracks the patient's breathing. To the extent that there is a high or suddenly changing leak, or the patient's ventilation is low, the rate of change of phase (respiratory rate) smoothly reverts to the specified target respiratory rate. Longer or deeper hypopneas are permitted to the extent that ventilation is on average adequate. To the extent that the servo gain is set high to prevent Cheyne Stokes breathing, shorter and shallower pauses are permitted. Airflow filtering uses an adaptive filter, which shortens it's time constant if the subject is breathing rapidly, to give very fast response times, and lenthens if the subject is breathing slowly, to help eliminate cardiogenic artifact. The fuzzy changing leak detection algorithm, the fuzzy phase detection algorithm with its differential handling of brief expiratory pauses, and handling of changing leak, together with the smooth waveform severally and cooperatively make the system relatively immune to the effects of sudden leaks. By suitably setting various parameters, the system can operate in CPAP, bilevel spontaneous, bilevel timed, proportional assist ventilation, volume cycled ventilation, and volume cycled servo-ventilation, and therefore all these modes are subsets of the present embodiment. However, the present embodiment permits states of operation that can not be achieved by any of the above states, and is therefore distinct from them.
Notes
[0175] Note 1: in this second embodiment, the names and symbols used for various quantities may be different to those used in the first embodiment.
Note 2: The term “swing” is used to refer to the difference between desired instantaneous pressure at end inspiration and the desired instantaneous pressure at end expiration.
Note 3: A fuzzy membership function is taken as returning a value between zero for complete nonmembership and unity for complete membership. Fuzzy intersection A AND B is the lesser of A and B, fuzzy union A OR B is the larger of A and B, and fuzzy negation NOT A is 1−A.
Note 4: root(x) is the square root of x, abs(x) is the absolute value of x, sign(x) is −1 if x is negative, and +1 otherwise. An asterisk (*) is used to explicitly indicate multiplication where this might not be obvious from context.
Apparatus
[0176] The apparatus for the second embodiment is shown in FIG. 1 b . The blower 110 delivers air under pressure to the mask 111 via the air delivery hose 112 . Exhaled air is exhausted via the exhaust 113 in the mask 111 . The pneumotachograph 114 and a differential pressure transducer 115 measure the airflow in the nose 112 . The flow signal is delivered to the microprocessor 116 . Pressure at any convenient point 117 along the nose 112 is measured using a pressure transducer 118 . The output from the pressure transducer 118 is delivered to the microcontroller 116 and also to a motor servo 119 . The microprocessor 116 supplies the motor servo 119 with a pressure request signal, which is then compared with the signal from the pressure transducer 118 to control the blower motor 120 . User configurable parameters are loaded into the microprocessor 116 via a communications port 121 , and the computed mask pressure and flow can if desired be output via the communications port 121 .
Initialization
[0177] The following user adjustable parameters are specified and stored:
[0000]
max permissible
maximum permissible mask pressure
pressure
max swing
maximum permissible difference between end
inspiratory pressure and end expiratory pressure.
min swing
minimum permissible difference between end
inspiratory pressure and end expiratory pressure.
epap
end expiratory pressure
min permissible
minimum permissible mask pressure
pressure
target
minute ventilation is sevo-controlled to equal or
ventilation
exceed this quantity
target
Expected respiratory rate. If the patient is achieving no
frequency
respiratory airflow, the pressure will cycle at this
frequency.
target duty
Expected ratio of inspiratory time to cycle time. If the
cycle
patient is achieving no respiratory airflow, the
pressure will follow this duty cycle.
linear resistance
resistive unloading = linear resistance * f +
and quad
quad_resistance * f 2 sign(f), where f is the
resistance
respiratory airflow. where sign(x) = −1 for
x < 0, +1 otherwise
elastance
Unload at least this much elastance
servo gain
gain for servo-control of minute ventilation to at least
exceed target ventilation.
waveform
Elastic unloading waveform time constant as a fraction
time constant
of inspiratory duration. (0.0 = square wave)
hose
ΔP from pressure sensing port to inside mask = hose
resistance
resistance times the square of the flow in the
intervening tubing.
diffuser
Flow through the mask exhaust port = diffuser
conductance
conductance * root mask pressure
[0178] At initialization, the following are calculated from the above user-specified settings:
[0179] The expected duration of a respiratory cycle, of an inspiration, and of an expiration are set respectively to:
[0000] STD T TOT =60 /target respiratory rate
[0000]
STD T
I
=STD T
TOT
*target duty cycle
[0000]
STD T
E
STD T
TOT
−STD T
I
[0180] The standard rates of change of phase (revolutions per sec) during inspiration and expiration are set respectively to:
[0000] STD dφ I =0.5 /STD T I
[0000] STD dφ E =0.5 /STD T E
[0181] The instantaneous elastic support at any phase φ in the respiratory cycle is given by:
[0000] PEL (φ)=swing*π(φ)
[0000] where swing is the pressure at end inspiration minus the pressure at end expiration,
[0000] π(φ)= e −2 τφduring inspiration,
[0000] e −4 t(φ−0.5)during expiration
[0000] and τ is the user-selectable waveform time constant.
[0182] If τ=0, then π(φ) is a square wave. The maximum implemented value for τ=0.3, producing a waveform approximately as shown in FIG. 5 .
[0183] The mean value of π(φ) is calculated as follows:
[0000]
Π
BAR
=
0.5
∫
0
.05
Π
(
φ
)
φ
Operations Performed Every 20 Milliseconds
[0184] The following is an overview of routine processing done at 50 Hz:
measure flow at flow sensor and pressure at pressure sensing port calculate mask pressure and flow from sensor pressure and flow calculate conductance of mask leak calculate instantaneous airflow through leak calculate respiratory airflow and low pass filtered respiratory airflow calculate mask on-off status and lead-in calculate instantaneous and recent peak jamming calculate time constant for leak conductance calculations calculate phase in respiratory cycle update mean rates of change of phase for inspiration and expiration, lengths of inspiratory and expiratory times, and respiratory rate add hose pressure loss to EPAP pressure add resistive unloading calculate instantaneous elastic assistance required to servo-control ventilation estimate instantaneous elastic recoil pressure using various assumptions weight and combine estimates add servo pressure to yield desired sensor pressure servo-control motor speed to achieve desired sensor pressure
[0202] The details of each step will now be explained.
Measurement of Flow and Pressure
[0203] Flow is measured at the outlet of the blower using a pneumotachograph and differential pressure transducer. Pressure is measured at any convenient point between the blower outlet and the mask. A humidifier and/or anti-bacterial filter may be inserted between the pressure sensing port and the blower. Flow and pressure are digitized at 50 Hz using an A/D converter.
Calculation of Mask Flow and Pressure
[0204] The pressure loss from pressure measuring point to mask is calculated from the flow at the blower and the (quadratic) resistance from measuring point to mask.
[0000] Hose pressure loss=sign (flow)*hose resistance*flow 2
[0000] where sign(x)=−1 for x<0, +1 otherwise. The mask pressure is then calculated by subtracting the hose pressure loss from the measured sensor pressure:
[0000]
Mask pressure=sensor pressure−hose pressure loss
[0205] The flow through the mask exhaust diffuser is calculated from the known parabolic resistance of the diffuser holes, and the square root of the mask pressure:
[0000] diffuser flow=exhaust resistance*sign(mask pressure)*root( abs (mask pressure))
[0206] Finally, the mask flow is calculated:
[0000] mask flow=sensor flow−diffuser flow
[0207] The foregoing describes calculation of mask pressure and flow in the various treatment modes. In diagnostic mode, the patient is wearing only nasal cannulae, not a mask. The cannula is plugged into the pressure sensing port. The nasal airflow is calculated from the pressure, after a linearization step, and the mask pressure is set to zero by definition.
Conductance of Leak
[0208] The conductance of the leak is calculated as follows:
[0000] root mask pressure=sign( P MASK )√{right arrow over ( abs ( P MASK ))}
[0000] LP mask airflow=low pass filtered mask airflow
[0000] LP root mask pressure=low pass filtered root mask pressure
[0000] conductance of leak=LP mask airflow/LP root mask pressure
[0209] The time constant for the two low pass filtering steps is initialized to 10 seconds and adjusted dynamically thereafter (see below).
Instantaneous Flow Through Leak
[0210] The instantaneous flow through the leak is calculated from the instantaneous mask pressure and the conductance of the leak:
[0000] instantaneous leak=conductance of leak*root mask pressure
Respiratory Airflow
[0211] The respiratory airflow is the difference between the flow at the mask and the instantaneous leak:
[0000] respiratory airflow=mask flow−instantaneous leak
Low Pass Filtered Respiratory Airflow
[0212] Low pass filter the respiratory airflow to remove cardiogenic airflow and other noise. The time constant is dynamically adjusted to be 1/40 of the current estimated length of the respiratory cycle T TOT (initialized to STD_T TOT and updated below). This means that at high respiratory rates, there is only a short phase delay introduced by the filter, but at low respiratory rates, there is good rejection of cardiogenic airflow.
Mask On/Off Status
[0213] The mask is assumed to initially be off. An off-on transition is taken as occurring when the respiratory airflow first goes above 0.2 L/sec, and an on-off transition is taken as occurring if the mask pressure is less than 2 cmH 2 O for more than 1.5 seconds.
Lead-In
[0214] Lead-in is a quantity that runs from zero if the mask is off, or has just been donned, to 1.0 if the mask has been on for 20 seconds or more, as shown in FIG. 6 .
Calculation of Instantaneous Jamming Index, J
[0215] J is the fuzzy extent to which the impedance of the leak has suddenly changed. It is calculated as the fuzzy extent to which the absolute magnitude of the respiratory airflow is large for longer than expected.
[0216] The fuzzy extent A I to which the airflow has been positive for longer than expected is calculated from the time t ZI since the last positive-going zero crossing of the calculated respiratory airflow signal, and the expected duration STD T I of a normal inspiration for the particular subject, using the fuzzy membership function shown in FIG. 7 .
[0217] The fuzzy extent B I to which the airflow is large and positive is calculated from the instantaneous respiratory airflow using the fuzzy membership function shown in FIG. 8 .
[0218] The fuzzy extent I I to which the leak has suddenly increased is calculated by calculating the fuzzy intersection (lesser) of A I and B I .
[0219] Precisely symmetrical calculations are performed for expiration, deriving I E . as the fuzzy extent to which the leak has suddenly decreased. A E is calculated from T ZE and T E , B E is calculated from minus f RESP , and I E is the fuzzy intersection of A E and B E . The instantaneous jamming index J is calculated as the fuzzy union (larger) of indices I I and I E .
Recent Peak Jamming
[0220] If the instantaneous jamming index is larger than the current value of the recent peak jamming index, then the recent peak jamming index is set to equal the instantaneous jamming index. Otherwise, the recent peak jamming index is set to equal the instantaneous jamming index low pass filtered with a time constant of 10 seconds. An electrical analogy of the calculation is shown in FIG. 9 .
Time Constant for Leak Conductance Calculations
[0221] If the conductance of the leak suddenly changes, then the calculated conductance will initially be incorrect, and will gradually approach the correct value at a rate which will be slow if the time constant of the low pass filters is long, and fast if the time constant is short. Conversely, if the impedance of the leak is steady, the longer the time constant the more accurate the calculation of the instantaneous leak. Therefore, it is desirable to lengthen the time constant to the extent that the leak is steady, reduce the time constant to the extent that the leak has suddenly changed, and to use intermediately longer or shorter time constants if it is intermediately the case that the leak is steady.
[0222] If there is a large and sudden increase in the conductance of the leak, then the calculated respiratory airflow will be incorrect. In particular, during apparent inspiration, the calculated respiratory airflow will be large positive for a time that is large compared with the expected duration of a normal inspiration. Conversely, if there is a sudden decrease in conductance of the leak, then during apparent expiration the calculated respiratory airflow will be large negative for a time that is large compared with the duration of normal expiration.
[0223] Therefore, the time constant for the calculation of the conductance of the leak is adjusted depending on J PEAK , which is a measure of the fuzzy extent that the leak has recently suddenly changed, as shown in FIG. 10 .
[0224] In operation, to the extent that there has recently been a sudden and large change in the leak, J PEAK will be large, and the time constant for the calculation of the conductance of the leak will be small, allowing rapid convergence on the new value of the leakage conductance. Conversely, if the leak is steady for a long time, J PEAK will be small, and the time constant for calculation of the leakage conductance will be large, enabling accurate calculation of the instantaneous respiratory airflow. In the spectrum of intermediate situations, where the calculated instantaneous respiratory airflow is larger and for longer periods, J PEAK will be progressively larger, and the time constant for the calculation of the leak will progressively reduce. For example, at a moment in time where it is uncertain whether the leak is in fact constant, and the subject has merely commenced a large sigh, or whether in fact there has been a sudden increase in the leak, the index will be of an intermediate value, and the time constant for calculation of the impedance of the leak will also be of an intermediate value. The advantage is that some corrective action will occur very early, but without momentary total loss of knowledge of the impedance of the leak.
Instantaneous Phase in Respiratory Cycle
[0225] The current phase φ runs from 0 for start of inspiration to 0.5 for start of expiration to 1.0 for end expiration=start of next inspiration. Nine separate features (peaks, zero crossings, plateaux, and some intermediate points) are identified on the waveform, as shown in FIG. 11 .
Calculation of Normalized Respiratory Airflow
[0226] The filtered respiratory airflow is normalized with respect to the user specified target ventilation as follows:
[0000] standard airflow=target ventilation/7.5 L/min
[0000] f ′=filtered respiratory airflow/standard airflow
[0227] Next, the fuzzy membership in fuzzy sets large negative, small negative, zero, small positive, and large positive, describing the instantaneous airflow is calculated using the membership functions shown in FIG. 12 . For example, if the normalized airflow is 0.25, then the airflow is large negative to extent 0.0, small negative to extent 0.0, zero to extent 0.5, small positive to extent 0.5, large positive to extent 0.00.
Calculation of Normalized Rate of Change of Airflow
[0228] The rate of change of filtered respiratory airflow is calculated and normalized to a target ventilation of 7.5 L/min at 15 breaths/min as follows:
standard df/dt=standard airflow*target frequency/15 calculate d(filtered airflow)/dt low pass filter with a time constant of 8/50 seconds normalize by dividing by standard df/dt
[0233] Now evaluate the membership of normalized df/dt in the fuzzy sets falling, steady, and rising, whose membership functions are shown in FIG. 13 .
Calculation of Ventilation, Normalized Ventilation, and Hypopnea
[0000]
ventilation=abs (respiratory airflow),
low pass filtered with a time constant of STD T TOT .
normalized ventilation=ventilation/standard airflow
[0237] Hypopnea is the fuzzy extent to which the normalized ventilation is zero. The membership function for hypopnea is shown in FIG. 14 .
Calculation of Recent Ventilation, Normalized Recent Ventilation, and Hyperpnea
[0238] Recent ventilation is also a low pass filtered abs(respiratory airflow), but filtered with an adjustable time constant, calculated from servo gain (specified by the user) as shown in FIG. 15 . For example, if the servo gain is set to the maximum value of 0.3, the time constant is zero, and recent ventilation equals instantaneous abs(respiratory airflow). Conversely, if servo gain is zero, the time constant is twice STD T TOT , the expected length of a typical breath.
Target absolute airflow=2*target ventilation
normalized recent ventilation=recent ventilation/target absolute airflow
[0241] Hyperpnea is the fuzzy extent to which the recent ventilation is large. The membership function for hyperpnea is shown in FIG. 16 .
Big Leak
[0242] The fuzzy extent to which there is a big leak is calculated from the membership function shown in FIG. 17 .
[0000] Additional Fuzzy Sets Concerned with Fuzzy “Triggering”
[0243] Membership in fuzzy sets switch negative and switch positive are calculated from the normalized respiratory airflow using the membership functions shown in FIG. 18 , and membership in fuzzy sets insp_phase and exp_phase are calculated from the current phase f using the membership functions shown in FIG. 19 .
Fuzzy Inference Rules for Phase
[0244] Procedure W(y) calculates the area of an isosceles triangle of unit height and unit base, truncated at height y as shown in FIG. 20 . In the calculations that follow, recall that fuzzy intersection a AND b is the smaller of a and b, fuzzy union a OR b is the larger of a and b, and fuzzy negation NOT a is 1−a.
[0245] The first fuzzy rule indicates that lacking any other information the phase is to increase at a standard rate. This rule is unconditionally true, and has a very heavy weighting, especially if there is a large leak, or there has recently been a sudden change in the leak, or there is a hypopnea.
[0000] W STANDARD =8+16 *J PEAK +16*hyopopnea+16*big leak
[0246] The next batch of fuzzy rules correspond to the detection of various features of a typical flow-vs-time curve. These rules all have unit weighting, and are conditional upon the fuzzy membership in the indicated sets:
W EARLY INSP =W(rise and small positive) W PEAK INSP =W(large positive AND steady AND NOT recent peak jamming)
[0249] W LATE INSP =W(fall AND small positive)
W EARLY EXP =W(fall AND small negative) W PEAK EXP =W(large negative AND steady) W LATE EXP =W(rise AND small negative)
[0253] The next rule indicates that there is a legitimate expiratory pause (as opposed to an apnea) if there has been a recent hyperpnea and the leak has not recently changed:
[0000] W PAUSE =(hyperpnea AND NOT J PEAK )* W (steady AND zero)
[0254] Recalling that the time constant for hyperpnea gets shorter as servo gain increases, the permitted length of expiratory pause gets shorter and shorter as the servo gain increases, and becomes zero at maximum servo gain. The rationale for this is that (i) high servo gain plus long pauses in breathing will result in “hunting” of the servo-as controller, and (ii) in general high servo gain is used if the subject's chemoreceptor responses are very brisk, and suppression of long apneas or hypopneas will help prevent the subject's own internal servo-control from hunting, thereby helping prevent Cheyne-Stokes breathing.
[0255] Finally, there are two phase-switching rules. During regular quiet breathing at roughly the expected rate, these rules should not strongly activate, but they are there to handle irregular breathing or breathing at unusual rates. They have very heavy weightings.
[0000] W TRIG INSP =32 W (expiratory phase AND switch positive)
[0000] W TRIG EXP =32 W (inspiratory phase AND switch negative)
Defuzzification
[0256] For each of the ten fuzzy rules above, we attach phase angles φN, as shown in Table ZZZ. Note that φN are in revolutions, not radians. We now place the ten masses W(N) calculated above at the appropriate phase angles φ N around the unit circle, and take the centroid.
[0000]
Rule
N
φ N
STANDARD
1
current φ
TRIG INSP
2
0.00
EARLY INSP
3
0.10
PEAK INSP
4
0.30
LATE INSP
5
0.50
TRIG EXP
6
0.5 + 0.05 k
EARLY EXP
7
0.5 + 0.10 k
PEAK EXP
8
0.5 + 0.20 k
LATE EXP
9
0.5 + 0.4 k
EXP PAUSE
10
0.5 + 0.5 k
where k = STD T I /STD T E .
[0257] Note that if the user has entered very short duty cycle, k will be small. For example a normal duty cycle is 40%, giving k=40/60=0.67. Thus the expiratory peak will be associated with a phase angle of 0.5+0.2*0.67=0.63, corresponding 26% of the way into expiratory time, and the expiratory pause would start at 0.5+0.5*0.67=0.83, corresponding to 67% of the way into expiratory time. Conversely, if the duty cycle is set to 20% in a patient with severe obstructive lung disease, features 6 through 10 will be skewed or compressed into early expiration, generating an appropriately longer expiratory pause.
[0258] The new estimate of the phase is the centroid, in polar coordinates, of the above ten rules:
[0000]
centroid
=
arctan
(
∑
W
N
sin
φ
N
∑
W
N
cos
φ
N
)
[0259] The change in phase dφ from the current phase φ to the centroid is calculated in polar coordinates. Thus if the centroid is 0.01 and the current phase is 0.99, the change in phase is dφ=0.02. Conversely, if the centroid is 0.99 and the current phase is 0.01, then dφ=−0.02. The new phase is then set to the centroid:
[0000] φ=centroid
[0260] This concludes the calculation of the instantaneous phase in the respiratory cycle φ.
Estimated Mean Duration of Inspiration, Expiration, Cycle Time, and Respiratory Rate
[0261] If the current phase is inspiratory (φ<0.5) the estimated duration of inspiration T I is updated:
LP(dφ I )=low pass filtered dφ with a time constant of 4*STD T TOT Clip LP(dφ I ) to the range (0.5/STD T I )/2 to 4(0.5/STD T I ) T I =0.5/clipped LP(dφI)
[0265] Conversely, if the current phase is expiratory, (φ>=0.5) the estimated duration of expiration T E is updated:
LP(dφ E )=low pass filtered dφ with a time constant of 4*STD T TOT Clip LP(dφE) to the range (0.5/STD T E )/2 to 4(0.5/STD T E ) TE=0.5/clipped LP(dφ E )
[0268] The purpose of the clipping is firstly to prevent division by zero, and also so that the calculated T I and T E are never more than a factor of 4 shorter or a factor of 2 longer than expected.
[0269] Finally, the observed mean duration of a breath T TOT and respiratory rate RR are:
[0000]
T
TOT
=T
I
+T
E
[0000] RR= 60 /T TOT
Resistive Unloading
[0270] The resistive unloading is the pressure drop across the patient's upper and lower airways, calculated from the respiratory airflow and resistance values stored in SRAM
f=respiratory airflow truncated to +/−2 L/sec resistive unloading=airway resistance*f+ upper airway resistance*f 2 *sign(f)
Instantaneous Elastic Assistance
[0274] The purpose of the instantaneous elastic assistance is to provide a pressure which balances some or all of the elastic deflating pressure supplied by the springiness of the lungs and chest wall (instantaneous elastic pressure), plus an additional component required to servo-control the minute ventilation to at least exceed on average a pre-set target ventilation. In addition, a minimum swing, always present, is added to the total. The user-specified parameter elastance is preset to say 50-75% of the known or estimated elastance of the patient's lung and chest wall. The various components are calculated as follows:
Instantaneous Assistance Based on Minimum Pressure Swing Set by Physician:
[0275] instantaneous minimum assistance=minimum swing*π(φ)
Elastic Assistance Required to Servo-Control Ventilation to Equal or Exceed Target
[0276] The quantity servo swing is the additional pressure modulation amplitude required to servo-control the minute ventilation to at least equal on average a pre-set target ventilation.
[0277] Minute ventilation is defined as the total number of litres inspired or expired per minute. However, we can't wait for a whole minute, or even several seconds, to calculate it, because we wish to be able to prevent apneas or hypopneas lasting even a few seconds, and a PI controller based on an average ventilation over a few seconds would be either sluggish or unstable,
[0278] The quantity actually servo-controlled is half the absolute value of the instantaneous respiratory airflow. A simple clipped integral controller with no damping works very satisfactorily. The controller gain and maximum output ramp up over the first few seconds after putting the mask on.
[0279] If we have had a sudden increase in mouth leak, airflow will be nonzero for a long time. A side effect is that the ventilation will be falsely measured as well above target, and the amount of servo assistance will be falsely reduced to zero. To prevent this, to the extent that the fuzzy recent peak jamming index is large, we hold the degree of servo assistance at its recent average value, prior to the jamming.
[0280] The algorithm for calculating servo swing is as follows:
error=target ventilation−abs(respiratory airflow)/2 servo swing=S error*servo gain*sample interval clip servo swing to range 0 to 20 cmH 2 O*lead-in set recent servo swing=
servo swing low pass filtered with a time constant of 25 sec.
clip servo swing to be at most J PEAK *recent servo swing
[0287] The instantaneous servo assistance is calculated by multiplying servo swing by the previously calculated pressure waveform template:
[0000] instantaneous servo assistance=servo swing*π(φ)
Estimating Instantaneous Elastic Pressure
[0288] The instantaneous pressure required to unload the elastic work of inspiring against the user-specified elastance is the specified elastance times the instantaneous inspired volume. Unfortunately, calculating instantaneous inspired volume simply by integrating respiratory airflow with respect to time does not work in practice for three reasons: firstly leaks cause explosive run-away of the integration. Secondly, the integrator is reset at the start of each inspiration, and this point is difficult to detect reliably. Thirdly, and crucially, if the patient is making no efforts, nothing will happen.
[0289] Therefore, four separate estimates are made, and a weighted average taken.
[0000] Estimate 1: Exact Instantaneous Elastic Recoil Calculated from Instantaneous Tidal Volume, with a Correction for Sudden Change in Leak
[0290] The first estimate is the instantaneous elastic recoil of a specified elastance at the estimated instantaneous inspired volume, calculated by multiplying the specified elastance by the integral of a weighted respiratory airflow with respect to time, reset to zero if the respiratory phase is expiratory. The respiratory airflow is weighted by the fuzzy negation of the recent peak jamming index J PEAK , to partly ameliorate an explosive run-away of the integral during brief periods of sudden increase in leak, before the leak detector has had time to adapt to the changing leak. In the case where the leak is very steady, J PEAK will be zero, the weighting will be unity, and the inspired volume will be calculated normally and correctly. In the case where the leak increases suddenly, J PEAK will rapidly increase, the weighting will decrease, and although typically the calculated inspired volume will be incorrect, the over-estimation of inspired volume will be ameliorated. Calculations are as follows:
Instantaneous volume=integral of respiratory airflow*(1−J PEAK )dt if phase is expiratory (0.5<φ<1.0 revolutions) reset integral to zero estimate 1=instantaneous volume*elastance
Estimate 2: Based on Assumption that the Tidal Volume Equals the Target Tidal Volume
[0294] The quantity standard swing is the additional pressure modulation amplitude that would unload the specified elastance for a breath of a preset target tidal volume.
target tidal volume=target ventilation/target frequency standard swing=elastance*target tidal volume estimate 2=standard swing*π(φ)
Estimate 3: Based on Assumption that the Tidal Volume Equals the Target Tidal Volume Divided by the Observed Mean Respiratory Rate RR Calculated Previously.
Estimate 3=elastance*target ventilation/RR*π(φ)
Estimate 4: Based on Assumption that this Breath is Much Like Recent Breaths
[0299] The instantaneous assistance based on the assumption that the elastic work for this breath is similar to that for recent breaths is calculated as follows:
LP elastic assistance=instantaneous elastic assistance
low pass filtered with a time constant of 2 STD T TOT
estimate 4=LP elastic assistance*π(φ)/P BAR
[0303] The above algorithm works correctly even if π(φ) is dynamically changed on-the-fly by the user, from square to a smooth or vice versa. For example, if an 8 cmH2O square wave (π BAR =1) adequately assists the patient, then a sawtooth wave (π BAR =0.5) will require 16 cmH 2 O swing to produce the same average assistance.
Best Estimate of Instantaneous Elastic Recoil Pressure
[0304] Next, calculate the pressure required to unload a best estimate of the actual elastic recoil pressure based on a weighted average of the above. If π(φ) is set to the smoothest setting, the estimate is based equally on all the above estimates of instantaneous elastic recoil. If π(φ) is a square wave, the estimate is based on all the above estimates except for estimate 1, because a square wave is maximal at φ=0, whereas estimate 1 is zero at φ=0. Intermediate waveforms are handled intermediately. Quantity smoothness runs from zero for a square wave to 1 for a waveform time constant of 0.3 or above.
smoothness=waveform time constant/0.3 instantaneous recoil=(smoothness*estimate 1+
estimate 2+estimate 3+estimate 4)/(smoothness+3)
[0308] Now add the estimates based on minimum and servo swing, truncate so as not to exceed a maximum swing set by the user. Reduce (lead in gradually) if the mask has only just been put on.
I=instantaneous minimum assistance+instantaneous servo assistance+instantaneous recoil Truncate I to be less than preset maximum permissible swing instantaneous elastic assistance=I*lead-in
[0311] This completes the calculation of instantaneous elastic assistance.
Desired Pressure at Sensor
[0000]
desired sensor pressure=epap+hose pressure loss+resistive unloading+instantaneous elastic assistance
Servo Control of Motor Speed
[0313] In the final step, the measured pressure at the sensor is servo-controlled to equal the desired sensor pressure, using for example a clipped pseudodifferential controller to adjust the motor current. Reference can be made to FIG. 1 in this regard.
Device Performance
[0314] FIGS. 21-27 each show an actual 60 second recording displaying an aspect of the second embodiment. All recordings are from a normal subject trained to perform the required manoeuvres. Calculated respiratory airflow, mask pressure, and respiratory phase are calculated using the algorithms disclosed above, output via a serial port, and plotted digitally.
[0315] In FIGS. 21-26 respiratory airflow is shown as the darker tracing, the vertical scale for flow being ±L/sec, inspiration upwards. The vertical scale for the pressure (light trace) is 0.2 cmH 2 O.
[0316] FIG. 21 is recorded with the servo gain set to 0.1 cmH 2 O/L/sec/sec, which is suitable for subjects with normal chemoflexes. The subject is breathing well above the minimum ventilation, and a particularly deep breath (sigh) is taken at point (a). As is usual, respiratory effort ceases following the sigh, at point (c). The device correctly permits a short central apnea (b), as indicated by the device remaining at the end expiratory pressure during the period marked (b). Conversely FIG. 22 shows that if there is no preceding deep breath, when efforts cease at (a), the pressure correctly continues to cycle, thus preventing any hypoxia. FIG. 23 is recorded with servo gain set high, as would be appropriate for a subject with abnormally high chemoreflexes such as is typically the case with Cheyne-Stokes breathing. Now when effort ceases at arrow (a), pressure continues to cycle and a central apnea is no longer permitted, despite preceding deep breathing. This is advantageous for preventing the next cycle of Cheyne-Stokes breathing.
[0317] The above correct behaviour is also exhibited by a time mode device, but is very different to that of a spontaneous mode bilevel device, or equally of proportional assist ventilation, both of which would fail to cycle after all central apneas, regardless of appropriateness.
[0318] FIG. 24 shows automatically increasing end-inspiratory pressure as the subject makes voluntarily deeper inspiratory efforts. The desirable behaviour is in common with PAV, but is different to that of a simple bilevel device, which would maintain a constant level of support despite an increased patient requirement, or to a volume cycled device, which would actually decrease support at a time of increasing need.
[0319] FIG. 25 is recorded with a somewhat more square waveform selected. This figure shows automatically increasing pressure support when the subject voluntarily attempts to resist by stiffening the chest wall at point (a). This desirable behaviour is common with PAV and volume cycled devices, with the expectation that PAV cannot selectively deliver a squarer waveform. It is distinct from a simple bilevel device which would not augment the level of support with increasing need.
[0320] FIG. 26 shows that with sudden onset of a severe 1.4 L/sec leak at (a), the flow signal returns to baseline (b) within the span of a single breath, and pressure continues to cycle correctly throughout. Although timed mode devices can also continue to cycle correctly in the face of sudden changing leak, the are unable to follow the subject's respiratory rate when required (as shown in FIG. 27 ). Other known bilevel devices and PAV mis-trigger for longer or shorter periods following onset of a sudden sever leak, and PAV can deliver greatly excessive pressures under these conditions.
[0321] FIG. 27 shows an actual 60 second tracing showing respiratory airflow (heavy trace ±1 L/sec full scale) and respiratory phase as a continuous variable (light trace, 0 to 1 revolution), with high respiratory rate in the left half of the trace and low respiratory rate in the right half of the trace. This trace demonstrates that the invention can determine phase as a continuous variable.
Advantageous Aspects of Embodiments of the Invention
Use of Phase as a Continuous Variable.
[0322] In the prior art, phase is taken as a categorical variable, with two values:
[0323] inspiration and expiration. Errors in the detection of start of inspiration and start of expiration produce categorical errors in delivered pressure. Conversely, here, phase is treated as a continuous variable having values between zero and unity. Thus categorical errors in measurement of phase are avoided.
Adjustable Filter Frequency and Allowance for Phase Delay
[0324] By using a short time constant when the subject is breathing rapidly, and a long time constant when the subject is breathing slowly, the filter introduces a fixed phase delay which is always a small fraction of a respiratory cycle. Thus unnecessary phase delays can be avoided, but cardiogenic artifact can be rejected in subjects who are breathing slowly. Furthermore, because phase is treated as a continuous variable, it is possible to largely compensate for the delay in the low pass filter.
Within-Breath Pressure Regulation as a Continuous Function of Respiratory Phase.
[0325] With all prior art there is an intrusive discontinuous change in pressure, either at the start of inspiration or at the start of expiration. Here, the pressure change is continuous, and therefore more comfortable.
[0326] With proportional assist ventilation, the instantaneous pressure is a function of instantaneous volume into the breath. This means that a sudden large leak can cause explosive pressure run-away. Here, where instantaneous pressure is a function of instantaneous phase rather than tidal volume, this is avoided.
Between-Breath Pressure-Regulation as a Function of Average Inspiratory Duration.
[0327] Average inspiratory duration is easier to calculate in the presence of leak than is tidal volume. By taking advantage of a correlation between average inspiratory duration and average tidal volume, it is possible to adjust the amplitude of modulation to suit the average tidal volume.
Provision of a Pressure Component for Unloading Turbulent Upper Airway Resistance, and Avoiding Cardiogenic Pressure Instabilities.
[0328] Although Younes describes the use of a component of pressure proportional to the square of respiratory airflow to unload the resistance of external apparatus, the resistance of the external apparatus in embodiments of the present invention is typically negligible. Conversely, embodiments of the present invention describes two uses for such a component proportional to the square of respiratory airflow that were not anticipated by Younes. Firstly, sleeping subjects, and subjects with a blocked nose, have a large resistance proportional to the square of airflow, and a pressure component proportional to the square of airflow can be used to unload the anatomical upper airway resistance. Secondly, small nonrespiratory airflow components due to heartbeat or other artifact, when squared, produces negligible pressure modulation, so that the use of such a component yields relative immunity to such nonrespiratory airflow.
Smooth Transition Between Spontaneous and Controlled Breathing
[0329] There is a smooth, seamless gradation from flexibly tracking the subject's respiratory pattern during spontaneous breathing well above the target ventilation, to fully controlling the duration, depth, and phase of breathing if the subject is making no efforts, via a transitional period in which the subject can make progressively smaller changes to the timing and depth of breathing. A smooth transition avoids categorization errors when ventilation is near but not at the desired threshold. The advantage is that the transition from spontaneous to controlled ventilation occurs unobtrusively to the subject. This can be especially important in a subject attempting to go to sleep. A similar smooth transition can occur in the reverse direction, as a subject awakens and resumes spontaneous respiratory efforts. | 1a
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TECHNICAL FIELD OF THE INVENTION
The present invention relates generally to the field of furniture accessories and, more particularly, to an improved apparatus for raising the level of an item.
SUMMARY OF THE INVENTION
One aspect of the invention generally pertains to an improved apparatus for raising the level of a piece of furniture to a desired height.
Another aspect of the invention pertains to a riser component that may be combined and stacked with other identical components and oriented in variable directions to create a unique decorative appearance.
In accordance with the above aspects of the invention, there is provided a multi-orientation stacking riser that includes a main section; a protruding mating section extending from one surface of the main section; and a recessed mating section formed in an opposite surface of the main section, and wherein the recessed mating section accommodates insertion of a protruding mating section of an identical stacking riser in at least first and second positions.
These aspects are merely illustrative of the innumerable aspects associated with the present invention and should not be deemed as limiting in any manner. These and other aspects, features and advantages of the present invention will become apparent from the following detailed description when taken in conjunction with the referenced drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
Reference is now made more particularly to the drawings, which illustrate the best presently known mode of carrying out the invention and wherein similar reference characters indicate the same parts throughout the views.
FIG. 1 is a top perspective view of a multi-orientation, stacking riser according to one exemplary embodiment of the present invention.
FIG. 2 is a bottom perspective view of the riser of FIG. 1 .
FIG. 3 is a side view of the riser of FIG. 1 .
FIG. 4 is a top view of the riser of FIG. 1
FIG. 5 is a bottom view of the riser of FIG. 1 .
FIG. 6 is a perspective view of a series of stacked risers according to another embodiment.
DETAILED DESCRIPTION
In the following detailed description numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be understood by those skilled in the art that the present invention may be practiced without these specific details. For example, the invention is not limited in scope to the particular type of industry application depicted in the figures. In other instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the present invention.
FIGS. 1-6 illustrate a multi-orientation, stacking riser 10 according to an exemplary embodiment of the present invention. In pertinent part, the riser 10 includes a main section 12 , a protruding mating section 14 , and a recessed mating section 16 . In the preferred embodiment, the foregoing sections are integrally formed with one another, for example by injection molding same. The main section 12 provides the primary supporting body for the riser 10 . The protruding 14 and recessed 16 mating sections cooperate with the recessed and protruding, respectively, mating sections of one or more other risers to securely mount one riser on top of another in one of a multiple of respective orientations of the risers.
The protruding mating section 14 extends from a top surface 18 of the main section 12 . In the illustrated embodiment of FIGS. 1-6 , the protruding mating section 14 is provided with square outer dimensions. The outer dimensions of the protruding mating section 14 are sized in a manner to cooperate with the recessed mating section 16 as discussed below.
The recessed mating section 16 is advantageously formed in a bottom surface 20 of the main section 12 opposite to the top surface 18 . The references to top and bottom surfaces herein are used solely for the purposes of illustration and to describe the general basic positional relationship between the protruding 14 and recessed 16 mating surfaces. The positioning of the protruding 14 and recessed 16 mating sections is not limited to the top and bottom surfaces of the main section 12 depending upon the manner of application of the riser 10 .
The recessed mating section 16 is formed by a depression in the bottom surface 20 of the main section 12 , and, thus, the recessed mating section 16 extends into the interior of the main section 12 . In the case of the illustrated embodiment, the interior of the main section 12 includes a series of ribs that extend from outer walls 24 of the main section 12 toward the middle of the interior of the main section 12 . The ribs lend structural support to the main section 12 of the riser 10 while minimizing the weight of the riser 10 and the amount of material required to form the riser 10 .
The recessed mating section 16 is formed by a geometric rib 26 that is formed in a shape that is complementary to the outer dimensions of the protruding mating section 14 . In the illustrated, preferred embodiment, the geometric rib 26 is provided in the form of an eight-pointed “star” that is centered with the interior of the main section 12 . The geometric rib 26 is connected with interior top surface 18 of the main section 12 . It is further connected with one or more of the side walls of the main section 12 either directly or by means of first support ribs 28 . The geometric rib 26 may also be supported by a series of second support ribs 30 that extend within the geometric rib 26 from one side to the other. Both the geometric rib 26 and the first support ribs 28 extend to the bottom surface 20 of the main section 12 . In contrast, the second support ribs 30 located within the geometric rib 26 do not extend entirely to the bottom surface 20 . Those of skill in the art will recognize that the bottom surface 20 in this context is not a solid surface but rather the plane formed by the bottom edges of the outer walls 24 of the main section 12 .
The difference in height between the geometric rib 26 and the second support ribs 30 creates a recess so that the second support ribs 30 do not interfere with the positioning of the protruding mating section 12 within the recessed mating section 16 defined by the geometric rib 26 and, furthermore, help define a depth of the recessed mating section 16 to help control how far the protruding mating section 12 extends into the recessed mating section 16 . In a preferred embodiment, the difference in height between the geometric rib 26 and the second support ribs 30 is approximately equal to a height of the protruding mating section 14 . In this manner, two stacked risers 10 will contact one another both at a junction of the bottom of the outer walls 24 with the top surface 18 and a junction of the top of the protruding mating section 14 with the bottom of the second support ribs 30 , resulting in increased stability and strength of the stacked risers.
The relationship between the protruding mating section 14 and recessed mating section 16 will now be described in more detail. It will be seen that the outer dimension D of the protruding mating section 14 corresponds, with a tolerance for clearance and for manufacturing variances, to the inner dimension d of the recessed mating section 16 to allow insertion of the protruding mating section 14 into the recessed mating section 16 . As illustrated in FIGS. 3 and 4 , the dimensions D and d of the protruding mating section 14 and recessed mating section 16 , respectively, are consistent around both of these sections. Therefore, the protruding mating section 14 and recessed mating section 16 may be rotated relative to one another while still allowing insertion of the protruding mating section 14 into the recessed mating section 16 . More particularly, the shape of the recessed mating section 16 allows for discrete forty-five degree) (45°) rotations—and subsequent insertions—of the protruding mating section 14 of one riser relative to the recessed mating section 16 of another riser.
One advantage in the ability to readily vary the orientation of one riser relative to another can be seen in FIG. 6 . In the illustrated embodiment, each individual riser is molded in the form of a hard back book; other shapes also being suitable for the risers. By varying the relative positioning of one riser to another, differing appearances of stacked books supporting a bed or other piece of furniture can be created.
In a preferred embodiment, the riser 10 is injection molded from a suitable plastic material. While the illustrated embodiment of the riser 10 is provided with a series of ribs for internal support of the main section 12 and forming of the recessed mating section 16 , it is also contemplated within the scope of the invention for the main section 12 to be formed from a solid block of material with the recessed mating section 16 being a depression in the otherwise solid block.
While the preferred embodiment has been illustrated with a protruding mating section 14 and recessed mating section 16 in the described shapes, other embodiments may utilize other complementary shapes. For example, the protruding mating section 14 and recessed mating section 16 may each be provided in the shape of a circle, which would allow a greater range of relative angular adjustment of the stacked risers.
The preferred embodiments of the invention have been described above to explain the principles of the invention and its practical application to thereby enable others skilled in the art to utilize the invention in the best mode known to the inventors. However, as various modifications could be made in the constructions and methods herein described and illustrated without departing from the scope of the invention, it is intended that all matter contained in the foregoing description or shown in the accompanying drawings shall be interpreted as illustrative rather than limiting. Thus, the breadth and scope of the present invention should not be limited by the above-described exemplary embodiment, but should be defined only in accordance with the following claims appended hereto and their equivalents. | 1a
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates generally to hoisting equipment and more particularly, to a portable lifting apparatus for lifting and transferring incapacitated persons.
2. Background Information
It is well known that persons confined to a bed due to illness, age, and so forth possess such limited mobility that movement or transfer is extremely difficult. Improper transfer can result in serious complications to the individual. For instance, the need to move a patient immediately after an operation is necessary yet a dangerous proposition as any movement of the body may undo the surgeon's most careful work. Just as important is the need to transfer a bed ridden person for bathing or exercise so as to facilitate recovery.
In a hospital setting, a transfer is typically performed by a number of hospital workers in order to comfortably lift a patient from one position to another. If the transfer is made only by hand, the hospital personnel risk injury to their backs. If the transfer utilizes too few personnel or requires reaching in an awkward position, the personnel may strain their own bodies. Despite the number of personnel employed to assist in the transfer, the patient is simply susceptible to injury from anyone who touches or lifts incorrectly.
For these reasons, a number of devices are presently available for lifting and lowering of incapacitated persons from a bed, chair, bath or the like position. U.S. Pat. No. 5,185,895, issued to Gagne, sets forth a patient lift device consisting of a base frame having vertically oriented guideposts wherein a carriage assembly moves along the guideposts in response to an operator applied control signal. An arm assembly projects over the person who is placed into a sling for lifting. The patent discloses a basic lift and transferring apparatus of the prior art. The problem with such a device is the size necessary in order to accomplish the intended service. In particular, the prior art device employs elongated legs and a boom which is necessary to lift a patient. This prevents the device from being easily transferred or stored. The length of the components are necessary so that the apparatus can fit beneath a bed or chair yet provide sufficient support during the lifting process.
Thus a primary problem with the instant apparatus, as well as the remainder of the known prior art, is that the support and lifting structure must be sized adequately in order to support the lifting of the patient. However, the structure interferes with transportation and storage of the device. Since all components in the prior art remain in an extended position, they may cause a person to trip or run into the device. Such a device is difficult to transport and store for the legs and boom remain in an outward position.
U.S. Pat. No. 5,084,921 is another example of a patient lift and transfer apparatus having a unitary frame which consists of a caster wheel equipped U-shaped horizontal disposed frame. The invention discloses a unique vertically disposed pivotally biased arm to lift a patient supporting sling for moving a patient. Again the legs of this apparatus are capable of being placed beneath a patient's bed providing sufficient support for the lifting apparatus as well as the patient. However, no provision is made for storage or transportation of the apparatus.
U.S. Pat. No. 4,712,257 is still another patient lift device consisting of a lifting arm and sling hanger supported by a rigid frame having a U-shaped base structure using wheels for ease of frame movement. The invention further discloses the use of a sling having spaced apart attachment points for use in combination with a vertical bearing to prevent swinging movement of a patient placed within the sling.
U.S. Pat. No. 5,077,844 sets forth an apparatus for lifting and moving patients wherein the frame is permanently attached to a fixed structure. This apparatus eliminates the need for legs but limits the use to non-portable placement.
U.S. Pat. No. 4,484,366 sets forth a patient transfer device which again relies upon the use of a fixed base which fits beneath the patient's chair or bed making the unit impractical to store in a compact position. U.S. Pat. No. 5,185,895 discloses an apparatus for lifting patients and transporting them. The apparatus is based upon electrical motors to provide assistance in patient movement wherein the arm members can telescope and then retract. This apparatus does not teach the retraction of the arms for purposes of storage or transportation.
Thus, there is a need for a lifting and transferring apparatus which is simple to operate and retracts into a compact position to permit ease of storage and transportation of the apparatus.
SUMMARY OF THE INVENTION
The present invention satisfies this need through provision of a retractable lifting apparatus. The apparatus meets the particular problems commonly found in hospitals and convalescent homes where short term lifting capabilities are necessary. Unique to this invention is the ability to lift over five hundred pounds yet retract in size for purposes of transporting and storage. In operation the support legs provide an eighty inch stance. In a retracted position, the support legs are pivoted upward leaving a frame footprint of approximately thirty inches. The invention consists of a miniature crane comprising a boom with a hoist mounted at the end of the boom. The boom is coupled to the portable frame and held in its operating horizontal position by a collapsible crutch allowing the boom to fold over into a nearly vertical position. An electric motor driven linear actuator makes extension and retraction of the boom effortless and a solenoid is used to pull the over-center hinge of the crutch to allow folding.
Similarly, support legs extend outwardly from the frame and are locked in position by a collapsible strut. Both the boom crutch and the leg strut each use over-center lockable hinges with confirming LED's that illuminate to verify the position of the components as well as the locked or stored position. For storage a leg hoist is used to retract a cable, by a pivotal motion, lifting the legs to an upright position after a solenoid pulls the over-center hinge of the strut to allow folding.
Once the apparatus is in a retracted position the unit can be easily moved by unlocking frame mounted wheels. In a preferred embodiment the apparatus uses five wheels, four of which are lockable caster wheels similar to those found on stretchers. Hand brakes on the frame provide a means for stopping the unit from rolling during transporting. In an alternative embodiment, the hand brakes must be depressed in order to release the wheels thus eliminating the need for separate wheel locks.
In the extended position, an operator can maneuver the hoist over a patient's bed wherein a hook is available for attaching to a patient sling. The sling is placed beneath the patient so as to facilitate support during transfer. The hoist is capable of lifting up to five hundred pounds and the boom has an angular range of motion of approximately forty degrees with a twenty degree extension tolerance. Movement of the boom in a angular rotation is performed by use of an electric motor.
A simplified control panel is provided for operation of all moving components and consists of a resilient ball that is free swinging and easily accessible by the operator despite their position. On one side of the control mechanism is the boom and leg controls, depression of which will allow the motors to fully extend the components for operation. The LED's will blink and light either as red or green depending upon status of component placement. Located on the opposite side of the control panel are operation switches for moving the hoist upward or downward and the angular movement of the boom. Indicator lights are provided to illuminate if the equipment is in operation.
Thus, an objective of the instant invention is to provide a patient lift device or apparatus that is simple to operate and employs retractable components so as to permit storage in a closet or transportation through doorways.
Yet another objective of the instant invention is to disclose the use of collapsible struts with confirming indicator lights for support of load bearing and stability components.
Yet still another objective of the instant invention is to provide a device that can be operated by a single person and is easily moveable in confined areas such as those found in a hospital or convalescent home.
Still another objective of the instant invention is to teach the use of brakes for stopping or locking the wheels of portable lift equipment.
Another objective of the instant invention is to provide a lifting apparatus that can be placed into operation, from a stored condition, in less than two minutes. The extending components geared so as to meet this time frame yet provide a mode of extension that is stable for use in fragile environments.
Other objects and advantages of this invention will become apparent from the following description taken in conjunction with the accompanying drawings wherein are set forth, by way of illustration and example, certain embodiments of this invention. The drawings constitute a part of this specification and include exemplary embodiments of the present invention and illustrate various objects and features thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side plane view of the instant invention in an operating position;
FIG. 2 is a side plane view of the instant invention in a retracted position;
FIG. 3 is a top plane view;
FIG. 4 is an enlarged partial cross-sectional side view of the boom head;
FIG. 5 is a front plane view of a control ball; and
FIG. 6 is a back plane view of the control ball.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Although the invention is described in terms of a specific embodiment, it will be readily apparent to those skilled in this art that various modifications, rearrangements and substitutions can be made without departing from the spirit of the invention. The scope of the invention is defined by the claims appended hereto.
Now referring to FIG. 1, shown is the preferred embodiment of the instant invention 10 comprising a base frame 12 having five wheels 14 secured to the bottom of said frame 12. Wheels 14 are placed around the perimeter of the base frame 12 and preferably have a central locking and steering ability similar to conventional stretchers wherein they can be fully locked, locked to roll straight ahead, or free wheel. In such an embodiment, two levers, not shown, are mounted on each end of the frame 12. One lever locks two wheels at that end forcing the united to roll straight ahead for optimum steering. The back wheels pivot free for steering purposes. Alternatively, foot operate levers 15 provide simplified engagement of the wheel locks.
Pivotally mounted to an end 13 of the base frame 12 is a first leg 16 having a shoe plate 18 mounted at a distal end 19 of the leg 16. Structure 20 provides a support housing for electric motors used for operating the components as well as an upper articulating point 21 for the legs 16 and 16A. A first strut 22 is pivotally coupled to said upper articulating point 21 and to the illustrated leg 16 at lower pivot point 26. The strut 22 utilizes a centrally disposed over-center hinge 28 which folds inward so as to allow the leg 16 into a vertical stance for purposes of storage. To retract the legs, motor 50 is mechanically linked to the legs 16 and 16A and boom motor 52 provides retraction of the boom 34 in a similar manner. A hoist motor 54 provides the lifting and lowering of the hook 58, and a swing motor 56 is used to modulate the angular arc of the boom 34.
The support frame 20 includes hand grips 30 placed along an upper rail 31 providing an operator with a predetermined position for moving of the lifting device. The handgrips 30 can be accompanied by hand brakes, not shown, for use in preventing wheel 14 rotation. In such an embodiment, the operator can prevent movement of the unit by simply squeezing a hand brake in a similar fashion as a brake used on a bicycle. Once stopped, the apparatus can be locked in position through the use of the aforementioned wheel locks 15.
An alternate embodiment is to use hand grips that apply constant braking force so as to require the operator to maintain their hands on the apparatus during transportation. This is especially useful in those circumstances where a ramp is encountered during transportation. In such an embodiment, should a unit free roll down a ramp the brakes will engage to bring the unit to a stop.
Boom head 32 is supported by the frame 20 and is shown in its extended position. Extension of the boom 34 is made possible by an electric motor driven linear actuator 66 which extends crutch 36 which is coupled to the boom 34 by upper pivot point 38 and lower pivot point 40. The centrally disposed hinge 42 is forced over-center by the linear actuator causing said hinge to lock in a fixed position. Storage of the boom occurs by folding of the boom 34 downward by allowing the boom 34 to fold within the confines of the frame 20 by reversal of the above steps. Similarly, the legs 16 are folded upward by the inward movement of the strut hinge 28 so as to provide a compact unit that stores in a small closet and can be maneuvered through doorways. An additional cable runs parallel to strut 22 and when said cable is pulled in by the leg motor, after the solenoid releases the over-center hinge, the leg folds to the near vertical position.
Now referring to FIG. 2, shown is the lifting device 10 in a retracted position wherein the base frame 12 provides the footprint for the structure 20 made portable by the wheels 14. The boom 34 is shown in its downwardly folded position while the legs 16 are shown in an upwardly folded position, all within the confines of the support structure 20. As depicted by this view, the crutch 36 is hinged 42 at a center point allowing the boom 34 to form a near vertical position thus eliminating the space necessary for a conventional hoisting unit and preventing the possibility of harm to an operator who inattentively walks into a fully extended boom. The over-center hinge is pulled from its locked state by use of a boom motor 52 which pulls the crutch cable 64, see FIG. 1, causing the crutch 36 to fold in the center. Linear actuator 66 operates to place the boom 34 in an extended or upright position.
Similarly, the legs 16 fold upright to maintain the unit's small storage footprint while further eliminating an unguarded leg extension common among those units in the industry, thus eliminating the possibility of injury to tripping an individual attempting to step over an extended support leg. The strut 22 is hinged 28 at a center point allowing the leg 16 to form a near vertical position. The over-center hinge is pulled from its locked state by use of a leg motor 50 which pulls the strut cable 61, see FIG. 1, causing the strut 22 to fold in the center. Gravity operates to bias the leg 16 into the extended position. A spring, not shown, can be incorporated in the leg to facilitate the biasing of the leg in an extended position.
FIG. 3 sets forth a top view of the instant device 10 in a fully extended form illustrating the wide U-shaped structure. Leg 16A operates in conjunction with leg 16 providing enhanced stability during operation. Each leg is raised and lowered by use of the same electric leg motor 50 so to operate in unison at all times. The leg support position is made possible wherein strut 22 and 22A is in a fully extended position allowing the strut hinges 28 and 28A to be locked in position forcing the shoe skid 18 and 18A to press against the floor. The stance provides stability for the boom 34 as it extends outward over the patient to be lifted.
In operation, the device 10 is moved into position so that the legs and boom 34 can extend without interference. As the unit is electrically powered, an AC cord is provided for insertion into an available wall socket to power the electrical motors, namely, the leg hoist 50, the hoist motor 52, the swing motor 54, and the boom motor linear actuator 66. Control of the system is performed by a control panel positioned in a hand held control ball fabricated from a three inch thick solid resilient ball as described later in this specification.
Placement of the leg and boom components in an operating position is accomplished by depressing a button on the control panel which simultaneously operates the leg motor 50 and boom motor linear actuator 66 allowing the legs 16 & 16A and the boom 34 to extend into their operating position. The operator may stop the extension procedure at any time should the legs or boom encounter interference. LED lamps are provided to represent the position of the legs and boom. The lamps will change from a blinking red color to a continuous green color when sensors, not shown, confirm a positive lock in the extended position similar to the indicators used with airplane landing gear.
The boom 34 has an angular sweep D 1 between legs 16 and 16A allowing the operator to pick up a patient at one position and transport the patient to a second position. Boom swing angle is approximately forty degrees with a twenty degree tolerance. The reach of the boom is sixty inches, slightly less than the preferred leg reach of approximately eighty inches. In operation it is recommended that a patient is placed upon a support sling wherein the boom 34 is swung over the patient in a lifting bar properly positioned over the support sling. This will minimize any swinging tendency as the support sling and patient is pulled upward. A hook 58 is located at the end of the boom 34. During this position the device 10 can be rolled slightly so as to facilitate correct positioning. Once the device 10 is properly located the wheels can be locked by use of the foot lever 15. A frame mounted lever, not shown, can be used to lock the wheels in a position allowing straight roll.
Using the control panel a button is provided to lower the hook 58 until the lifting assembly is attached. Raising the patient is performed by depressing a button on the control panel allowing upward movement so as the patient and sling are above both departure and arrival surfaces. The patient can then be swung from the departure surface to the arrival surface by provision of a right and left directional control button allowing movement of the boom 34. The patient is then unhooked from the hook 58 and the device 10 is positioned such that the legs 16 and boom 34 can be retracted without interference.
When the unit is to be transported or stored, a control button is provided so as to retract the legs and boom, the movement can be halted at any point if necessary. During the retraction the LED's representing the legs and the boom will blink red until sensors (not shown) detect a positive latch for storage. At that point, the LED's will stop blinking and be in a continuous red position. The device 10 can then be turned off and the AC cord unplugged and coiled for storage with the device 10.
Referring to FIG. 4 the boom 34 is mounted on a rotatable boom head 32 that provides a pivot point 62 for one end of the boom 34 that is used in the retracted state. In particular the pivot point 62 allows the boom 34 to fold downward in a retracted position. The hinge 42 is an over-center hinge causing the crutch to lock into position. Collapsing of the boom requires that the hinge 42 is pulled off center by the cable 64 by a solenoid, not shown. The rotatable sleeve is manufactured from light weight aluminum having a five and a half inch diameter which is rotatably coupled to the frame 20 by a rotatable bearing 74 located at the bottom of the head 32 to allow rotation about a predetermined angle. The frame 20 incorporates a support post 76 which is placed on the inner side surface of the pipe 72 having a plurality of inwardly facing centering components which are plastic guides 78 maintaining a fixed distance between the head pipe 72 and the support post 76.
FIG. 5 illustrates a first side of the control system in its preferred embodiment comprising a hand held control ball 90 fabricated from a three inch diameter solid resilient ball. A control panel 91 is mounted in a recess 93 inside the ball 90 wherein a coiled cord, not shown, suspends the ball 90 at a convenient height for the operator to use. The rubber portion 95 of the ball 90 protects both the key pad 91 from damage and accidental button activation should the ball 90 swing free. Depressing of the control button 92 labeled "E" causes the legs and boom to extend so that the leg and boom actuator motor allow their respective latches to extend and lock into position. The leg motor is recommended to be geared to extend the legs at a linear speed at approximately 1 (one) inch per second. Optical sensors, such as Honeywell ultra thin reflective sensors are utilized to confirm that the legs have extended and locked before the hoist can be operated. The reflective sensors each contain an optical infrared emitting diode and a detector mounted in side by side converging optical axis. The detector responds to the radiant power only when a reflector object passes within the field of view. Similarly, the boom extends allowing the over-center hinge on the crutch to lock into position wherein the aforementioned optical sensor confirms the fully locked position by lighting of the LED lights for the legs 96, 98 and the boom 100. During retraction the retraction button 94 is depressed wherein the legs and the boom return to their retracted position and the LED lights 96, 98, and 100 illuminate to indicate the stored position.
The back side of the control panel shown in FIG. 6 causes the hoist to move in the upward position by depressing of directional positioning switches. Depressing of an up switch 102 will operate the hoist motor for lifting of the hook. Depressing of a down switch 104 will operate the hoist motor for lowering of the hook. Movement of the boom to the left is accomplished by depressing the left switch 106 and movement of the hoist to the right is accomplished by depressing of the right switch 108. Lights are provided for indication of the leg 110 lock, boom 112 lock and wheel 114 lock. The hoist cable and pulleys should be rated for at least one-thousand pounds with a preferred linear cable speed of about 1 (one) inch per second. The hoist motor should be able to drive the cable reel via a worm gear thus the weight on the cable cannot cause the cable reel to rotate.
It is to be understood that while I have illustrated and described certain forms of my invention, it is not to be limited to the specific forms or arrangement of parts herein describe and shown. It will be apparent to those skilled in the art that various changes may be made without departing from the scope of the invention and the invention is not to be considered limited to what is shown in the drawings and described in the specification. | 1a
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This is a Divisional of copending application Ser. No. 07/790,490, filed on Nov. 12, 1991 now U.S. Pat. No. 5,197,964.
BACKGROUND OF THE INVENTION
I. Field of the Invention
This invention relates generally to the design of an electrosurgical instrument and more particularly to an electrosurgical instrument for insertion into a laparoscopic trocar or endoscope and having one electrode which is movable relative to a stationary electrode. When the movable electrode is brought within a close predetermined distance to the fixed electrode and a voltage is applied across these electrodes, an arc is created for effecting radio frequency cutting or coagulation of a polyp or other tissue captured between the two electrodes. The device is especially adapted for trimming small polyps from the wall of the colon and, subsequently, cauterizing the remaining tissue at the site of the polyp removal. The device can also be utilized to coagulate vascular tissue areas.
II. Discussion of the Prior Art
Bipolar electrosurgical instruments typically feature a handle or housing which supports a pair of closely spaced conductive electrodes at a distal tip. These electrodes typically are stationary and extend distally from the tip and have a dielectric, such as air, therebetween. Neither is movable with respect to the other. In those electrosurgical instruments where at least one electrode is moveable, forceps-type electrodes which are movable by squeezing the electrodes toward one another, are commonly involved. In this forceps configuration, each electrode moves essentially equidistantly towards the other in one action.
U.S. Pat. No. 4,353,371, issued to Cosman, discloses a bipolar surgical instrument with longitudinally side-biting electrodes, which Is typical of the forceps-type designs. The forceps' blades are squeezed equidistantly towards one another along a longitudinal axis, as a coagulating potential is applied. Both blades of the forceps pivot towards one another within an insulating element which maintains electrical isolation at their bases. This configuration requires that the blades be placed at a right angle to the tissue to be cut if a smooth, even removal of tissue is desired.
U.S. Pat. No. 1,978,495, issued to Landau, discloses a medical instrument for the removal of tonsils. Pressure applied on a handle pushes an electrode toward a conductor. Increasing pressure eventually positions the electrode at a point where current is permitted to flow, whereupon a blade is advanced to sever the tonsil. In operation, a contact on a spring touches the conductor portion of the handle and maintains an open circuit for cutting. However, continuing pressure on the handle eventually advances the conductor forward until it is advanced to a region on the handle which is specifically dimensioned to break contact. Release of pressure on the handle permits the electrode to retreat and re-establish the circuit while the contact and handle are touching. Although exemplary of a movable electrode configuration, this device is awkward in applications other than tonsillectomies.
U.S. Pat. No. 373,399, issued to Hamilton, discloses an electrode for forming clots in varicose veins. In this device, a J-shaped rod has an electrode placed at its tip. A second electrode is placed in opposing relation on a slightly curved rod. Each electrode terminates at a conducting wire and is held within a pair of retainers. The "J"-shaped rod is held securely, but the curved rod may be displaced Proximally or distally. An adjustable stop regulates the extent of proximal or distal movement and, thus, prevents the approach of the two electrodes beyond a desired limit. After the device is positioned within body tissues, a coagulating electrical current is applied. Although this device also provides an example of a configuration for a movable electrode, this "J"-shaped rod requires greater clearance than is available in some electrosurgical applications.
It is accordingly a principal object of the present invention to provide a new and improved method and apparatus for bipolar cauterization of tissue featuring one stationary electrode and one movable electrode.
Another object of the present invention is to provide a new and improved method and electrocauterizing apparatus for encompassing polyps and the like then severing them in a guillotine fashion.
It is yet another object of the present invention to provide such a new and improved electrocauterizing apparatus dimensioned for insertion within a laparoscopic trocar or endoscope.
A further object of the present invention is to provide an electrocauterizing apparatus with a moveable electrode, further including electrocoagulating traces for coagulation of blood in the treatment region.
SUMMARY OF THE INVENTION
An electrosurgical instrument for trimming small polyps from the wall of the colon and, subsequently, cauterizing the tissue at the site of the polyp material is disclosed. Five embodiments are shown, each of which includes one stationary electrode and one movable electrode. When the movable electrode is brought into a close, predetermined distance from a fixed electrode and a voltage is applied across the electrodes, an arc is created for effecting electrosurgical cutting of a polyp or coagulating other tissue which has been captured between the two electrodes. The electrodes have a rectangular shape and operate in a guillotine fashion. In one embodiment, the outer electrode moves with respect to the remainder of the assembly. In another embodiment, an inner electrode moves with respect to a fixed outer electrode. In yet another embodiment, a hook-type blade contains the electrode and either an outer hook or an inner, reciprocating blade electrode, or both, may be moveable.
The electrodes are fitted into a distal insulating plug, which is inserted into the distal end of the instrument. An optional electrocoagulating feature includes metal traces inlaid upon the peripheral surface of the insulating plug. These traces act as a bipolar pair when RF voltage is applied across them, thus electrocoagulating tissue and fluids with which they are brought in contact.
The aforementioned objects and advantages of the invention will become subsequently apparent and reside in the details of construction and operation as more fully hereinafter described and claimed, reference being had to the accompanying drawings forming a part thereof, wherein like numerals refer to like parts throughout.
DESCRIPTION OF THE DRAWINGS
FIG. 1 depicts a partial,, side cross-sectional view of a preferred embodiment of the present invention;
FIG. 2 depicts a perspective, enlarged view of a preferred electrode configuration used on the device of FIG. 1;
FIG. 3 depicts a partial, side cross-sectional view of an alternative embodiment of the present invention;
FIG. 4 depicts a partial, side cross-sectional view of another alternative embodiment of the present invention;
FIG. 5 is a perspective view of the distal end of the embodiment of FIG. 4;
FIG. 6 depicts a side, cross-sectional view of an alternative tip arrangement for the present invention;
FIG. 7 depicts an end view of the tip arrangement of FIG. 6;
FIG. 8 depicts a side, cross-sectional view of yet another tip arrangement for the present invention;
FIG. 9 depicts a side, cross-sectional view of another alternative tip arrangement for the present invention;
FIG. 10 depicts an end view of the tip arrangement of FIG. 9; and
FIG. 11 depicts a side, cross-sectional end view of yet another electrode configuration for the present invention; and
FIG. 12 depicts an end view of the tip arrangement of FIG. 11.
DESCRIPTION OF THE PREFERRED EMBODIMENT
A preferred embodiment of the bipolar electrosurgical instrument of the present invention is shown in FIG. 1. Generally designated as 10, the instrument is comprised of a tubular member 12 having a proximal end 14 and a distal end 16. Fitted into the distal end 16 is a cylindrical insulating plug 18, preferably comprised of ceramic, or the like. Mounted upon a distal end surface 20 of plug 18 is a surface electrode 22, preferably of stainless steel, tungsten or tungsten alloy. With no limitation intended, and as better seen in FIG. 2, electrode 22 preferably has a pentagon shaped cross-section, providing a knife edge 24 facing outward from the end 20 of insulating plug 18. Distal end surface 20 of plug 18 may preferably be generally circular or oval.
A longitudinal bore 26 is drilled or otherwise formed lengthwise through plug 18, communicating with the lumen of tubular member 12. An actuator or push rod member 28 is preferably made of plastic or covered with a nonconductive material and extends through tubular member 12. Near the distal end of tubular member 12, it is joined, as at junction 48, with an "L"-shaped rigid support member or rod, such as stainless steel rod 30, which is inserted through bore 26. Rod 30 further includes blade electrode 32, preferably of stainless steel, tungsten or tungsten alloy, and which is disposed to operably cooperate with surface electrode 22.
The actuator member 28 extends through the length of the tubular member 12 and terminates at its proximal end in a thumb loop 34. Alternatively, the rigid support rod 30 may be comprised of a one-piece rod which extends the full length of member 12 and protrudes from its proximal end, as depicted in FIG. 4. A pair of rigid finger loops 36 and 38 are attached at the proximal end 14 of the tubular member 12 to provide a secure grip for moving actuator member 28 and concomitantly, stainless steel support rod 30, reciprocally within the bore 26, causing electrode 32 to move toward or away from electrode 22 on plug 18.
A pair of flexible conductive wires 40 and 42 are insulated from one another and extend through tubular member 12. A conventional cord 44, with electrical connector 46 on its free end, is electrically joined to the wires 40 and 42 at their proximal ends to facilitate their connection to an electrosurgical generator. The distal ends of wires 40 and 42 are electrically joined to electrodes 22 and 32, respectively. Specifically, conductive wire 40 extends the full length of tubular member 12 from cord 44 to surface electrode 22. Conductive wire 42 extends from cord 44 to a junction point 48, where it is mechanically and electrically joined to steel rod 30. When the thumb loop 34 and actuator member 28 are formed from plastic, there is no danger of shock to the surgeon. If a one-piece metal push rod is used, the thumb loop 34 should be appropriately insulated.
It is suggested that cord 44 be supplied with RF voltage from an RF source 50. Control of this supply may be attained by use of a conventional on/off foot switch 52, as known in the art. When the foot switch is depressed, a circuit is completed and electrical current is permitted to flow from the electrosurgical generator 50 and through electrodes 22 and 32 when tissue is captured therebetween. One skilled in the art will readily recognize that a finger-operated switch, such as switch 92 in FIG. 4, mounted on housing 12 is equally useful to provide current in a controlled fashion to electrodes 22 and 32.
FIG. 3 depicts a cross-sectional view showing an alternative tip arrangement for the present invention. In this embodiment, blade electrode 32 is mounted on a rigid support member 30 which is stationary. However, the insulating plug 54 is made moveable by virtue of being rigidly affixed to an actuator member such as stainless steel rod 56. A thumb loop 58 is affixed at its proximal end and coated with a thin, insulative coating (not shown). Thumb loop 58 is positioned in opposable relation to finger loops 36 and 38 on the tubular member 12, as in the previous embodiment. Thus, moving thumb loop 58 in a distal direction will simultaneously extend plug 54 beyond the distal end of member 12 and toward stationary blade electrode 32. Stationary blade electrode 32 may be mounted on support rod 30, which is secured in retainer 60 comprised of a block of plastic. Movement of thumb loop 58 brings cutting edge 24 toward or away from stationary electrode 32. When radio frequency (RF) energy from source 62 is applied using foot switch 64, a polyp or other tissue segment held between electrodes 22 and 32 will be severed.
FIG. 4 depicts an alternative embodiment featuring a variation of the plug shown in FIG. 3 and eliminating the foot switch option. Designated generally as 80, this cylindrical plug can similarly be made to extend outward from the distal end of tubular member 12 by movement of a thumb switch. As better seen in FIG. 5, the plug 80 features metal traces 82 and 84 inlaid in noncontacting and spiral relation upon the peripheral surface 86. When energized, these traces 82 and 84 function as bipolar electrodes for effecting electrocoagulation of tissue and blood. Additional flexible wire conductors 88 and 90 pass through the tubular member and supply RF voltage to these traces, which are preferably comprised of a tungsten alloy. To activate the electrocoagulating electrodes 82 and 84, conductors 88 and 90 are joined to thumb switch 92. When thumb switch 92 is advanced distally to lock on detent 93, the circuit is completed and the traces 82 and 84 are energized. When the circuit is completed, RF voltage is supplied via cord 44 from RF source 62.
The electrodes 22 and 32 must be energized independently from traces 82 and 84. Push button 99 mounted on thumb switch 92 is connected to conductors 40 and 42 and cord 44. It permits the user to exactly control the duration of cutting by the duration it is depressed.
The plug 80 may also be extended or retracted. A rigid actuator member 94 is affixed to a sliding thumb switch 96. Movement in a distal direction extends the plug 80, while proximal movement retracts it. Slippage is prevented by detents 98.
FIGS. 6 and 8 depict alternative embodiments for the seductive electrodes 22 and 32 of FIGS. 1-4. A pair of generally U-shaped electrodes either pass through or are secured within a plug member, such as plug 100. In FIG. 6, the legs of the moveable U-shaped electrode 102 are embedded and fixed within an oval-shaped plug 100, better seen in FIG. 7. They are securely held in place with, for example, beads of potting material 104 and 106. Stationary electrode 108 is dimensioned to be slightly larger in total surface area than electrode 102. Bores have been drilled through the insulating plug 100 to receive legs 110 and 112 of electrode 108. These legs 110, 112 extend into tubular member 12 and are secured in a pair of nonconductive retainers 114 and 116. A rigid actuator means, as depicted in FIG. 3, includes a stainless steel rod 118, which extends through tubular member 12 to a thumb loop, as in previously described embodiments. The rod 118 is securely affixed at its distal end to plug 100 so translational movement of the thumb loop causes the end plug carrying electrode 102 to be displaced along the longitudinal axis of tubular member 12 toward or away from fixed electrode 108.
The converse is depicted by plug 120 in FIG. 8. The legs of moveable electrode 122 are embedded within plug 120 and secured with potting material 124 and 126. Fixed electrode 128 is disposed coaxially with moveable electrode 122 and has legs 130 and 132 which extend through bores 134 and 136 in plug 120 to retainers 138 and 140 inside tubular member 12. Plug 120 is similarly affixed to an actuator means, here depicted as stainless steel rod 142, which extends to a thumb loop (not shown), as in previous embodiments.
It is well within the contemplation of one skilled in the art that although the electrodes in FIGS. 6 and 8 are depicted as being somewhat rectangular in shape, electrodes 102, 108, 122 and 128 may be dimensioned in various curved configurations as well. An example is provided in FIG. 9, wherein electrodes 150 and 152 feature distal curves to provide a scoop-like excision in tissue. Furthermore, as better seen in FIG. 10, plug 120 may have a circular distal surface.
One skilled in the art will appreciate that many variations in electrode configuration are possible, but such variations do not depart from the spirit of the present invention. For example, FIGS. 11 and 12 show a variant of the embodiment of FIG. 10, in which the electrode tips 160 and 162 have been flattened into a plane perpendicular to that of the longitudinal axis of the tubular member 12.
In operation, a surgeon grasps tubular member 12 at its proximal end, inserting his thumb and fingers in loops 34, 36 and 38. The distal portion of the electrosurgical instrument is then advanced through a laparoscopic trocar or endoscope and the distal end carrying or otherwise supporting the bipolar electrodes is positioned near the tissue to be removed. By moving thumb loop 34 toward tubular member 12, electrode 30 in FIG. 1 is moved distally from electrode 22. In the embodiment of FIG. 8, electrode 122 is moved distally from electrode 128. In the embodiments of FIGS. 3, 4 and 5, the thumb loop 34, 54 is pulled proximally. This draws the plug (54, 86 or 100) proximally and away from the electrode (32 or 108). In all embodiments, movement of the thumb loop, as herein described, provides a gap into which the tissue to be excised is inserted. Upon reciprocal movement and simultaneous application of radio frequency energy, the tissue is electrocauterized and severed. To provide enhanced electrocoagulation, traces such as depicted in FIG. 4, may be included on all embodiments.
This invention has been described herein in considerable detail in order to comply with the Patent Statutes and to provide those skilled in the art with the information needed to apply the novel principles and to construct and use such specialized components as are required. However, it is to be understood that the invention can be carried out by specifically different equipment and devices and that various modifications, both as to equipment details and operating procedures, can be accomplished without departing from the scope of the invention itself. | 1a
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to an improvement in the treatment of Parkinson's disease and related disorders. More specifically, the present invention introduces novel formulations of the combination carbidopa and levodopa, the current mainstay of therapy.
2. Background and Prior Art
Parkinson's disease is associated with the depletion of dopamine from cells in the corpus striatum. Since dopamine does not cross the blood brain barrier and cannot therefore be used to treat Parkinson's disease, its immediate precursor, levodopa, is used instead because it penetrates the brain where it is decarboxylated to dopamine. But levodopa is also decarboxylated to dopamine in peripheral tissues and consequently only a small portion of administered levodopa is transported unchanged to the brain. This reaction can be blocked by carbidopa which inhibits decarboxylation of peripheral levodopa but cannot itself cross the blood brain barrier and has no effect on the metabolism of levodopa in the brain.
The combination of carbidopa and levodopa is considered to be the most effective treatment for symptoms of Parkinson's disease (The Medical Letter, 35:31-34, 1993). Nevertheless, certain limitations become apparent within two to five years of initiating combination therapy. As the disease progresses, the benefit from each dose becomes shorter (“the wearing off effect”) and some patients fluctuate unpredictably between mobility and immobility (“the on-off effect”). “On” periods are usually associated with high plasma levodopa concentrations and often include abnormal involuntary movements, i.e., dyskinesias. “Off” periods have been correlated with low plasma levodopa and bradykinetic episodes.
In an effort to reduce the occurrence of “wearing off” and “on-off” phenomena, a controlled release oral dosage combination was introduced with claims of slow and simultaneous release of carbidopa and levodopa from the formulation (U.S. Pat. No. 4,900,755 issued Feb. 13, 1990). Data from clinical trials cited in the patent indicate that effective antiparkinson effects were achieved with fewer daily doses of the controlled release form as compared with the conventional combination.
Nevertheless, there remains a significant flaw in the therapeutic application of controlled release carbidopa-levodopa; that is the considerable delay in onset of action. Mean time to peak concentration in healthy elderly subjects was found to be two hours for controlled release carbidopa-levodopa and only 0.5 hours for the conventional form (Physicians Desk Ref., 47th Ed., p. 976, 1993). A controlled release dosage form that could also provide rapid onset of action, at least equivalent to that of conventional carbidopa-levodopa would have an obvious clinical advantage over current therapy.
The strategy proposed in the present invention is it to formulate oral dosage forms containing both immediate release carbidopa-levodopa and controlled release carbidopa-levodopa. Ingestion would provide rapid onset antiparkinson activity via the immediate release component followed by sustained therapeutic activity from the controlled release component.
SUMMARY OF THE INVENTION
It is the purpose and principal object of this invention to provide an improved method for the treatment of Parkinson's disease by using novel formulations of the combination carbidopa-levodopa which a) are effective in preventing the symptoms of Parkinson's disease and yet which b) act rapidly avoiding significant onset delay common to the standard controlled release therapy.
DETAILED DESCRIPTION
The present invention concerns a method for treating Parkinsons's disease using an oral dosage formulation comprising an immediate release layer of 10-25 mg of carbidopa and 50-200 mg of levodopa and a sustained release layer of 25-75 mg of carbidopa and 100-400 mg of levodopa whereby, following administration, carbidopa and levodopa are available for rapid and sustained therapeutic action.
An oral dosage formulation in the present method can be further characterized by a sustained release core depot of carbidopa-levodopa overcoated by an immediate release layer of carbidopa-levodopa.
Another aspect of the orally administering the dosage comprises administering a multilayer tablet comprising at least one layer of sustained release carbidopa-levodopa adjacent to at least one layer of immediate release carbidopa-levodopa. If desired, the layers in tablet are separated by an excipient layer.
Another aspect of the invention therefore concerns a pharmaceutical composition in oral dosage form for treating Parkinson's disease, which comprises a combination of an immediate release portion of a combination of carbidopa and levodopa and a sustained release portion of a combination of carbidopa and levodopa and a pharmaceutically acceptable vehicle. The composition is effective in treating Parkinson's disease. The dosage form is such that carbidopa and levodopa are available for immediate and sustained therapeutic action upon administration. The pharmaceutical composition can be in a dosage form that comprises a sustained release core portion of carbidopa and levodopa overcoated by an immediate release layer of carbidopa and levodopa. The pharmaceutical composition can also be in a dosage form that comprises a multilayer tablet which comprises at lease one layer of sustained release carbidopa-levodopa adjacent to at least one layer of immediate release carbidopa-levodopa.
In the pharmaceutical composition, in dosage form, an immediate release portion comprises about 10-25 mg of carbidopa and 50-200 mg of levodopa and a sustained release portion comprises about 25-75 mg of carbidopa and 100-400 mg of levodopa. The pharmaceutical composition in dosage form can comprise a sustained release core portion of carbidopa-levodopa overcoated by an immediate release layer of carbidopa-levodopa. The pharmaceutical composition in the dosage form can comprise a multilayer tablet of at least one layer of sustained release carbidopa-levodopa adjacent to at least one layer of immediate release carbidopa-levodopa.
The novel oral dosage formulations of the present invention each contain immediate release and controlled release components of the antiparkinson agents carbidopa (5-200 mg) and levodopa (25-600 mg). The conventional immediate release combination of carbidopa-levodopa reaches peak plasma concentrations in 30 minutes whereas the onset of the controlled release component is two hours followed by prolonged release over a four- to six-hour period.
The usual daily therapeutic dose of levodopa, when administered with carbidopa, is 300 to 750 mg and the dose of carbidopa approximately 75 mg per day but the latter is apparently devoid of adverse effects even at doses of 400 mg per day (J. E. Ahlskog, Hosp. Form., 27:146, 1992). Although the optimum daily dosage of carbidopa-levodopa must ultimately be determined by titrating each patient, a preferred range for twice daily maintenance therapy may include immediate release of 10-25 mg carbidopa and 50-200 mg levodopa and sustained release of 25-75 mg carbidopa and 100-400 mg levodopa.
Specific examples of these formulations are cited below. The amount and excipients listed can be changed through methods known to those skilled in the preparation of immediate and sustained release dosage forms. Some of these methods are available in Remington's Pharmaceutical Sciences, 17th Ed., 1985, a standard reference in the field.
EXAMPLE 1
A two compartment tablet consisting of a core layer of sustained release carbidopa-levodopa overcoated with a layer of immediate release carbidopa-levodopa. The core ingredients are blended separately (as are the outer layer ingredients), compressed to produce core tablets and then overcoated with the compressed outer layer blend using a suitable coating press.
Ingredient
Mg per Tablet
Outer Layer (Immediate Release)
Carbidopa
25.0
Levodopa
100.0
Microcrystalline Cellulose
224.0
Croscarmellose Sodium
15.0
Silicon Dioxide
3.0
Magnesium Stearate
3.0
Core Layer (Sustained Release)
Carbidopa
50.0
Levodopa
200.0
Methocel E4M Premium CR
80.0
Microcrystalline Cellulose
61.0
Silicon Dioxide
2.0
Magnesium Stearate
2.0
EXAMPLE 2
A bilayer or multilayer tablet consisting of one layer of sustained release carbidopa-levodopa either adjacent to a layer of immediate release carbidopa-levodopa or separated by an additional excipient layer. The ingredients from each layer are blended separately, then compressed to produce a layered tablet using a suitable layered press.
Ingredient
Mg per Tablet
Layer 1 (Immediate Release)
Carbidopa
12.5
Levodopa
50.0
Microcrystalline Cellulose
123.5
Silicon Dioxide
2.0
Magnesium Stearate
10.0
Layer 2 (Sustained Release)
Carbidopa
37.5
Levodopa
150.0
Methocel E4M Premium CR
80.0
Microcrystalline Cellulose
53.5
Silicon Dioxide
2.0
Magnesium Stearate
2.0
EXAMPLE 3
An oral dosage form, such as a capsule or compressed tablet, containing immediate and sustained release carbidopa-levodopa pellets prepared by the following methods:
1. Dissolve Povidone in isopropyl alcohol (10% w/w)
2. Disperse micronized carbidopa and levodopa in Povidone solution
3. Layer the slurry from step 2 onto sugar spheres to form core pellets using a fluid-bed with a Wurster air suspension coating column
4. Dissolve ethyl cellulose and polyethylene glycol 4000 in methylene chloride and methanol (4:1) mixture (5% w/w)
5. Coat pellets from step 3 with polymer solution from step 4 in a fluid-bed with a Wurster air suspension coating column.
Appropriate amounts of uncoated core pellets containing immediate release carbidopa-levodopa (step 3) and polymer coated pellets containing sustained release carbidopa-levodopa (step 5) are included in an oral dosage form to provide the desired ratio of immediate and sustained release carbidopa-levodopa.
Ingredient
% by Weight
Uncoated Core Pellets
(Immediate Release)
Carbidopa
12.5
Levodopa
50.0
Povidone (K-30)
17.5
Sugar Spheres (35-40 Mesh)
20.0
Coated Pellets
(Sustained Release)
Core Pellet
94.0
Ethyl Cellulose
4.5
Polyethylene Glycol 4000
1.5 | 1a
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CROSS REFERENCE TO RELATED APPLICATION
[0001] This application claims priority to copending U.S. provisional application entitled, “Seafood Preservation Process,” having Ser. No. 60/241,921, filed Oct. 20, 2000, which is entirely incorporated herein by reference.
TECHNICAL FIELD
[0002] The present invention is generally related to the preservation of seafood and other food products for consumer consumption, and more particularly is related to a process for preserving fish by treating fish with smoke and ozone to retard degradation of the fish and maintain the fresh-like appearance of the fish. Optionally, the fish can then be frozen to further prolong its shelf life
BACKGROUND OF THE INVENTION
[0003] The preservation of fish has been a major concern for fishermen and fish processors for centuries. Originally man salted and dried fish to preserve it. Since the advent of mechanical refrigeration, the fish have been preserved by freezing and refrigeration, thus permitting fishermen to make longer fishing trips, as well as transport the fish long distances over land or water.
[0004] The length of time over which fish maintains its freshness is commonly referred to as its shelf life. The shelf life of fish is determined by a number of factors, including the total number of each type of bacteria initially present, the specific types of bacteria present, the temperature of the flesh of the fish and of the surrounding atmosphere, and the pH of the fish. It is known that to extend the shelf life of fish, one may, for example, reduce the number of bacteria present using chemical means, freezing or other methods, create an acidic pH and/or maintain the product below 5° C. in its fresh state. The most common process employed to extend the shelf life of fish is freezing.
[0005] An inherent problem with freezing fish is its loss of the “fresh” attributes such as a “pink” or “red” meat color to both the fish flesh and the “blood line” in the fish. The loss of these attributes causes the value of the frozen fish to be much less than the value of fish that has not been previously frozen. This loss of value is an interpretation of the quality of the fish by the consumer. The color of the flesh and blood line of the fish is a major factor in the selling of seafood at the consumer level. Most consumers purchase fish with their “eyes” rather than with any other factor, such as smell, taste or texture. Therefore, it is desirable to maintain the “fresh” pink/red color of the seafood products as long as possible in order to sell the product at a premium to consumers.
[0006] Although many factors may effect changes to the color of fish products, the main reduction of color results from damage to the hemoglobin pigments in the fish. Several of the primary causes for the reduction of hemoglobin pigments, resulting in a corresponding reduction in the “fresh” color of the fish, include oxidation of the “red” hemoglobin pigments in the flesh to a “brown” color; bacterial decomposition of the cells containing the hemoglobin pigments; and destruction and oxidation of the hemoglobin pigment during freezing.
[0007] Most unfrozen fish is considered “fresh” for as many as 30 days from catching. However, unfrozen fish this old usually contains high levels of dangerous bacterial decomposition. Bacterial decomposition of fish is the cellular breakdown of the flesh of the fish due to the digestive enzymes of bacteria present on or within the flesh of the fish. Conversely, frozen fish is usually frozen upon catching which reduces the likelihood that the fish will contain significant or harmful levels of bacterial decomposition.
[0008] In order to preserve the freshness of the fish and maintain the color of the flesh and blood line to a satisfactory consumer level, processes using smoking and freezing techniques have been applied.
[0009] Smoking of fish has been one of the major forms of fish preservation for centuries. Smoking involves the burning of organic substances, such as wood, to produce a complex mix of over 400 separate chemical compounds. These compounds, when continually exposed to fish flesh, are absorbed into the meat over time and impart a smoke flavor to the flesh. The smoke compounds act as a natural “bacteriostat” and greatly increase the refrigerated shelf life of the flesh (up to three times the un-smoked shelf life). Smoking of fish increases the shelf life by killing a majority of the bacteria initially present, and then creating an acidic environment that slows the growth of bacteria over time in refrigerated conditions. The compounds in the smoke that are primarily responsible for the extension of the shelf life of fish are the aldehydes and phenols, as well as CO, CO 2 , NO, NO 2 , which are the main gaseous components of smoke. These compounds maintain the “fresh” color of the fish, as well as prevent the growth of bacteria both on the surface of the fish and within the flesh.
[0010] However, one of the problems inherent in smoking fish products to impart preservation properties is that the smoke odor and/or smoke taste remains present in the fish flesh. Additionally, smoke that is produced from organic fuel materials typically contains particulates, such as creosote, tar, soot, etc., which are undesirable elements to have in contact with the fish product. Thus, it is beneficial to provide a smoke that has had some of the particulate removed and further remove the smoke odor/taste while still maintaining the extended shelf life.
[0011] U.S. Pat. No. 5,972,401 to Kowalski discloses a process for manufacturing a tasteless, super-purified smoke for the treatment of seafood and meat. The super-purified smoke is then applied to seafood or meat to preserve the freshness, color, texture, and natural flavor, particularly after the seafood or meat is frozen and thawed. Kowalski teaches that the smoke must be super-purified by filtering out a substantial amount of odor and taste imparting particulate matter and gaseous vapors, thereby recovering the smoke in a tasteless form. Thus, Kowalski is limited in that it requires that the smoke be super-purified into a tasteless form in order to prevent the impartation of the smoke odor or taste to the seafood or meat products.
[0012] U.S. Pat. No. 5,484,619 to Yamaoka discloses a process for smoking fish and meat at low temperatures, thereby conferring a smoked flavor and taste, and further preventing decomposition and discoloration of the fish or meat. As in Kowalski, the smoke is filtered to remove the larger particulates and provide a smoke that will preserve, sterilize and aid in maintaining the color of the flesh of the fish or meat. However, Yamaoka teaches that the smoke odor or taste will remain in the fish or meat and that the temperature of application of the smoke is important. Specifically, the Yamaoka smoke preservation process must be carried out at extremely low temperatures (between 0 and 5° C.) in order to maintain the freshness and quality of the fish or meat products Therefore, Yamaoka is limited to a smoke process for preserving fish or meat products wherein the product will retain a smoke odor or taste, and the process is further limited to a narrow range of temperature conditions.
[0013] U.S. Pat. No. 2,120,237 to Brenner et al. discloses a method for partially drying and then smoking fish fillets to preserve them. The fish fillets were first dried to remove a substantial portion of the moisture present and then treated within a smoke atmosphere. This method imparted a smoke flavor to the dried fillets and aided in the prevention of the fish deterioration.
[0014] It is also known to preserve the freshness or color of fish or other meat products by several other methods of treatment. U.S. Pat. No. 3,859,450 to Alsina teaches that melanosis (blackening) in shellfish is prevented by application of an innocuous acid solution followed by carbon dioxide gas. The resultant chemical reaction between the acid solution and the carbon dioxide produces carbonic anhydride that penetrates the shellfish and prevents melanosis during preservation by freezing. The process also discloses that the use of a food preservative, such as metabisulphite, will prolong the preservation of the original taste and texture of the shellfish after thawing.
[0015] U.S. Pat. No. 4,522,835 to Woodruff et al. discloses a process for maintaining good color in meat, poultry and fish products. Specifically, Woodruff teaches that subjecting the product to an atmosphere containing a low oxygen concentration and followed by an atmosphere containing a small amount of carbon monoxide will convert oxymyoglobin to carboxymyoglobin. The process produces a red color in the product and permits lengthy refrigeration of the product (two to three weeks). Further preservation is accomplished by Woodruff by maintaining the product in a modified carbon dioxide atmosphere or by freezing.
[0016] U.S. Pat. No. 5,540,942 to Tokoro teaches that the freshness of meat or fish may be improved by treatment with ubidecarenone to prevent discoloration of the product. The ubidecarenone additive prevents the oxidation of the haem pigments, thereby maintaining the red color of “fresh” product by preventing discoloration to a brown or gray appearance.
[0017] Ozone, a GRAS (generally regarded as safe) substance, has been used for more than ten years to sanitize, deodorize and prevent bacterial growth in food items. Its main strength is in the killing of surface and subsurface bacteria that lead to decomposition of fish flesh during refrigerated storage. Ozone may be applied using a gaseous or liquid medium or a combination thereof.
[0018] U.S. Pat. No. 5,783,242 to Teague discloses a process of treating poultry with ozone and ozone dissolved in water to reduce the population of contaminating organisms. The product is first subjected to a solution containing ozone and then exposed to a gaseous atmosphere containing ozone. The product is also subjected intermittently to UV exposure which further acts as a bactericide and decomposes any ozone remaining on the product into oxygen.
[0019] Although, it is known that the foregoing techniques may be used to preserve the fish flesh itself, these techniques often result in an appearance of fish that has lost its “fresh” attributes. Accordingly, without the ‘pink’ or ‘red’ color of the fish flesh, consumers often consider such preserved fish as “not fresh,” resulting in a lower sales price for the fish. The foregoing techniques claim to maintain the color of the fish do so with the addition of chemical additives and preservatives which can alter the taste and texture of the fish or be toxic in certain dosages to humans. Additionally, maintaining the “fresh” attributes of the fish is not taught when the fish is preserved or further preserved by freezing.
[0020] Therefore, a heretofore unaddressed need exists in the industry to satisfy the aforementioned deficiencies and inadequacies and provide a preserved fish that retains all of the qualities and characteristics of a “day caught” fish.
SUMMARY OF THE INVENTION
[0021] Through research and product development, the inventors have devised a process for fish preservation that results in the production of an extremely high quality, fresh seafood product line with extended shelf life characteristics. The fish products are preserved using smoke and ozone so as to maintain the qualities and characteristics of freshly caught fish.
[0022] The process allows the transportation of fresh and frozen seafood items from remote areas of the world in a safe, sanitary and economical way. However, Applicants' preservation process has overcome the drawbacks of typical freezing techniques and allows the consumer to receive a high quality, extremely safe fish with the taste, texture and attributes of freshly caught fish. The fish appears “fresh” to consumers as it retains its red, or bright, color and is, thus, more appealing.
[0023] In general, the process includes the steps of smoking of fresh fish, treating it with ozone and optionally freezing the fish. When a smoke and ozone process is utilized, the shelf life is extended and the fish retains more of its “fresh” color. The smoke/ozone process retains the “fresh” color and extends shelf life of the fish flesh by binding the carbon monoxide molecule to the heam pigment in the hemoglobin molecule in such a way that it takes much greater than normal oxidative force to oxidize the hemoglobin molecule. Furthermore, the smoke/ozone process aids in the prevention of bacterial decomposition and maintains the hemoglobin molecule (red color) during freezing and frozen storage by binding it with a CO molecule.
[0024] Optionally, the smoke/ozone process can include the steps of wiping the flesh of the fish with alcohol one to three times during the preservation process, before or after smoking the fish. The application of alcohol to the exterior of the fish kills surface and shallow bacteria on contact with the alcohol. The fish would be placed in a modified “smoke” atmosphere for 1 to 72 hours, with the length of time depending on the thickness of the fish product, with thicker products requiring more time than thinner products. If the smoke is applied to the fish while in a vacuum chamber, the time required for the smoke application can be reduced to less than a minute. During the smoking step, a vast majority of “aerobic” bacteria die as there is no oxygen available for them to breathe. The smoking step additionally creates an acidic pH in the fish by the dissolution of free carbon dioxide, present in the smoke, into the fish. The acidic pH prevents the growth of bacteria during the “fresh” stages of the process. An optional final step can involve freezing the product to kill an additional percentage of the bacteria present on the product The fish product can be initially prepared into appropriately sized sections or fillets in order to accelerate the smoke/ozone application steps.
[0025] With the use of this fish preservation process, the shelf life of the product is increased, usually from about 2-3 days after the product is landed to about 10-12 days. This increase in shelf life after the product has been treated allows the product to be shipped to remote areas requiring longer shipping times. Also, the final processing of the product into consumer-ready forms, including cutting, portioning and packing the product, can be performed at the central processing facility. This avoids the necessity of having to perform the final processing of the product at the store level.
[0026] Other processes, systems, methods, features and advantages of the present invention will be or will become apparent to one with skill in the art upon examination of the following drawings and detailed description. It is intended that all such additional processes, systems, methods, features and advantages be included within this description, be within the scope of the present invention, and be protected by the accompanying claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] The invention can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present invention. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views.
[0028] [0028]FIG. 1 is a cross sectional view of an open top liquid container with a basket of fish products immersed in a brine.
[0029] FIGS. 2 - 4 are schematic elevational views of a vacuum bag and the fish products contained therein, showing the bag in its relaxed, vacuum and inflated configurations, respectively.
[0030] [0030]FIG. 5 is a schematic view of the smoke machine.
[0031] [0031]FIG. 6 is a side elevational view of the centrifuge used in the smoke machine.
[0032] [0032]FIG. 7 is a cross section of the centrifuge, taken along lines 7 - 7 of FIG. 6.
[0033] [0033]FIG. 8 is a side view of the bag filling device
[0034] [0034]FIG. 9 is a perspective view of the ozone dipping tank and basket.
[0035] [0035]FIG. 10 is a plan view of the ozone chamber used for fish steaks.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0036] The inventors have devised a process for preserving seafood products and other meat products of various types. Typically, the first step of the process involves the initial preparation of the fish product into appropriately sized sections 101 . The skin and bones may either be removed or may be left on. As shown in FIG. 6, if the fish is of the pelagic species, such as salmon or tuna, the fish can be cut into loin portions or steaks 102 . If any loin portion has a thickness that is too big for expedient smoke and/or ozone treatment, the loins can be cut into steaks.
[0037] As shown in FIG. 1, the sized fish product 101 is placed in a single layer in a basket 105 or porous tray, preferably plastic, and the basket with the fish is immersed into an aqueous solution 104 of salt and baking soda in a container 103 . The container 103 for the aqueous solution should have sufficient dimensions such that the fish products 101 are maintained in a single layer and are completely immersed in the aqueous solution 104 . The aqueous solution 104 preferably is a thoroughly mixed solution in a ratio of approximately ten liters of cold water at approximately 2 to 5° C., 200 grams of salt and 100 grams of baking soda.
[0038] The fish product 101 in the basket 105 is completely immersed in the aqueous solution 104 for approximately twenty seconds, after which time it is removed with the basket from the container 103 and the excess aqueous solution 104 is allowed to drain away from the fish. The fish product 101 usually is then patted dry using a porous plastic sponge, or the like, (not shown in the drawings) that has been previously sanitized in alcohol.
[0039] As shown in FIG. 2, the dry fish products 101 are then inserted into a vacuum bag 106 or another type of container in a single layer of the products. It is acceptable for the products to come in contact with each other. As shown in FIG. 3, the vacuum bag 106 or other type of vacuum container is vacuum sealed about the products using a conventional vacuum packaging machine (not shown). The vacuum seal formed about the products should be tight enough to remove substantially all of the air from the container 106 , but not so tight as to damage or flatten the fish product.
[0040] Once the air has been removed from the sealed container 106 , the container is filled with filtered smoke 107 as shown in FIG. 4. The container 103 should be filled with smoke until there is a slight pressure on the container. The container should remain sealed, such as with heat sealing of the layers of a plastic bag together, to prevent any of the smoke from exiting the bag 106 .
[0041] The smoke can be generated by a smoke machine 110 , as shown in FIG. 5. The smoke machine 110 includes a smoke generator 111 , a smoke cooler 112 , a centrifugal precipitator or centrifuge 114 , motor 115 , a centrifuge fan 116 and connecting belt and sheaves 118 . Motor 115 rotates centrifuge fan through the belt and sheaves in a conventional arrangement. Dirty smoke draw chamber 120 and its suction fan 121 draw the dense or dirty smoke from the centrifuge through mid height exhaust conduit 122 , and push the smoke through a filter 124 to the atmosphere. Some of the heavier precipitates of the smoke will move down the converging interior wall 125 of the centrifuge housing 126 through the open bottom to a water trap 128 .
[0042] The clean smoke is gathered at the vertical axis of the converging conical interior wall of the centrifuge by the inlet opening 129 of the clean smoke exhaust conduit 130 . The clean smoke exhaust conduit leads to clean smoke exhaust compressor 131 , through filters 132 to smoke storage tank 134 .
[0043] It would be apparent to one skilled in the art to modify the aforementioned embodiment of the smoke machine 110 by the addition or deletion of certain devices without substantially altering the purpose of supplying a filtered smoke. The smoke generator 111 is of conventional construction and is adapted for the burning of wood or other organic material for the generation of smoke. The smoke is passed from the smoke generator 111 through the smoke cooling conduits 113 of the smoke cooler 112 Cold water is circulated about the smoke cooling conduits to chill the smoke from about 900 degrees F. as it exits the smoke machine to about 400 degrees F. before moving into the centrifuge.
[0044] After the smoke has been generated by the smoke generator 111 and passed through the smoke cooler 112 , it is passed through the centrifuge 114 . The centrifuge 114 removes the majority of the particulate phase, i.e. any particle larger than approximately one micron, of the smoke. The particulate phase, which contains mainly ash and tar, is removed by running the product through the centrifuge 114 (see FIGS. 5 and 6 showing typical centrifuge design and implementation). The centrifuge 114 creates a cyclone effect inside the main chamber 117 by spinning a “squirrel cage” fan blade 116 at a speed of approximately between 3600 and 4000 rpm. The spinning action causes the heavy particulates of the smoke, mainly tar, to be flung by centrifugal force against the inside surface of the perimeter wall 125 of the chamber 126 at high velocity. The heavy particulates then move down the inside wall and funnel down to a collecting receptacle or water trap 128 at the bottom of the conical chamber 126 . The collecting receptacle 128 is partially filled with water at the lower open end of the centrifuge 114 so as to trap the heavy smoke particulates being exhausted by the precipitator. With the heavy particulate phase removed, the lighter, cleaner smoke at the center of the vertical axis 119 of the centrifuge 114 enters the outflow pipe and is directed into the smoke storage tank 134 .
[0045] Excess uncleaned smoke is directed through mid height exhaust conduit 122 and through exhaust suction fan 121 . Fan 121 is a variable speed fan that regulates the amount of smoke drawn through the system.
[0046] The clean smoke is dispensed on demand from the centrifuge 114 by the compressor 131 . The resulting clean smoke exits the centrifuge 114 with a very clear appearance. It is directed by the compressor 131 and its connection hoses through a final filtering device 132 and is collected and maintained in a smoke storage tank 134 . When a smoke storage tank is filled with smoke it is refrigerated and stored for later use.
[0047] As illustrated in FIG. 8, the cooled cleaned smoke is later inserted into the vacuum bag 106 with the fish product 101 by placing the hollow needle 140 of an air chuck 141 , which is connected to the smoke storage tank 134 via clean smoke dispensing conduit 142 , into the bag 106 and pulling the trigger mechanism 144 . This opens a valve and allows the clean smoke to move into the vacuum bag 106 . For high volume production, the bag 106 can be filled by using a modified atmosphere packaging system like the CVP AT600. If another type of vacuum chamber is used, not a bag, the smoke can be dispensed into the chamber by using a valve controlled conduit.
[0048] The filtered smoke will have an initial level of CO/CO 2 in the vacuum chamber and the CO/CO 2 level should be periodically measured. When the CO/CO 2 level begins to decline appreciably, the vacuum chamber is voided of and refilled with smoke until the color characteristics of the fish have stabilized. This procedure should preferably occur at a temperature range of 0 degrees C. to 5 degrees C. and can take anywhere from 1 minute to 72 hours depending on the type of fish product and the characteristics of the smoke and the method of applying the smoke. After this, the smoked fish product is placed in an ozonated environment at a temperature range of about 0 degrees C. to 5 degrees C. and is maintained in the ozonated environment until the odor of smoke is no longer detectable. Depending on the type of fish product and the amount of smoke odor that the product has absorbed during the smoking step, it may take anywhere from 1 minute to 72 hours depending on the type of fish product, the characteristics of the smoke, and the method of applying smoke, for the smoke odor to be sufficiently diminished that it is no longer detectable. The fish product is then removed, vacuum sealed and can be optionally frozen using conventional freezing techniques. When it is desired to use or display the fish product, the fish product is defrosted. The present process for preserving the fish product results in a refreshed fish product that closely parallels a day caught fish in quality, characteristics and appearance.
[0049] When the decline of the CO/CO 2 level slows appreciably during the smoke application process, the remaining smoke should be removed from the vacuum chamber 106 and replaced with another charge of smoke, as might be necessary. The smoking step should be repeated until the color characteristics of the fish product 101 have stabilized. Depending on the type of fish product 101 , the temperature and the smoke characteristics, it may take between approximately twelve to seventy-two hours at atmospheric pressure to satisfactorily complete the smoking step. However, if the smoke is applied in a vacuum chamber at a reduced pressure to the product, the smoke application step can be performed in minutes.
[0050] Once the smoking step is complete, the fish product 101 is removed from the vacuum chamber 106 and may be patted dry using a porous plastic sponge, or the like, sanitized with alcohol. The product is checked for smoke odor. As shown in FIG. 9, the fish product 101 is then placed in a basket 150 or other porous tray device. The fish product 101 may be situated within the basket 150 in either a single or double layer configuration. The basket 150 is then immersed into an ozone dipping tank 151 , that contains chilled (at about 5° C.) ozonated water 152 (approximately 2 ppm ozone) for between approximately one minute and one hour. The product can be left in the ozonated water for more than one hour, if desired.
[0051] The odor of the fish product 101 is periodically monitored by removing the basket 150 from the ozonated water 152 and sniffing to detect a smoke odor. At the point that the smoke odor is no longer noted, the fish product 101 should be removed from the ozonated water 152 and any excess ozonated water 152 should be allowed to drain away from the basket 150 .
[0052] The fish product 101 is then placed in a vacuum bag and vacuum sealed. The fish product 101 can be left unfrozen or can be frozen for even longer shelf life, using conventional freezing techniques. If frozen, the fish product 101 should be stored and maintained at temperatures below −18° C.
[0053] When the use of the frozen fish product 101 is desired, the product is defrosted while in the bag by either placing the bag in a cooler between 2 and 5° C. or by placing the bag in a basin of cold water. The refreshed fish product 101 will substantially retain the quality and characteristics of a freshly caught fish and may then be displayed or maintained at refrigerated temperatures for up to six more days.
[0054] If the fish product 101 is tuna, or other pelagic species, the ozone step is applied using a different technique. As shown in FIG. 10, instead of using the ozone dipping tank 151 , pelagic fish steaks 102 can be ozonated in an ozone chamber 160 for better results. FIG. 6 illustrates an ozone chamber 160 design comprising an ozone generator 161 , intake 162 , deflector 164 , chamber 165 , exhaust 166 and product holding rack 168 . After the fish steaks 102 have been smoked and optionally wiped with an alcohol soaked sponge, the fish steaks 102 are placed on racks 168 in the ozone chamber 165 . The fish steaks 102 should remain in the ozone chamber 165 for approximately one minute to four hours or until they reach the desired level of smoke odor. Once the fish steaks 102 have been ozonated, they can be placed in a vacuum bag and vacuum sealed. For freezing they are placed in a vacuum bag and are vacuum sealed. For fresh fish, the fish are placed in distribution-ready packages.
[0055] As with the fish product 101 , when the frozen fish steaks 102 are to be used, the bag is defrosted by either placing the bag in a cooler between 2 and 5° C. or by placing the bag in a basin of cold water. The refreshed fish steaks 102 will retain qualities and characteristics of a fresh caught fish and may then be displayed or maintained at refrigerated temperatures for up to six more days.
[0056] Although the aforementioned embodiments are directed to fish products, it is anticipated by the inventors that the claimed preservation process may be applied with equally satisfactory results for fish, beef, pork, poultry and crustaceans. Additionally, the methods for applying the smoke and ozone, and for freezing may be varied from those specifically disclosed herein.
[0057] Particularly, it is anticipated by the inventors that the smoke may be applied under atmospheric, vacuum or pressured conditions and in any suitable containment vehicle, including heated or refrigerated conditions. The smoke itself may be comprised of any smoke suitable for treatment of food products for human consumption; may be generated by any number of means including, but not limited to, combustion, transformation between solid or liquid state to gaseous state, friction, pyrolysis, aerobically, anarobically, electrical heating or direct flame; and may be used in its whole or filtered state. If the smoke is filtered to remove any component of the smoke, such filtering may be performed by any physical means, carbon filtering, ice column filtering, centrifugal force, electrostatic force, or other known means of separating out a component of smoke. The smoke may be applied to the products in an open, batch, closed or flow-through system.
[0058] Likewise, the ozone treatments disclosed above in the preferred embodiments are not exclusive. The inventors anticipate that the ozone may be applied using any type of carrier medium including, but not limited to, air, gases, water, fluids or solids and under atmospheric, vacuum or pressured environments and in any suitable containment vehicle, including heated or refrigerated conditions. The ozone that is applied is not limited to “pure” ozone, but may be in reaction form, mixtures, solutions or other form. The ozone may be applied to the products in an open, batch, closed or flow-through system.
[0059] The freezing step of the preservation process may be accomplished using any number of conventional freezing applications. Particularly, it is anticipated by the Applicants that suitable freezing can occur under atmospheric, vacuum and pressured conditions in gaseous, liquid or solid freezing mediums or combinations thereof.
[0060] While the process described herein involves the treatment of fresh fish, a similar process can be applied to frozen fish. One such process is to thaw the frozen fish and later apply the smoke and ozone to the fish. A preferred process of treating frozen fish is to simultaneously thaw and smoke the fish in a chamber. This can be done in a vacuum chamber. This eliminates the exposure of the fish to standard atmosphere as it thaws.
[0061] It should be emphasized that the above-described embodiments of the present invention, particularly, any “preferred” embodiments, are merely possible examples of implementations, merely set forth for a clear understanding of the principles of the invention. Variations and modifications may be made to the above-described embodiments of the invention without departing from the spirit and principles of the invention. All such modifications and variations are intended to be included herein within the scope of this disclosure and the present invention and protected by the following claims. | 1a
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] (Not applicable)
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] (Not applicable)
BACKGROUND OF THE INVENTION
[0003] This instant invention relates to the methods of off-loading shrimp and other small crustaceans from the holds and storage bins of trawlers and other fishing vessels. At this time at many locations along the gulf coast of the United States and other coastal areas of the world where shrimp, mullet, and other small size sea food catches are off-loaded from the holds and bins of fishing trawlers and other fishing vessels, a slow hand labor process is utilized wherein men with shovels of various configurations load the catch onto portable conveyer belts, or into buckets or nets to be lifted up onto the dock for weighing and processing.
[0004] This instant invention seeks to remedy the present costly and slow, semi-manual, labor-intensive, sea food damaging method of off loading small size seafood catches by adapting modern very high volume vacuum technology to vacuuming the catch from the holds or other storage areas of ships and boats into a specially designed vacuum cyclone seafood collection retainer. The vacuumed catch will enter the cyclone retainer at a minimal angle to the inside circular sidewall through a uniquely designed internally smooth vacuum inlet port with no internal ridges or rings in order to minimize damage to the catch in the vacuum process.
[0005] Vacuum cyclones have been designed for many purposes but none to date have been designed to off-load small size seafood catches to a dock causing minimal damage to the product in the process.
[0006] An example of a specific use of a cyclone is shown in U.S. Pat. No. 6,506,311 issued Jan. 14, 2003 to Richard DeGarmo et al. DeGarmo discloses a cyclone, fed wet material by an auger-blower system that separates the wet material into a substantially wet and a substantially solid portion.
[0007] A second example is a polycyclonic vacuum collector for non-stop environmental remediation as disclosed in U.S. Pat. No. 6,471,751 issued on Oct. 29, 2002 to Stavros Semanderes et al. Semanderes discloses a vacuum collector comprised of a first and a second drum in series. Vacuum producing motors mounted atop the second drum pull contaminant laden air through the first drum where the majority of contaminants are deposited, thence into the second drum where more contaminants are deposited, and then through HEPA filters and out through the vacuum-producing motors.
[0008] In U.S. Pat. No. 6,491,875 issued to Paolo Palmas on Dec. 10, 2002, Palmas discloses a single stage of cyclones to separate particulate catalyst from combustion gases to reduce particulate emissions to acceptable levels.
[0009] Cyclones can be used to collect and concentrate particles in a specific size range as disclosed in U.S. Pat. No. 6,156,212 issued to Daniel J. Raider et al on Dec. 5, 2000.
[0010] Tore Joss discloses the use of cyclones using combined co-current and counter current spins to separate different specific gravities in a liquid in U.S. Pat. No. 6,132,494 issued Oct. 17, 2000.
[0011] A domestic vacuum cleaner with multiple cyclones arranged in cascade so as to capture coarser and then finer particles from dust-laden air is disclosed in U.S. Pat. No. 6,083,292 issued Jul. 4, 2000 to Silvano Fumagalli.
[0012] In U.S. Pat. No. 6,022,390 issued to Juha Jakkula on Feb. 8, 2000, a multi-port cyclone is disclosed that more efficiently separates solids from gases than single-port cyclones.
[0013] A separation apparatus for separating a mixture of materials that behave as a liquid using a cyclone having an inlet switchable into at least two conditions and a plurality of cyclones enclosed in a pressure vessel is disclosed in U.S. Pat. No. 5,947,300 issued to Neville E. Lange on Sept. 7, 1999.
[0014] Tore Joss discloses in U.S. Pat. No. 5,711,374 issued on Jan. 27, 1998, a method for cyclone separation of oil and water in a cyclone positioned down hole so as to be able to reinject the water into the reservoir.
[0015] William Robinson, in U.S. Pat. No. 4,956,000 issued on Sep. 11, 1990 discloses a hydro cyclone divided into sections. Robinson discloses that previous sectioned cyclones were connected with flanged joints. Robinson describes a method for joining cyclone sections in such a way that the end of one section fits internally into the following section and the sections are held together by at least two eccentric locks of the folding strap type at each joint.
[0016] U.S. Pat. No. 4,123,364, issued Oct. 31, 1978 to Richard H. Mozley discloses a cyclone assembled from a kit with all components arranged so as to push-fit into each other and held together as an assembly by axial pressure between the centers of the end plates. Said axial pressure being supplied by a single tighten able rod member extending between said end plates.
[0017] Other U.S. patents such as U.S. Pat. No. 5,275,634 issued Jan. 4, 1994 to Erich Kramer and U.S. Pat. No. 5,160,356 issued Nov. 3, 1992 to James Dyson discloses methods of cleaning cyclones.
SUMMARY OF THE INVENTION
[0018] This invention provides a relatively fast, economical method to off load shrimp, mullet, and other small sized seafood catches from the holds of trawlers and other fishing boats onto the dock for weighing and processing with a minimum of damage.
[0019] The main component of the system is comprised of a specially designed vacuum cyclone collection vessel into which the shrimp are vacuumed from the hold of a shrimp boat. Said collection vessel is mounted on top of four braced support legs. The bottom of each pair of said support legs are connected to sections of steel or other metal angle stock that allow the cyclone collection vessel to be placed up on a watertight trough into which shrimp are collected. A powerful vacuum producing air pump pulls air from the interior of the cyclone collection vessel through a segment of vacuum hose fluidically connecting the input of the vacuum-producing pump to the output of said cyclone collection vessel. Said vacuum hose segment is attached to the outlet port of said collection vessel located in the center of the top of said collection vessel. The inlet cyclone vacuum port is positioned on the sidewall of said collection vessel near the top cover plate of said cyclone collection vessel, and aligned horizontally and tangentially to the side of the vessel so that product entering the cyclone at high speed will contact the curved inner surface of the vessel at a low angle of attack.
[0020] The forward speed of the product, a mixture of shrimp, ice, salt, and water if present, will decrease as it moves along the curved inner surface of the cyclone. The product will fall and accumulate in said cyclone from the bottom up. The accumulation of shrimp et al, in said cyclone collection vessel, can be seen through a first and a second vertical sight glass located on the side of the center section of the cyclone. The bottom section of said cyclone is funnel shaped to a rectangle at the bottom. Placed in the rectangular bottom is a hinged door that may have enough spring loaded tension to hold the door up in the closed position when the cyclone retainer is empty and when source vacuum is absent. Alternatively a slide type door may be utilized. Both door types may or may not have a latch.
[0021] The vacuum supply connected to the outlet port in the center of the top of the cyclone collection unit provides sufficient vacuum to cause atmospheric pressure to press all segment sections of said collection unit together with sufficient force to create an airtight seal along the gasket material between said cyclone collection vessel segments, and to hold the bottom cover closed when the cover is supporting the contents of said collection vessel filled with a combination of shrimp, ice, and water if present. After vacuum suction is removed from said cyclone vacuum supply connection in the center of said top cover plate, the bottom rectangular cover, if not latched, will swing down to the open position under the weight of the contents of the collection vessel. The shrimp et al will fall into the collection trough and be removed by a conveyer belt passing beneath said collection vessel. In the event that the contents of said cyclone retainer will not fall through said open bottom rectangular cover plate, one or more back flush ports are provided on said top cover for the purpose of injecting high pressure water downward and in a direction that will tend to perpetuate the cyclonic movement of the shrimp et al, and forcefully flush out said vacuum cyclone retainer contents.
[0022] Further objects and advantages of the invented seafood cyclone collection retainer and system include:
[0023] A large single stage cyclone collection vessel manufactured in three or four easy to assemble sections, with each section able to be lifted and assembled by two men.
[0024] A uniquely designed vacuum suction inlet port with no internal ridges or protrusions to damage vacuumed shrimp.
[0025] The cyclone collection vessel and its' required vacuum pump and internal combustion engine may be mounted on a trailer or skid and easily transportable.
[0026] Virtually nonstop, inexpensive, time saving unloading of shrimp and other small type fish and crustacean cargo from the holds and live wells of shrimp boats and other fishing vessels.
[0027] Very limited damage to off loaded shrimp, fish, and crustacean cargo.
[0028] Simple and safe. No accessible moving parts and elimination of most hand labor to move a seafood cargo from a ship to a dock.
[0029] High durability because the single stage cyclone collection vessel has no moving parts other than the single hinged trap or sliding door on the bottom.
[0030] Thus a new simple single stage cyclonic collection system designed for the fast, efficient, and safe unloading of a shrimp boat or any boat or ship carrying a cargo of small seafood has been invented.
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] [0031]FIG. 1 shows an external view of an assembled vacuum cyclone seafood collection retainer.
[0032] [0032]FIG. 2 shows the unassembled physical arrangement of the main components of the vacuum cyclone collection retainer.
[0033] [0033]FIG. 3A shows a top view of a first design of the top cover and integral strainer of the vacuum cyclone seafood collection retainer.
[0034] [0034]FIG. 3B shows a cross-section of a first design of the vacuum cyclone collection retainer top cover with an integral strainer.
[0035] [0035]FIG. 4A shows a top view of a second design of the vacuum cyclone collection retainer top cover with attached strainer and additional under cover braces.
[0036] [0036]FIG. 4B shows a cross-section of a second design of the top cover with attached strainer and additional under cover braces.
[0037] [0037]FIG. 5A shows the vacuum inlet suction hose port and suction hose attachment.
[0038] [0038]FIG. 5B shows a bottom up view of a swing down trap door.
[0039] [0039]FIG. 5C shows a bottom up view of a sliding door.
DETAILED DESCRIPTION OF THE INVENTION
PREFERRED EMBODIMENT
[0040] Preferred embodiment 10 of the invented vacuum cyclone seafood collection retainer shown in FIG. 1 is comprised of a cover plate 21 , said cover plate having a diameter inside of annular retainer lip 12 sufficient to fit over the center tubular shaped sleeve section 13 . Cover plate 21 has a centrally located six inch inner diameter vacuum source connection port 14 , said cover plate having external bracing 11 , and annular retainer lip 12 around the outer edge of said cover plate 21 . Said retainer lip 12 fits securely over and around the top flange, (described in FIG. 2), of four-foot outer diameter tube, sleeve, or center section 13 of the cyclone. Said cover plate has one or more back flush high-pressure water hose connections 62 . A seven inch inner diameter vacuum suction inlet port 19 is mounted horizontally near the top edge of said cyclone tube section 13 , proximate the lip of said cover plate 21 . Said inlet port 19 is smoothly transitioned into said tube section 13 so that seafood vacuumed into said inlet port 19 make no hard contact with the inner surface of said tube section 13 , but rather gently contact the inner surface of said tube section 13 , and slow by the friction of cyclonic movement against the inner surface of said tube section 13 and fall gently to the bottom of said vacuum cyclone collection retainer 10 . The vacuum suction hose attachment end of aluminum inlet port 19 has two slots 25 beginning at the hose end of said port 19 and continuing parallel with the direction of said port 19 for four inches. Said slots 25 allow a clamp to pull the seven inch inside diameter aluminum sleeve 19 tight against a six and seven eights inch outside diameter reinforced vacuum hose end placed into said port 19 . A four-inch diameter version of said port 19 may be used for small size shrimp. Visual indication of the amount of shrimp vacuumed into said cyclone 10 is obtained through sight glasses 24 . Structural support ring 15 is mounted circumferentially around the outside of said center section 13 midway between the ends. Retainer lip 20 is attached around the bottom edge of said tube center section 13 , and fits snugly over and around the top edge of base section 17 of said cyclone collection retainer. Four braced legs 18 , approximately two feet in length, support base section 17 and are attached to angle bars 22 and 23 . A bottom mounted cover 20 A is attached to said base section 17 by a spring-loaded hinge 16 .
[0041] [0041]FIG. 2 A preferred first cyclonic tube 28 shown in FIG. 2 is a sleeve made of steel or aluminum, though vessels of other shapes and sizes and material composition may be used. Tube 28 has a sidewall 29 , an annular flange 32 around the top of said sidewall 29 , and a flat annular gasket 38 cemented to the top surface of said annular flange 32 . Vacuum suction inlet port 34 is positioned to feed shrimp, ice, water, and air into drum 28 against wall 29 tangentially to limit the force of impact of the shrimp against said sidewall 29 and minimize damage to said shrimp. A support ring 35 made of steel or other material is positioned near the center of the length of said tube and around the circumference of said tube. An annular flange 33 is located around the circumference of the bottom end of said tube 28 and annular retaining lip 26 is attached thereto, and positioned to hang below the bottom edge of said tube.
[0042] The vacuum cyclone seafood collection retainer base section 30 has annular flange 36 around the top edge of said base section. A flat annular gasket 27 is cemented to said flange 36 .
[0043] Cover plate 31 has an annular retainer lip 40 mounted around the circumference of said cover 31 so that the retainer lip 40 is below the bottom surface of said cover 31 , and said retainer lip 40 will fit down around the top flange 32 of center section 28 so that cover 31 contacts gasket 38 mounted on flange 32 of center section 28 . Cover plate 31 also has one or more high pressure water line connections 63 used to back flush shrimp or other sea food down and out of said cyclone retainer in the event the contents of said cyclone jam together and will not fall through the open bottom section door.
[0044] Base section 30 is set atop a rectangular trough through which moves a conveyer belt, and into which the shrimp laden base section 30 of the vacuum cycle seafood retainer is emptied. Tube section 28 is lifted onto bottom section 30 so that flange 33 and retainer lip 26 fits over flange 36 of base section 30 , and flange 33 contacts gasket 27 of base section 30 . Top section 31 is set upon tube center section 28 so that said top section contacts annular gasket 38 on flange 32 .
[0045] After the three vacuum cyclone sections, top section 31 , center section 28 , and base section 30 have been assembled, a first section of vacuum supply hose is connected between vacuum supply port 37 of cover 31 and a centrally located vacuum supply tank (not shown). Said vacuum supply tank is equipped with a liquid blocking float valve. Said vacuum supply tank may connect to a second and a third section of vacuum supply hoses for connection to a second and third vacuum cyclone seafood collection retainers 10 of FIG. 1. The centrally located vacuum supply tank is connected in turn through a fourth section of vacuum supply hose to a vacuum source pump (not shown) of sufficient capacity and power to maintain a constant working vacuum for a single cyclone seafood collection retainer 10 under all working conditions. If multiple vacuum cyclone retainers 10 are connected to a common vacuum source tank (not shown), vacuum can be switched to the on condition for only one tank at a time. When source vacuum is supplied to the assembled vacuum cyclone retainer 10 in FIG. 1, outside atmospheric pressure against the top cover 21 , and base section 17 , force top cover 21 and base section 17 of FIG. 1 against gaskets 38 and 27 shown in FIG. 2, with sufficient force to make airtight connections. A first end of a first vacuum suction hose (not shown) is attached to vacuum suction inlet port 25 of FIG. 1. A second end of said first vacuum suction hose with attached guide pole is used in a shrimp boat cargo hold to off load the shrimp cargo. Said shrimp are collected into said vacuum cyclone seafood collection retainer 10 of FIG. 1 until a visible indication of the level of shrimp collected into said vacuum cyclone collection retainer 10 , as shown in sight glasses 24 , indicates an optimum collection level and source vacuum is removed from vacuum suction source port 14 .
[0046] [0046]FIG. 3A depicts a top view of cover plate 41 with back flush ports 64 , and designates cross section view 3 B.
[0047] [0047]FIG. 3B shows a cross section view of top cover 46 , suction supply hose attachment section 47 , hose attachment flange 42 , and annular cover retainer lip 45 . A cross section of integral screen 44 with screen holes 43 is shown. The total area of the provided screen holes 43 is 50% greater than the cross section area of the 6-inch suction hose inlet so that shrimp screen 44 air flow turbulence does not impede the source vacuum.
[0048] [0048]FIG. 4A is a top view of a second version cover 52 with back flush ports 65 and a detachable screen 53 , and defines cut away view 4 B.
[0049] [0049]FIG. 4B shows a cut away side view of second version cover 48 , cover screen attachment 51 , screen attachment flange 50 , and cover 48 screen attachment flange 49 .
[0050] [0050]FIG. 5A is a depiction of vacuum suction port 59 . The suction port 59 is constructed of aluminum and has one or more horizontal slots 56 at the hose attachment end. The 7.0 inch inside diameter port 59 will accept into it a 6⅞ inch outside diameter section of suction hose, (not shown). An annular aluminum ring 58 is welded into position in the vacuum suction port 59 . The reinforced end of an inserted vacuum suction hose buts against said ring 58 , that acts as a stop for said hose end. The thickness of said ring 58 is less than the thickness of said reinforced end of said reinforced vacuum hose end so that vacuumed shrimp will transition from hose to inlet port 59 and not hit any obstruction. Circular clamp 57 can then be tightened and the aluminum end of port 59 will flex together and grip the reinforced end of said vacuum suction hose.
[0051] [0051]FIG. 5B is a bottom up view of a vacuum cyclone collection retainer bottom door. Said door 54 is a trap door type with spring-loaded hinge 55 . Said door 54 will be held in the closed position by outside atmospheric pressure against said door due to the vacuum within the cyclone retainer even with a full load of shrimp. Said door will open under the weight of the supported load of shrimp when vacuum is removed from the vacuum inlet port of said cyclone retainer.
[0052] [0052]FIG. 5C is a second bottom up view of a vacuum cyclone retainer bottom door. Door 61 is a sliding door and slides in tracks 60 . The sliding door 61 may be used when sufficient space is not available to use trap door 54 . | 1a
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FIELD OF THE INVENTION
The present invention relates generally to medical equipment, and more particularly to medical equipment used for inserting objects into the body of a patient during a surgical procedure.
BACKGROUND OF THE INVENTION
Typically, surgical procedures require the insertion of a drain tube to drain the surgical site while the patient is recovering from surgery. In use, the distal end of the drain tube is located at the surgical site in the patient's body, and the proximal end extends out of the patient's body, with the skin of the patient sutured snugly around the tube to retain it in place. While the patient is recovering, the proximal end of the tube is connected to a suction/collection device to drain fluids that would otherwise accumulate at the surgical site.
Frequently, the drain tube is extended out of the body through an incision separate from the major incision through which the surgical procedure is performed. There are two principal reasons for this. First, it is omen desired to position the tube so that fluids accumulating at the surgical site are drained downward by gravity. Many times this requires a separate, smaller incision to properly position the drain tube. Second, it may be medically inadvisable to extend a drain tube through a major incision while the patient is recovering. In general, it is difficult to suture large incisions around a drain tube so that the skin tissue is sealed around the tube to prevent fluid leakage. Hence, a separate, smaller incision is made to receive the drain tube.
When a separate, smaller incision is made to receive a drain tube, the tube is usually first inserted into the patient through the major surgical incision. Subsequently, a medical instrument is inserted through the smaller incision to grasp the proximal end of the drain tube. The medical instrument is then withdrawn to thread the drain tube through the smaller incision. The tube is withdrawn from the smaller incision until the distal end of the tube is properly positioned at the surgical site. Thereafter, the skin of the patient is sutured around the drain tube to retain it in place.
There are drawbacks with the foregoing procedure for threading a drain tube through a separate, smaller incision. First, often it is difficult to grasp the end of the drain tube with the medical instrument. Second, it is medically advisable to make the second, smaller incision as small as possible to minimize trauma to the patient, to minimize recovery time, and to facilitate sealing the tissue around the tube. However, the incision must be made large enough to accommodate the medical instrument while it is grasping the drain tube. More particularly, the medical instrument includes a pair of jaws that are used to grasp the tube. Generally, the incision must be made significantly larger than the cross-sectional area of the drain tube to accommodate the width of the jaws while they are in an expanded position, grasping the drain tube therebetween.
Problems also arise in laparoscopic medical procedures when inserting a drain tube into a patient. In a laparoscopic medical procedure, the surgery is accomplished through access ports. That is, small incisions are made in the patient, and an access port is inserted in each incision, giving medical personnel access to the interior of the body. Medical personnel then insert cameras and instruments through the access ports to perform the medical procedure.
When a laparoscopic procedure occurs within the intra-abdominal cavity of a patient, it is common to pressurize the cavity with a gas to enable the camera to provide medical personnel with a better view of the body's interior and to provide more room to perform the medical procedure. Usually, the access ports are constructed with valves which may be closed when the patient's intra-abdominal cavity is pressurized so that the gas cannot escape, and thus, deflate this space. In addition, the access ports normally have internal seals that seal against laparoscopic medical equipment that extends through the ports. Hence, pressurization gas is substantially prevented from escaping from the intra-abdominal cavity during the insertion and use of laparoscopic medical equipment through the access ports.
In a laparoscopic medical procedure, a drain tube is placed in position by threading the proximal end of the drain tube through a first access port. Thereafter, a medical instrument is inserted through a second access port to grasp the proximal end of the drain tube. The medical instrument is then withdrawn from the second access port while grasping the drain tube to draw the distal end of the tube into the intra-abdominal cavity through the first access port. The medical instrument is withdrawn until the distal end of the tube is properly positioned at the surgical site. Alternatively, the entire drain tube is threaded into the intra-abdominal cavity and the distal end of the tube positioned at the desired location before the proximal end of the tube is withdrawn through a second access port site with a medical instrument. Once the drain tube has been properly positioned, the second access port is removed and the skin of the patient is sutured snugly around the drain tube to retain the tube.
Problems exist with inserting a drain tube into a patient during a laparoscopic procedure. First, while the drain tube is being threaded through the laparoscopic operating port, the pressurization gas escapes from the abdominal cavity through the drain tube itself. Second, when a medical instrument is used to grasp the drain tube, many times the jaws of the surgical instrument are expanded to a width, with the drain tube therebetween, such that the surgical instrument cannot be withdrawn through the laparoscopic operating port. As such, the operating port must be removed to withdraw the proximal end of the drain tube, thereby losing inflation pressure.
The present invention addresses the foregoing problems with inserting a drain tube into a patient.
SUMMARY OF THE INVENTION
The present invention provides a plug for the end of a drain tube introduced into a patient during a medical procedure. The drain tube is introduced through an opening, or incision in the patient's body leading to the interior of the patient's body. A medical instrument is used to extract the drain tube out through the opening in the patient's body.
The plug includes an elongated insertion section of a cross-sectional area sized for slidable insertion into the end of the drain tube. A grasping section, for grasping by the medical instrument, projects longitudinally from the insertion section. The grasping section includes a tip portion opposite the insertion section and a base portion located between the tip portion and the insertion section. The cross-sectional size of the base portion is greater than the cross-sectional size of the tip portion, wherein the cross-sectional size of the grasping section decreases in the direction extending away from the insertion section.
The grasping section includes a thin-section member projecting longitudinally from the tip for presenting a thin cross-section for grasping by the medical instrument. In a preferred embodiment, the thin-section member is in the form of a tab. Preferably the tab includes a generally planar area bounded by a rim forming a raised lip to facilitate grasping and retention by the medical instrument. In an alternate embodiment, the thin-section member is in the form of a loop.
In a preferred embodiment a retaining section is located between the insertion section and the grasping section. The retaining section has a cross-sectional size less than the cross sectional size of the base portion of the grasping section. The plug is inserted into the drain tube until the end of the drain tube extends past the insertion section, and over the retaining section. The tube tends to contract around the smaller cross-sectional area of the retaining section to retain the plug in engagement within the drain tube.
BRIEF DESCRIPTION OF THE DRAWINGS
The foregoing aspects and many of the attendant advantages of this invention will become more readily appreciated as the same becomes better understood by reference to the following detailed description, when taken in conjunction with the accompanying drawings, wherein:
FIG. 1 illustrates a plug constructed in accordance with the present invention, being used to introduce a drain tube into the body of a patient; and
FIG. 2 is an enlarged view of the plug of FIG. 1, shown exploded away from the end of the drain tube.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIG. 1, a representation of a patient's intra-abdominal cavity 10 is illustrated. This is the area within a patient's abdomen, behind the abdominal wall 12, where internal organs are located. Two conventional, laparoscopic operating ports 14 and 16 are shown in FIG. 1, having been inserted through the abdominal wall 12 of the patient, such that the ports extend into the intra-abdominal cavity 10. Before proceeding with a detailed description of the present invention, a brief description of the laparoscopic operating ports 14 and 16 is first provided.
Laparoscopic operating ports 14 and 16 both include a cylindrically-shaped, hollow tube 18 extending forwardly from an enlarged, generally rectangular body portion 20. At the forward end of the body portion 20, adjacent the hollow tube 18, are two shoulders 22, projecting laterally from opposite sides of the body portion 20. Each shoulder is generally in the shape of a right triangle to present an abutment for the user's fingers when grasping the port. The hollow tube 18 mates with the body portion 20 so that the longitudinal axes of each part are coincident. The laparoscopic operating ports 14 and 16 are inserted into the intra-abdominal cavity 10 up to near the body portion 20. The remaining portions of the laparoscopic operating ports 14 and 16 are disposed outside the body of the patient.
Laparoscopic operating port 16 includes a valve 24, for the introduction of pressurization gas into the intra-abdominal cavity 10. Valve 24 on laparoscopic operating port 16 is shown attached to a delivery tube 26. The other end of the tube 26, in turn, connects to a source of pressurization gas 28. When valve 24 on laparoscopic operating port 16 is open, pressurization gas flows from source 28, through tube 26, through valve 24, and through the laparoscopic operating port 16 into the intra-abdominal cavity 10 of the patient. The intra-abdominal cavity 10 is normally pressurized in this way with carbon dioxide during a laparoscopic surgery to approximately 15 mm Hg. This properly inflates the intra-abdominal cavity 10, permitting medical procedures to be more easily accomplished within the intra-abdominal cavity.
The body portions 20 of the laparoscopic operating ports 14 and 16 have an internal passageway 30 extending through it coincident with the longitudinal axis of the body portion. The hollow tube 18 mates with the body portion 20 of the laparoscopic operating port 14, 16, such that internal passageway 30 extends from hollow tube 18 through body portion 20 of the laparoscopic operating port.
The laparoscopic operating ports 14, 16 include an internal gate valve, not shown, for closing off the internal passageway 30 within the body portions 20. Pivot handles 34 are provided for manually operating the valves. When the valve is closed, its handle 34 is positioned generally perpendicularly to the longitudinal axis of hollow tube 18 and body portion 20. Ideally, the valve is spring biased in closed position. When the handle 34 is rotated clockwise approximately 30°, the valve is opened.
A lip seal 32 is located just inside the rearward entrance to the internal passageway 30, in the body portion 20 of laparoscopic operating ports 14, 16. Seal 32 is generally annularly shaped and surrounds the internal passageway 30. Seal 32 is designed to extend around instruments that are inserted into laparoscopic operating ports 14, 16 through the gate valve as long as the exterior size of the instrument closely corresponds with the interior size of the port, to prevent fluid leakage through passageway 30 of the laparoscopic operating ports 14, 16, and into the environment.
A medical instrument 36 is shown inserted through laparoscopic operating port 16 and into the intra-abdominal cavity 10 of the patient. The seal 32, within the internal passageway of the port, presses against the circumference of the instrument 36 as it is inserted into the port and substantially prevents pressurization gas from escaping through the port while instrument 36 is being used.
A drain tube 38 is shown inserted through the laparoscopic operating port 14. The seal 32 within the laparoscopic operating port 14 presses against the tube 38 to prevent the leakage of fluid between the port and the tube.
A plug 40 in accordance with the present invention is shown inserted into the end of the drain tube 38 that extends through laparoscopic operating portion 14 into the intra-abdominal cavity 10 of the patient. Illustrated in FIG. 2 is an enlarged view of the plug 40, shown engaged with the drain tube 38. The plug 40 is preferably made of plastic, or other appropriate material, that is lightweight, substantially impervious to the passage of fluids, and has good moisture resistant properties to body fluids. In a preferred embodiment, the plug is of integral, one-piece construction. In alternate embodiments, the different sections of the plug may be separately formed and then combined.
The plug 40 includes an elongated insertion section 42 which is sized to be inserted into the end of the drain tube 38. Drain tubes, such as tube 38, used in laparoscopic surgery typically have internal diameters ranging from about 5 to 10 mm. The insertion section 42 is substantially cylindrical in shape having a rounded, generally hemispherical distal end 44. The hemispherical shape of the distal end 44 facilitates insertion of the plug 40 into the drain tube 38. Preferably, the diameter of the insertion section 42 is sized such that the insertion section 42 can be snugly slid into the end of the drain tube 38.
The plug 40 includes a retaining section 46 that extends longitudinally from the opposite end of the insertion section 42. The retaining section 46 is substantially cylindrical and is generally coaxially aligned with the insertion section 42. The retaining section is substantially shorter in length relative to the insertion section 42.
The diameter of the retaining section 46 is somewhat less, at least 0.02 inch, than the diameter of the insertion section 42. The insertion section 42 of the plug 40 is inserted into the drain tube 38 until the drain tube 38 extends beyond the proximal end of the insertion section, and surrounds the retaining section 46. Because the insertion section 42 snugly fits within the drain tube 38, the drain tube 38 is somewhat radially stretched as the insertion section is inserted therein. Thus, when the end of the drain tube 38 is slid past the proximal end of the insertion section 42, the drain tube tends to radially contract around the smaller diameter retaining section 46. This helps to retain the drain tube 38 over the insertion section 42 of the plug 40.
The plug also includes a gasping section 48 that extends longitudinally from the end of the retaining section 46, in the direction opposite the insertion section 42. The gasping section 48 preferably includes a generally cylindrical portion 50 that extends substantially coaxially from the retaining section 46. Ideally, but not mandatorily, the cylindrical portion is larger in diameter than the diameter of the insertion section 42. Thus, the plug 40 is inserted into the drain tube 38 until the end of the drain tube abuts the cylindrical portion 50. The larger diameter of the cylindrical portion 50 therefore serves as a stop to limit the distance the plug 40 is inserted into the drain tube 38. However, preferably the diameter of the cylindrical portion 50 does not exceed the outside diameter of the drain tube 38 as will be discussed more fully below.
The gasping section of the plug 40 also includes a generally conical portion 52 extending substantially coaxially from the end of the cylindrical portion 50, opposite the retaining section 46. The conical portion 52 gradually decreases in diameter to a distal tip 56.
A thin tab 58 extends from the tip 56. Preferably, the tab 58 is generally in the shape of a circle. However, in alternate embodiments of the present invention, the tab 58 may have other geometries, such as an oval, or a triangle by way of illustrative, nonlimiting examples. In the preferred embodiment, the tab 58 extends from the conical portion 52 such that the central axis of the tab 58 is generally aligned with the central axis of the conical portion 52.
Preferably, the tab 58 includes a generally planar central region 60 which is surrounded by a marginal rim 62 that projects on either side of the planar region 60 to form a raised, annular lip. The tab may be quite thin, but still be of sufficient structural integrity to be gasped by the instrument 36 and the attached tube 38 pulled through port 14 and out port 16, as described below. In this regard, if the plug 40 is composed of polypropylene, polyurethane or similar polymer plastic, the tab may be of a thickness of from about 0.01 to 0.04 inches. The lip may extend above and below the tab from about 0.01 to 0.04 inches.
In alternate embodiments, the planar area 60 of the tab can be eliminated, leaving a loop, or opening bounded by the rim 62. In the alternate embodiments, the rim 62 may be flexible. Thus the ring may be formed of string, nylon filament, plastic or other similar materials. In general, the purpose of the loop or tab 58 is to form a projecting member that presents a thin cross section for grasping by the medical instrument 36.
The plug 40 is used as follows: Prior to inserting the tube 38 through a laparoscopic operating port 14, the plug 40 is inserted into the drain tube 38. Thereafter, the plug 40 is inserted through the laparoscopic operating port 14 into the intra-abdominal cavity 10 of the patient, with the drain tube 38 trailing the plug 40. The plug 40 serves to substantially seal the end of the drain tube 38 so that pressurization gas within the intra-abdominal cavity 10 cannot escape through the drain tube while it is being inserted through the laparoscopic operating port 14.
After the plug 40 has been inserted into the intra-abdominal cavity 10, a medical instrument 36 is extended through a second laparoscopic operating port 16. The end of the instrument 36 is used to grasp the tab 58 at the end of the plug 40. Subsequently, the instrument 36 is withdrawn through the second laparoscopic operating port 16, thereby threading the plug 40 and drain tube 38 through the second laparoscopic operating port. Thus, it is desirable that the largest outside diameter of the plug 40 not exceed the outside diameter of the drain tube 38 to facilitate threading the plug and drain tube through the ports 14 and 16.
The drain tube 38 and plug 40 are withdrawn through the second laparoscopic operating port 16, until the trailing end of the drain tube 38 is properly positioned within the intra-abdominal cavity 10. When the trailing end of the drain tube 38 has been properly positioned and the surgical procedure completed, the laparoscopic operating ports 14 and 16 are removed. In particular, the second laparoscopic operating port 16 is withdrawn over the drain tube 38, and the skin tissue of the patient is sutured around the drain tube 38.
The use of the plug 40 in accordance with the present invention provides several advantages. First, the plug 40 serves to substantially seal the end of the drain tube 38 when it is being inserted through the laparoscopic operating port 14. This prevents pressurization gas in the intra-abdominal cavity 10 of the patient from escaping through the drain tube 38.
Second, the tab 58 at the end of the plug 40 facilitates grasping by the medical instrument 36. Moreover, tab 58 is thin enough that when the medical instrument 36 is grasping the plug 40, the jaws of the instrument do not remain open to the extent that the medical instrument cannot be withdrawn through the laparoscopic operating port 16. If the plug is not used so that the instrument must clamp on to the end of the tube 38 itself, the jaws of the medical instrument 36 remain open to the extent that the medical instrument cannot be withdrawn through the laparoscopic operating port 16.
Third, the rim 62 around the outer periphery of the tab 58 serves to facilitate a firm grasp by the medical instrument 36, i.e., help prevent the jaws of the instrument from disengaging from the tab. As noted above, in alternate embodiments, the central planar area 60 of the tab 58 may be removed, leaving a loop. Thus, in the alternate embodiments, a medical instrument having a hook-type end could be used to hook the loop.
Fourth, the conical portion 52 of the plug 40 serves to center the plug as it is being drawn into the second laparoscopic operating port 16 by the medical instrument 36. In alternate embodiments, the cylindrical portion 50 of the plug 40 can be eliminated.
The plug 40 also provides advantages in surgical procedures that are accomplished without the use of laparoscopic operating ports. As discussed above in the Background of the Invention section of this specification, a drain tube is typically extended out of a second, smaller incision, separate from the major incision through which the surgical procedure is performed. When it is desired to extend a drain tube 38 out of the second, smaller incision, the drain tube, having the plug 40 engaged therewith, may be inserted into the patient through the major incision. A medical instrument 36 inserted through the second, smaller incision, can be used to grasp tab 58 of the plug 40. The drain tube 38 is threaded through the second, smaller incision by withdrawing the medical instrument from the smaller incision.
Use of the plug 40 in the foregoing manner is advantageous because the medical instrument 36 can be used to more readily and securely grasp the tab 58 of the plug, as opposed to the drain tube 38 itself. Further, the tab 58 is significantly thinner than the drain tube 38. Thus, the jaws of the medical instrument 36 are substantially contracted even when grasping the tab 58. The medical instrument 36 can therefore be used to thread the drain tube 38 through a smaller incision to help reduce patient trauma and recovery time. The same advantages are provided in alternative embodiments where the planar area 60 of the tab is removed to form a loop for grasping by the medical instrument 36.
Finally, the conical portion 52 of the plug 40 serves to center the plug as it is being withdrawn through the second, smaller incision.
While a preferred embodiment of the invention has been illustrated and described, it will be appreciated that various changes can be made therein without departing from the spirit and scope of the invention. | 1a
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BACKGROUND OF THE INVENTION
Heart disease is the leading cause of death in the United States. A heart attack (also known as an Acute Myocardial Infarction (AMI)) typically results from a thrombus that obstructs blood flow in one or more coronary arteries. AMI is a common and life-threatening complication of coronary heart disease. The sooner that perfusion of the myocardium is restored (e.g., with injection of a thrombolytic medication such as tissue plasminogen activator (tPA)), the better the prognosis and survival of the patient from the heart attack. The extent of damage to the myocardium is strongly dependent upon the length of time prior to restoration of blood flow to the heart muscle.
Myocardial ischemia is caused by a temporary imbalance of blood (oxygen) supply and demand in the heart muscle. It is typically provoked by physical activity or other causes of increased heart rate when one or more of the coronary arteries are obstructed by atherosclerosis. Patients will often (but not always) experience chest discomfort (angina) when the heart muscle is experiencing ischemia.
Acute myocardial infarction and ischemia may be detected from a patient's electrocardiogram (ECG) by noting an ST segment shift (i.e., voltage change) over a relatively short (less than 5 minutes) period of time. However, without knowing the patient's normal ECG pattern detection from standard 12 lead ECG can be unreliable. In addition, ideal placement of subcutaneous electrodes for detection of ST segment shifts as they would relate to a subcutaneously implanted device has not been explored in the prior art.
Fischell et al in U.S. Pat. Nos. 6,112,116 and 6,272,379 describe implantable systems for detecting the onset of acute myocardial infarction and providing both treatment and alarming to the patient. While Fischell et al discuss the detection of a shift in the S-T segment of the patient's electrogram from an electrode within the heart as the trigger for alarms; it may be desirable to provide more sophisticated detection algorithms to reduce the probability of false positive and false negative detection. In addition while these patents describe some desirable aspects of programming such systems, it may be desirable to provide additional programmability and alarm control features.
Although anti-tachycardia pacemakers and Implantable Cardiac Defibrillators (ICDs) can detect heart arrhythmias, none are currently designed to detect ischemia and acute myocardial infarction events independently or in conjunction with arrhythmias.
In U.S. Pat. Nos. 6,112,116 and 6,272,379 Fischell et al, discuss the storage of recorded electrogram and/or electrocardiogram data; however techniques to optimally store the appropriate electrogram and/or electrocardiogram data and other appropriate data in a limited amount of system memory are not detailed.
In U.S. Pat. No. 5,497,780 by M. Zehender, a device is described that has a “goal of eliminating . . . cardiac rhythm abnormality.” To do this, Zehender requires exactly two electrodes placed within the heart and exactly one electrode placed outside the heart. Although multiple electrodes could be used, the most practical sensor for providing an electrogram to detect a heart attack would use a single electrode placed within or near to the heart.
Zehender's drawing of the algorithm consists of a single box labeled ST SIGNAL ANALYSIS with no details of what the analysis comprises. His only description of his detection algorithm is to use a comparison of the ECG to a reference signal of a normal ECG curve. Zehender does not discuss any details to teach an algorithm by which such a comparison can be made, nor does Zehender explain how one identifies the “normal ECG curve”. Each patient will likely have a different “normal” baseline ECG that will be an essential part of any system or algorithm for detection of a heart attack or ischemia.
In addition, Zehender suggests that an ST signal analysis should be carried out every three minutes. It may be desirable to use both longer and shorter time intervals than 3 minutes so as to capture certain changes in ECG that are seen early on or later on in the evolution of an acute myocardial infarction. Longer observation periods will also be important to account for minor slowly evolving changes in the “baseline” ECG. Zehender has no mention of detection of ischemia having different normal curves based on heart rate. To differentiate from exercise induced ischemia and acute myocardial infarction, it may be important to correlate ST segment shifts with heart rate or R—R interval.
Finally, Zehender teaches that “if an insufficient blood supply in comparison to the reference signal occurs, the corresponding abnormal ST segments can be stored in the memory in digital form or as a numerical event in order to be available for associated telemetry at any time.” Storing only abnormal ECG segments may miss important changes in baseline ECG. Thus it is desirable to store some historical ECG segments in memory even if they are not “abnormal”.
The Reveal™ subcutaneous loop Holter monitor sold by Medtronic uses two case electrodes spaced by about 3 inches to record electrocardiogram information looking for arrhythmias. It has no real capability to detect ST segment shift and its high pass filtering would in fact preclude accurate detection of changes in the low frequency aspects of the heart's electrical signal. Also the spacing of the electrodes it too close together to be able to effectively detect and record ST segment shifts. Similarly, current external Holter monitors are primarily designed for capturing arrhythmia related signals from the heart.
Although often described as an electrocardiogram (ECG), the stored electrical signal from the heart as measured from electrodes within the body should be termed an “electrogram”. The early detection of an acute myocardial infarction or exercise induced myocardial ischemia caused by an increased heart rate or exertion is feasible using a system that notes a change in a patient's electrogram. The portion of such a system that includes the means to detect a cardiac event is defined herein as a “cardiosaver” and the entire system including the cardiosaver and the external portions of the system is defined herein as a “guardian system.”
Furthermore, although the masculine pronouns “he” and “his” are used herein, it should be understood that the patient or the medical practitioner who treats the patient could be a man or a woman. Still further the term; “medical practitioner” shall be used herein to mean any person who might be involved in the medical treatment of a patient. Such a medical practitioner would include, but is not limited to, a medical doctor (e.g., a general practice physician, an internist or a cardiologist), a medical technician, a paramedic, a nurse or an electrogram analyst. A “cardiac event” includes an acute myocardial infarction, ischemia caused by effort (such as exercise) and/or an elevated heart rate, bradycardia, tachycardia or an arrhythmia such as atrial fibrillation, atrial flutter, ventricular fibrillation, and premature ventricular or atrial contractions (PVCs or PACs).
For the purposes of this specification, the terms “detection” and “identification” of a cardiac event have the same meaning.
For the purpose of this invention, the term “electrocardiogram” is defined to be the heart electrical signals from one or more skin surface electrode(s) that are placed in a position to indicate the heart's electrical activity (depolarization and repolarization). An electrocardiogram segment refers to the recording of electrocardiogram data for either a specific length of time, such as 10 seconds, or a specific number of heart beats, such as 10 beats. For the purposes of this specification the PQ segment of a patient's electrocardiogram is the typically flat segment of a beat of an electrocardiogram that occurs just before the R wave.
For the purpose of this invention, the term “electrogram” is defined to be the heart electrical signals from one or more implanted electrode(s) that are placed in a position to indicate the heart's electrical activity (depolarization and repolarization). An electrogram segment refers to the recording of electrogram data for either a specific length of time, such as 10 seconds, or a specific number of heart beats, such as 10 beats. For the purposes of this specification the PQ segment of a patient's electrogram is the typically flat segment of an electrogram that occurs just before the R wave. For the purposes of this specification, the terms “detection” and “identification” of a cardiac event have the same meaning. A beat is defined as a sub-segment of an electrogram or electrocardiogram segment containing exactly one R wave.
Heart signal parameters are defined to be any measured or calculated value created during the processing of one or more beats of electrogram data. Heart signal parameters include PQ segment average value, ST segment average value, R wave peak value, ST deviation, ST shift, average signal strength, T wave peak height, T wave average value, T wave deviation, heart rate and R—R interval.
SUMMARY OF THE INVENTION
The present invention is a system for the detection of cardiac events (a guardian system) that includes a device called a cardiosaver, a physician's programmer and an external alarm system. The present invention envisions a system for early detection of an acute myocardial infarction or exercise induced myocardial ischemia caused by an increased heart rate or exertion. In the preferred embodiment of the present invention, the cardiosaver is implanted along with the electrodes. In an alternate embodiment, the cardiosaver and the electrodes could be external but attached to the patient's body. Although the following descriptions of the present invention in most cases refer to the preferred embodiment of an implanted cardiosaver processing electrogram data from implanted electrodes, the techniques described are equally applicable to the alternate embodiment where the external cardiosaver processes electrocardiogram data from skin surface electrodes.
In the preferred embodiment of the cardiosaver either or both subcutaneous electrodes or electrodes located on a pacemaker type right ventricular or atrial leads will be used. It is also envisioned that one or more electrodes may be placed within the superior vena cava. One version of the implanted cardiosaver device using subcutaneous electrodes would have an electrode located under the skin on the patient's left side. This could be best located between 2 and 20 inches below the patient's left arm pit. The cardiosaver case that would act as the indifferent electrode would typically be implanted like a pacemaker under the skin on the left side of the patient's chest.
Using one or more detection algorithms, the cardiosaver can detect a change in the patient's electrogram that is indicative of a cardiac event, such as an acute myocardial infarction, within five minutes after it occurs and then automatically warn the patient that the event is occurring. To provide this warning, the guardian system includes an internal alarm sub-system (internal alarm means) within the cardiosaver and/or an external alarm system (external alarm means). In the preferred, implanted embodiment, the cardiosaver communicates with the external alarm system using a wireless radio-frequency (RF) signal.
The internal alarm means generates an internal alarm signal to warn the patient. The internal alarm signal may be a mechanical vibration, a sound or a subcutaneous electrical tickle. The external alarm system (external alarm means) will generate an external alarm signal to warn the patient. The external alarm signal is typically a sound that can be used alone or in combination with the internal alarm signal. The internal or external alarm signals would be used to alert the patient to at least two different types of conditions: a major event alarm signaling the detection of a major cardiac event (e.g. a heart attack) and the need for immediate medical attention, and a less critical “SEE DOCTOR” alarm signaling the detection of a less serious non life threatening condition such as exercise induced ischemia. The SEE DOCTOR alarm signal would be used to tell the patient that he is not in immediate danger but should arrange an appointment with his doctor in the near future. In addition to the signaling of less critical cardiac events, the SEE DOCTOR alarm signal could also signal the patient when the cardiosaver battery is getting low.
In the preferred embodiment, in a major event alarm the internal alarm signal would be applied periodically, for example, with three pulses every 5 seconds after the detection of a major cardiac event. It is also envisioned that the less critical “SEE DOCTOR” alarm, would be signaled in a different way, such as one pulse every 7 seconds.
The external alarm system is a hand-held portable device that may include any or all the following features:
1. an external alarm means to generate an external alarm signal to alert the patient.
2. the capability to receive cardiac event alarm, recorded electrogram and other data from the cardiosaver
3. the capability to transmit the cardiac event alarm, recorded electrogram and other data collected by the cardiosaver to a medical practitioner at a remote location.
4. an “alarm-off” button that when depressed can acknowledge that the patient is aware of the alarm and will turn off internal and external alarm signals.
5. a display (typically an LCD panel) to provide information and/or instructions to the patient by a text message and the display of segments of the patient's electrogram.
6. the ability to provide messages including instructions to the patient via a pre-recorded human voice.
7. a patient initiated electrogram capture initiated by a “Panic Button” to allow the patient, even when there has been no alarm, to initiate transmission of electrogram data from the cardiosaver to the external alarm system for transmission to a medical practitioner.
8. a patient initiated electrogram capture to initiate transmission of electrogram data from the cardiosaver to the external alarm system for display to a medical practitioner using the display on the external alarm system.
9. the capability to automatically turn the internal and external alarms off after a reasonable time period that is typically less than 30 minutes if the alarm-off button is not used.
Text and/or spoken instructions may include a message that the patient should promptly take some predetermined medication such as chewing an aspirin, placing a nitroglycerine tablet under his tongue, inhaling or nasal spraying a single or multiple drug combination and/or injecting thrombolytic drugs into a subcutaneous drug port. The messaging displayed by or spoken from the external alarm system and/or a phone call from a medical practitioner who receives the alarm could also inform the patient that he should wait for the arrival of emergency medical services or he should promptly proceed to an emergency medical facility. It is envisioned that the external alarm system can have direct connection to a telephone line and/or work through cell phone or other wireless networks.
If a patient seeks care in an emergency room, the external alarm system could provide a display to the medical practitioners in the emergency room of both the electrogram segment that caused the alarm and the baseline electrogram segment against which the electrogram that caused the alarm was compared. The ability to display both baseline and alarm electrogram segments will significantly improve the ability of the emergency room physician to properly identify AMI.
The preferred embodiment of the external alarm system consists of an external alarm transceiver and a handheld computer. The external alarm transceiver having a standardized interface, such as Compact Flash adapter interface, a secure digital (SD) card interface, a multi-media card interface, a memory stick interface or a PCMCIA card interface. The standardized interface will allow the external alarm transceiver to connect into a similar standardized interface slot that is present in many handheld computers such as a Palm Pilot or Pocket PC. An advantage of this embodiment is that the handheld computer can cost effectively supply the capability for text and graphics display and for playing spoken messages.
Using a handheld computer, such as the Thera™ by Audiovox™ that combines a Pocket PC with having an SD/Multimedia interface slot with a cell phone having wireless internet access, is a solution that can easily be programmed to provide communication between the external alarm system and a diagnostic center staffed with medical practitioners.
The panic button feature, which allows a patient-initiated electrogram capture and transmission to a medical practitioner, will provide the patient with a sense of security knowing that, if he detects symptoms of a heart-related ailment such as left arm pain, chest pain or palpitations, he can get a fast review of his electrogram. Such a review would allow the diagnosis of arrhythmias, such as premature atrial or ventricular beats, atrial fibrillation, atrial flutter or other heart rhythm irregularities. The medical practitioner could then advise the patient what action, if any, should be taken. The guardian system would also be programmed to send an alarm in the case of ventricular fibrillation so that a caretaker of the patient could be informed to immediately provide a defibrillation electrical stimulus. This is practical as home defibrillation units are now commercially available. It is also possible that, in patients prone to ventricular fibrillation following a myocardial infarction, such a home defibrillator could be placed on the patient's chest to allow rapid defibrillation should ventricular fibrillation occur while waiting for the emergency medical services to arrive.
The physician's programmer provides the patient's doctor with the capability to set cardiosaver cardiac event detection parameters. The programmer communicates with the cardiosaver using the wireless communication capability that also allows the external alarm system to communicate with the cardiosaver. The programmer can also be used to upload and review electrogram data captured by the cardiosaver including electrogram segments captured before, during and after a cardiac event.
An extremely important capability of the present invention is the use of a continuously adapting cardiac event detection program that compares extracted features from a recently captured electrogram segment with the same features extracted from a baseline electrogram segment at a predetermined time in the past. For example, the thresholds for detecting an excessive ST shift would be appropriately adjusted to account for slow changes in electrode sensitivity or ST segment levels over time. It may also be desirable to choose the predetermined time in the past for comparison to take into account daily cycles in the patient's heart electrical signals. Thus, a preferred embodiment of the present invention would use a baseline for comparison that is collected approximately 24 hours prior to the electrogram segment being examined. Such a system would adapt to both minor (benign) slow changes in the patient's baseline electrogram as well as any daily cycle.
Use of a system that adapts to slowly changing baseline conditions is of great importance in the time following the implantation of electrode leads in the heart. This is because there can be a significant “injury current” present just after implantation of an electrode and for a time of up to a month, as the implanted electrode heals into the wall of the heart. Such an injury current may produce a depressed ST segment that deviates from a normal isoelectric electrogram where the PQ and ST segments are at approximately the same voltage. Although the ST segment may be depressed due to this injury current, the occurrence of an acute myocardial infarction can still be detected since an acute myocardial infarction will still cause a significant shift from this “injury current” ST baseline electrogram. Alternately, the present invention might be implanted and the detector could be turned on after healing of the electrodes into the wall of the heart. This healing would be noted in most cases by the evolution to an isoelectric electrogram (i.e., PQ and ST segments with approximately the same voltages).
The present invention's ST detection technique involves recording and processing baseline electrogram segments to calculate the threshold for myocardial infarction and/or ischemia detection. These baseline electrogram segments would typically be collected, processed and stored once an hour or with any other appropriate time interval.
A preferred embodiment of the present invention would save and process a 10 second baseline electrogram segment once every hour. Every 30 seconds the cardiosaver would save and process a 10 second long recent electrogram segment. The cardiosaver would compare the recent electrogram segment with the baseline electrogram segment from approximately 24 hours before (i.e. 24±½ hour before).
The processing of each of the hourly baseline electrogram segments would involve calculating the average electrogram signal strength as well as calculating the average “ST deviation”. The ST deviation for a single beat of an electrogram segment is defined to be the difference between the average ST segment voltage and the average PQ segment voltage. The average ST deviation of the baseline electrogram segment is the average of the ST deviation of multiple (at least two) beats within the baseline electrogram segment.
The following detailed description of the drawings fully describes how the ST and PQ segments are measured and averaged.
An important aspect of the present invention is the capability to adjust the location in time and duration of the ST and PQ segments used for the calculation of ST shifts. The present invention is initially programmed with the time interval between peak of the R wave of a beat and the start of the PQ and ST segments of that beat set for the patient's normal heart rate. As the patient's heart rate changes during daily activities, the present invention will adjust these time intervals for each beat proportional to the R—R interval for that beat. In other words, if the R—R interval shortens (higher heart rate) then the ST and PQ segments would move closer to the R wave peak and would become shorter. ST and PQ segments of a beat within an electrogram segment are defined herein as sub-segments of the electrogram segment.
The difference between the ST deviation on any single beat in a recently collected electrogram segment and a baseline average ST deviation extracted from a baseline electrogram segment is defined herein as the “ST shift” for that beat. The present invention envisions that detection of acute myocardial infarction and/or ischemia would be based on comparing the ST shift of one or more beats with a predetermined detection threshold “H ST ”.
In U.S. application Ser. No. 1,005,1743 that is incorporated herein by reference, Fischell describes a fixed threshold for detection that is programmed by the patient's doctor. The present invention envisions that the threshold should rather be based on some percentage “P ST ” of the average signal strength extracted from the baseline electrogram segment where P ST is a programmable parameter of the cardiosaver device. The “signal strength” can be measured as peak signal voltage, RMS signal voltage or as some other indication of signal strength such as the difference between the average PQ segment amplitude and the peak R wave amplitude.
Similarly, it is envisioned that the value of P ST might be adjusted as a function of heart rate so that a higher threshold could be used if the heart rate is elevated, so as to not trigger on exercise that in some patients will cause minor ST segment shifts when there is not a heart attack occurring. Alternately, lower thresholds might be used with higher heart rates to enhance sensitivity to detect exercise-induced ischemia. One embodiment of the present invention has a table stored in memory where values of P ST for a preset number of heart rate ranges, (e.g. 50-80, 81-90, 91-100, 101-120, 121-140) might be stored for use by the cardiosaver detection algorithm in determining if an acute myocardial infarction or exercise induced ischemia is present.
Thus it is envisioned that the present invention would use the baseline electrogram segments in 3 ways.
1. To calculate a baseline average value of a feature such as ST deviation that is then subtracted from the value of the same feature in recently captured electrogram segments to calculate the shift in the value of that feature. E.g. the baseline average ST deviation is subtracted from the amplitude of the ST deviation on each beat in a recently captured electrogram segment to yield the ST shift for that beat.
2. To provide an average signal strength used in calculating the threshold for detection of a cardiac event. This will improve detection by compensating for slow changes in electrogram signal strength over relatively long periods of time.
3. To provide a medical practitioner with information that will facilitate diagnosis of the patient's condition. For example, the baseline electrogram segment may be transmitted to a remotely located medical practitioner and/or displayed directly to a medical practitioner in the emergency room.
For the purposes of the present invention, the term adaptive detection algorithm is hereby defined as a detection algorithm for a cardiac event where at least one detection-related threshold adapts over time so as to compensate for relatively slow (longer than an hour) changes in the patient's normal electrogram.
It is also envisioned that the present invention could have specific programming to identify a very low heart rate (bradycardia) or a very high heart rate (tachycardia or fibrillation). While a very low heart rate is usually not of immediate danger to the patient, its persistence could indicate the need for a pacemaker. As a result, the present invention could use the “SEE DOCTOR” alarm along with an optional message sent to the external alarm system to alert the patient that his heart rate is too low and that he should see his doctor as soon as convenient. On the other hand, a very high heart rate can signal immediate danger thus it would be desirable to alarm the patient in a manner similar to that of acute myocardial infarction detection. What is more, detections of excessive ST shift during high heart rates may be difficult and if the high heart rate is the result of a heart attack then it is envisioned that the programming of the present invention would use a major event counter that would turn on the alarm if the device detects a combination of excessive ST shift and overly high heart rate.
Another early indication of acute myocardial infarction is a rapid change in the morphology of the T wave. Unfortunately, there are many non-AMI causes of changes in the morphology of a T wave. However, these changes typically occur slowly while the changes from an AMI occur rapidly. Therefore one embodiment of this invention uses detection of a change in the T wave as compared to a baseline collected a short time (less than 30 minutes) in the past. The best embodiment is probably using a baseline collected between 1 and 5 minutes in the past. Such a T wave detector could look at the amplitude of the peak of the T wave. An alternate embodiment of the T wave detector might look at the average value of the entire T wave as compared to the baseline. The threshold for T wave shift detection, like that of ST shift detection, can be a percentage P T of the average signal strength of the baseline electrogram segment. P T could differ from P ST if both detectors are used simultaneously by the cardiosaver.
In its simplest form, the “guardian system” includes only the cardiosaver and a physician's programmer. Although the cardiosaver could function without an external alarm system where the internal alarm signal stays on for a preset period of time, the external alarm system is highly desirable. One reason it is desirable is the button on the external alarm system that provides the means for of turning off the alarm in either or both the implanted device (cardiosaver) and the external alarm system. Another very important function of the external alarm system is to facilitate display of both the baseline and alarm electrogram segments to a treating physician to facilitate rapid diagnosis and treatment for the patient.
Thus it is an object of this invention is to have a cardiosaver designed to detect the occurrence of a cardiac event by comparing baseline electrogram data from a first predetermined time with recent electrogram data from a second predetermined time.
Another object of the present invention is to have a cardiac event detected by comparing at least one heart signal parameter extracted from an electrogram segment captured at a first predetermined time by an implantable cardiosaver with the same at least one heart signal parameter extracted from an electrogram segment captured at a second predetermined time.
Another object of the present invention is to have acute myocardial infarction detected by comparing recent electrogram data to baseline electrogram data from the same time of day (i.e. approximately 24 hours in the past).
Another object of the present invention is to have acute myocardial infarction detected by comparing the ST deviation of the beats in a recently collected electrogram segment to the average ST deviation of two or more beats of a baseline electrogram segment.
Another object of the present invention is to have the threshold(s) for detecting the occurrence of a cardiac event adjusted by a cardiosaver device to compensate for slow changes in the average signal level of the patient's electrogram.
Another object of the present invention is to have the threshold for detection of a cardiac event adjusted by a cardiosaver device to compensate for daily cyclic changes in the average signal level of the patient's electrogram.
Another object of the present invention is to have an external alarm system including an alarm off button that will turn off either or both internal and external alarm signals initiated by an implanted cardiosaver.
Another object of the present invention is to have the alarm signal generated by a cardiosaver automatically turn off after a preset period of time.
Still another object of this invention is to use the cardiosaver to warn the patient that an acute myocardial infarction has occurred by means of a subcutaneous vibration.
Still another object of this invention is to have the cardiac event detection require that at least a majority of the beats exhibit an excessive ST shift before identifying an acute myocardial infarction.
Still another object of this invention is to have the cardiac event detection require that excessive ST shift still be present in at least two electrogram segments separated by a preset period of time.
Still another object of this invention is to have the cardiac event detection require that excessive ST shift still be present in at least three electrogram segments separated by preset periods of time.
Yet another object of the present invention is to have a threshold for detection of excessive ST shift that is dependent upon the average signal strength calculated from a baseline electrogram segment.
Yet another object of the present invention is to have a threshold for detection of excessive ST shift that is a function of the difference between the average PQ segment amplitude and the R wave peak amplitude of a baseline electrogram segment.
Yet another object of the present invention is to have a threshold for detection of excessive ST shift that is a function of the average minimum to maximum amplitude for at least two beats calculated from a baseline electrogram segment.
Yet another object of the present invention is to have the ability to detect a cardiac event by the shift in the amplitude of the T wave of an electrogram segment at a second predetermined time as compared with the average baseline T wave amplitude from a baseline electrogram segment at a first predetermined time.
Yet another object of the present invention is to have the ability to detect a cardiac event by the shift in the T wave deviation of at least one beat of an electrogram segment at a second predetermined time as compared with the average baseline T wave deviation from an electrogram segment at a first predetermined time.
Yet another object of the present invention is to have the first and second predetermined times for T wave amplitude and/or deviation comparison be separated by less than 30 minutes.
Yet another object of the present invention is to have the baseline electrogram segment used for ST segment shift detection and the baseline electrogram segment used for T wave shift detection be collected at different times.
Yet another object of the present invention is to have an individualized (patient specific) “normal” heart rate range such that the upper and lower limits of “normal” are programmable using the cardiosaver programmer.
Yet another object of the present invention is to have one or more individualized (patient specific) “elevated” heart rate ranges such that the upper and lower limits of each “elevated” range are programmable using the cardiosaver programmer.
Yet another object of the present invention is to allow the threshold for detection of an excessive ST shift be different for the “normal” heart rate range as compared to one or more “elevated” heart rate ranges.
These and other objects and advantages of this invention will become obvious to a person of ordinary skill in this art upon reading of the detailed description of this invention including the associated drawings as presented herein.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates a guardian system for the detection of a cardiac event and for warning the patient that a cardiac event is occurring.
FIG. 2 illustrates a normal electrogram pattern and also shows a superimposed elevated ST segment that would be indicative of an acute myocardial infarction.
FIG. 3 is a plan view of the cardiosaver showing the cardiosaver electronics module and two electrical leads each having one electrode.
FIG. 4 is a block diagram of the cardiosaver.
FIG. 5 is a block diagram of the cardiosaver event detection program.
FIG. 6 illustrates the extracted electrogram segment features used to calculate ST shift.
FIG. 7 is a block diagram of the baseline parameter extraction subroutine of the cardiosaver event detection program.
FIG. 8 is a block diagram of the alarm subroutine of the cardiosaver event detection program.
FIG. 9 is a block diagram of the hi/low heart rate subroutine of the cardiosaver event detection program.
FIG. 10 is a block diagram of the ischemia subroutine of the cardiosaver event detection program
FIG. 11 is a diagram of the conditions that trigger cardiosaver alarms.
FIG. 12 is a block diagram of the unsteady heart rate subroutine of the cardiosaver event detection program.
FIG. 13 is an alternate embodiment of the guardian system.
FIG. 14 illustrates the preferred physical embodiment of the external alarm transceiver.
FIG. 15 illustrates the physical embodiment of the combined external alarm transceiver and pocket PC.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 illustrates one embodiment of the guardian system 10 consisting of an implanted cardiosaver 5 and external equipment 7 . The battery powered cardiosaver 5 contains electronic circuitry that can detect a cardiac event such as an acute myocardial infarction or arrhythmia and warn the patient when the event occurs. The cardiosaver 5 can store the patient's electrogram for later readout and can send wireless signals 53 to and receive wireless signals 54 from the external equipment 7 . The functioning of the cardiosaver 5 will be explained in greater detail with the assistance of FIG. 4 .
The cardiosaver 5 has two leads 12 and 15 that have multi-wire electrical conductors with surrounding insulation. The lead 12 is shown with two electrodes 13 and 14 . The lead 15 has subcutaneous electrodes 16 and 17 . In fact, the cardiosaver 5 could utilize as few as one lead or as many as three and each lead could have as few as one electrode or as many as eight electrodes. Furthermore, electrodes 8 and 9 could be placed on the outer surface of the cardiosaver 5 without any wires being placed externally to the cardiosaver 5 .
The lead 12 in FIG. 1 could advantageously be placed through the patient's vascular system with the electrode 14 being placed into the apex of the right ventricle. The lead 12 with electrode 13 could be placed in the right ventricle or right atrium or the superior vena cava similar to the placement of leads for pacemakers and Implantable Coronary Defibrillators (ICDs). The metal case 11 of the cardiosaver 5 could serve as an indifferent electrode with either or both electrodes 13 and/or 14 being active electrodes. It is also conceived that the electrodes 13 and 14 could be used as bipolar electrodes. Alternately, the lead 12 in FIG. 1 could advantageously be placed through the patient's vascular system with the electrode 14 being placed into the apex of the left ventricle. The electrode 13 could be placed in the left atrium.
The lead 15 could advantageously be placed subcutaneously at any location where the electrodes 16 and/or 17 would provide a good electrogram signal indicative of the electrical activity of the heart. Again for this lead 15 , the case 11 of the cardiosaver 5 could be an indifferent electrode and the electrodes 16 and/or 17 could be active electrodes or electrodes 16 and 17 could function together as bipolar electrodes. The cardiosaver 5 could operate with only one lead and as few as one active electrode with the case of the cardiosaver 5 being an indifferent electrode. The guardian system 10 described herein can readily operate with only two electrodes.
One embodiment of the cardiosaver device 5 using subcutaneous lead 15 would have the electrode 17 located under the skin on the patient's left side. This could be best located between 2 and 20 inches below the patient's left arm pit. The cardiosaver case 11 could act as the indifferent electrode and would typically be implanted under the skin on the left side of the patient's chest.
FIG. 1 also shows the external equipment 7 that consists of a physician's programmer 68 having an antenna 70 , an external alarm system 60 including a charger 166 . The external equipment 7 provides means to interact with the cardiosaver 5 . These interactions include programming the cardiosaver 5 , retrieving data collected by the cardiosaver 5 and handling alarms generated by the cardiosaver 5 .
The purpose of the physician's programmer 68 shown in FIG. 1 is to set and/or change the operating parameters of the implantable cardiosaver 5 and to read out data stored in the memory of the cardiosaver 5 such as stored electrogram segments. This would be accomplished by transmission of a wireless signal 54 from the programmer 68 to the cardiosaver 5 and receiving of telemetry by the wireless signal 53 from the cardiosaver 5 to the programmer 68 . When a laptop computer is used as the physician's programmer 68 , it would require connection to a wireless transceiver for communicating with the cardiosaver 5 . Such a transceiver could be connected via a standard interface such as a USB, serial or parallel port or it could be inserted into the laptop's PCMCIA card slot. The screen on the laptop would be used to provide guidance to the physician in communicating with the cardiosaver 5 . Also, the screen could be used to display both real time and stored electrograms that are read out from the cardiosaver 5 .
In FIG. 1, the external alarm system 60 has a patient operated initiator 55 , an alarm disable button 59 , a panic button 52 , an alarm transceiver 56 , an alarm speaker 57 and an antenna 161 and can communicate with emergency medical services 67 with the modem 165 via the communication link 65 .
If a cardiac event is detected by the cardiosaver 5 , an alarm message is sent by a wireless signal 53 to the alarm transceiver 56 via the antenna 161 . When the alarm is received by the alarm transceiver 56 a signal 58 is sent to the loudspeaker 57 . The signal 58 will cause the loudspeaker to emit an external alarm signal 51 to warn the patient that an event has occurred. Examples of external alarm signals 51 include a periodic buzzing, a sequence of tones and/or a speech message that instructs the patient as to what actions should be taken. Furthermore, the alarm transceiver 56 can, depending upon the nature of the signal 53 , send an outgoing signal over the link 65 to contact emergency medical services 67 . When the detection of an acute myocardial infarction is the cause of the alarm, the alarm transceiver 56 could automatically notify emergency medical services 67 that a heart attack has occurred and an ambulance could be sent to treat the patient and to bring him to a hospital emergency room.
If the remote communication with emergency medical services 67 is enabled and a cardiac event alarm is sent within the signal 53 , the modem 165 will establish the data communications link 65 over which a message will be transmitted to the emergency medical services 67 . The message sent over the link 65 may include any or all of the following information: (1) a specific patient is having an acute myocardial infarction or other cardiac event, (2) the patient's name, address and a brief medical history, (3) a map and/or directions to where the patient is located, (4) the patient's stored electrogram including baseline electrogram data and the specific electrogram segment that generated the alarm (5) continuous real time electrogram data, and (6) a prescription written by the patient's personal physician as to the type and amount of drug to be administered to the patient in the event of a heart attack. If the emergency medical services 67 includes an emergency room at a hospital, information can be transmitted that the patient has had a cardiac event and should be on his way to the emergency room. In this manner the medical practitioners at the emergency room could be prepared for the patient's arrival.
The communications link 65 can be either a wired or wireless telephone connection that allows the alarm transceiver 56 to call out to emergency medical services 67 . The typical external alarm system 60 might be built into a Pocket PC or Palm Pilot PDA where the alarm transceiver 56 and modem 165 are built into insertable cards having a standardized interface such as compact flash cards, PCMCIA cards, multimedia, memory stick or secure digital (SD) cards. The modem 165 can be a wireless modem such as the Sierra AirCard 300 or the modem 165 may be a wired modem that connects to a standard telephone line. The modem 165 can also be integrated into the alarm transceiver 56 .
The purpose of the patient operated initiator 55 is to give the patient the capability for initiating transmission of the most recently captured electrogram segment from the cardiosaver 5 to the external alarm system 60 . This will enable the electrogram segment to be displayed for a medical practitioner. The alarm disable button 59 will turn off the internal alarm signal generated within the cardiosaver 5 and/or the external alarm signal 51 played through the speaker 57 .
The patient might press the panic button 52 in the event that the patient feels that he is experiencing a cardiac event. The panic button 52 will initiate the transmission from the cardiosaver 5 to the external alarm system 60 via the wireless signal 53 of both recent and baseline electrogram segments. The external alarm system 60 will then retransmit these data via the link 65 to emergency medical services 67 where a medical practitioner will view the electrogram data. The remote medical practitioner could then analyze the electrogram data and call the patient back to offer advice as to whether this is an emergency situation or the situation could be routinely handled by the patient's personal physician at some later time.
It is envisioned that there may be preset limits within the external alarm system 60 that prevent the patient operated initiator 55 and/or panic button from being used more than a certain number of times a day to prevent the patient from running down the batteries in the cardiosaver 5 and external alarm system 60 as wireless transmission takes a relatively large amount of power as compared with other functional operation of these devices.
FIG. 2 illustrates a typical electrogram signal from some pair of implanted electrodes such as the electrode 14 and the case 11 of FIG. 3 overlaid with an elevated ST segment 4 . The various portions of the electrogram are shown as the P, Q, R, S, and T waves. These are all shown as portions of a heavy solid line in FIG. 2 . The normal ST segment 3 is also shown in FIG. 2 .
When an acute myocardial infarction occurs, there is typically an elevation (or depression) of the ST segment 4 as shown by the light solid line in FIG. 2 . It is this shift of the ST segment 4 as compared to the baseline ST segment 3 that is a clear indicator that an acute myocardial infarction has occurred in a significant portion of the patient's myocardium.
Although an elevated ST segment 4 can be a good indicator of an acute myocardial infarction, other indicators such as a sudden change of heart rate or heart wall motion, intra-coronary blood pressure or a sudden decrease in blood pO 2 could also be used as independent sensing means or those signals could be used in addition to the voltage shift of the ST segment 4 .
It is important to note that the electrogram from implanted electrodes may provide a faster detection of an ST segment shift as compared to an electrocardiogram signal obtained from skin surface electrodes. Thus the electrogram from implanted electrodes as described herein is the preferred embodiment of the present invention.
It is also well known that the T wave can shift very quickly when a heart attack occurs. It is envisioned that the present invention might detect this T wave shift as compared to a time of 1 to 5 minutes in the past.
It is anticipated that when a patient who has a stenosis in a coronary artery is performing a comparatively strenuous exercise his heart rate increases and he can develop exercise induced ischemia that will also result in a shift of the ST segment of his electrogram. This is particularly true for patients who have undergone balloon angioplasty with or without stent implantation. Such patients will be informed by their own physician that, if their cardiosaver 5 of FIG. 1 activates an alarm during exercise, that it may be indicative of the progression of an arterial stenosis in one of the heart's arteries. Such a patient would be advised to stop all exertion immediately and if the alarm signal goes away as his heart rate slows, the patient should see his doctor as soon as convenient. If the alarm signal does not go away as the patient's heart rate slows down into the normal range then the cardiosaver will change the alarm signal to indicate that the patient should immediately seek medical care. As previously described, the cardiosaver 5 could emit a different signal if there is a heart attack as compared to the signal that would be produced if there were ischemia resulting from exercise.
It is also envisioned that heart rate and the rate of change of heart rate experienced during an ST segment voltage shift can be used to indicate which alarm should be produced by the cardiosaver 5 . Specifically, an ST segment shift at a near normal heart rate would indicate an acute myocardial infarction. An ST segment shift when there is an elevated heart rate (e.g., greater than 100 bpm) would generally be indicative of a progressing stenosis in a coronary artery. In any case, if a sufficient ST segment shift occurs that results in an alarm from the cardiosaver 5 , the patient should promptly seek medical care to determine the cause of the alarm.
It should be understood that, depending on a patient's medical condition, a vigorous exercise might be as energetic as running a long distance or merely going up a flight of stairs. After the cardiosaver 5 is implanted in a patient who has undergone a stent implant, he should have a stress test to determine his level of ST segment shift that is associated with the highest level of exercise that he can attain. The patient's heart rate should then be noted and the cardiosaver thresholds for detection, described with FIGS. 5 through 9, should be programmed so as to not alarm at ST segment shifts observed during exercise. Then if at a later time the patient experiences an increased shift of his ST segment at that pre-determined heart rate or within a heart rate range, then an alarm indicating ischemia can be programmed to occur. The occurrence of such an alarm can indicate that there is a progression in the narrowing of some coronary artery that may require angiography to determine if angioplasty, possibly including stent implantation, is required.
The alarm signal associated with an excessive ST shift caused by an acute myocardial infarction can be quite different from the “SEE DOCTOR” alarm means associated with progressing ischemia during exercise. For example, the SEE DOCTOR alarm signal might be an audio signal that occurs once every 5 to 10 seconds. A different alarm signal, for example an audio signal that is three buzzes every 3 to 5 seconds, may be used to indicate a major cardiac event such as an acute myocardial infarction. Similar alarm signal timing would typically be used for both internal alarm signals generated by the alarm sub-system 48 of FIG. 4 and external alarm signals generated by the external alarm system 60 .
In any case, a patient can be taught to recognize which signal occurs for these different circumstances so that he can take immediate response if an acute myocardial infarction is indicated but can take a non-emergency response if progression of the narrowing of a stenosis or some other less critical condition is indicated. It should be understood that other distinctly different audio alarm patterns could be used for different arrhythmias such as atrial fibrillation, atrial flutter, PVC's, PAC's, etc. A capability of the physician's programmer 68 of FIG. 1 would be to program different alarm signal patterns, enable or disable detection and/or generation of associated alarm signals in the cardiosaver for any one or more of these various cardiac events. Also, the intensity of the audio alarm, vibration or electrical tickle alarm could be adjusted to suit the needs of different patients. In order to familiarize the patient with the different alarm signals, the programmer 68 of the present invention would have the capability to turn each of the different alarm signals on and off.
FIG. 3 is a plan view of the cardiosaver 5 having a case 11 and a plastic header 20 . The case 11 contains the battery 22 and the electronics module 18 . This type of package is well known for pacemakers, implantable defibrillators and implantable tissue stimulators. Electrical conductors placed through the plastic header 20 connect the electronics module 18 to the electrical leads 12 and 15 , which have respectively electrodes 14 and 17 . The on-case electrodes 8 and 9 of FIG. 1 are not shown in FIG. 3 . It should also be understood that the cardiosaver 5 can function with only two electrodes, one of which could be the case 11 . All the different configurations for electrodes shown in FIGS. 1 and 3, such as the electrodes 8 , 9 , 13 , 14 , 16 or the metal case 11 are shown only to indicate that there are a variety of possible electrode arrangements that can be used with the cardiosaver 5 .
On the metal case 11 , a conducting disc 31 mounted onto an insulating disc 32 can be used to provide a subcutaneous electrical tickle to warn the patient that an acute myocardial infarction is occurring or to act as an independent electrode.
FIG. 4 is a block diagram of the cardiosaver 5 with battery 22 . The electrodes 14 and 17 connect with wires 12 and 15 respectively to the amplifier 36 that is also connected to the case 11 acting as an indifferent electrode. As two or more electrodes 12 and 15 are shown here, the amplifier 36 would be a multi-channel amplifier. The amplified electrogram signals 37 from the amplifier 36 are then converted to digital signals 38 by the analog-to-digital converter 41 . The digital electrogram signals 38 are buffered in the First-In-First-Out (FIFO) memory 42 . Processor means shown in FIG. 4 as the central processing unit (CPU) 44 coupled to memory means shown in FIG. 4 as the Random Access Memory (RAM) 47 can process the digital electrogram data 38 stored the FIFO 42 according to the programming instructions stored in the program memory 45 . This programming (i.e. software) enables the cardiosaver 5 to detect the occurrence of a cardiac event such as an acute myocardial infarction.
A clock/timing sub-system 49 provides the means for timing specific activities of the cardiosaver 5 including the absolute or relative time stamping of detected cardiac events. The clock/timing sub-system 49 can also facilitate power savings by causing components of the cardiosaver 5 to go into a low power standby mode in between times for electrogram signal collection and processing. Such cycled power savings techniques are often used in implantable pacemakers and defibrillators. In an alternate embodiment, the clock/timing sub-system can be provided by a program subroutine run by the central processing unit 44 .
In an advanced embodiment of the present invention, the clock/timing circuitry 49 would count for a first period (e.g. 20 seconds) then it would enable the analog-to-digital converter 41 and FIFO 42 to begin storing data, after a second period (e.g. 10 seconds) the timing circuitry 49 would wake up the CPU 44 from its low power standby mode. The CPU 44 would then process the 10 seconds of data in a very short time (typically less than a second) and go back to low power mode. This would allow an on off duty cycle of the CPU 44 which often draws the most power of less than 2 seconds per minute while actually collecting electrogram data for 20 seconds per minute.
In a preferred embodiment of the present invention the RAM 47 includes specific memory locations for 3 sets of electrogram segment storage. These are the recent electrogram storage 472 that would store the last 2 to 10 minutes of recently recorded electrogram segments so that the electrogram data leading in the period just before the onset of a cardiac event can be reviewed at a later time by the patient's physician using the physician's programmer 68 of FIG. 1 . For example, the recent electrogram storage 472 might contain eight 10 second long electrogram segments that were captured every 30 seconds over the last 4 minutes.
The baseline electrogram memory 474 would provide storage for baseline electrogram segments collected at preset times over one or more days. For example, the baseline electrogram memory 474 might contain 24 baseline electrogram segments of 10 seconds duration, one from each hour for the last day.
The event memory 476 occupies the largest part of the RAM 47 . The event memory 476 is not overwritten on a regular schedule as are the recent electrogram memory 472 and baseline electrogram memory 474 but is typically maintained until read out by the patient's physician with the programmer 68 of FIG. 1 . At the time a cardiac event like excessive ST shift indicating an acute myocardial infarction is detected by the CPU 44 , all (or part) of the entire contents of the baseline and recent electrogram memories 472 and 474 would typically be copied into the event memory 476 so as to save the pre-event data for later physician review.
The RAM 47 also contains memory sections for programmable parameters 471 and calculated baseline data 475 . The programmable parameters 471 include the upper and lower limits for the normal and elevated heart rate ranges, and physician programmed parameters related to the cardiac event detection processes stored in the program memory 45 . The calculated baseline data 475 contain detection parameters extracted from the baseline electrogram segments stored in the baseline electrogram memory 474 . Calculated baseline data 475 and programmable parameters 471 would typically be saved to the event memory 476 following the detection of a cardiac event. The RAM 47 also includes patient data 473 that may include the patient's name, address, telephone number, medical history, insurance information, doctor's name, and specific prescriptions for different medications to be administered by medical practitioners in the event of different cardiac events.
It is envisioned that the cardiosaver 5 could also contain pacemaker circuitry 170 and/or defibrillator circuitry 180 similar to the cardiosaver systems described by Fischell in U.S. Pat. No. 6,240,049.
The alarm sub-system 48 contains the circuitry and transducers to produce the internal alarm signals for the cardiosaver 5 . The internal alarm signal can be a mechanical vibration, a sound or a subcutaneous electrical tickle or shock.
The telemetry sub-system 46 with antenna 35 provides the cardiosaver 5 the means for two-way wireless communication to and from the external equipment 7 of FIG. 1 . Existing radiofrequency transceiver chip sets such as the Ash transceiver hybrids produced by RF Microdevices, Inc. can readily provide such two-way wireless communication over a range of up to 10 meters from the patient. It is also envisioned that short range telemetry such as that typically used in pacemakers and defibrillators could also be applied to the cardiosaver 5 . It is also envisioned that standard wireless protocols such as Bluetooth and 802.11a or 802.11b might be used to allow communication with a wider group of peripheral devices.
A magnet sensor 190 may be incorporated into the cardiosaver 5 . An important use of the magnet sensor 190 is to turn on the cardiosaver 5 on just before programming and implantation. This would reduce wasted battery life in the period between the times that the cardiosaver 5 is packaged at the factory until the day it is implanted.
FIG. 5 illustrates in the form of a block diagram the operation of the heart signal processing program 450 for cardiac event detection by the cardiosaver 5 of FIGS. 1-4. The heart signal processing program 450 is an example of one of many such detection programs whose instructions could reside in the program memory 45 for use by the CPU 44 of the cardiosaver 5 as shown in FIG. 4 . The main section of the heart signal processing program 450 begins with step 451 where the event counter “k” is set to zero indicating there have been no detected events. Next, in step 452 the cardiosaver 5 is said to sleep for X seconds. The term sleep here indicates that for a period of X seconds, the cardiosaver 5 would either be placed in a low power standby mode (if available) or would otherwise simply wait for a time of X seconds before moving to step 453 . Step 453 following 452 has an electrogram segment representing Y seconds of electrogram data captured into the FIFO buffer 42 of FIG. 4 . σ is the data sampling rate in samples per second, thus the total number of samples collected in step 453 is a multiplied by Y. It is envisioned that X would be a time between 5 seconds and 5 minutes with 20 seconds as a preferred value. Y would be between 3 and 30 seconds with 10 seconds as a preferred value. σ is typically between 100 and 500 samples per second with 200 samples per second being a preferred value.
After being captured, in step 454 , the Y seconds of electrogram data representing the most recent electrogram segment is transferred to the recent electrogram memory 472 of FIG. 4 . At this time the processing and analysis of the data begins. Throughout the remainder of this detailed description of the drawings, the “Y second long electrogram segment” refers to the most recently collected Y seconds of electrogram data that have been captured and transferred to the recent electrogram memory 472 by the steps 453 and 454 . The term “recent electrogram segments” refers to all of the electrogram segments stored in the recent electrogram memory 472 . For example, there could be eight total 10 second long recent electrogram segments that were captured at 30 second intervals over a 4 minute period.
The first processing step following the collection of the Y second long electrogram segment is step 455 that measures the intervals between the R waves in the most Y second long electrogram segment. These R—R intervals are then used to calculate the average heart rate and R—R interval variation for the Y second long electrogram segment. If the average heart rate is below a programmed low heart rate limit ρ low or above a programmed high heart rate limit ρ high , it is considered “out-of-range” and a Hi/Low heart rate subroutine 420 (see FIG. 9) is run to properly respond to the condition.
If the R—R interval variation within the Y second long electrogram segment is more than a programmed limit, the hi/low heart rate subroutine is also run. This is an important feature of the present invention as PVC's and unstable heart rhythms such as a bigeminal rhythm can cause errors in an ST shift detection algorithm that is works best with a steady heart rhythm. One embodiment of the present invention identifies an unsteady heart rate by comparing the two shortest R—R intervals and the 2 longest intervals in the Y second long electrogram segment. If the difference between both of the two shortest R—R intervals and the average of the two longest R—R intervals are more than a programmed percentage α, an unsteady heart rate is identified. For example the programmed percentage α might be 25% so that if the two shortest R—R intervals are each more than 25% less than the average of the two longest R—R intervals, then the heart rate is unsteady. It is envisioned that if longer times Y are used for electrogram segment collection then it might require 3 or more “short” beats to indicated an unsteady heart rate. Any beat that is not too short is classified by step 455 as a normal beat. ρ low , ρ high and α are programmable parameters typically set using the programmer 68 during programming of the cardiosaver 5 . Typical values for ρ low and ρ high would be 50 and 140 beats per minute respectively.
If the heart rate is not high, low or unsteady as checked in step 455 , the heart signal processing program 450 moves to step 456 where the average heart rate is compared to a programmed normal range between ρ low and ρ elevated where ρ elevated is the elevated heart rate limit that defines the upper limit of the “normal range” (e.g. 80 beats per minute). If the patient's heart rate is elevated but not out-of-range (i.e. above ρ high ), the patient may be exercising and the ischemia subroutine 480 allows for different cardiac event detection criteria during elevated heart rates to reduce false positive detections of acute myocardial infarction and to detect exercise induced ischemia. An example of one embodiment of the ischemia subroutine 480 is illustrated in FIG. 10 .
Although the above specification describes low, high and elevated heart rate limits ρ low , ρ high and ρ elevated , it is envisioned that instead of heart rate (i.e. beats per second) the limits and decision making could be set in terms or R wave to R wave (R—R) interval with the low, high and elevated limits are for R—R interval and are expressed in seconds per beat, milliseconds per beat or samples per beat.
If the average heart rate of the patient is within the “normal” range in step 456 , then the program 450 moves to step 457 where it looks for an excessive ST shift on M out of N beats as compared with the baseline electrogram segment collected at a time U±W minutes in the past. U can be any time from 1 minute to 48 hours but to allow for daily cycles U=24 hours is a preferred embodiment. W is half the interval between times when the baseline data is saved and can be any time from 10 seconds to 12 hours. For a U of 24 hours, a preferred setting would have W equal to half an hour so that the current Y second long electrogram segment is always being compared with a baseline electrogram segment from 24±½ hour before. This also means that baseline electrogram segments are saved and processed to extract detection parameters at an interval of twice W (2W). I.e., if W is half an hour, then the baseline data is saved and processed once an hour. M can be any number from 1 to 30 and N can be any number from M to 100. An example of a typical M and N used would be 6 out of 8 beats. It is envisioned that the first of the 8 beats will typically be the beat including the 2 nd R wave in the Y second long electrogram segment collected in steps 453 and 454 .
An alternate to ST shift detection in step 457 is to process just the T wave, which can change its peak or average amplitude rapidly if there is a heart attack. The T wave can, however change its amplitude slowly under normal conditions so a T wave shift detector would need a much shorter time U than that of a detector using the ST segment before the T wave. If the detector is checking for such T wave shift, i.e. a voltage shift of the T wave part of the ST segment, then it may be desirable to check against a baseline where U is 1 to 30 minutes and W is 15 seconds to 15 minutes. For example, U=3 minutes and W=15 seconds is a preferred setting to catch a quickly changing T wave. This would also allow use of recent electrogram segments stored in the recent electrogram memory of FIG. 4 as baseline electrogram segments for T wave shift detection. It is envisioned that the programmer 68 of FIG. 1 would allow the patient's doctor to program the cardiosaver 5 to use ST segment shift or T wave shift detectors by themselves, or together simultaneously. If both were used then the programmer 68 would allow the patient's doctor to choose whether a positive detection will result if either technique detects an event or only if both detect an event.
If the average heart rate is in the normal range, is not unsteady and there is no cardiac event detection in step 457 , (i.e. the electrogram signal is indicative of a “normal” heart signal for the patient), the heart signal processing program 450 checks in step 458 if it is more than the interval of 2W minutes since the last time baseline data was captured. If it has been more than 2W, the baseline parameter extraction subroutine 440 of FIG. 7 is run.
The parameters X, Y, U and W are stored with the programmable parameters 471 in the RAM 47 in FIG. 4 . These parameters may be permanently set at the time of manufacturing of the cardiosaver 5 or they may be programmed through the programmer 68 of FIG. 1 . The calculated criteria for cardiac event detection extracted from the baseline electrogram segments stored in baseline electrogram memory 474 are stored in the calculated baseline data memory 475 of the RAM 47 .
A typical configuration of the heart signal processing program 450 using only an ST shift detector, would use a sleep of X=20 seconds, followed by collection of a Y=10 second long electrogram segment. If the patient's heart rate is in a normal range of between 50 and 80 beats per minute, step 457 would check for an excessive shift of the ST segment in 6 out of 8 of the beats as compared with baseline data collected 24±½ hour previously.
If there has been a detected excessive ST shift in M out of N beats in step 457 , the ST Verification Subroutine 460 is run to be sure that the detected event is not a transitory change in the electrogram.
The ST Verification Subroutine 460 begins with step 461 where the recently collected Y second long electrogram segment is saved to the event memory 476 of FIG. 4 for later review by the patient's doctor.
The ST shift verification subroutine 460 then increments the event counter k by 1 (step 462 ) and then checks (step 463 ) if k is equal to 3 (i.e. 3 events is the trigger for an alarm. If k=3 then the alarm subroutine 490 illustrated in FIG. 8 is run, thus declaring that there has been a positive detection of a major cardiac event. FIG. 11 illustrates examples of the combinations of conditions that can lead to k=3 and the running of the alarm subroutine 490 .
Although step 463 is shown checking if k=3 as the condition for running the alarm subroutine 490 , the number of events required could be a programmable parameter from k=1 to k=20. Even higher possible values than k=20 might be used to avoid false positive detections. With current average times from onset of a heart attack to arrival at a treatment center of 3 hours, a few minutes delay for a device that should enable the patient to easily reach a treatment center within 30 minutes is valuable if it improves the reliability of detection.
In step 463 if k is less than 3 then the ST shift verification subroutine 460 proceeds to sleep Z seconds in step 464 followed by collection (step 465 ) and saving (step 466 ) to the next location in the recent electrogram memory 472 of FIG. 4 of a new Y second long electrogram segment. Z seconds can be different from the X seconds used in step 452 to allow the ST shift verification subroutine 460 to look over longer (or shorter) intervals than the main program so as to best verify the positive detection of step 457 . The term sleep here has the same connotation as in step 452 . A preferred embodiment of the present invention uses Z=X=20 seconds.
The ST shift verification subroutine 460 then checks for heart rate out-of-range or unsteady in step 467 . As described with respect to step 455 above, heart rate out-of-range means that the average heart rate in the Y second long electrogram segment is below the low heart rate limit ρ low or above the high heart rate limit ρ high .
If the heart rate is out-of range or unsteady step 467 will initiate the Hi/Low subroutine 420 . If the heart rate is not out-of range or unsteady, then step 468 follows to check if the heart rate is normal or elevated similar to step 456 above. If the heart rate is elevated, the ischemia subroutine 480 is run. The reason for checking if the heart rate has changed is that acute myocardial infarction can induce high heart rates from tachycardia or fibrillation that might mask the ST shift but are in of themselves major cardiac events whose detection will increment the event counter k.
If the heart rate is in the normal range (i.e. not elevated), then step 469 checks for an excessive ST and/or T wave shift in M out of N beats of the Y second long electrogram segment as compared with the baseline data extracted U±W minutes in the past (similar to step 457 ). If no excessive ST and/or T wave shift is seen, the subroutine 460 returns to step 458 of the heart signal processing program 450 and then eventually back to step 451 , the start of heart signal processing program 450 . In step 451 , k is set back to 0 so that only if there are cardiac events detected in three (k) successive Y second long electrogram segments, will the alarm subroutine 490 be run. In a preferred embodiment of the present invention, steps 457 and 469 only examine M out of N “normal” beats, ignoring any beats that are too short as determined by step 455 .
It is important to note, that baseline data is extracted only when the heart rate is within the normal range and there is not an excessive ST or T wave shift in M out of N beats. In one embodiment of the present invention, this is improved further by having the baseline parameter extraction subroutine 440 only process normal beats that individually do not exhibit an excessive ST and/or T wave shift.
FIG. 6 illustrates the features of a single normal beat 500 of an electrogram segment and a single beat 500 ′ of an AMI electrogram segment that has a significant ST segment shift as compared with the normal beat 500 . Such ST segment shifting occurs within minutes following the occlusion of a coronary artery during an AMI. The beats 500 and 500 ′ show typical heart beat wave elements labeled P, Q, R, S, and T. The definition of a beat such as the beat 500 is a sub-segment of an electrogram segment containing exactly one R wave and including the P and Q elements before the R wave and the S and T elements following the R wave.
For the purposes of detection algorithms, different sub-segments, elements and calculated values related to the beats 500 and 500 ′ are hereby specified. The peak of the R wave of the beat 500 occurs at the time T R ( 509 ). The PQ segment 501 and ST segment 505 are sub-segments of the
a. The PQ segment 501 has a time duration D PQ ( 506 ) and starts T PQ ( 502 ) milliseconds before the time T R ( 509 ).
b. The ST segment 505 has a time duration D ST ( 508 ) and starts T ST ( 502 ) milliseconds after the time T R ( 509 ).
The PQ segment 501 ′ and ST segment 505 ′ are sub-segments of the beat 500 ′ and are located in time with respect to the time T′ R ( 509 ′) as follows:
c. The PQ segment 501 ′ has a time duration D PQ ( 506 ) and starts T PQ ( 502 ) milliseconds before the time T′ R ( 509 ′).
d. The ST segment 505 ′ has a time duration D ST ( 508 ) and starts T ST ( 502 ) milliseconds after the time T′ R ( 509 ′).
The ST segments 505 and 505 ′ and the PQ segments 501 and 501 ′ are examples of sub-segments of the electrical signals from a patient's heart. The R wave and T wave are also sub-segments. The dashed lines V PQ ( 512 ) and V ST ( 514 ) illustrate the average voltage amplitudes of the PQ and ST segments 501 and 505 respectively for the normal beat 500 . Similarly the dashed lines V′ PQ ( 512 ′) and V′ ST ( 514 ′) illustrate the average amplitudes of the PQ and ST segments 501 ′ and 505 ′ respectively for the beat 500 ′. The “ST deviation” ΔV ( 510 ) of the normal beat 500 and the ST deviation ΔV AMI ( 510 ′) of the AMI electrogram beat 500 ′ are defined as:
ΔV ( 510 )=V ST ( 514 )−V PQ ( 512 )
ΔV AMI ( 510 ′)=V′ ST ( 514 ′)−V′ PQ ( 512 ′)
Note that the both beats 500 and 500 ′ are analyzed using the same time offsets T PQ and T ST from the peak of the R wave and the same durations D PQ and D ST . In this example, the beats 500 and 500 ′ are of the same time duration (i.e. the same heart rate). The parameters T PQ , T ST , D PQ and D ST would typically be set with the programmer 68 of FIG. 1 by the patient's doctor at the time the cardiosaver 5 is implanted so as to best match the morphology of the patient's electrogram signal and normal heart rate. V PQ ( 512 ), V ST ( 514 ), V R ( 503 ) and ΔV ( 510 ) are examples of per-beat heart signal parameters for the beat 500 .
Although it may be effective to fix the values of time offsets T PQ ( 502 ) and T ST ( 504 ) and the durations D PQ ( 506 ) and D ST ( 508 ), it is envisioned that the time offsets T PQ and T ST and the durations D PQ and D ST could be automatically adjusted by the cardiosaver 5 to account for changes in the patient's heart rate. If the heart rate increases or decreases, as compared with the patient's normal heart rate, it envisioned that the offsets T PQ ( 502 ) and T ST ( 504 ) and/or the durations D PQ ( 506 ) and D ST ( 508 ) could vary depending upon the R—R interval between beats or the average R—R interval for an electrogram segment. A simple technique for doing this would vary the offsets T PQ and T ST and the durations D PQ and D ST in proportion to the change in R—R interval. For example if the patient's normal heart rate is 60 beats per minute, the R—R interval is 1 second; at 80 beats per minute the R—R interval is 0.75 seconds, a 25% decrease. This could automatically produce a 25% decrease in the values of T PQ , T ST , D PQ and D ST . Alternately, the values for T PQ , T ST , D PQ and D ST could be fixed for each of up to 20 preset heart rate ranges. In either case, it is envisioned that after the device has been implanted, the patient's physician would, through the programmer 68 of FIG. 1, download from the cardiosaver 5 to the programmer 68 , a recent electrogram segment from the recent electrogram memory 472 . The physician would then use the programmer 68 to select the values of T PQ , T ST , D PQ and D ST for the heart rate in the downloaded recent electrogram segment. The programmer 68 would then allow the physician to choose to either manually specify the values of T PQ , T ST , D PQ and D ST for each heart rate range or have the cardiosaver 5 automatically adjust the values of T PQ , T ST , D PQ and D ST based on the R—R interval for each beat of any electrogram segment collected in the future by the cardiosaver 5 . It is also envisioned that only the offset times, T PQ and T ST , might be automatically adjusted and the durations D PQ and D ST would be fixed so that the average values of the ST and PQ segments V PQ ( 512 ), V ST ( 514 ), V′ PQ ( 512 ′) and V′ ST ( 514 ′) would always use the same number of data samples for averaging.
An example of a sequence of steps used to calculate the ST deviation 510 for the normal beat 500 are as follows:
1. Identify the time T R ( 509 ) for the peak of the R wave for the beat 500 ,
2. Calculate the time since the previous R wave and use that time to look up or calculate the values of T PQ , T ST , D PQ and D ST .
3. Average the amplitude of the PQ segment 501 between the times (T R −T PQ ) and (T R −T PQ +D PQ ) to create the PQ segment average amplitude V PQ ( 512 ),
4. Average the amplitude of the ST segment 505 between the times (T R +T ST ) and (T R +T ST +D ST ) to create the ST segment average amplitude V ST ( 514 ),
5. Subtract V PQ ( 512 ) from V ST ( 514 ) to produce the ST deviation ΔV ( 510 ) for the beat 500 .
Although only one normal beat 500 is shown here, there would typically be multiple beats saved in the Y second long electrogram segments stored in the recent electrogram memory 472 and the baseline electrogram memory 474 of FIG. 4 . At preset time intervals during the day step 458 of FIG. 5 will run the baseline parameter extraction subroutine 440 that will calculate the “average baseline ST deviation” ΔV BASE defined as the average of the ST deviations ΔV ( 510 ) for at least two beats of a baseline electrogram segment. Typically the ST deviation of 4 to 8 beats of the baseline electrogram segment will be averaged to produce the average baseline ST deviation ΔV BASE .
For each of “i” preset times during the day (at a time interval of approximately 2W) an average baseline ST deviation ΔV BASE (i) will be calculated and saved in the calculated baseline data memory 475 for later comparison with the ST deviation ΔV ( 510 ) of each beat of a recently collected electrogram. For example, in a preferred embodiment of the present invention, the average baseline ST deviation ΔV BASE (i) is collected once an hour and there are be 24 values of ΔV BASE (i) (ΔV BASE (1), ΔV BASE ( 2 ) . . . ΔV BASE (24)) stored in the calculated baseline data memory 475 of FIG. 4 . An excessive ST shift for a single beat of a recently collected electrogram segment is then detected when the ST deviation ΔV for that beat shifts by more than a predetermined threshold amplitude from the average baseline ST deviation ΔV BASE (i) collected approximately 24 hours before.
The ST shift of a given beat is calculated by subtracting the appropriate averaged baseline ST deviation ΔV BASE (i) from the ST deviation ΔV for that beat. Assuming the R—R interval indicates that the heart rate for a beat is in the normal range then an excessive ST shift for a single beat is detected if (ΔV−ΔV BASE (i)) is greater than the normal ST shift threshold H normal for the normal heart rate range. The heart signal processing program 450 of FIG. 5 requires that such an excessive ST shift be positively identified in M out of N beats in three successive recent electrogram segments before the alarm subroutine 490 is activated. The threshold H normal may be a fixed value that does not change over time and is set at the time of programming of the cardiosaver 5 with the programmer 68 of FIG. 1 .
In a preferred embodiment, the threshold for detection of excessive ST shift is not fixed but is calculated as H ST (i) from the i'th baseline electrogram segment stored in the baseline electrogram memory 474 of FIG. 4 . To do this the difference between the amplitude of the peak of the R wave V R ( 503 ) and the average PQ segment amplitude V PQ ( 512 ) are calculated for each of at least 2 beats of each baseline electrogram segment by the baseline parameter extraction subroutine 440 . The average value ΔR(i) of this difference (V R −V PQ ) for at least two beats of the i'th baseline electrogram segment can be used to produce a threshold for ST shift detection H ST (i) that is proportional to the signal strength of the i'th baseline electrogram segment. The advantage of this technique is that, if the signal strength of the electrogram changes slowly over time, the threshold H ST (i) for ST shift detection will change in proportion.
The preferred embodiment of the present invention would have a preset percentage P ST that is multiplied by ΔR(i) to obtain the threshold H ST (i)=P ST ×ΔR(i). Thus, the threshold H ST (i) would be a fixed percentage of the average height of the R wave peaks over the ST segments of the i'th baseline electrogram segment. For example, if P ST is 25% an excessive ST shift on a given beat would be detected if the ST shift (Δ V −ΔV BASE (i)) is greater than the threshold H ST (i) where H ST (i) is 25% of the average PQ to R height ΔR(i) of the i'th baseline electrogram segment.
In a preferred embodiment of the present invention heart signal processing program 450 of FIG. 5, the value X and Z are both 20 seconds, Y is 10 seconds, 2W is 60 minutes, U is 24 hours, W is 30 minutes, M is 6 and N is 8. Therefore the steps 457 and 469 of FIG. 5 will check for excessive ST shifts in 6 out of 8 beats from of the Y=10 second long electrogram segment captured every 30 seconds as compared with parameters extracted from the baseline electrogram segment captured 24±½ hour before. In this preferred embodiment baseline electrogram segments are captured once per hour.
FIG. 7 illustrates a preferred embodiment of the baseline extraction subroutine 440 . The subroutine 440 begins in step 439 by saving in the i'th memory location in baseline electrogram memory 474 of FIG. 4, the last Y second long electrogram segment saved into the “Recent” electrogram memory in step 454 of FIG. 5 . This Y seconds of electrogram data then becomes the baseline electrogram segment for calculating parameters for detection to be used during the 2W long period of time U±W minutes in the future.
Next in step 441 the baseline extraction subroutine 440 finds the R wave peak times T R (j) for the 1 st through (N+2) th beat (j=1 through N+2) in the baseline electrogram segment saved in step 439 . This is a total of N+2 beats. Each time T R (j) is typically counted from the beginning of the Y second long electrogram segment until the peak of the j'th R wave. Next in step 442 the average R—R interval of the i'th baseline electrogram segment RR(i) is calculated by averaging the R—R intervals for each of the N+1 beats (j=2 through N+2) where the R—R interval for beat j is T R (j)−T R (j−1). For example, for beat 2, the R—R interval is the time interval from the R wave peak of beat 1 (the very first R wave) to the R wave peak of beat 2. I.e. R—R intervals before and after each of the N beats j=2 through j=N+1 are calculated. This step also identifies any R—R intervals that are out of the “normal” range as defined in the programming of the cardiosaver 5 . In a preferred embodiment of the present invention, baseline data will only be extracted from “normal” beats. A normal beat is one in which the R—R interval both before and after the R wave is in the “normal range. This is a preferred technique to use as a too short R—R interval before the R wave can affect the PQ segment amplitude and a too short R—R interval after the R wave can affect the ST segment amplitude, either of which could produce a false indication of excessive ST shift.
Next in step 443 the offsets T PQ , T ST , D PQ and D ST (see FIG. 6) are calculated. In one embodiment, T PQ and T ST are the percentages φ PQ and φ ST multiplied by the average R—R interval RR(i) respectively. This technique will adjust the location of the start of the PQ and ST segments to account for changes in heart rate. The percentages φ PQ and φ ST would be selected by the patient's doctor based on “normal” electrogram segments analyzed by the programmer 68 of FIG. 1 . Another embodiment of the present invention uses fixed time offsets T PQ and T ST that are programmed by the patient's doctor. Similarly the duration of the PQ and ST segments D PQ and D ST (see FIG. 6) can be calculated by multiplying the percentages δ PQ and δ ST times the average R—R interval RR(i) respectively. The percentages δ PQ and δ ST would also be selected by the patient's doctor using the programmer 68 . The preferred embodiment of the present invention uses fixed segment durations D PQ and D ST that are programmed by the patient's doctor. Using fixed durations D PQ and D ST has the advantage of keeping the same number of samples averaged in each calculation of the average PQ and ST segment amplitudes V PQ and V ST respectively.
Next in step 444 for each of the N beats (j=2 through N+1) identified by step 422 as a normal beat, V PQ (j) the average of the PQ segment amplitude of the j'th beat over the duration D PQ beginning T PQ before the peak T R (j) and V ST (j) the average ST segment amplitude of the j'th beat over the duration D ST beginning T ST after the time T R (j) are calculated. Similarly, step 444 calculates the peak T wave heights V T (j).
For each beat the ST deviation ΔV ST (j) that is the difference between V ST (j) and V PQ (j) is then calculated in step 445 . Similarly, step 445 calculates the T wave deviation ΔV(j) that is the difference between V T (j) and V PQ (j). It should be noted that step 455 of FIG. 5 will only allow the baseline extraction subroutine to be run if less than 2 too short beats are present, thus at least N−2 of the N beats used for baseline data extraction will be normal beats. Although there is a limit here of less than 2 short beats, it is envisioned that other minimum numbers of short beats than 2 might also be used.
Next in step 446 the ST deviation ΔV ST (j) for all normal beats within the N beats is averaged to produce the i'th average baseline ST deviation ΔV BASE (i). Similarly, in step 446 the T wave deviation ΔV T (j) for all normal beats within the N beats is averaged to produce the i'th average baseline T wave deviation ΔT BASE (i).
An alternate embodiment of the present invention would also check for excessive ST shift on each normal beat and exclude any such beats from the average baseline ST deviation and T wave deviation calculations.
Next in step 447 , ΔR(i) the average of the height of the peak of the j'th R wave above the average PQ segment V PQ (j) is calculated for the normal beats. ΔR(i) acts as an indication of the average signal strength of the i'th baseline electrogram segment. ΔR(i) is used to provide a detection threshold for excessive ST shift that will adapt to slow changes in electrogram signal strength over time. This is of most value following implant as the sensitivity of the electrodes 14 and 17 may change as the implant site heals.
ΔT BASE (i) can either be the average of the signal samples of the entire T waves or it can be the average of the peak amplitude of the T waves in the normal beats. It is also envisioned, that if both ST and T wave shift detection are used, a cardiac event could be declared if either excessive ST shift or T wave shift detects a change (this is preferred) or the program could require that both excessive ST shift and T wave shift be present.
Next in step 448 , the threshold for ST shift detection for normal heart rates H ST (i) is calculated by multiplying the programmed threshold percentage P ST of ΔR(i). Also in step 448 , if the T wave shift detector is being used, the threshold for T wave shift detection for normal heart rates H T (i) is calculated by multiplying the programmed threshold percentage P T of ΔR(i).
Finally in step 449 , the extracted baseline parameters ΔV BASE (i), ΔT BASE (i), ΔR(i), H ST (i) and H T (i) are saved to the calculated baseline data memory 475 . The baseline extraction subroutine 440 has ended and the program returns to the main heart signal processing program 450 step 451 of FIG. 5 .
One embodiment of ST shift and T wave shift detection might use a baseline for ST shift detection that is 24±½ hour before and a baseline for T wave shift that is 1 to 4 minutes in the past. This would require that the baseline extraction subroutine 440 be run for T wave shift parameters approximately every 60 seconds and for ST segment parameters every hour.
Although the baseline extraction subroutine 440 is described here as using the same “N” as the number of beats processed as the ST shift detection steps 457 and 469 of FIG. 5, it is envisioned that either a greater or lesser number of beats could be used for baseline extraction as compared with the number of beats “N” checked for excessive ST shifts in FIG. 5 .
Typical values used for the baseline extraction subroutine 440 as shown in FIG. 7 would be N=8 to average the data over 8 beats using beats 2 through 9 of the Y second long electrogram segment. However, it is envisioned that as few as 1 beat or as many as 100 beats or higher could be used to calculate the parameters extracted by subroutine 440 . Also even though the preferred embodiment of the present invention extracts baseline data only from “normal” beats, it is envisioned that using all 8 beats would usually yield an acceptable result.
Although the baseline extraction subroutine 440 shows the extraction of parameters for identifying excessive ST shifts and T wave shifts, the cardiosaver 5 would function with either of these detection methods or could use other techniques to measure the changes in electrogram signals indicating one or more coronary event.
FIG. 8 illustrates a preferred embodiment of the alarm subroutine 490 . The alarm subroutine 490 is run when there have been a sufficient number of events detected to warrant a major event cardiac alarm to the patient. The alarm subroutine 490 begins with step 491 where the entire contents of both baseline electrogram memory 474 and recent electrogram memory 472 of FIG. 4 are saved into the event memory 476 . This saves the above mentioned electrogram data in a place where it is not overwritten by new baseline or recent electrogram data to allow the patient's physician to review the electrogram segments collected during a period of time that occurred before the alarm. In a preferred embodiment with 24 baseline electrogram segments collected once per hour, and 8 recent electrogram segments collected every 30 seconds, the physician will be able to review a significant amount of electrogram data from the 4 minutes just before the cardiac event as well as being able to see any changes in the 24 hours before the event.
Next; in step 492 the internal alarm signal is turned on by having the CPU 44 of FIG. 4 cause the alarm sub-system 48 to activate a major event alarm signal.
Next in step 493 the alarm subroutine instructs the CPU 44 to send a major event alarm message to the external alarm system 60 of FIG. 1 through the telemetry sub-system 46 and antenna 35 of the cardiosaver 5 of FIG. 4 . The alarm message is sent once every L 1 seconds for L 2 minutes. During this time step 494 waits for an acknowledgement that the external alarm has received the alarm message. After L 2 minutes, if no acknowledgement is received, the cardiosaver 5 of FIG. 1 gives up trying to contact the external alarm system 60 . If an acknowledgement is received before L 2 minutes, step 495 transmits alarm related data to the external alarm system. This alarm related data would typically include the cause of the alarm, baseline and last event electrogram segments and the time at which the cardiac event was detected.
Next in step 496 , the cardiosaver 5 transmits to the external alarm system 60 of FIG. 1 other data selected by the patient's physician using the programmer 69 during programming of the cardiosaver. These data may include the detection thresholds H ST (i), H T (i) and other parameters and electrogram segments stored in the cardiosaver memory 47 .
Once the internal alarm signal has been activated by step 492 , it will stay on until the clock/timing sub-system 49 of FIG. 4 indicates that a preset time interval of L 3 minutes has elapsed or the cardiosaver 5 receives a signal from the external alarm system 60 of FIG. 1 requesting the alarm be turned off.
To save power in the implantable cardiosaver 5 , step 496 might check once every minute for the turn off signal from the external alarm system 60 while the external alarm system 60 would transmit the signal continuously for slightly more than a minute so that it will not be missed. It is also envisioned that when the alarm is sent to the external alarm system 60 , the internal clock 49 of the cardiosaver 5 and the external alarm system 60 can be synchronized so that the programming in the external alarm system 60 will know when to the second, that the cardiosaver will be looking for the turn off signal.
At this point in the alarm subroutine 490 step 497 begins to record and save to event memory 476 of FIG. 4, an E second long electrogram segment every F seconds for G hours, to allow the patient's physician and/or emergency room medical professional to read out the patient's electrogram over time following the events that triggered the alarm. This is of particular significance if the patient, his caregiver or paramedic injects a thrombolytic or anti-platelet drug to attempt to relieve the blood clot causing the acute myocardial infarction. By examining the data following the injection, the effect on the patient can be noted and appropriate further treatment prescribed.
In step 498 the alarm subroutine will then wait until a reset signal is received from the physician's programmer 68 or the patient operated initiator 55 of the external alarm system 60 of FIG. 1 . The reset signal would typically be given after the event memory 476 of FIG. 4 has been transferred to a component of the external equipment 7 of FIG. 1 . The reset signal will clear the event memory 476 (step 499 ) and restart the main program 450 at step 451 .
If no reset signal is received in L 6 hours, then the alarm subroutine 490 returns to step 451 of FIG. 5 and the cardiosaver 5 will once again begin processing electrogram segments to detect a cardiac event. If another event is then detected, the section of event memory 476 used for saving post-event electrogram data would be overwritten with the pre-event electrogram data from the new event. This process will continue until all event memory is used. I.e. it is more important to see the electrogram data leading up to an event than the data following detection.
FIG. 9 illustrates the function of the hi/low heart rate subroutine 420 . The hi/low heart rate subroutine is meant to run when the patient's heart rate is below the normal range (e.g. 50 to 80 beats per minute) or above the elevated range that can occur during exercise (e.g. 80 to 140 beats per minute). A low heart rate (bradycardia) may indicate the need for a pacemaker and should prompt a “SEE DOCTOR” warning to the patient if it does not go away after a programmed period of time. Very high heart rate can be indicative of tachycardia or ventricular fibrillation and is serious if it does not quickly go away and should warrant a major event alarm like a detected AMI.
The hi/low heart rate subroutine 420 begins with step 421 where the electrogram segment of Y seconds collected in steps 453 and 454 of FIG. 5 is saved to the event memory 476 (step 421 ) because the patient's doctor may wish to know that the high or low heart rate occurred. Once the Y second long electrogram segment is saved, step 422 of the hi/low heart rate subroutine 420 directs the processing in different directions depending on if the heart rate is too high, too low or unsteady. If unsteady, the unsteady heart rate subroutine 410 illustrated in FIG. 12 is run. If it is too high, step 423 increments the event counter k by 1, then step 424 checks whether the event counter k is equal to 3. Although this embodiment uses k=3 events as the trigger to run the alarm subroutine 490 it is envisioned that k=1 or 2 or k values higher than 3 can also be used.
In step 424 , If k=3 then the alarm subroutine 490 illustrated in FIG. 8 is run. If k less than 3 then in step 425 the hi/low heart rate subroutine 420 waits for “B” seconds and checks again in step 426 if the heart rate is still too high. If the heart rate is still too high, the hi/low heart rate subroutine 420 returns to step 423 where the event counter is incremented by 1. If the heart rate remains high, the hi/low heart rate subroutine 420 will loop until k is equal to 3 and the alarm subroutine 490 is run. If the heart rate does not remain high in step 426 , the hi/low heart rate subroutine 420 will return to step 453 of the main heart signal processing program 450 illustrated in FIG. 5 . ST shift amplitude is not checked during the high heart rate section of the hi/low heart rate subroutine 420 as the presence of a very high heart rate could alter the detection of changes in ST and PQ segments of the electrogram giving false indications. Very high heart rate is, by itself, extremely dangerous to the patient and is therefore a major cardiac event.
If in step 422 , the heart rate is too low rather than too high, the hi/low heart rate subroutine 420 will proceed to step 431 where the Y second long electrogram segment is checked for an excessive ST shift in the same way as step 457 of the main heart signal processing program 450 illustrated in FIG. 5 . In other words, the ST deviation on M out of N beats must be shifted at least H ST (i) from the baseline average ST deviation ΔV BASE (i) of the i'th baseline electrogram segment. If there is a detected excessive ST shift in step 431 , the hi/low heart rate subroutine 420 returns to run the ST shift verification subroutine 460 illustrated in FIG. 5 .
If there is not an excessive ST shift detected in step 431 , step 432 causes the hi/low heart rate subroutine 420 in step 432 to wait for “C” seconds then buffer and save a new Y second long electrogram segment as in steps 453 and 454 of the main heart signal processing program 450 of FIG. 5 . Once the new Y second long electrogram segment is collected, the hi/low heart rate subroutine 420 checks in step 433 if the heart rate is still too low. If it is no longer too low, the system returns to step 455 of the main heart signal processing program 450 illustrated in FIG. 5 . If the heart rate remains too low, then step 434 checks for an excessive ST shift. If there is an excessive ST shift in step 434 , the hi/low heart rate subroutine 420 returns to run the ST shift verification subroutine 460 of FIG. 5 . If there is not an excessive ST shift detected in step 434 , step 435 causes the hi/low heart rate subroutine 420 in step 435 to wait for another “C” seconds then buffer and save another Y second long electrogram segment as in steps 453 and 454 of the main heart signal processing program 450 of FIG. 5 . Once this Y second long electrogram segment is collected, the hi/low heart rate subroutine 420 checks in step 436 if the heart rate is still too low (for the 3 rd time). If it is no longer too low, the system returns to step 455 of the main heart signal processing program 450 of FIG. 5 . If the heart rate remains too low, then step 437 checks for an excessive ST shift. If there is an excessive ST shift in step 437 , the hi/low heart rate subroutine 420 returns to run the ST shift verification subroutine 460 of FIG. 5 . If there is not an excessive ST shift detected in step 437 , the step 438 saves the contents of the most recently collected Y second long electrogram segment and the to the event memory 476 for later review by the patient's doctor.
If the hi/low heart rate subroutine 420 reaches step 438 then the patient's heart rate has been too low even after two waits of “C” seconds. Now the hi/low heart rate subroutine 420 proceeds to step 427 to turn on the internal “SEE DOCTOR” alarm signal. Step 427 also sends out to the external alarm system 60 of FIG. 1, a signal to activate the “SEE DOCTOR” alarm signal of the external alarm system 60 that may include a text or played speech message indicating the cause of the alarm. E.G. the external alarm system speaker 57 of FIG. 1 could emit warning tones and a text message could be displayed or the speaker 57 might emit a spoken warning message to the patient.
Note that during the checking for continued low heart rate, ST shift amplitudes are still checked after each wait because it is well known that low heart rate can be a byproduct of an acute myocardial infarction.
Finally in step 428 , the hi/low heart rate subroutine 420 will keep the “SEE DOCTOR” alarm signal turned on for L 4 minutes or until receipt of a signal from the external alarm system 60 to turn off the alarm signal. After the “SEE DOCTOR alarm signal is enabled, the low heart rate limit, below which the hi/low heart rate subroutine 420 is run, is changed by step 429 to be just below the average heart rate measured in step 436 . Once the patient is warned to go see the doctor, additional warnings will be annoying and therefore the low rate limit is best changed. This allows the hi/low heart rate subroutine 420 to then return to step 452 of the main program where it will continue to monitor ST shift amplitudes to provide early detection of acute myocardial infarction. Actual programming of the cardiosaver 5 may use R—R interval instead of heart rate and it is understood that either is sufficient and one can be easily computed from the other.
FIG. 10 illustrates the ischemia subroutine 480 that provides decision making for the cardiosaver 5 in the event of an elevated heart rate such as that would occur during exercise by the patient. The ischemia subroutine 480 uses a beat counter j to indicate the beat within a Y second long electrogram segment. A beat is defined as a sub-segment containing exactly one R wave of the Y second long electrogram segment. The ischemia subroutine 480 begins in step 481 by initializing the beat counter j to a value of 2. Then in step 482 , the R—R interval range A for the beat j is determined. For example that there could be between 4 R—R interval ranges A=1 to 4 of 750 to 670, 670 to 600, 600 to 500 and 500 to 430 milliseconds respectively. These would correspond to heart rate intervals of 80 to 90, 90 to 100, 100 to 120 and 120 to 140 beats per minute. The number of ranges A and the upper and lower limit of each range would be programmable by the patient's physician from the programmer 68 of FIG. 1 .
Next in step 483 the programmed ischemia multiplier μ(A) is retrieved from the programmable parameters 471 of FIG. 4 . μ(A) is the allowable factor increase or decrease in ST shift detection threshold for the R—R interval range A. In other words, because the patient may have some ischemia during elevated heart rates from exercise, the patient's physician can program μ(A)s that are greater than 1 and might increase with each successive heart rate range. For example, if the R—R interval ranges are 750 to 670, 670 to 600, 600 to 500 and 500 to 430 milliseconds the corresponding μ(A)s might be 1.1, 1.2, 1.3 and 1.5. This would require that the ST shift in the R—R interval range of A=4 (500 to 430 milliseconds) be one and a half times as large as during normal heart rates in order to qualify as a cardiac event. It is envisioned that the patient could undergo an exercise stress test at a time after implant when the implanted leads have healed into the wall of the heart and electrogram segments captured by the cardiosaver 5 during that stress test would be reviewed by the patient's physician to determine the appropriate range intervals and ischemia multipliers to help identify a worsening of the patient's exercise induced ischemia from the time when the stress test is conducted.
It is also envisioned that in order to detect smaller changes in vessel narrowing than a full acute myocardial infarction, the cardiosaver 5 of FIGS. 1-4 might use μ(A)s that are less than one. For example, if the R—R interval ranges are 750 to 670, 670 to 600, 600 to 500 and 500 to 430 milliseconds the corresponding μ(A)s might be 0.5, 0.6, 0.7 and 0.8. Thus in this example, in the R—R interval range of 750 to 670 milliseconds, the threshold for ischemia detection would be half of what it is for the normal heart rate range.
Once the ischemia multiplier has been retrieved, step 484 calculates the ischemia ST shift threshold θ(A) for the R—R interval range A where θ(A)=H ST (i)×μ(A) where H ST (i) is the current ST shift threshold for normal heart rates. Next in step 485 , the ischemia subroutine 480 checks if for the beat j the ST shift is greater than the ischemia threshold θ(A). If it is not greater, step 487 then checks if the N'th beat has been examined. If the ST shift of the j'th beat exceeds the ischemia threshold θ(A) then step 486 checks if M beats with ST shifts greater than θ(A) have been seen. If they have not been seen proceed to step 487 . If in step 487 , the Nth beat has been examined, return to step 451 of the main heart signal processing program 450 of FIG. 5 . If N beats have not yet been examined, increment j by 1 in step 489 and loop back to step 482 .
If M beats with excessive ST shift are found by step 486 , step 581 saves the current Y second long electrogram segment to the Event Memory 476 , then in step 582 the event counter k is incremented by 1 followed by step 583 checking if k is equal to 3. If k is less than 3 then the ischemia subroutine 480 continues by sleeping for Z seconds in step 584 , then buffering a new Y second long electrogram segment in step 585 , saving in step 586 the new Y second long electrogram segment to the next location in recent electrogram memory 472 of FIG. 4 . and then checking if the heart rate is still elevated in step 587 . If the heart rate is still elevated in step 587 , the loop checking for ischemia is run again starting with step 481 . If the heart rate is no longer elevated then step 588 checks if the heart rate is too high, too low or unsteady. If such is the case, the hi/low heart rate subroutine 420 is run. If the heart rate is not high, low or unsteady, the ischemia subroutine 480 ends and the program returns to step 469 of the ST shift verification subroutine 460 of FIG. 5 . This will allow an excessive ST shift detected at elevated heart rate that stays shifted when the heart rate returns to normal to quickly trigger the AMI alarm. This works because k is either 1 or 2 at this point so either 2 or 1 more detection of excessive ST shift with normal heart rate will cause a major event AMI alarm. If however k=3 in step 582 , then the last detection of excessive ST shift occurred during an elevated heart rate and will be treated as exercise induced ischemia rather than an acute myocardial infarction.
So if k=3 (i.e. exercise induced ischemia has been detected) in step 582 the ischemia subroutine 480 moves on to step 681 where it checks if it has been more than L 5 minutes since the first time that exercise induced ischemia was detected where k=3 in step 583 .
If it has been less than L 5 minutes since the first detection of exercise induced ischemia then the internal SEE DOCTOR alarm signal is turned on by step 682 if it has not already been activated. If it has been more than L 5 minutes, then the alarm subroutine 490 is run. This will change the SEE DOCTOR alarm signal previously started in step 682 to a major event AMI alarm if the excessive ST shift at an elevated heart rate does not go away within L 5 minutes. Similarly, if the patient stops exercising and his heart rate returns to normal but the excessive ST shift remains, then the alarm subroutine 490 will also be run.
If it has been less than L 5 minutes and the SEE DOCTOR alarm signal has not been already been activated, step 683 next sends a message to the external alarm system 60 of FIG. 1 to activate the SEE DOCTOR external alarm signal and indicate to the patient by a text of spoken message that he should stop whatever he is doing, and sit or lie down to get his heart rate to return to normal. Following this, in step 684 the ischemia subroutine 480 will keep the SEE DOCTOR alarm signal on for L 4 minutes from the first time it is turned on or until the receipt of an off signal from the alarm disable button 59 of the external alarm system 60 of FIG. 1 . The program then returns to step 451 of the main program 451 of FIG. 5 to continue to examine the patient's heart signals.
FIG. 11 diagrams the alarm conditions 600 that are examples of the combinations of major and minor events that can trigger an internal alarm signal (and/or external alarm signal for the guardian system of FIG. 1 . Box 610 shows the combinations 611 through 617 of major cardiac events that can cause the alarm subroutine 490 to be run. These include the following:
611 . 3 ST shift events (detections of excessive ST shift) with either a normal heart rate or a low heart rate.
612 . 2 ST shift events with a normal or low heart rate and 1 event from heart rate too high.
613 . 1 ST shift event with a normal or low heart rate and 2 events from heart rate too high.
614 . 3 events from heart rate too high.
615 . 3 ST shift events with either a normal, low or elevated heart rate (ischemia) where the last detection is at a normal or low heart rate.
616 . 3 events (excessive ST shift or high heart rate) where the last event is high heart rate.
617 . An ischemia alarm indication from conditions in box 620 that remains for more than L 5 minutes after the first detection of ischemia.
The ischemia alarm conditions 620 include:
621 . 3 ST shift events with either a normal, low or elevated heart rate (ischemia) where the last detection is at an elevated heart rate.
622 . Any 3 events including a too high heart rate event where the last detection is an excessive ST shift at an elevated heart rate.
If either of the ischemia alarm conditions 620 is met and it is less than L 5 minutes since the exercise induced ischemia was first detected, then the SEE DOCTOR alarm signal will be turned on by step 682 of the ischemia subroutine 480 if it has not already been activated.
Box 630 shows the other minor event alarm conditions including the bradycardia alarm condition 632 that is three successive electrogram segments collected with heart rate too low and the unsteady heart rate alarm condition 635 that is caused by more than P unsteady % of beats having a too short R—R interval. These will trigger the SEE DOCTOR alarm signal initiated by step 427 of the hi/low heart rate subroutine 420 for the bradycardia alarm condition 632 and step 416 of the unsteady hart rate subroutine 410 for the unsteady heart rate alarm condition 635 . Also triggering the SEE DOCTOR alarm signal is a low battery condition 636 .
FIG. 12 is a block diagram illustrating the unsteady heart rate subroutine 410 . The subroutine 410 is run if the R—R interval varies greatly over many of the beats in the Y second long electrogram segment collected by steps 453 and 454 of the main heart signal processing program 450 . As previously described, one technique for identifying such an unsteady heart rate is to compare the two shortest R—R intervals and the 2 longest intervals. If the difference between the both of the two shortest and the average of the two longest R—R intervals are more than a programmed percentage α, an unsteady heart rate is identified. For example the programmed percentage a might be 25% so that if the two shortest R—R intervals are each more than 25% less than the average of the two longest R—R intervals, then the heart rate is unsteady. It is envisioned that if a longer time Y is used for electrogram segment collection then it might require 3 or more “short” beats to indicated an unsteady heart rate. If there is zero or one short beat, the main heart signal processing program 450 will move on to step 456 having marked all of the “normal” beats in the Y second long electrogram segment. A normal beat is defined as a beat including where the R—R intervals before and after the R wave are both in the normal range (i.e. not too short).
The unsteady heart rate subroutine 410 begins in step 411 by checking for at least N normal beats in the most recently collected electrogram data. When the subroutine begins there is only one Y second long electrogram segment being examined. If there are not N normal beats, then an additional Y second long electrogram segment is collected in step 412 . Step 411 then will check for N normal beats in the two Y second long electrogram segments (i.e. 2Y seconds of electrogram data). This loop of steps 411 and 412 , where each time Y additional seconds of electrogram is collected, will continue until N normal beats are found.
It is envisioned that step 411 could also check for beats with elevated heart rate R—R intervals or might include elevated heart rate beats as “normal” beats by expanding the allowed range of the R—R interval for a normal beat. Once N “normal” beats are found by step 411 , then step 413 checks for an excessive ST shift in M out of the N normal beats similar to step 457 of FIG. 5 . Step 413 could also (as in step 457 of FIG. 5) look for an excessive T wave shift. If an excessive ST shift (and/or T wave shift) is detected by step 413 , the program returns to the ST shift verification subroutine 460 of FIG. 5 .
If excessive ST shift (and/or T wave shift) are not detected by step 413 , then step 414 checks if more than P unsteady % of all the beats (not just the normal beats) in the electrogram data collected have a too short R—R interval as defined above by the programmed parameter α. If not the program returns to step 451 of the main heart signal processing program 450 of FIG. 5 . If, however, more than P unsteady % of the beats have a short R—R intervals, then step 415 saves all the current electrogram data to event memory 476 of FIG. 4 and step 416 turns on the SEE DOCTOR alarm signal with the internal alarm sub-system 48 of FIG. 4 and also initiates an external alarm signal by the external alarm system 60 of FIG. 1 with a text or spoken message to the patient indicating that the SEE DOCTOR alarm signal is the result of detection of unsteady heart rate. As in the case of other SEE DOCTOR alarm signals, step 417 will keep the “See Doctor” alarm mechanism turned on for L 4 minutes or until receipt of a signal from the external alarm system 60 to turn off the alarm.
FIG. 13 shows a modified embodiment of the guardian system 510 . The cardiosaver implant 505 with lead 512 , electrode 514 , antenna 516 , header 520 and metal case 511 would be implanted subcutaneously in a patient at risk of having a serious cardiac event such as an acute myocardial infarction. The lead 512 could be placed either subcutaneously or into the patient's heart. The case 511 would act as the indifferent electrode. The system 510 also included external equipment that includes a physician's programmer 510 an external alarm transceiver 560 and a pocket PC 540 with charger 566 . The external alarm transceiver 560 has its own battery 561 and includes an alarm disable button 562 radiofrequency transceiver 563 , speaker 564 antenna 565 and standard interface card 552 . The cardiosaver 505 has the same capabilities as the cardiosaver 5 of FIGS. 1 through 4.
The standardized interface card 552 of the external alarm transceiver 510 can be inserted into a standardized interface card slot in a handheld or laptop computer. The pocket PC 540 is such a handheld computer. The physician's programmer 510 is typically a laptop computer. Such standardized card slots include compact flash card slots, PCMCIA adapter (PC adapter) card slots, memory stick card slots, Secure Digital (SD) card slots and Multi-Media card slots. The external alarm transceiver 510 is designed to operate by itself as a self-contained external alarm system, however when inserted into the standardized card slot in the pocket PC 540 , the combination forms an external alarm system with enhanced functionality. For example, in stand alone mode without the pocket PC 540 , the external alarm transceiver 560 can receive alarm notifications from the cardiosaver implant 505 and can produce an external alarm signal by generating one or more sounds through the speaker 564 . These sounds can wake the patient up or provide additional alerting to that provided by the internal alarm signal generated by the cardiosaver 505 . The alarm disable button 562 can acknowledge and turn off both external and internal alarm signals. The standalone external alarm transceiver 560 therefore provides key functionality could be small enough to wear on a chain around the neck or on a belt.
When plugged into the pocket PC 540 , the external alarm transceiver 560 can facilitate the display of text messages to the patient and electrogram data that is transmitted from the cardiosaver 505 . The pocket PC 540 also enables the patient operated initiator 55 and panic button 52 capabilities of the external alarm system 60 of FIG. 1 . Being a pocket PC also readily allows connection to wireless communication capabilities such as wireless internet access that will facilitate retransmission of data to a medical practitioner at a geographically remote location. It is also envisioned that the charger 566 could recharge the batter 551 when the external alarm adaptor 560 is plugged into the pocket PC 540 .
The external alarm transceiver 560 can also serve as the wireless two-way communications interface between the cardiosaver 505 and the programmer 510 . The physician's programmer 510 is typically a laptop computer running some version of the Microsoft Windows operating system. As such, any or the above standardized slot interfaces can be either directly interfaced to such a laptop computer or interfaced using a readily available conversion adaptor. For example, almost all laptop computers have a PCMCIA slot and PCMCIA card adaptors are available for compact flash cards, Secure Digital cards etc. Thus the external alarm adaptor 560 could provide the interface to the physician's programmer 510 . This provides additional security as each cardiosaver implant 505 and external alarm adaptor 560 could be uniquely paired with built in security codes so that to program the implant 505 , the physician would need the patient's external alarm adaptor 560 that would act both as a wireless transceiver and as a security key.
Although the guardian system 10 as described herein could clearly operate as a stand-alone system, it is clearly conceivable to utilize the guardian system 10 with additional pacemaker or implanted defibrillator circuitry. As shown in FIG. 4, pacemaker circuitry 170 and/or defibrillator circuitry 180 could be made part of any cardiosaver 5 or 505 . Furthermore, two separate devices (one pacemaker or one defibrillator plus one cardiosaver 5 ) could be implanted within the same patient.
FIG. 14 illustrates a preferred physical embodiment of the external alarm transceiver 560 having standardized interface card 552 , alarm disable button 562 labeled “ALARM OFF” and speaker 564 . It is also envisioned that by depressing and holding the alarm disable button 562 for a minimum length of time, when there is not an alarm, the external alarm transceiver could verify the operational status of the cardiosaver 505 and emit a confirming sound from the speaker 564 .
FIG. 15 illustrates the physical embodiment of the combined external alarm transceiver 560 and pocket PC 540 where the standardized interface card 552 has been inserted into a matching standardized interface card slot the pocket PC 540 . The screen 542 of the pocket PC 540 shows an example of the display produced by an external alarm system following the detection of an acute myocardial infarction by the cardiosaver 505 . The screen 542 of FIG. 15 displays the time of the alarm, the recent electrogram segment from which the cardiac event was detected and the baseline electrogram segment used for comparison in the cardiac event detection. Such a display would greatly facilitate diagnosis of the patient's condition upon arrival at an emergency room and could eliminate the need for additional electrocardiogram measurements before the patient is treated.
Although throughout this specification all patients have been referred to in the masculine gender, it is of course understood that patients could be male or female. Furthermore, although the only electrogram indications for an acute myocardial infarction that are discussed herein are shifts involving the ST segment and T wave height, it should be understood that other changes in the electrogram (depending on where in the heart the occlusion has occurred and where the electrodes are placed) could also be used to determine that an acute myocardial infarction is occurring. Furthermore, sensors such as heart motion sensors, or devices to measure pressure, pO 2 or any other indication of an acute myocardial infarction or cardiac events could be used independently or in conjunction with a ST segment or T wave shift detectors to sense a cardiac event.
It is also envisioned that all of the processing techniques described herein for an implantable cardiosaver are applicable to a guardian system configuration using skin surface electrodes and a non-implanted cardiosaver 5 the term electrogram would be replaced by the term electrocardiogram. Thus the cardiosaver device described in FIGS. 5 through 12 would also function as a monitoring device that is completely external to the patient.
Various other modifications, adaptations, and alternative designs are of course possible in light of the above teachings. Therefore, it should be understood at this time that, within the scope of the appended claims, the invention can be practiced otherwise than as specifically described herein. | 1a
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This application is a continuation-in-part of U.S. Pat. application No. 08/994,500 filed Dec. 24, 1997 now abandoned.
FIELD OF THE INVENTION
The present invention relates to an insole for a shoe. In particular, the present invention relates to an insole device that can rehabilitate a foot by stimulating a proprioceptive response in the wearer's foot.
BACKGROUND OF THE INVENTION
Professionals dealing with gait related pathologies generally accept that a large majority of persons will, at some time in their lives, suffer some form of gait related pain or dysfunction. It is well accepted that, in the majority of case, the mechanism underlying the pathology, injury, or dysfunction is biomechanically related to the interface between the foot and the ground, during the support phase of the gait cycle.
It has been proposed that providing a device to create a proprioceptive, or internal, feedback stimulus to a wearer's foot can directly target the underlying pathology, injury or dysfunction. Such a device is disclosed in U.S. Pat. No. 5,404,659 to Burk et al. As disclosed in U.S. Pat. No. 5,404,659, an arch rehabilitative catalyst stimulates the Golgi tendon organ, which in turn, stimulates the musculoskeletal structure of the foot to rehabilitate the foot structure. The catalyst is an asymmetrically domed hump, which creates a mild to strong discomfort to initially stimulate the Golgi tendon organ.
However, it has been found that the device disclosed in U.S. Pat. No. 5,404,659 does not function as described, and that the majority of wearers find the device too uncomfortable to use. In particular, when subjected to conventional vertical compressive forces of a person walking in the range of 2.5 times body weight, the device is designed to deflect between 40% and 60% of its maximum height, and when subject to only one times a person's weight, there should be no deflection. Rather than stimulate the Golgi tendon organ to create a proprioceptive response, deflections in this range can cause sever pain to a wearer, as there is insufficient give, and the wearer is always aware of the presence of the device. In addition, as disclosed in U.S. Pat. No. 5,504,659, the device has an ideal apex height of 5.25% to 7.6% of the total foot length. A device build according to these dimensions results in an overly high arch height, and can cause severe discomfort, and possible injury, to a wearer. It is further disclosed that the absolute, non-weight bearing height of the device should be the same regardless of body weight and arch height. This is clearly wrong, since different wearers will have different comfort thresholds and arch heights.
In general, the device disclosed in U.S. Pat. No. 5,404,659 does not function as described. Wearers would find the device too hard to use successfully, and rather than stimulating a proprioceptive response, the device would cause pain and discomfort at each step. The pain engendered in the foot of a wearer would, in fact, cause the wearer to limit the pressure applied to the foot to avoid the discomfort, rather than exercising the foot by creating an imperceptible stimulation as it is stated goal.
SUMMARY OF THE INVENTION
The present invention provides a shoe insole or midsole units that utilize proprioceptive feedback mechanisms in the human body to increase the structural integrity of the human foot. The improvements will introduce provisions allowing the arch rehabilitative catalyst to be consistently located at the desired anatomical location as well as to ease the interaction of the arch rehabilitative catalyst and the wearer. Improvements will also be presented to provide an increased longevity of the arch rehabilitative catalyst, as well to provide a gradual multi-directional interfacing with the arch rehabilitative catalyst.
According to one aspect of the invention there is provided an improved arch rehabilitative catalyst. In another aspect of the invention there is provided an improved ease of inter-changing of the arch rehabilitative catalyst. In another aspect of the invention there is provided designs and systems which improve the longevity of the rebound, deflection and compression characteristics of the arch rehabilitative catalyst by introducing a mechanical device. In another aspect of the invention there is provided an improved mechanism allowing gradual multi-directional introduction of the arch rehabilitative catalyst to the plantar aspect of the foot.
According to other aspects of the invention there are provided a number of designs for maintaining the proper location of the arch rehabilitative catalyst through the introduction of geometric cavities and matching insertable resilient members with the presence of vertical sidewall interaction. Provisions to the design of these geometric cavities and matching insertable devices will be shown as a system to allow for ease of inter-changing of the arch rehabilitative catalyst support.
According to yet another aspect of the invention there is provided a tapered heel skive allowing for medial to lateral, as well as anterior to posterior gradual body weight acceptance onto the arch rehabilitative catalyst to increase the comfort of the invention.
DESCRIPTION OF THE DRAWINGS
Preferred embodiments of the present invention will now be described, by way of example only, by reference to the attached drawings, in which:
FIG. 1 is a medial sagittal view of an insole showing the location of an arch rehabilitative catalyst relative to foot placement on the insole or midsole;
FIG. 2 is a dorsal view of an insole showing the location of an arch rehabilitative catalyst relative to foot placement;
FIG. 3 is perspective view of a cantilever spring device of the present invention showing an undercarriage and positioning apertures;
FIG. 4 is a sagittal plane cross-sectional view of the insole or midsole and the cantilever spring device of FIG. 3, through section A-A′ of FIG.2;
FIG. 5 is a perspective view of an alternative embodiment of the cantilever spring device of the present invention to be designed into the undercarriage;
FIG. 6 is a perspective view of another embodiment utilizing a domed shape coil spring device of the present invention showing an undercarriage and positioning apertures;
FIG. 7 is a frontal plane cross-sectional view of further embodiment of a domed shaped coil spring device of the present invention through section B-B′ of FIG. 6;
FIGS. 8 a and 8 b are frontal and sagittal plane cross sectional views of the insole or midsole through sections A-A′ and B-B ′ of FIG. 2 showing the positioning of a rectangular receptacle cavity in the area of the arch rehabilitative catalyst, respectively;
FIG. 9 is a plantar aspect view of the arch rehabilitative catalyst and the rectangular receptacle cavity in the arch rehabilitative catalyst shown in FIGS. 8 a and 8 b;
FIG. 10 is a perspective view of an insert that can be inserted into the rectangular receptacle cavity in the arch rehabilitative catalyst;
FIGS. 11 a and 11 b are frontal and sagittal plane view of further embodiment of the insole or midsole through sections A-A′ and B-B′ of FIG. 2 showing the positioning of a rectangular pyramidal receptacle cavity in the arch rehabilitative catalyst;
FIG. 12 is a plantar aspect view of the arch rehabilitative catalyst and the rectangular pyramidal receptacle cavity in the arch rehabilitative catalyst shown in FIGS 11 a and 11 b;
FIG. 13 a perspective view of an insert that can be inserted into the rectangular pyramidal receptacle cavity in the arch rehabilitative catalyst;
FIGS. 14 a and 14 b are frontal and sagittal plane views of another embodiment of an insole through sections A-A′ and b-B′ showing the positioning of a rectangular receptacle cavity with curvilinear ends in the arch rehabilitative catalyst;
FIG. 15 a plantar aspect view of the arch rehabilitative catalyst and the rectangular receptacle cavity with curvilinear ends in the arch rehabilitative catalyst shown in FIGS. 14 a and 14 b;
FIG. 16 is a perspective view of an insert that can be inserted into the rectangular receptacle cavity with curvilinear ends in the arch rehabilitative catalyst shown in FIGS. 14 a and 14 b;
FIG. 17 a perspective view of further embodiment of a domed shaped insert with positioning and security ribs on its dorsal aspect;
FIG. 18 is a frontal cross-sectional view of the arch rehabilitative catalyst and insole or midsole through section B-B′ of FIG. 2 showing the domed shaped insert with 2 positioning and security ribs of FIG. 17;
FIG. 19 a frontal cross-sectional view of another embodiment of a arch rehabilitative catalyst and insole or midsole through section B-B′ of FIG. 2 showing the domed shaped insert with a singular positioning and security rib;
FIG. 20 a medial sagittal view of another embodiment the invention showing the location of the arch rehabilitative catalyst relative to foot placement on the insole or midsole and the posterior heel skive;
FIG. 21 view of the heel region of the insole or midsole device illustrating the location and characteristics of the tapered heel skive as shown in FIG. 20;
FIG. 22 a frontal plane cross sectional view through section C-C′ of FIG. 21 showing the geometric characteristics of the posterior heel skive;
FIGS. 23 a and 23 b are frontal and sagittal plane views of further embodiment of the insole or midsole of the invention through sections A-A′ and B-B ′ of FIG. 2 showing the positioning of a rectangular receptacle cavity in the arch rehabilitative catalyst with the cavity displaying a combination of vertical sidewalls and tapered sidewalls.
DETAILED DESCRIPTION
Referring to FIGS. 1 and 2, an insole or midsole device 1 is shown. Device 1 has a dorsal surface contacting the underside of a foot. A proprioceptive catalyst 4 is located in the midsection of device 1 , substantially aligned with the apex of the foot's arch system. The apex of the arch system is shown at the target area “A” shown in FIGS. 1 and 2, and is defined as the intersection of the navicular 5 , lateral cuneiform 6 , and the cuboid 7 bones, or slightly medial thereof. As will be understood by those of skill in the art, a wearer's foot comprises the bones of the foot, interconnected by ligaments. A layer of muscle is attached to the bones by tendons, and covered by a thick layer of fat tissue which is finally covered by a layer of skin.
The proprioceptive catalyst 4 has an area and perimeter 9 defined by an anterior arc, a posterior arc, a medial arc, and a lateral arc. Preferably, the anterior are has its maximum point lateral to the 2 nd metatarsal and medial to the 3 rd metatarsal, and does not extend in an anterior direction more that 70% of the total foot length, nor less than 60%; the posterior arc has its maximum point medial to the literal tubercle of the calcancus and lateral to the medial tubercle, and does not extent in a posterior direction at any point less that 15% of the foot's total length or greater that 25% of the foot's total length; the medial and lateral arcs do not exceed the medial and lateral boundaries created by the foot itself; and the proprioceptive catalyst 4 is entirely within the periphery set by the metatarsal heads, calcaneus, and lateral and medial borders of the foot.
Proprioceptive catalyst 4 is an asymmetric dome with its apex aligned with target area “A”, as described above, when viewed from where a sagittal plane. The height the catalyst 4 at the apex should ensure that, when a user is at rest, target area “A” is at a height between 5.28% and 7.6% of the foot's total length. The present inventor has found that this corresponds to an actual catalyst height of in the range of 1% to 5% of the foot's length, with an ideal ration of approximately 3.6% of a wearer's foot length.
Preferably, catalyst 4 should be manufactured in such a fashion, and of such a material, that it displays certain preferred compression and rebound characteristics. For example, when the catalyst is subjected to the vertical forces of a person standing at rest, the catalyst will display a deflection between 40% and 100% of its maximum height.
A first embodiment of the present invention is shown in FIGS. 3 and 7. Referring to FIG. 3 and 4, the device 1 interfaces with an undercarriage 11 from a sagittal plane view through section A-A′. Undercarriage 11 has a heel region 3 and midfoot region 10 . The midfoot region 10 defines a catalyst 4 supported by a resilient member in the form of a doomed cantilever spring device 12 . Cantilever legs 13 flex and compress into voids 14 , thereby allowing compression of the the legs 13 without the legs 13 interfering with each other during compression. The apex 8 of the catalyst, in the form of a cantilever spring device 12 provides a positioning aperture 17 aligned with a positioning pion 18 in the device 1 . Positioning apertures 15 are also aligned with positioning pins 16 of the device 1 to ensure the proper placement and maintenance of placement of the catalyst 4 and its apex 8 . Vertical side walls 23 of the positioning pins 16 and the positioning apertures 15 act to prevent anterior/posterior and medial/lateral shifting of the inserted mechanism as provided in FIGS. 3, 4 , 5 and 6 . The apertures 15 and corresponding placement pins 16 can be located at any location on the device 1 and the undercarriage 11 as seen fit by design and functionality. Differences in body weight, activity and foot type can be compensated for by the selection of materials for fabrication of the undercarriage 11 and the cantilever spring device 12 , or the thickness of the undercarriage 11 and the cantilever spring device 12 . The undercarriage 11 and the cantilever spring device 12 can be formed through injection moulding or vacuum forming and stamping. Polymers such as Delrin, Hytrel and Zytel from E.I. DuPont, PVC, Pebax or layered fabric and resin combinations such as fiberglass or graphite can provide the desired physical and material properties.
An advantage of device 1 is the high flex fatigue characteristics of the materials of choice. This will enable the device 1 , and in particular the catalyst 4 , to be used for much longer periods of time than that disclosed in other shoe insole or midsole units that utilize proprioceptive feedback mechanisms in the human body to increase the structural integrity of the human foot. The desire regulation of the vertical maximum distance from the supporting surface of the device 1 to the apex 8 of the catalyst 4 occurs as forces are applied vertically to the cantilever mechanism at is apex 8 .
FIG. 5 illustrates an alternative design to the cantilever spring device 12 where the legs 13 of the cantilever spring device 12 deflect and move away from the centre region. A rear finger 20 on the spring device 12 in FIG. 5 can be molded as an integral part of the undercarriage 11 or permanently affixed to an undercarriage 11 . Each leg 13 of the cantilever spring device 12 has a foot 19 that permits it to smoothly elongate without becoming obstructed by friction between the lower surface of the foot 19 and the layer of the inside of the shoe with which ii is in contact. This embodiment as illustrate in FIG. 5, also incorporates positioning pins 18 and 16 , and positioning apertures 15 and 17 and their inherent vertical sidewalls 23 to ensure the proper placement of the catalyst 4 and its apex 8 which maintains the catalyst in its position.
FIG. 6 shows a further configuration for the resilient member supporting catalyst 4 of the present invention. It involves the incorporation of a coiled spring device 21 to be aligned to the target area of the apex 8 of the foot's arch system as defined and to be affixed to or designed as an integral part of the undercarriage 11 . This is illustrated in FIG. 6 where a perspective view of the coied spring device 21 is shown. Again the incorporation of positioning pins 16 and the positioning apertures 15 and the vertical sidewalls 23 created therein prevent any medial/lateral and anterior/posterior shifting of the mechanism and ensure its proper placement.
It is believed that the specific characteristics that are desired the cantilever spring mechanisms of the present invention can be attained in at least two different ways. The first of these is to use the design, particularly the design characteristics of the legs 13 as a constant, and adopt different grades of the aforementioned polymers, or similar. The calculation of the vertical force being applied and the use of trigonometry will allow the simple calculation of the force vector representing that going down the legs 13 , and this can be used to determine the desired polymer, or grade of polymer, based on its flex modulus: F=(KX); where F is the force being applied vertically at the apex 8 , K is the spring constant which can be provided through the flex modulus, and X is the distance that the spring changes in length, in this case the difference between the resting height “H+X” and the height “H” when the cantilever is compressed through the application of a vertical force applied at the target area.
The second method of attaining the desired rebound and compression characteristics would be to hold the polymer of choice as a constant and alter the thickness of the legs 13 as shown in FIGS. 3, 4 and 5 . The use of the flex modulus information, relative to material thickness, will be able to provide the necessary information as to determine the ideal material thickness. The benefit of this, is its ability to provide a variable deflection rate. That is the cantilever mechanism 12 can be designed to react equally efficiently when subjected to varying forces through varying thickness of the legs 13 . An example of which is the integration of thicker legs 13 if the application is such that it provides an activity or an environmental stress characteristic of greater vertical loading, such as the activity of basketball compared to walking, or 150 kg athlete compared to a 80 kg athlete, both having the same shoe size.
The benefits of the improved rehabilitative catalyst of the present invention are generally threefold. First, the position pins 16 and the positioning apertures 15 and their complimentary vertical sidewalls 23 ensure the proper placement of the catalyst 4 and the maintenance of the placement. Second, by properly integrating a resilient member with the polymers and materials of choice as discussed, the catalyst is capable of showing extremely high durability characteristics. Third, the resilient member can be designed to obtain the desired compression and spring characteristics required for a particular application. The maintenance of these properties is benefical because:
I) The rebound characterisitics ensure that the catalyst 4 will return to its original apex height 8 , thereby ensuring contact with the apex of the foot's arch system. This contact provides a catalyst to stimulate the proprioceptive mechanism necessary for the proper restructuring of the foot's arch systems' musculosketal characteristics.
II) The compression characteristics allow the human foot's arch system to deflect in a natural manner and thereby the human arch system an act as a natural cushioning mechanism. This also prevents any bracing effects from occurring.
III) The compression characteristics allow the human foot arch system to deflect in a natural manner thereby allowing eccentric contractions of the foot's plantar musculature to occur. This regulates the velocity of arch deflection as well as allows the series and parallel spring characteristics of the muscle to store energy and contribute that stored energy to effective propulsion.
In another aspect of the invention it is desirable to redesign the geometric nature of the plantar aspect of the device 1 in the region of the catalyst 4 to facilitate the easy removal and insertion of an appropriately shaped resilent member 26 , as per a few of the options presented in FIGS. 10, 13 , 16 , and 17 , to provide the necessary rebound, compression and deflection traits necessitated by the wearer and to provide vertical walls 25 and 31 thereby ensuring proper positioning of the resilient member 26 and catalyst and to ensure the proper maintenance of the desired position. The insertable resilient member 26 allows for customization of the catalyst in the same manner as discussed with reference to the legs 13 of the spring device. The resilient member 26 can be provided in a variety of foam type materials of a variety of heights, hardnessess and compression sets to address body weight requirements, foot type characteristics, or activity of usage.
Previous inventions have featured a catalyst having a receptacle in the form of a cavity having no vertical walls to ensure proper positioning of the filler object or insert 26 or mechanism and to ensure the proper maintenance of the desired position.
The removal and insertion of resilient members into the aforementioned curvilinear cavity has revealed two shortcomings, the first of these was that when a lower strength adhesive system was used that facilitated the ease of removal and insertion of the resilient member the resilient member was predisposed to shift out of position when subjected to the medial/lateral shearing forces that are characteristic of normal gait. This shifting prevented the resilient member from being maintained in the desired position as outlined.
The second shortcoming was evident when an adhesive system of adequate strength was used to ensure the positional maintenance of the resilient member. The adhesives used proved to display tensile strength properties far in excess of the surrounding devide 1 material and the resilient member. Attempts to dislodge the resilient member for the purpose of inserting a newer resilient member as necessitated by the foot re-structuring initiated by the invention, proved to cause substantial damage to the device 1 material to the extent rendering the device 1 unusable.
FIGS. 8 through 19 reveal options that are available with respect to the redesign of a system that ensures the proper placement of the resislient member 26 , the maintenance of that placement and the easy removal and insertion of the resilient member 26 .
FIGS. 8 thorugh 10 reveal an device 1 , with a forefoot region 2 , a heel region 3 and with an catalyst 4 with a distinct apex 8 , the target area aligned with the anatomical region encompassing the intersection of the navicular 5 , lateral cuneiform 6 , and the cuboid 7 bones. The plantar surface of the device 1 in the region set forth by the boundaries of the caralyst 4 is charcterized by a geometric cavity 24 . The cavity displays vertical walls 25 for resisting medial-lateral shifting of the resilient member 26 and vertical walls 31 for resisting anterior-posterior shifting of the rsilient member 26 . The preferred embodiment as detailed in FIGS. 8 through 10 reveal a geometric cavity 24 of a rectangular nature and a resilient member 26 of a corresponding rectangular nature with vertical side walls 27 designed to engage with the vertical sidewalls 25 and 31 of the cavity 24 .
FIGS. 11 through 13 show a device 1 , with a forefoot region 2 , a heel region 3 and with a catalyst 4 with an apex 8 , the apex aligned witha target area in the foot defined by the anatomical region encompassing the intersection of the navicular 5 , lateral cuneiform 6 , and the cuboid 7 bones. The plantar surface of the deive 1 in the region set forth by the boundaries of the catalyst 4 is characterized by a geometric cavity 24 . The cavity displays vertical walls 25 for engaging with vertical sidewalls 27 of the resilient member 26 for resisting medial-lateral shifting of the filler resilient member 26 and vertical walls 31 for engaging with the vertical sidewalls 27 of the resilient member 26 for resisting anterior-posterior shifting of the resilient member 26 . The preferred embodiment as detailed in FIGS. 11 through 13 reveals a geometric cavity 24 of a pyramidal stacked rectangular nature and a resilient member 26 of a corresponding pyramidal stacked rectangular nature. In reference to this configuration it is possible to have the rectangular layers 30 each as an insatiable filler object or insert layer and therefore each of a different material and/or differing material properties. In this manner the variable rate deflection concept outlined earlier can be attained while maintaining and ensuring the proper positioning of the catalyst 4 , apex 8 and the resilient member 26 . This variable deflection benefit an also be achieved through the method as provided in FIGS. 8 through 10 by allowing the resilient member 26 to be constructed through the application of stacked layers where each layer is capable of displaying individual deflection, compression and reboudn characteristics.
FIGS. 14 through 16 display a geometric configuration consistent with FIGS. 8 through 10 with the exception of the anterior and posterior most ends of the resilient member 26 , and the anterior and posterior walls of the geometric cavity 24 , are curvilinear in nature.
The geometric cavity 24 can also be designed to facilitate the insertion of an appropriately matching shaped resilient member other than of foam type material providing the desired rebound, deflection and rebound characteristics. The resilient member can take the form of a compressive mechanical system such as coil spring devices, bi-value spring devices, cantilever spring devices, or fluid filled structures, including gas filled structures. The resilient member is designed to fill the geometric cavity such that the vertical sidewalls 25 and 31 of the geometric cavity 24 engage the resilient member and ensure the proper permanent placement of the resilient member. The compressive nature of the resilient member can be linear in nature or can provide a vaiable rate of deflection.
FIGS. 17 through 19 illustrate a mechanism allowing a resilient member 26 of similar shape and design as the curvilinear geometric cavity 24 to be inserted into the curvilinear geometric cavity 24 without risk of the resilient member 26 deviating from its desired position. In this aspect of the disclosure apertures 29 are present in the catalyst 4 area of the device 1 which are aligned to receive positiongin and security ribs 28 designed as an integral characteristic of the resilient member 26 . The positioning and security ribs 28 have vertical sidewalls 27 which engage with the vertical sidewalls 25 an 31 of the insole or midsole to prevent any medial-lateral shifting or posterior-anterior shifting of the position of the resilient member 26 .
FIG. 23 reveals a preferred method of ensuring the presence of vertical sidewalls 31 and 25 in the geometric cavity 24 necessary to secure the resilient member 26 and providing an intrinsic cantilever effect. Vertical sidewalls 31 and 25 extend vertically downwardly from a maximum height, a predetermined distance, such that the distance is less than the maximum vertical distance from the inside maximum height of the geometric cavity 24 and the plantar supporting surface of the insole 1 . The lower portion of the geometric cavity 24 is characterized by sidewalls 36 that are tapered. This design further utilizes the material properties of the insole body to provide a futher cantilevler effect as well as allowing a pumping action upon compression capable of circulating air throughout the in-shoe environment.
In another aspect of the invention, device 1 as described, has a heel region 3 comprised of a tapered skive 32 , as shown in FIG. 20, wherein the maximum skive thickness corresponds with the sagittal plane midline of the calaneus and tapers by means of a sagittal angle to a level equal to the maximum thickness of the device 1 at the posterior most part of the device 1 .
In this the tapered 32 serves to reduce the velocity of the foot once it is planted on the ground at heal strike in normal heel to toe ambulation. This functions as a precaution by allowing the foot to be slowly lowered unto the catalyst 4 . In doing so, any risk of impact related injury to the foots arch system is reduced as well as increasing the intial comfort of the device 1 by allowing the pressure application to be more gradual.
The tapered skive provided for in other inventions are sufficiently able to perform effectively during an uni-directional ambulation but was designed such that it was not very effective in reducing the impact velocity when the foot was planted medially or laterally as in multi-directional sports. The purpose of slowly lowering the foot onto the catalyst 4 is still maintained during uni-directional ambulation through the sagittal plane taper created by the slope existing from the anterior most edge 33 and the posterior most edge of the device 1 , and this effect can now also be provided for when the insole or midsole device 1 is used in multi-directional sports by the design addition of the medial skive 34 and the lateral skive 35 . Again this serves to function as a precaution by allowing the foot to be slowly lowered unto the catalyst 4 . In doing so, any risk of impact related injury to the foot's arch system is reduced, as well as increasing the initial comfort of the insole or midsole 1 by allowing the pressure application to be more gradual. A non-symmetric altering of the medial and lateral skive 34 and 35 such that their angulations are different can be desirable for the design and creation of sport specific insole or midsoles.
It is understood that the above embodiments are illustrative of the invention and can be varied or amended with departing from the scope of the invention as defined in the appended claims. | 1a
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The subject invention generally pertains to dental implants and more specifically to a method for adjusting the position of a drill bushing used for installing the implant.
2. Description of Related Art
Various dental implant methods and devices have been developed for replacing one or more missing teeth in a person's jaw with prosthetic teeth. For many prosthetic teeth, a final product comprises three basic components: an implant, an abutment, and a crown. The crown is the exposed portion of the prosthesis that resembles one or more teeth. The implant is an anchor that becomes attached to the jawbone, and the abutment couples the crown to the implant.
To install the implant, a hole is usually drilled into the patient's jawbone, and the implant is inserted into the hole.
A drill bushing attached to a stent can be used to help guide the drill bit, as disclosed in PCT Publication WO 99/26540 and U.S. Pat. Nos. 5,015,183; 5,133,660; 5,718,579. A drill bushing, unfortunately, can be difficult to align in the proper direction.
Although the image of implants have been tilted, translated and otherwise manipulated with respect to an image of a jawbone, such image manipulations fail to show how the orientation of an existing drill bushing may need to be adjusted to achieve a desired drill trajectory.
Thus, a need exists for a better method of aligning a drill bushing to a patient's jawbone.
SUMMARY OF THE INVENTION
To adjust the angular position of a drill bushing used in a dental implant process, it is an object of some embodiments of the invention to adjust a trajectory image of the drill bushing relative to a jaw image of the patient.
Another object of some embodiments is to allow a user to move the trajectory image relative to the jaw image to determine how far the actual drill bushing may need to be tilted.
Another object of some embodiments is to use a computer mouse to move the trajectory image of the drill bushing.
Another object of some embodiments is to use a computer keyboard to move the trajectory image of the drill bushing.
Another object of some embodiments is to use an electronic inclinometer to move the trajectory image of the drill bushing.
Another object of some embodiments to adjust the position of the trajectory image along two dimensional planes that are at right angles to each other.
Another object of some embodiments is to simultaneously adjust the trajectory image and the actual drill bushing, thereby achieving generally instantaneous feedback.
Another object of some embodiments is to use tomography in creating an overall image that depicts the trajectory image and the jaw image.
One or more of these and other objects of the invention are provided by creating an overall image that shows a trajectory of a drill bushing in relation to a patient's jaw, wherein the overall image shows a trajectory image that represents the trajectory of the drill bushing and a jaw image that represents the jaw; and moving the trajectory image relative to the jaw image.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a perspective view of a tomograph system being used to help create at least one overall image of a drill bushing in relation to a patient's jaw.
FIG. 2 is a schematic view that illustrates moving a trajectory image relative to a jaw image.
FIG. 3 is a schematic view similar to FIG. 2 but showing two trajectory images at another position.
DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 shows a tomograph or a series of X-rays being taken of a patient 10 that has a surgical dental stent 12 engaging the patient's jaw. The term, “jaw” refers to that part of a patient's body that comprises one or more of the following: teeth, gums, and/or jawbone (upper or lower). Stent 12 is a conventional surgical dental stent that mates with the patient's jaw and can be produced in various ways that are well known to those skilled in the art. A drill bushing 14 is attached to stent 12 in an area of a missing tooth. Bushing 14 can help guide a drill bit in drilling a hole into the patient's jaw. An implant can then be inserted into the hole and anchored to the jaw.
Bushing 14 is preferably made of a material that can be detected by the X-rays, so at least one overall image 16 a can be created which shows bushing 14 and/or its trajectory (i.e., the bushing's longitudinal centerline) in relation to the patient's jaw 18 as shown in FIGS. 2 and 3 . Overall image 16 a , for example, shows a trajectory image 20 a and a jaw image 22 a that are displayed on a conventional computer monitor 24 controlled by a computer 26 . Trajectory image 20 a represents the trajectory of bushing 14 , and jaw image 22 a represents the patient's jaw. In some cases, monitor 24 also displays a second overall image 16 b where the first overall image 16 a presents a front view of the patient's jaw, and the second overall image 16 b is a side view. Thus, the two views 16 a and 16 b are taken along planes that are intersecting and preferably perpendicular to each other.
The equipment and method for taking a tomographical scan is well known to those skilled in the art. Tomography generally involves creating a computer-generated image from a plurality of X-rays as indicated by lines 15 and 17 . Other terms used for tomography include, but are not limited to, CT scan (computed tomographical scan), EIT (electrical impedance tomography), CAT scan (computerized axial tomography). System 19 is schematically illustrated to represent all types tomography systems. Some examples of system 19 include, but are not limited to a CommCAT IS-2000, Panorex CMT, and a Panorex CMT Plus, all of which are products of Imaging Sciences International, Inc., of Hatfield, Pa.
FIG. 2 shows that the trajectory of bushing 14 is not aimed directly into the patient's jawbone 30 , so trajectory images 20 a and 20 b can be moved or tilted to correct the misalignment. Moving trajectory images 20 a and 20 b can be done in various ways.
In some cases, overall images 16 a and 16 b are created by importing, “cut-and-pasting,” or otherwise incorporating a tomograph into an appropriate software program. One example of such a program includes, but is not limited to, “Micrografx Designer, Technical Edition” by Micrografx, Inc. of Richardson, Tex. Using a standard “click-and-drag” technique, a conventional computer mouse 32 (or keyboard 34 , depending on the software) can be used to move or tilt trajectory images 20 a and 20 b (which can be a centerline drawn using the Micrografx software). An angular displacement or degree to which trajectory images 20 a and 20 b are tilted can be displayed in areas 36 and 38 and manually recorded for later reference.
Next, stent 12 with bushing 14 can be placed onto a model 36 of the patient's jaw. Model 36 can be cast or otherwise made in a conventional manner well known to those skilled in the art. A tool 38 or lever can be inserted into bushing 14 , and tool 38 can then be manually tilted based upon the angular displacement values displayed in areas 36 and 38 . The extent to which tool 38 tilts bushing 14 can be measured using a clinometer 40 (electronic or otherwise) that is mounted to or otherwise associated with tool 38 . The term, “clinometer” refers to any tool for measuring a change in inclination.
In some cases, clinometer 40 comprises two electronic levels 42 and 44 that are perpendicular to each other. The angle readings from levels 42 and 44 can be communicated to computer 26 so that trajectory images 20 a and 20 b tilt in response to tilting tool 38 . The angle reading from level 42 tilts trajectory image 20 b , and the angle reading from level 44 tilts trajectory image 20 a . In effect, tool 38 functions as a joystick with trajectory images 20 a and 20 b following the joystick's movements. The joystick inserted into bushing 14 can be tilted in various directions and angles until trajectory images 20 a ′ and 20 b ′ point directly into jawbone 30 as shown by images 16 a ′ and 16 b ′ of FIG. 3 . Electronic levels 42 and 44 can be any inclination measuring instrument that provides an electronic signal whose value (analog or digital) can be inputted into a computer using a conventional appropriate I/O board or module.
Once drill bushing 14 is properly aimed, bushing 14 can be permanently affixed to stent 12 using a conventional bonding material. Stent 12 can then be returned to the patient's mouth where bushing 14 can help guide the drill bit in drilling the implant hole in the patient's jawbone.
Although the invention is described with reference to a preferred embodiment, it should be appreciated by those skilled in the art that various modifications are well within the scope of the invention. Therefore, the scope of the invention is to be determined by reference to the following claims. | 1a
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BACKGROUND OF THE INVENTION
[0001] The present disclosure relates to infusion systems generally and specifically to the use of a y-port device during intravenous therapy.
[0002] Intravenous therapy is one of the most common health care procedures. Hospitalized, home care, and other patients receive fluids, pharmaceuticals, and blood products via a vascular access device inserted into the vascular system. Infusion therapy may be used to treat an infection, provide anesthesia or analgesia, provide nutritional support, treat cancerous growths, maintain blood pressure and heart rhythm, or many other clinically significant uses.
[0003] Intravenous therapy is facilitated by vascular access devices located outside the vascular system of a patient (extravascular devices). Extravascular devices that may access a patient's peripheral or central vasculature, either directly or indirectly include closed access devices, such as the BD Q-SYTE closed Luer access device of Becton, Dickinson and Company; syringes; split access devices; catheters; and intravenous (IV) fluid chambers. A vascular device may be indwelling for short term (days), moderate term (weeks), or long term (months to years). A vascular access device may be used for continuous infusion therapy or for intermittent therapy.
[0004] A common vascular access device is a plastic catheter that is inserted into a patient's vein. The catheter length may vary from a few centimeters for peripheral access to many centimeters for central access. The catheter may be inserted transcutaneously or may be surgically implanted beneath the patient's skin. The catheter, or any other extravascular device attached thereto, may have a single lumen or multiple lumens for infusion of many fluids simultaneously. For example, a catheter may be attached to a section of tubing wherein the section of tubing is also attached to an IV fluid chamber. This configuration allows the patient to receive fluids through the catheter without having the fluid chamber located near the catheter.
[0005] A vascular access device is commonly incorporated into an infusion system. For example, a vascular access device may be attached to a first end of a section of tubing wherein the second end of the tubing is attached to an IV fluid chamber. The infusion system may include an access port. For example, the access port may be incorporated into the middle portion of the section of tubing thereby allowing for multiple, concurrent therapies using the same vascular access device. For example, if a first therapeutic agent is contained in an IV fluid chamber and being administered to a patient via a catheter, a second therapeutic agent may be administered simultaneously through the access port of the catheter without interrupting the administration of the first therapeutic agent. One commonly used access port is a y-port.
[0006] A y-port is commonly coupled to a vascular access device via a section of tubing. The y-port is generally adapted to receive a pair of connector tips through which fluids and/or therapeutic agents may be administered. Typically, one of the connector tips is attached to a length of tubing to which is also connected an IV fluid chamber. The remaining access port is typically designed to allow access for a sharp needle or a blunt probe. This is accomplished by inserting an accessible plug or valve into the access port. For example, the plug or valve may be a split septum or a puncturable septum. A split septum is a solid or semi-solid plug that has been cut through the center such that an access channel is created. This access channel is opened only by forcing a correctly sized object through the channel and into the interior of the y-port. A puncturable septum is a solid or semi-solid plug that is capable of being punctured by a sharp needle. Both types of septum are typically designed to close upon withdrawal of the probe such that the fluid within the interior of the y-port is unable to exit the plug or valve.
[0007] Traditional placement of the plug or valve in a y-port creates undesirable dead spaces within the interior of the y-port. These dead spaces are created by positioning the valve or plug within the opening of the access port such that the outer surface of the valve or plug is near the opening of the access port and the inner surface of the valve or plug is located at a position recessed from the fluid channel of the y-port. This recessed position creates a cove within the interior of the y-port where aberrant currents are formed causing the rate of flow to decrease, backflows to occur and fluid to be trapped and/or concentrated. This effect is undesirable for several reasons.
[0008] The effect is undesirable because if medication is trapped in the dead space, the medication will not be delivered to the patient as expected. The obvious drawback of this effect is that undelivered medication is unable to provide an intended benefit to the patient. This means that a patient may suffer due to the inability of the clinician to effectively deliver the medication to the patient. For example, a clinician may administer a first bolus of a medication through the y-port expecting a desired effect. Upon lack of the desired effect, the clinician may administer a second, larger bolus wherein an infused combination of the second larger bolus and the remainder of the first bolus. Additionally, the clinician may choose to administer a second bolus of a different medication wherein the mixing of the second bolus and the remaining first bolus results in an undesired effect in the patient or in the infusion system. Such an effect may be an allergic reaction in the patient or a precipitation of the mediations in the y-port thereby clogging the y-port or clogging the patient's vein resulting in vascular damage.
[0009] As medication is trapped in the dead space, the medication may become concentrated. Generally, fluid flows from the IV fluid chamber though the tubing of the infusion system, through the y-port interior, into the vascular access device and into the patient's vascular system. Infusion systems are designed such that the flow of fluid from an IV fluid chamber to a patient's vascular system is continuous and efficient. The cove created by the recessed position of the valve or plug disrupts the continuous and efficient flow of the infusion system by creating aberrant currents, backflows and/or eddies within the interior of the y-port. These disruptions result in a reduced rate of flow within the dead space, thereby preventing the trapped medication from efficiently mixing with the fluid flowing through the y-port.
[0010] As a result, the medication becomes concentrated within the dead space. Upon subsequent usage of the y-port, the concentrated medication may be forced into the patient's vascular system with adverse results. For example, when sedating a newborn for a surgical procedure, the limited volume of the neonatal patient's vascular system requires that boluses of medication be highly concentrated thereby minimizing the volume of the bolus. When the highly concentrated bolus is infused via a y-port, only a portion of the desired medication is actually received by the patient while the remainder of the bolus is trapped in the dead space. Following the procedure, as subsequent therapeutic agents are administered to aid the patient's recovery, the stored, highly concentrated medication is forced from the dead space and administered to the patient thereby prolonging the sedated state of the patient.
[0011] Therefore, a need exists for systems and methods that eliminate aberrant currents within the y-port device, yet still provide convenient access to the infusion system.
BRIEF SUMMARY OF THE INVENTION
[0012] The present invention has been developed in response to problems and needs in the art that have not been fully resolved by currently available infusion systems, devices, and methods for intravenous therapy. Specifically, the current invention addresses problems in the art associated with aberrant currents present in y-port devices. Dead space, as used in reference to the current invention, is an area within a channel of fluid where the flow of the fluid is diverted and/or the flow rate of the fluid is decreased such that a portion of the fluid becomes stagnant and/or concentrated. These dead spaces may be formed due to recessed areas within the fluid channel thereby creating aberrant currents within the flow path. Thus, these developed systems, devices, and methods provide an infusion system that eliminates dead space thereby ensuring that liquids are infused directly into the flow path of the infusion system and ultimately into the vascular system of the patient.
[0013] The y-port device of the present invention may include a first tubular member having a first end and a second end and extending in a generally longitudinal direction. The y-port device may also include a second tubular member intersecting the first tubular member and forming a junction wherein a fluid channel is created between the first and second tubular members. The fluid channel is continuous and generally uniform in diameter such that the dynamics of the fluid flow are uniform throughout the interior of the y-port. The y-port device may also include an access valve or plug through which the infusion system may be accessed. The access valve or plug may include a one-way access valve, such as a split septum or a puncturable septum. For example, a split septum may include a dividing wall wherein the two halves of the wall are biased together such that a barrier is formed. This barrier is penetrable by a correctly sized probe wherein the probe may include a blunt cannula. A puncturable septum may include a membrane that is positioned within the first tubular member so as to form a seal between the exterior and the interior of the y-port. The membrane is capable of being penetrated or punctured by a sharp probe wherein the sharp probe may include a needle. Upon removal of the sharp probe, the walls of the membrane are biased radially inwardly thereby enclosing the access channel created by the sharp probe. Each type of septum may comprise a solid or semi-solid material.
[0014] It is also anticipated that the y-port device may include a multi-way access valve such that fluids may be added to or withdrawn from the infusion system. For example, the multi-way access valve may include a flow-stop valve, a ball valve or a multi-turn valve. Additionally, it is anticipated that a non-valve feature may be used in place of an access valve. For example, a plug or cap may be used wherein the plug or cap is placed within the first tubular member and designed so as eliminate any recessed cove between the terminal end of the cap or plug and the flow path.
[0015] The valve may be housed within the first tubular member and extend from the first end of the first tubular member to the junction of the first and second tubular members. The access valve terminates in an angle generally corresponding to the angle of the junction between the first and second tubular members. For example, if the junction of the first and second tubular member is at an angle of 120°, then the valve will terminate at an angle of 120°. Thus the inner profile of the second tubular member is maintained by the terminal end of the access valve. In this way, the terminal end of the access valve creates a direct interface with the flow path such that no recessed cove exists between the terminal end of the access valve and the flow path.
[0016] The direct interface between the terminal end of the access valve and the flow path ensures that any fluid infused into the infusion system is infused directly into the flow path and ultimately into the vascular system of the patient. The lack of dead space prevents the formation of a concentrated reserve of the infused fluid within the fluid channel. The direct interface of the terminal end of the plug and the flow path ensures that the flow path is continuous in one direction thereby eliminating eddies or fluid pockets in the infusion system where fluid may gather and concentrate.
[0017] A method of preventing undesired concentrations of one fluid within a stream of a second fluid may be accomplished by incorporating the valve or plug of the present invention into a desired infusion system. For example, a clinician may select an infusion system for a specific need and incorporate a y-port device that has been modified to include an access valve or plug that eliminates any recessed cove within the interior of the y-port device. Additionally, a clinician may select an infusion system for a specific need and incorporate an access valve or plug into the system thereby eliminating any recessed cove within the infusion system thereby eliminating any potential for undesired concentration of one fluid within a stream of a second fluid.
[0018] An infusion system may include a y-port device comprising a valve means wherein the positioning of the terminal end of the valve means eliminates dead space within the interior of the y-port device. The valve means may also be penetrable such that the interior of the y-port device may be accessed through the valve means. The valve means may also be positioned to facilitate direct access into the fluid channel of the y-port device when the valve means is utilized to access the interior of the y-port device.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0019] In order that the manner in which the above-recited and other features and advantages of the invention are obtained will be readily understood, a more particular description of the invention briefly described above will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings. These drawings depict only typical embodiments of the invention and are not therefore to be considered to limit the scope of the invention.
[0020] FIG. 1 is a perspective view of the y-port device as incorporated into an infusion system.
[0021] FIG. 2 is a cross section view of the y-port device showing the valve and the orientation of the valve with respect to the fluid channel.
[0022] FIG. 3 is a partially cut-away perspective view of the y-port device with a split septum and respective probe.
[0023] FIG. 4 is a partially cut-away perspective view of the y-port device with a puncturable septum and respective probe.
[0024] FIG. 5 is a partially cut-away view of the y-port device with a split septum as penetrated by a probe.
DETAILED DESCRIPTION OF THE INVENTION
[0025] The presently preferred embodiments of the present invention will be best understood by reference to the drawings, wherein like reference numbers indicate identical or functionally similar elements. It will be readily understood that the components of the present invention, as generally described and illustrated in the figures herein, could be arranged and designed in a wide variety of different configurations. Thus, the following more detailed description, as represented in the figures, is not intended to limit the scope of the invention as claimed, but is merely representative of presently preferred embodiments of the invention.
[0026] Referring now to FIGS. 1 and 2 , a y-port device 10 is illustrated in an infusion system 12 wherein a patient 14 receives intravenous therapy via the insertion of a catheter tube 16 into the patient 14 . The infusion system 12 comprises a catheter tube 16 , a y-port device 10 , and intravenous tubing 21 . The infusion system may also include a pre-filled sterile container of fluids 22 or any other source of fluid and/or therapeutic agent. The y-port device 10 provides an access point in the catheter tube 16 thereby allowing a user and/or clinician to access the patient's vascular system 18 without disturbing the catheter insertion site 20 or the pre-filled, sterile container of fluids 22 . The y-port device 10 permits access to the catheter tube via a valve 24 as located with a first tubular member 26 of the y-port device 10 . The valve 24 may be any valve adaptable to the present invention.
[0027] For example, the valve may be a septum, where the septum may be bypassed in order to access the interior of the y-port device. In one embodiment the valve 24 is a split septum 46 wherein the septum 24 is cut in a generally longitudinal direction 30 such that a split 46 is created through the center of the valve 24 , this split 46 forming an access channel through the center of the valve 24 . The septum split 46 may be biased so as to remain in a closed position until the walls of the split 46 are forced apart by the introduction of a probe 53 into the split 46 . The probe 53 may be a blunt cannula 48 , such as a male Luer, or any probe-like structure appropriately sized and adapted to access the fluid channel 38 of the infusion system 12 through the valve 24 .
[0028] In another embodiment, as illustrated in FIG. 4 , the valve 24 is a penetrable membrane 50 wherein the penetrable membrane 50 comprises a solid or semi-solid plug which may be penetrated by a sharp probe. The sharp probe may be a hypodermic needle 52 or any needle-like structure adapted to penetrate the membrane 24 and access the fluid channel 38 of the infusion system 12 . In one embodiment, the puncturable membrane 50 comprises a material that is capable of being punctured with a needle 52 whereupon the needle 52 cuts through the membrane 50 and creates an access path through the membrane 50 into the fluid channel 38 . The walls of the access path are forced apart by the presence of the needle 52 such that when the needle 52 is removed from the membrane 50 , the access path resumes a closed position thereby preventing a flashback and/or leakage of the fluid contained in the infusion system 12 .
[0029] Again referring to FIGS. 1 & 2 , the patient's vascular system 18 is accessed as a probe 53 is inserted into the valve 24 whereupon the probe tip 54 is introduced into a flow path 44 . Once the probe tip 54 is introduced into the flow path, the user and/or clinicians may access the patient's vascular system 18 through the infusion system 12 .
[0030] Referring now to FIG. 2 , the y-port device 10 is comprised of a first tubular member 26 having a first end 32 and a second end 34 and extending in a generally longitudinal direction 30 . The first tubular member 26 is generally cylindrical but may include other hollow, tube-like configurations such as square tubing or multi-angular tubing. The first tubular member 26 comprises a rigid, plastic material but may include flexible, pliable or non-rigid materials as well such as nylon tubing, polyurethane tubing, surgical tubing or Teflon tubing. In one embodiment, the first tubular member 26 comprises polypropylene material and is rigid.
[0031] The first tubular member 26 further comprises a first end 32 with an inner diameter to accommodate the fitting of a valve 24 . The inner diameter of the first end 32 is engineered to receive the valve 24 such that the valve 24 fits securely within the first end 32 in a fluidtight fashion. The valve 24 may be secured within the first end 32 by friction, by an adhesive and/or by a complimentary design wherein the valve 24 contains a feature that is complimented by a feature located on the interior surface of the first end 32 of the first tubular member 26 such that the valve 24 and the first end 32 are locked together in a fluidtight fashion.
[0032] The first tubular member 26 further comprises a second end 34 . The second end 34 is located at the end opposite to the first end 32 and has an inner diameter engineered to support intravenous tubing 16 such that the intravenous tubing 16 is irreversibly supported by the inner walls of the second end 34 of the first tubular member 26 in a fluidtight fashion. The intravenous tubing 16 may be supported by friction, an adhesive and/or by a complimentary design wherein the outer surface of the intravenous tubing 16 contains a feature that is complimented by a feature located on the interior surface of the second end 34 of the first tubular member 26 such that the intravenous tubing 16 and the second end 34 are locked together in a fluidtight fashion.
[0033] The y-port device 10 further comprises a second tubular member 28 . The second tubular member 28 is generally cylindrical but may include other hollow, tube-like configurations such as square tubing or multi-angular tubing. The second tubular member 28 comprises a rigid, plastic material but may include flexible, pliable or non-rigid materials such as nylon tubing, polyurethane tubing, surgical tubing or Teflon tubing. In one embodiment, the second tubular member 28 comprises polypropylene material and is rigid. The second tubular member 28 further comprises a first end 37 with an inner diameter engineered to support intravenous tubing 16 such that the intravenous tubing 16 is irreversibly supported by the inner walls of the first end 37 of the second tubular member 28 in a fluidtight fashion. The intravenous tubing 16 may be supported by friction, an adhesive and/or by a complimentary design wherein the outer surface of the intravenous tubing 16 contains a feature that is complimented by a feature located on the interior surface of the first end 37 of the second tubular member 28 such that the intravenous tubing 16 and the first end 37 are locked together in a fluidtight fashion.
[0034] The second tubular member 28 further comprises a second end 39 . The second end 39 forms a junction 36 with the first tubular member 26 and the second tubular member 28 intersects the first tubular member 26 an angle θ of 90° or greater. For example, in one embodiment the second tubular member 28 intersects the first tubular member 26 at an angle θ of 120°. In another embodiment, the second tubular member 28 intersects the first tubular member 26 at an angle θ that provides a continuous fluid channel 38 through the interior of the y-port device 10 . In another embodiment, the angle θ is selected to provide adequate clearance between the first end 32 of the first tubular member 26 and the first end 37 of the second tubular member 28 such that a clinician may access the valve 24 without being encumbered by the position of the second tubular member 28 .
[0035] The junction 36 between the first tubular member 26 and the second tubular member 28 may be formed by various plastic molding techniques including plastic injection molding and compression molding, and/or by various plastic joining techniques including heated tool, hot gas, laser welding, mechanical fastening and chemical bonding.
[0036] The y-port device comprises a valve 24 , as previously discussed. The valve 24 is positioned within the first tubular member 26 such that a first end 40 of the valve 24 corresponds to the first end 32 of the first tubular member 26 . The second end 42 of the valve 24 is angled at an angle θ′ generally corresponding to the angle θ of the intersecting second tubular member 28 . For example, in one embodiment, the junction 36 is at an angle θ of 120° and the second end 42 of the valve 24 is at an angle θ′ of 120°. In another embodiment, the junction 36 is at an angle θ that provides a continuous fluid channel 38 through the interior of the y-port device 10 and the second end 42 of the valve 24 is at an angle θ′ which is equal to angle θ.
[0037] The second end 42 of the valve 24 abuts the fluid channel 38 such that there is no recessed cove or gap between the fluid channel 38 and the second end 42 of the valve 24 . The second end 42 of the valve 24 extends up to the fluid channel 38 , but does not extend into the fluid channel 38 . The flow path 44 runs through the fluid channel 38 and is in direct fluid communication with the second end 42 of the valve 24 such that the second end 42 comprises a portion of the perimeter of the fluid channel 38 , but does not disrupt and/or divert the flow path 44 . For example, in one embodiment a fluid enters the fluid channel 38 through the second tubular member 28 and continues through the fluid channel 38 bypassing the valve 24 and following the flow path 44 through the interior of the y-port device 10 , through the second end 34 of the first tubular member 26 and out of the y-port device 10 . In this same embodiment, the fluid bypasses the second end 42 of the valve 24 without changing its velocity or flow pattern due to the presence of the valve 24 . The interface between the second end 42 of the valve 24 and the fluid in the fluid channel 38 results in a uniform flow pattern and velocity of the fluid through the fluid channel 38 of the y-port adapter 10 .
[0038] Referring now to FIGS. 2-4 , the valve 24 may include a split septum 46 . The valve 24 may include a solid or semi-solid plug that is split in such a way as to allow a probe 53 access to the fluid channel 38 through the septum split 46 (discussed above in detail). The first end 40 of the valve 24 may extend to the rim of the first end 32 of the first tubular member 26 such that the first end 40 of the valve 24 may be cleaned and/or sterilized prior to insertion of a probe 53 . For example, in one embodiment the first end 40 of the valve 24 is sterilized with an alcohol swap prior to the introduction of a blunt, male Luer into the split 46 of the valve 24 . In another embodiment, the first end 40 of the valve 24 is sterilized with an alcohol swap prior to puncturing the membrane 50 of the valve 24 with a hypodermic needle 52 .
[0039] The first end 32 of the first tubular member 26 may be modified to include a feature 58 for attaching additional components of the infusion system. For example, in one embodiment the feature 58 is male threads adapted to compatibly receive female threads incorporated into one end of a probe 53 , such as a male Luer. In another embodiment, the feature 58 is a raised portion of the outer surface of the first tubular member 26 wherein the raised portion is designed to receive a complementary clip 60 as incorporated into a probe 53 , such as a male Luer. In this same embodiment, the complementary clip 60 engages the external feature 58 in a reversible manner such that the complementary clip 60 includes a pressure sensitive clasp or pinching mechanism 62 whereby a user and/or clinician may pinch the mechanism 62 to release the complementary clip 60 from the external feature 58 . It is also anticipated that the first end 37 of the second tubular member 28 and the second end 34 of the first tubular member 26 may also be modified to include a feature 58 for attaching additional components of the infusion system 12 as described above.
[0040] Referring now to FIG. 5 , the valve 24 is positioned such that upon penetration of a probe 53 the probe tip 54 exits the second end 42 of the valve 24 directly into the fluid channel 38 permitting a fluid 56 to be infused directly into the flow path 44 thereby ensuring that all of the intended fluid 56 is infused into the infusion system 12 and into the patient's vascular system 18 (not shown). The fluid channel 38 is configured such that the inner diameter of the fluid channel 38 is greater than the outer diameter of the probe 53 such that the probe 53 may enter the fluid channel 38 without blocking the flow path 44 .
[0041] The present invention may be embodied in other specific forms without departing from its structures, methods, or other essential characteristics as broadly described herein and claimed hereinafter. For example, the present invention may be incorporated into any system comprising a valve and a fluid channel where undesirable stagnation or concentration of one fluid within another fluid occurs. For example, the present invention may be applied in a coolant system where a fluid with a first temperature is released into a fluid with a second temperature by means of a valve, wherein a concentration or stagnation of the first fluid within the second fluid, due to the recessed positioning of the valve, is undesirable. The described embodiments are to be considered in all respects only as illustrative, and not restrictive. The scope of the invention is, therefore, indicated by the appended claims, rather than by the foregoing description. All changes that come within the meaning and range of equivalency of the claims are to be embraced within their scope. | 1a
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BACKGROUND OF THE INVENTION
The present invention relates generally to an apparatus and method for heating and spinning feedstock materials. More particularly, the present invention relates to an improved apparatus and method for heating and spinning solid, non-solubilized feedstock material capable of undergoing intraparticle flow with the application of heat and force such as corn syrup solids, sucrose, polymers and the like where the heating of such materials is external to a spinning apparatus.
Various machines have been devised for the melting and spinning of meltable materials, especially sugar through a "melt spin" process. A particularized form of the melt spin process is known as flash flow processing. This process is described in U.S. Pat. Nos. 4,855,326; 5,279,849 and 5,387,431 all of which are incorporated herein by reference. The feedstock material may be introduced into a spinning head of the spinning machine in solid form. The material is subjected to heat therein just prior to being spun out from the spinner head where it reforms and solidifies in the air.
Typical cotton candy spinning machines operate by a melt spin process and include a spinner head having a generally cylindrical apertured wall. Sugar in solid form, is introduced into the spinner head where it is melted. Spinning of the spinner head causes the melted sugar to be spun out through the apertures in the cylindrical wall where it solidifies into a floss-like structure which has become to be known as cotton candy. The characteristic shape and consistency of the spun material is influenced by several factors. These factors include the size and construction of the spinner head, the size, arrangement and location of the apertures in the cylindrical wall of the spinner head, as well as the manner in which heat is applied to the spinner head.
Numerous machines, designed specifically for spinning cotton candy, have employed various modifications of the spinner head construction in an effort to yield spun product.
U.S. Pat. No. 4,872,821 discloses a cotton candy spinning machine including a spinner head having stacked, slotted, cylindrical walls and coiled heating elements adjacent each wall. Sugar in solid form is introduced into the spinner head and propelled against the heating elements where it is melted. The molten sugar is spun out through the slots where it solidifies into the floss-like material known as cotton candy.
U.S. Pat. No. 3,930,043 discloses a machine which includes a helical resistance heating element positioned within a finely perforated shell. The heating element is supported against the inner wall of the shell by spacer elements. As the shell spins, molten sugar is extruded through the perforations. Similar machines are disclosed in U.S. Pat. Nos. 3,073,262 and 3,070,045.
U.S. Pat. No. 3,856,443 discloses another type of spinning machine wherein the perforated shell through which sugar is extruded functions as the resistance element of the heating means.
U.S. Pat. No. 1,489,342 discloses a spinner head having an annular heating element formed of a strip of electrical resistance material. The strip is bent as a flat spiral structure forming slanted stretches of heating element having narrow slots between them. The heating element melts the sugar which then passes through the slots between the stretches of the heating element and out through an apertured shell positioned thereabout.
While some of the above described machinery may perform satisfactorily for converting granular sugar into a floss-like material in the formation of cotton candy, it does not function entirely satisfactorily for spinning other materials which may have properties quite dissimilar to sugar or for other materials mixed with sugar, or for liquiflash processing. Nor does the above-described machinery have the capacity to yield product having a desired shape and size. In recent years, it has been increasingly desirable to spin not only feedstock such as sugar and materials combined with sugar, but also non-saccharides.
Attempts have been made to eliminate undesirable drawbacks of conventional machinery especially with regard to the spinning of feedstock including non-sugars as well as sugars combined with non-sugars, is shown and described in U.S. Pat. No. 5,427,811, which is incorporated by reference herein. The spinner head described therein is referred to as a "cable head" spinner. The cylindrical wall of the spinner head is formed by a heating element comprising a cable which is helically wound about the axis of rotation of the spinner head. In this way the heating element itself is used as the wall of the spinner head through which the material is ejected. U.S. Pat. No. 5,458,823, which is also incorporated by reference herein, attempts to solve the problem of non-uniform heating of the feedstock by incorporating discrete closely spaced elongate heating elements. The elements are peripherally spaced about the spinner head and may be individually heated in order to control the morphology of the of the expelled material.
All previously designed spinner heads for producing a spun product through a melt spin process, including flash flow and liquiflash processing have contained heaters built into the head. Such designs require considerable head mass for heater enclosure resulting in the loss of surface area for expelled product. In addition, power must be supplied to the rotating heaters. These requirements present significant obstacles to the scale up and production of larger and faster heads for both bead and floss production.
Many prior art spinner heads including the cable head utilize electrical resistance coils located on the spinning head in order to heat the material. Such head based heating sources limit the ability to focus the heat to the outermost surface of the head. The elements have a certain thickness over which the material must pass prior to expulsion. In addition the coils tend to heat the entire wall through conduction even if the coils are mounted on the wall's outer surface. This creates a heated flow path that may over heat the material leading to agglomeration.
In addition, many other problems and limitations arise in supplying electrical current to the rotating spinner head. Typically, current is supplied to rotating devices using a set of contacts or brushes located on the rotating device which frictionally engage a stationary ring to which power is supplied. Use of these components adds a extra degree of complexity to the head and present certain limitations.
The components, especially the contacts, have a finite working life after which they must be replaced. The contacts' life expectancy is inversely proportional to the amount of current carried therethrough. This presents a limitation to increasing the size of the spinning head since larger heads require more power, and therefore, more current. It is desirable to increase the spinner head size in order to both increase the yield of reformed product per head as well as to produce certain reformed morphologies. Large spinner heads, however, have previously not been feasible to employ due in part to the high maintenance cost associated with the low life cycles of the contacts. Furthermore, the life expectancy of the contacts is inversely proportional to the rotational velocity of the head due to the frictional engagement of the current transmitting components. Therefore, in order to maintain reasonable life expectancies the rotational velocity must be limited. This too limits the yield per head and morphologies that can be produced.
Additionally, the shape of the wall is very important in determining the morphology of the reformed product. It is desirable, therefore, to have as much design flexibility in the wall in order to create a variety of morphologies. As previously stated, incorporating a heating means such as heating elements or coils into the wall places constraints on the design of the processing wall, thereby limiting the variety of morphologies which can be produced. Head mounted heater coils also reduce the surface area that is available for exit points from which material may be expelled.
Another disadvantage of spinner head mounted heating means is the increased weight it encompasses. The heavier the head the more substantial the support and mounting means that are required to support the rotating load. In addition, the increased weight and complexity of the head mounted heating device increases the likelihood that the head will not be rotationally balanced. If the head is not rotationally balanced the loading on the supports will shift with every revolution resulting in vibration. These vibrations present a problem since they subject the support means, such as the shafts and bearings to stresses, thereby decreasing the service life of the material processing system.
In that regard, a need clearly exists for spinning machinery which provides the user with a means of heating the feedstock material without the limitations inherent in the use of heating coils located on the spinner head.
SUMMARY OF THE INVENTION
The present invention provides an improved apparatus and method for the flash flow and liquiflash processing of solid feedstock materials. The present invention provides a spinner head including a spinner head chamber defined by a perimetrical processing wall through which the solid feedstock material is processed. A device for rotating the spinner head about an axis of rotation is also provided to cause the feedstock material to be propelled toward and through the processing wall. A heating device is further provided which is separate from and exterior to the spinner head for heating the feedstock material to an elevated temperature to cause the processing as the feedstock material is projected against the processing wall.
The present invention further provides a spinner head which includes a base and a cover positioned over the base. A peripheral processing wall having a pattern of openings extends between the base and the cover. The processing wall may be formed by a plurality of substantially concentrically stacked rings, each of the rings having a plurality of radially extending grooves through which the feedstock may flow. The processing wall may have a varying diameter with the diameter diminishing as the wall extends axially away from an axial centerline. In addition, each ring may have a radial outer portion including a first lip and a second lip, with the first lip extending radially outwardly further than the second lip and wherein each of the rings is positioned such that the first lip is positioned toward the axial centerline. The spinner head is rotated about an axis of rotation to cause the feedstock material to be propelled toward and through gaps in the processing wall.
The present invention still further provides a method of processing feedstock material comprising the steps of providing a spinner head having a chamber bounded by a material processing wall through which the material is processed and introducing the feedstock material into the chamber. The head is then spun to propel the feedstock material toward and through the processing wall. The feedstock material is heated by a heating device disposed external to the spinner head to an elevated temperature sufficient to cause processing of the material at the processing wall. The processing wall may be heated as the feedstock material is forced toward and through the processing wall. Alternatively the material itself may be heated prior to the feedstock material contacting the processing wall.
As a result of the present invention, the spinner head need not be incorporated with the heating device, thereby providing several advantages. The processing wall may be formed in a variety of shapes and from a variety of materials since the need to incorporated a heating device is no longer required.
Another advantage of the present invention is the availability of the entire surface area of the processing wall to include exit points from which the material can be expelled.
A further advantage of the present invention is the ability to control the temperature of the flow path in order to achieve a desired morphology.
Yet a further advantage of the present invention is the reduction of weight and complexity of the spinner head thereby increasing the design flexibility with respect to the means for supporting the rotating head.
Still a further advantage of the present invention is ability to increase both the size and angular velocity of the spinner head since power no longer must be supplied to the head by contacts and rings.
It is to be understood that the apparatus and method of the present invention can be employed to form particles which are microspheres of a very narrow size range or fibrous floss type material or particles of a shape somewhat in between these extremes. By careful control of conditions, the apparatus of the present invention can be utilized to form particles of a predetermined shape. Conditions which must be controlled include: the heat necessary to bring a feedstock to an internal flow condition, the viscosity of the flowing feedstock; the centrifugal force necessary to move the flowing feedstock to the resistance of an ambient atmosphere which will subdivide the feedstock into particles; the temperature and relative flow of the atmosphere into which the molten feedstock is delivered for subdivision; and the distance needed in relation to the ambient atmosphere so that the expelled feedstock can virtually resolidify in the desired shape.
One skilled in the art can select a material to be processed according to the present invention. Guided by the heat and centrifugal force necessary to bring the selected feedstock under the proper conditions, the appropriate size and shape of the exit orifices in relation to the ambient atmosphere can be selected so as to virtually yield microspheres, floss or particle shapes somewhere in between.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A is a perspective view of a material processing apparatus for feeding, spinning and collecting spun materials;
FIG. 1B is a partial cutaway view of FIG. 1A showing a spinner head located within the interior of the basin;
FIG. 2A is an alternative embodiment of a material processing apparatus of the present invention;
FIG. 2B is a detail view of the spinner head assembly of FIG. 2A;
FIG. 3 is a sectional top plan view of the basin of FIG. 1B taken along line 3--3 thereof;
FIG. 4 is a partial cutaway view of the spinner head of FIG. 3 taken along line 4--4 thereof;
FIG. 5 is a vertical sectional view of an alternative embodiment of a spinner head of the present invention;
FIG. 6 is a partial cutaway view of the preferred embodiment of a spinner head of the present invention;
FIG. 7 is a top plan view of a ring of FIG. 6;
FIG. 8 is a detail view of a portion of the processing wall of FIG. 7;
FIG. 9 is a side orthogonal view of the spinner head of FIG. 6 shown with external heating sources.
FIG. 10 is a partial cutaway view showing an alternative embodiment of an external heat source.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention contemplates producing material through a flash heat and liquiflash spin process. More specifically, the present invention contemplates subjecting solid, non-solubilized feedstock material (feedstock) which is capable of undergoing intraparticle flash flow processing or liquiflash processing to a heat sufficient to cause the material to deform or liquefy and pass through an opening under force. The force used in the present invention is centrifugal force provided by a spinner head from which the feedstock material is expelled at a high speed. Preferably no external force is imposed upon the feedstock material after it has been expelled from the spinner head other than resistance provided by ambient atmosphere. The feedstock material so expelled instantly reforms as a solid having a changed morphology as a result of the material being expelled from the spinner head. The application of heat of this invention is unique in that it is externally located separate and apart from the spinner head thereby eliminating the complexities and design limitations inherent with head based heating apparatus. By controlling the amount and location of heat applied to the spinner head and/or the material itself as well as the openings through which the melted product is expelled, the present invention provides the ability to control the morphology of the material expelled from the spinner head.
As the feedstock material comes in contact with the heated wall the material deforms or liquefies enabling it to undergo intraparticle flash flow processing. This process is described in U.S. Pat. Nos. 4,855,326; 5,279,849 and 5,387,431. Liquiflash processing is the subject of co-owned U.S. patent application Ser. No. 08/330,412, now U.S. Pat. No. 5,683,720, the contents of which are hereby incorporated by reference.
Referring now to the drawings, FIG. 1A shows a material processing system 10 consisting of a hopper 12, a chute 14, a basin 16, a spinner head 60, shown in FIG. 1B, positioned within basin 16, a funnel 18 for directing material from the chute 14 to the spinner head, an external heating source 40 in the path of the material, and a base 20. The base contains a motor (not shown) for driving the spinner head in a manner as described in U.S. Pat. No. 4,872,821, which is incorporated herein by reference.
An alternative embodiment of the material processing system is shown in FIGS. 2A and 2B. The processing system shown may accommodate mass production of spun material. A spinner head 60 is suspended from a platform 11 over a collection bin 15. Collection bin 15 includes an output opening 19 through which the processed material may be removed from the collector to some form of conveyor. A volumetric material feed 22 is disposed above the platform and is in communication with spinner head 60 to convey a supply of material thereto. An external heating source 40 is further provided and may be suspended from platform 11 in spaced proximity to spinner head 60.
A spinner head suitable for flash flow processing in conjunction with an external heating source will now be described. Spinner head 60 shown in FIG. 4 includes a base 62, a cover 64 and a bottom plate 63 all of which are substantially annularly shaped. The base 62, cover 64 and bottom plate 63 may be formed from stainless steel or other suitable material. Cover 64 includes an opening 66 through which the feedstock material may be introduced into the spinner head. Spinner head 60 further includes a substantially cylindrical perimetrical processing wall 68 having an inner surface 70 and an outer surface 72. Wall 68 is disposed between bottom plate 63 and cover 64 forming a chamber 74 for flash flow processing. The wall 68 may be heated by the external heat source 40 to a temperature sufficient for flash flow processing. The wall 68 has a pattern of openings 69 passing therethrough to allow the feedstock material to be expelled.
Head 60 may also include a cover insulating ring 58 and a base insulating ring 56. Base insulating ring 56 is disposed between wall 68 and base 62, and cover insulating ring 58 is disposed between cover 64 and wall 68. Cover insulating ring 58 includes an opening concentric with cover opening 66 to allow for the introduction of feedstock. The insulating rings 56,58 are preferably made from a ceramic material or coated with a heat resistant polymer such as TEFLON. The insulators 56,58 restrict the conduction of thermal energy away from heated processing wall 68 to the cover and base, thereby allowing for the heat to be concentrated where required.
Wall 68 and the insulating rings 56,58 are secured between cover 64 and base 62 by four adjustable spacer assemblies 73. The assemblies are contained within the processing chamber 74. Each assembly includes a ceramic sleeve 76 and a nut fastener 78 at the top of cover 64 and a mating threaded portion in base 62 for cooperative attachment of a threaded stem 77. The assemblies 73 do not materially impede the projection of expelled product toward the processing wall 68.
Appropriate apparatus is connected to spinner head 60 for mating head 60 to a motor for permitting rotation of head 60 about axis A--A in a manner well known in the art. When spinner head 60 is supported from underneath, as shown in FIGS. 1B and 2B, base 62 further includes a stem 80 extending centrally downwardly. In applications where spinner head 60 is suspended below the drive motor, as shown in FIG. 10, stem 80 may extend upwardly from the cover 64 and attach to a motor shaft 32.
An alternative embodiment of spinner head 60' is shown in FIG. 5. Spinner head 60' includes a closed generally planar base 62' and a generally planar cover 64' aligned and spaced from base 62'. Cover 64' has an opening 66' to allow the introduction of feedstock material into head 60'. Spinner head 60' further includes a substantially cylindrical perimetrical processing wall 68' having an inner surface 70' and an outer surface 72'. Wall 68' is disposed between base 62' and cover 64' forming a chamber 74' for flash flow processing. The wall 68' has a pattern of openings 69' passing therethrough to allow the feedstock material to be expelled. A stem 80' extends centrally downwardly from the base 62' and includes a profile for mating with an appropriate mechanism such as a motor for permitting rotation of head 60' in a manner well known in the art. A base insulating ring 56' is disposed between base 62' and wall 68'. The cover 64' may be coated with a heat resistant polymer such as TEFLON.
In the alternative embodiment shown in FIG. 5, the ceramic sleeves 76' and threaded stems 77' are disposed outside processing chamber 74' and extend from a annular flange portion 65 of the cover into threaded portion of base 62'. Nut fasteners 78' are secured to the shafts 77' above annular flange portion 65.
It is within the contemplation of the present invention that the spinner head may be of any basic construction as known in the prior art.
The processing walls will now be more specifically described. As previously stated, the construction of processing wall and the size and shape of the openings 69 in wall 68 influence the morphology of the reformed product. This invention contemplates the use of various patterns of openings in order to produce a desired morphology. The pattern of openings in wall 68 may be of any one of the numerous configurations known in the art. Such shapes include vertical or circumferential slits, circular openings arranged in either vertical or circumferential rows. Various opening shapes are set forth in U.S. Pat. Nos. 5,458,823; 5,447,423; 5,445,769; and 5,427,881, as well as in copending and commonly assigned applications Ser. No. 08/854,344, filed May 12, 1997, now U.S. Pat. No. 5,834,033; and Ser. No. 08/874,215, filed Jun. 13, 1997, now U.S. Pat. No. 5,851,454, all of which are incorporated by reference herein. In addition, by providing a heat source external to the spinner head the openings and passages in the processing wall may take on many additional configurations that would not have been permitted with a spinner head based heating source.
One embodiment of processing wall 68 is shown in FIG. 4. Wall 68 contains a plurality of openings 69 spaced in cylindrical rings about wall 68. The diameter of the openings is 0.020 inches, ±0.004 inches, and the distance between openings is 0.100 inch. Wall thickness is as small as structurally feasible, in order to provide the shortest heat exposure for the material while still maintaining sufficient path length in order to obtain the desired morphology. While these dimensions define one embodiment of the spinner head 60 of this invention, their inclusion is exemplary and not intended as a limitation. Openings 69 may also be formed by any means, e.g., by laser, drilling, etc. Openings 69 may also be cone shaped in cross-section relative to the inner and outer wall surfaces.
Another embodiment of a wall configuration now possible due to the use of an external heating surface is a wall 68' made substantially of only a wire mesh material 82 as shown in FIG. 5. The wire mesh forms numerous openings 69' through which the material may be expelled. Mesh 82 is preferably a metallic woven screen of between 30-120 mesh having fine holes or perforations therethrough. The top and bottom portion of mesh 82 sits within and is supported by annular grooves 84, 86 formed in the inner surfaces of cover 64' and base insulating ring 56' respectively. The rotation of head 60' forces feedstock material against and through mesh 82 creating the desired morphology of the reformed product.
Now referring to FIG. 6, a preferred embodiment is shown of a spinner head which may be used with an external heat source. Spinner head 90 is preferably formed of a plurality of concentrically aligned stacked rings 92 secured together between a top and base plate 94, 96. Rings 92 form the material processing wall 104. Top plate 94 includes an aperture 98 for permitting feedstock material to enter an internal head chamber 100. Base plate 96 includes a stem 102 depending therefrom which provides a structure for coupling spinner head 90 to a motor (not shown). The rings 92 and top and base plates 94, 96 form chamber 100 which holds the feedstock material prior to its being expelled from the spinner head. Rings 92 preferably have a varying outside diameter portion such that when stacked together they form tapered processing wall 104 whose outside diameter diminishes as wall 104 extends axially away from an axial centerline. Such a tapered profile exposes a maximum amount of processing wall surface area to external heat source 40. Rings 92 are preferably formed of a thermally conductive material, such as stainless steel or aluminum, so that the heat energy imparted on the exposed portions of the rings will be conducted in toward chamber 100, thereby aiding in the processing of the feedstock material.
Referring additionally to FIGS. 7 and 8, each of rings 92 has a similar inside diameter dimension and are secured together by bolts 103 axially extending through annularly spaced radially inwardly extended lugs 97 formed on an inside diameter portion 93 of rings 92. The ring inside diameter portions 93 are separated by spacers 106 which assist in maintaining proper ring alignment.
Rings 92 are similarly configured although they have varying outside diameter dimensions in order to form a spinner head having a tapered processing wall. Accordingly, one ring will now be described in detail. Ring 92 is a generally Y-shaped member in cross-section having an inside diameter portion 93 which is substantially planar and to which ring 92 is secured to spinner head 90 as set forth above. Extending radially outwardly, ring 92 diverges into a first and second lip 108, 110 the first lip extending outwardly in the radial direction further than the second lip. Ring 92 is oriented within spinner head 90 such that the first lip 108, the longer of the two lips, is positioned toward the axial centerline of the spinner head 90 and the shorter lip positioned away therefrom. This orientation gives spinner head 90 its tapered profile. Between first and second lips 108, 110 is formed a generally U-shaped groove 112 which extends about the perimeter of ring 92.
Ring 92 further includes a plurality of radially extending annularly spaced grooves 114 formed on the axial outer surfaces of lips 108, 110. When lips of adjacently disposed rings engage each other, grooves 114 form channels 118 through which the feedstock material may flow from internal chamber 100 to outside head 90. In the preferred embodiment, rings 92 are so aligned such that a groove of one ring will be offset from a groove formed an opposed ring. Grooves 114 may have a variety of shapes and dimensions in order to produce a reformed product of desired morphology. The grooves may be formed as set forth in assignee's co-pending application Ser. No. 08/874,215 entitled "A Spinner Head Having Flow Resticting Inserts", now U.S. Pat. No. 5,851,454, the disclosure of which is incorporated by reference herein. For example, grooves may be V-shaped, U-shaped or square-shaped in cross-section.
In order to direct the feedstock material toward channels 118, ring 92 further includes tapered portions 116 extending from the upper and lower surface of the inside diameter to the lips. As shown in FIG. 6, tapered portions 116 of adjacently disposed rings form a V-shaped structure 117 leading toward the point where rings 92 abut and to the radially inward end of channels 118.
Spinner head 90 presents a processing wall having a surface area significantly greater than the substantially flat wall designs discussed above. Accordingly, such a design exposes a significant amount of surface to an adjacently disposed external heat source, and therefore, can absorb a significant amount of radiated energy. In order to maximize the energy absorption capabilities of spinner head 90, preferably two types of heat sources may be employed, as shown in FIG. 9.
One type of external heat source shown in FIG. 9 provides a generalized wave of heat energy 120 directed toward the upper and lower portion of spinner head 90. Generalized wave producing heat sources 40a are preferably located such that the heat energy originates from a position generally perpendicular to the tapered processing wall 104. Such an alignment will expose the perpendicular portion of the processing wall to substantially direct rays of heat energy thereby maximizing the energy absorbed as well as providing a generally uniform heating of the processing wall. Heat energy generated by such sources as infrared lamps or microwave transmitters may be used to provide this generalized energy wave. Processing wall 104 may be heated either alternatively or additionally by a discrete pin-point producing heat source 40b in which energy 122 is specifically directed to portions of the processing wall adjacent the exit point of channels 118. Pin point control of energy may be generated by such devices as a laser or a narrow jet of hot air or steam.
In order to provide the external heat required for flash flow processing various heat sources are contemplated. In the embodiment shown in FIG. 1B, heat source 40 is mounted through an opening in the wall 17 of basin 16 such that the heat is in proximity to spinner head 60. The heat source 40 is preferably an infrared lamp designed to produce radiant thermal energy. Such lamps are of a type commercially available. A 650 watt lamp located adjacent to wall 68 could provide suitable heat for intraparticle flash flow if the melt temperatures were about 75 degrees or so.
A major advantage of infrared heating is the ability to heat a surface which intercepts the radiation without heating the air or other objects that surround the surface intended to be heated. The thermal energy may be focused and directed toward processing wall 68, 68', 104 thereby heating the entire wall as it spins in the path of the radiant energy. Since the spinner head has a relatively high angular velocity, the entire surface of processing wall 68, 68', 104 becomes substantially uniformly heated by the radiant energy of heat source 40. Uniform heating is important since product quality under certain circumstances is contingent upon maintaining temperatures within a finite temperature range. In addition, processing wall 68, 68', 104 is preferably formed of a thermally conductive material such as aluminum so that the heat will be uniformly distributed through wall processing thereby reducing the occurrence of hot or cool spots. The processing walls may also be formed of stainless steel or any other heat conductive material.
The surface of the processing wall 68, 68', 104 may be finished to have a dull flat appearance in order to increase the materials absorption of the infrared energy and increase the temperature of the wall. Alternatively, the aluminum wall may coated by an anodizing process with a pigmented finish in order to increase energy absorption. A steel wall could likewise be plated with a pigmented coating. It is also within the contemplation of this invention that by varying the finish, the wall temperature can be affected thereby influencing the morphology of the reformed product.
In order to intensify and direct the infrared radiation, reflectors 48 may be used as shown in FIG. 3. Such reflectors allow for the efficient use of energy as the radiant energy is focused on the location where heat is required, i.e. the outer wall surface of the spinner head.
In an alternative embodiment, the heat source may be a microwave transmitter providing radiant energy to heat the feedstock directly for flash flow processing. The microwave transmitter generates microwave radiation at a frequency so as to heat the material prior to expulsion from the head. Typically for food cooking applications the microwave frequency employed is 2450 ±50MHz. However, frequencies of 915 ±15 MHZ are also commonly used. Heating of the material is achieved by the absorption of microwave energy by rotation of water molecules and translation of the ionic components of the feedstock. In this embodiment the processing wall is preferably formed of a material which is transparent to microwaves, such as glass or plastics, thereby allowing the radiation to pass through to the feedstock. The feedstock adjacent the processing wall will become heated to flash flow temperatures, liquefy and then be expelled through the wall openings producing the reformed product of desired morphology.
Alternatively, the processing wall may be made of a material which absorbs the microwave radiation and can withstand the elevated temperatures required for flash flow conditions. In this embodiment the wall becomes heated and transfers its heat to the material as it contacts the wall. The heated material is then capable of undergoing intraparticle flash flow processing.
The present invention also contemplates the use of laser energy as a means of heating the wall to a point where intraparticle flash flow processing may take place. The beam being focused and directed to engage the spinner head processes wall at the point where the material exits the head. It has been found that for microsphere formation the morophology of the sphere can be effected by controlling the temperature of the material after it has exited the head. For example the laser could be aimed at exit points of channels 118 of spinner head 90 as described above to keep the material fluid longer before cooling. The rotation of processing wall will ensure that the exit point 118 are uniformly treated.
The heat may also be imparted on the various spinner head embodiment described herein by way of heated forced air stream. This heating means may be superior to other heating means for forming certain morphologies due to the air flow produced and its affect upon the expelled material. The forced hot air stream may be produced in any conventional matter. As shown in FIG. 10, a blower 42 moves air over heating elements 44 and exits at an elevated temperature from a nozzle 46 located adjacent spinner head 60, thereby heating wall 68. Heating elements are preferably electrical resistance coils although the air may be heated in any conventional manner. Nozzle 46 is shaped to direct the heated air stream 47 over the axial length of the spinner head.
Other sources of external heating are within the contemplation of the present invention including but not limited to light and other filament sources, resistance heaters, induction-based devices, frictional devices and concentrated solar energy.
The material expelled from spinner head 60 is projected radially outwardly in all directions by centrifugal force. This requires that the heat source be shielded from the expelled material in order to prevent material build up on the heat source which could both block the radiant energy as well as burn the material. In order to protect the heat source, a shield 24 is provided. As shown in FIG. 3, shield 24 is mounted to basin wall and extends toward spinner head 60. In an alternative embodiment shown in FIG. 1B, shield 24 is attached to the bottom surface of basin adjacent to the spinner head and in between the head and the heat source. Another alternative embodiment would include the use of an air knife to assist in keeping reformulated product from building up on the heat source. An air knife consist of a stream of air that flows across the face of the heat source thereby preventing material buildup as well as removing the material once it engaged the heat source. The air stream could be continuous stream or an intermittent blast and activated only as required. A further alternative would be to mount the heat source 40 out of the material flow path as shown in FIGS. 2A and 2B.
The problem of reformed material coating the heat source is not present in the forced air method of generating the required heat since the forced air exiting nozzle 46 prevents the expelled material from blocking the path of the heat.
Thus, while there had been described what are the presently believed to be the preferred embodiments of the present invention, other and further modifications and changes can be made thereto without departing from the true spirit of the invention. It is intended to include all further and other modifications and changes which come within the true scope of the invention as set forth in the claims. | 1a
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TECHNICAL FIELD
This disclosure relates generally to pet carriers. More particularly, the disclosure relates to a deployable pet carrier for a motor vehicle, the carrier being conveniently disposed within the vehicle for easy access and use.
BACKGROUND
Persons often must travel in their motor vehicles with their pets, for example for veterinary appointments, when moving, or even simply for companionship. However, an unrestrained animal in a vehicle presents a driver distraction and so potentially a hazard. Additionally, in the event of even a minor collision, an unrestrained animal is subject to severe injury. Still more, even a small unrestrained pet subjected to deceleration forces in a collision becomes a dangerous projectile that can injure the vehicle occupants.
For these and other reasons, various means of restraining animals in a vehicle have been developed. It is known, for example, to restrain animals by attaching a leash or other tether at one end to a collar or harness worn by the animal and at the other end to a portion of the vehicle such as a seatbelt harness, door handle, etc. This type of restraint likewise risks injury to the animal during a collision, since the animal will travel at least a short distance before reaching the end of the leash, exacerbating the deceleration force of the collision. Also, a leashed pet may be less likely to exercise restraint in relieving itself in the vehicle at need.
It is likewise known to use pet carriers to transport an animal in a vehicle. These are typically simply conventional carriers or crates as would be used in a home, placed loose in the vehicle and into which the animal is placed prior to operating the vehicle. However, such loose crates likewise become projectiles during a collision, risking injury to vehicle occupants. Conventional crates or pet carriers, while effective in restraining an animal, are also inconvenient in that they occupy significant space in a vehicle even if no pet is present.
To solve this and other problems, the present disclosure relates at a high level to a deployable pet carrier. Advantageously, the described deployable pet carrier is configured for securing to a motor vehicle seat back, includes collapsible side walls for pet security, and further includes a convenient deploying mechanism.
SUMMARY
In accordance with the purposes and benefits described herein, in one aspect a deployable pet carrier assembly for a vehicle is described. The carrier assembly includes a sliding rail guide system configured to attach the pet carrier to a vehicle seat back and collapsible front, rear, and side walls defining a carrier structure when deployed. The sliding guide rail system includes front and rear guide rails configured to slidingly hold the pet carrier front wall and rear wall. An actuator is provided, configured to retain or release the pet carrier walls for transitioning the pet carrier between a collapsed configuration and a deployed configuration.
In embodiments, each of the pet carrier front wall and rear wall is defined by a plurality of intersecting rails configured to provide a collapsible grid. Likewise, in embodiments each of the pet carrier side walls is defined by a plurality of interconnected panels configured to provide a collapsible panel. A tray is provided to define a floor for the carrier.
In the following description, there are shown and described embodiments of the disclosed deployable pet carrier. As it should be realized, the carrier is capable of other, different embodiments and its several details are capable of modification in various, obvious aspects all without departing from the devices and methods as set forth and described in the following claims. Accordingly, the drawings and descriptions should be regarded as illustrative in nature and not as restrictive.
BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawing figures incorporated herein and forming a part of the specification, illustrate several aspects of the disclosed deployable pet carrier, and together with the description serve to explain certain principles thereof. In the drawing:
FIG. 1 depicts a deployable pet carrier according to the present disclosure;
FIG. 2 depicts deployed front and rear walls of the carrier of FIG. 1 ;
FIG. 3 depicts a deployed folding wall of the carrier of FIG. 1 ;
FIG. 4A depicts the carrier of FIG. 1 in the stored configuration, including an actuator embodiment for deploying the carrier;
FIG. 4B shows the actuator embodiment of FIG. 4A in isolation;
FIG. 5 depicts the carrier of FIG. 1 in the stored configuration, attached to an upright seat back of a second row seat of a motor vehicle;
FIG. 6 shows the carrier of FIG. 5 with the second row seat back folded forward; and
FIG. 7 depicts the carrier of FIG. 6 in the deployed configuration.
Reference will now be made in detail to embodiments of the disclosed deployable pet carrier, examples of which are illustrated in the accompanying drawing figures.
DETAILED DESCRIPTION
Turning to FIG. 1 , a collapsible pet carrier assembly 10 is depicted, configured for attaching to a vehicle seat back 12 . Broadly, the pet carrier assembly 10 includes collapsible front and rear walls 14 , 14 ′ and collapsible side walls 16 , 16 ′. Front and rear (not visible in this view) guide rails 18 , 18 ′ slidingly hold at least the front and rear walls 14 , 14 ′ and secure the pet carrier assembly 10 to the vehicle seat back 12 . In one embodiment, at least one edge of front and rear walls 14 , 14 ′ is pivotally attached to a corresponding end of guide rails 18 , 18 ′ (see arrow).
A tray 20 is provided which serves as a floor for the pet carrier 10 , optionally including a separate or integral perforated mat 22 . As will be appreciated, the mat 22 provides a surface for a pet (not shown) having greater grip, and further allows drainage of liquid onto tray 20 in the event the pet relieves itself. Conveniently, tray 20 and mat 22 are removable for ease of cleaning and replacement at need. Molded studs or other fasteners (not visible in this view) prevent inadvertent dislodgment of the tray 20 /mat 22 when the pet carrier assembly 10 is held in a stored configuration as discussed below.
In an embodiment (see FIG. 2 ), the front and rear walls 14 , 14 ′ are defined by a plurality of intersecting rails 24 , pivotally interconnected one to another to define a collapsible grid structure. A plurality of first rods 26 pivotally connect the edges of front wall 14 to the corresponding edges of rear wall 14 ′, similar in design to a collapsible laundry rack as is known in the art. Intersecting rails 24 may be pivotally interconnected by any suitable structure, such as by pins 28 as shown. In turn, for each of front and rear walls 14 , 14 ′, a lowermost end an intersecting rail 24 is pivotally connected to a corresponding end of front and rear guide rails 18 , 18 ′, such as by a pin 29 or in an alternative embodiment (not shown) by passing an end of a bottom-most first rod 26 through an aperture in an end of each of front and rear guide rails 18 , 18 ′. As will be appreciated, this feature of a plurality of intersecting rails 24 pivotally interconnected one to another to define collapsible front and rear walls 14 , 14 ′ allows altering a width dimension of front and rear walls 14 , 14 ′ during deployment and collapsing of the pet carrier assembly 10 as will be discussed.
An embodiment of side walls 16 , 16 ′ is shown in FIG. 3 . As shown therein, each of side walls 16 , 16 ′ is defined by a plurality of interconnected panels 30 . Each panel 30 is configured to pivotally accept a first rod 26 through a first edge thereof. In turn, each panel 30 is likewise configured to pivotally accept a second rod 32 through a second, opposed edge thereof, thus interconnecting the plurality of panels 30 to define a collapsible panel side wall that is substantially solid when the pet carrier 10 is in the deployed configuration. In the depicted embodiment, hinge structures 34 are defined in the first and second edges of the panels 30 to allow interconnection thereof as described. As will be appreciated, this feature of interconnected panels 30 to define collapsible side walls 16 , 16 ′ preserves a width dimension of side walls 16 , 16 ′ during deployment and collapsing of the pet carrier assembly 10 as will be discussed.
With reference to FIGS. 4A and 4B , the pet carrier assembly 10 further includes an actuator 36 for retaining the carrier in either the collapsed or the deployed configuration. In one embodiment, the actuator 36 is simply a pushbutton release 38 , including a spring 40 for biasing pushbutton 38 outwardly through a first bore 42 defined in front rail 18 . In this configuration, the pet carrier 10 is in the collapsed configuration shown in FIG. 4A . To deploy the carrier, a user need only urge the pushbutton 38 rearwardly against spring 40 (see arrow A) to clear bore 42 , and may then raise front/rear walls 14 , 14 ′ and side walls 16 , 16 ′ upwardly to a deployed configuration.
As the carrier is deployed, the “footprint” defined by front/rear walls 14 , 14 ′ and side walls 16 , 16 ′ decreases slightly, and pushbutton 38 translates laterally (see arrow B). As the carrier reaches the fully deployed configuration (see FIG. 7 ), pushbutton 38 reaches and engages a second bore 44 , thus maintaining deployed configuration until a user wishes to collapse the structure. Of course, the process of collapsing the carrier is simply the inverse of the process of deploying as described above.
Turning now to FIGS. 5-7 , conveniently the pet carrier assembly 10 is secured in the collapsed configuration to an upright vehicle V seatback 12 by guide rails 18 , 18 ′ (see FIG. 5 ). As shown, front wall 14 is disposed above rear wall 14 ′. In this configuration, actuator 36 is conveniently accessible to a user by way of passenger door D (not shown in this view, but see FIG. 6 ) when seatback 12 is folded forward. However, although the inverse relationship is also contemplated (rear wall 14 ′ disposed above front wall 14 ). Thus, the pet carrier assembly 10 is conveniently available for use at a moment's notice, but does not occupy a significant portion of the available storage space of, for example, the vehicle cargo area C.
To use the pet carrier assembly 10 , at least the portion of vehicle seat back 12 to which the carrier is secured is folded forward (see FIG. 6 ). Next, the pet carrier is deployed as described above, by operation of actuator 36 , and the carrier is translated to the deployed configuration ( FIG. 7 ). During this translation, as the front/rear walls 14 , 14 ′ and side walls 16 , 16 ′ are raised, the carrier footprint decreases slightly as described above, i.e. front/rear walls 14 , 14 ′ lessen in width and side wall 16 ′ translates towards side wall 16 without altering a width dimension thereof (note the greater portion of guide rails 18 , 18 ′ visible in the deployed configuration compared to the collapsed configuration of FIG. 6 ). Then, actuator 36 engages second bore 44 (not visible in this view) to retain the carrier in the deployed configuration.
Typically, a pet is placed on tray 20 /mat 22 before deploying the pet carrier assembly 10 as described above. This is because after deployment the vehicle roof/headliner is typically sufficiently near a top edge of front/rear walls 14 , 14 ′ and side walls 16 , 16 ′ that the vehicle roof/headliner serves as a de facto lid or top for the pet carrier assembly 10 . However, it will be appreciated that alternative configurations are possible, for example providing a separate lid or top (not shown) for a pet carrier assembly 10 having shorter walls or when using the pet carrier assembly in a vehicle having a higher roof/headliner to prevent the pet from inadvertently exiting the carrier.
Thus, it will be appreciated that a simple, effective vehicle-mounted pet carrier is provided, which is stored in a vehicle without significant negative impact on available storage space in the vehicle. The carrier is easily deployed for use as needed, and equally easily collapsed for storage when not needed. Obvious modifications and variations are possible in light of the above teachings. All such modifications and variations are within the scope of the appended claims when interpreted in accordance with the breadth to which they are fairly, legally and equitably entitled. | 1a
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BACKGROUND OF THE INVENTION
[0001] The present invention relates generally to farm implements and, more particularly, to a central fill system having a stowable ladder for a stack-fold planter.
[0002] Increasingly, farm implements have been designed to have frames that can be folded between field-working and transport positions. One such type of farm implement is a stack-fold planter, such as the 1230 Stackerbar planter from Case New Holland, LLC. Stack-fold planters generally consist of a center frame section and a pair of wing frame sections. In the field-working position, the wing frame sections are evenly aligned with the center frame section. In the transport position, however, the wing sections are lifted to a position directly above the center frame section, i.e., to a “stacked” position. In the stacked position, the width of the implement is generally that of the center frame section, thus making the implement better suited for transport along roads and between crops.
[0003] Openers are mounted to the frame sections at equal intervals, with each of the wing sections typically carrying one-half the number of openers mounted to the center frame section. The openers are designed to a cut a furrow into a planting surface, deposit seed and/or fertilizer into the furrow, and then pack the furrow. In this regard, each opener will have a seed box that is manually loaded with seed and/or fertilizer. Since the size of the seed box determines how much particulate matter the box can retain, there is generally a desire to have larger seed boxes for each of the openers. Since the larger seed boxes can hold more material, fewer refilling stops are needed when planting a field.
[0004] Larger seed boxes, however, have drawbacks. The additional material that can be carried by larger seed boxes adds to the overall weight of the openers, including those mounted to the wing sections. This additional weight can stress the lifting/lowering system that stacks the wing sections, or require a more robust system, which can add to the overall size, mass, complexity, and cost of the implement. Additionally, larger seed boxes can affect the spacing between adjacent openers, and thus the spacing between seed trenches that are formed by the openers. Larger spacing between seed trenches lower per acre crop yields. Further, it can be problematic and time consuming to individually fill each of the seed boxes, whether using bags or a conveyor system.
[0005] Many central fill systems for such stack-fold planters have a rearward platform accessible by a ladder that is fixed to a rearward edge of the platform. The platform provides a work space for an operator when refilling the central hoppers or visually inspecting the fill level in the hoppers. The ladder provides a means to access the platform. One known central fill system for a stack-fold planter includes means for raising the hoppers when the planter is in transport. It is believed that raising the hoppers provides better weight distribution and therefore allows for faster travel speeds when the planter is in transport. The transport position is commonly used as the position for the planter when being stored and serviced, particularly, the central fill system, such as the air blower and its related components, hoses, and the like. For systems having a fixed ladder mounted to the platform, the ladder constrains the workspace around the central fill system and creates a structure of which a service technician must be cognizant to avoid unnecessary contact. Alternately, the technician may find avoiding the fixed ladder cumbersome and therefore elect to remove the ladder.
SUMMARY OF THE INVENTION
[0006] The present invention is directed to a central fill system having a stowable ladder for use with a stack-fold implement. The bulk fill hopper assembly is mounted to the center frame section of the stack-fold implement and does not affect the narrowness of the stack-fold implement when in a stacked, transport position. The hopper assembly preferably includes a pair of bulk fill hoppers or tanks supported by cradle that is in turn supported by a pair of wheels. The cradle is removably coupled to the center frame section by a pair of rigid frame members. Parallel linkages interconnected the cradle and the wheels, and allow the wheels to, in effect, float to accommodate changes in terrain as the implement is being towed in either the working or transport positions. The rigid frame members preferably hold the position of the cradle constant but the position of the wheels change in response to changes in terrain. A ladder is provided that may be stowed adjacent the cradle when not being used, but may be slid rearward and lowered when its use is desired. A platform rearward of hoppers includes catches that engage the forward end of the ladder as the ladder is being withdrawn from its stowed position. The catches prevent the unintentional removal of the ladder from the central fill system.
[0007] According to one aspect of the invention, an agricultural implement is provided, and includes a tool bar adapted to be coupled to a prime mover, with the tool bar having an inner section and at least one outer section, and a plurality of row units coupled to the inner and outer sections of the tool bar. The implement further includes means for raising the outer section to a stacked position generally above the inner section, and a frame member coupled to and extending rearward from the inner section of the tool bar. A bulk fill hopper assembly is supported by the frame member and operative to deliver particulate material to the plurality of row units. The bulk fill hopper assembly includes a stowable ladder that when in use enables access to hopper(s) that store particulate matter that is ultimately delivered to the row units.
[0008] In accordance with another aspect of the invention, a central fill system for a stack-fold planter is provided. The central fill system includes a frame that supports one or more bulk fill hoppers or tanks, and is adapted to be coupled to a tool bar of the stack-fold planter. The frame further supports a platform rearward of the hoppers that provides a work space for adding product to the fill hoppers or visually inspecting the hoppers. A ladder is provided that is removably engaged with the platform such that when the platform is in a use-position, the ladder may be used to gain access to the platform. When not in use, the ladder may be stowed on the frame beneath the hoppers.
[0009] According to one object of the invention, a more efficient, greater material capacity stack-fold planter is provided.
[0010] It is another object of the invention to provide a stack-fold implement having a central bulk fill system.
[0011] It is a further object of the invention to provide a central bulk fill system for a stack-fold implement, such as a stack-fold planter.
[0012] It is yet another object of the invention to provide a central bulk fill system having a stowable ladder for use with a stack-fold planter.
[0013] Other objects, features, aspects, and advantages of the invention will become apparent to those skilled in the art from the following detailed description and accompanying drawings. It should be understood, however, that the detailed description and specific examples, while indicating preferred embodiments of the present invention, are given by way of illustration and not of limitation. Many changes and modifications may be made within the scope of the present invention without departing from the spirit thereof, and the invention includes all such modifications.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] Preferred exemplary embodiments of the invention are illustrated in the accompanying drawings in which like reference numerals represent like parts throughout.
[0015] In the drawings:
[0016] FIG. 1 is a pictorial view of an agricultural planting system comprised of a stack-fold planter coupled to a tractor;
[0017] FIG. 2 is an isometric view of the stack-fold planter of FIG. 1 in a field-working position;
[0018] FIG. 3 is a rear elevation view of the stack-fold planter of FIG. 1 in a stacked, transport position;
[0019] FIG. 4 is an isometric view of the central bulk fill system of FIG. 1 in a lowered, field working position;
[0020] FIG. 5 is a side elevation view of the central bulk fill system of FIG. 4 ;
[0021] FIG. 6 is a side elevation view of the central bulk fill system in a raised, transport position;
[0022] FIG. 7 is a rear isometric view of the central bulk fill system with a stowable ladder in a withdrawn ready-for-use position; and
[0023] FIG. 8 is a detailed view of the stowable ladder and platform arrangement.
DETAILED DESCRIPTION
[0024] Referring now to FIG. 1 , a planting system 10 according to one embodiment of the invention includes a stack-fold implement 12 , shown in a field working position, coupled to a prime mover 14 , e.g., tractor, in a known manner. For purposes of illustration, the stack-fold implement 12 is a row crop planter, which as shown in FIG. 2 , includes a frame 16 generally comprised of a center section 18 and wing sections 20 , 22 on opposite lateral sides of the center section. The center section 18 includes a tongue (not shown) that extends forwardly of the center section 18 for hitching the implement 12 to the prime mover 14 . Gauge wheels 24 on the frame sections 18 , 20 , and 22 set the seeding or cutting depth for the implement.
[0025] In the illustrated embodiment, sixteen openers 26 are mounted to the frame 16 at equally spaced intervals, but it is understood that more than or fewer than sixteen openers could be mounted to the frame 16 . As known in the art, the wing sections 20 , 22 may be raised to a transport position, as shown in FIG. 3 , in which the openers carried by the wing sections 20 , 22 are stacked over the center section 18 . As also known in the art, the openers 26 are designed to cut a furrow into the soil, deposit seed and/or fertilizer into the furrow, and then pack the furrow. Seed boxes or “mini-hoppers” 28 are optionally mounted to each of the openers 26 . The mini-hoppers 28 are preferably smaller than conventional mini-hoppers used with stack-fold crop row planters and thus hold less material than conventional seed boxes.
[0026] The present invention allows for smaller mini-hoppers as the invention provides for a central bulk fill assembly 30 that delivers material, such as seed and/or fertilizer, to the openers 26 and/or the mini-hoppers 28 . The central bulk fill assembly 30 preferably includes a pair of bulk fill hoppers 32 and 34 supported adjacently to one another on a cradle 36 . The cradle 36 is supported by a frame 38 that is mounted to the center section 18 by a set of rearwardly extending frame members 40 , 42 , and 44 . In a preferred embodiment, the frame members 40 , 42 , and 44 are removably coupled to center frame section 18 which allows the bulk fill assembly 30 to be removed from the implement 12 or added as an after-market add-on to an existing stack-fold implement.
[0027] The platform 38 is supported above the work surface (or transport surface) by a pair of wheels 46 , 48 that are each connected to the platform 40 by respective parallel linkages 50 , 52 . Each linkage includes an upper link 54 , 56 and a lower link 58 , 60 , respectively. In addition to the links 54 - 60 , a pair of lift arms 62 , 64 are provided. Lift arm 62 is coupled to frame member 44 at a knuckle 62 to which parallel linkage 50 is also connected. In a similar manner, lift arm 64 is coupled to frame member 40 at a knuckle 64 to which parallel linkage 52 is also connected. As shown particularly in FIG. 4 , the cradle 36 further includes a Y-beam 66 that is pivotally coupled to the center frame member 42 . As is customary for most central bulk fill assemblies, an air blower 68 is mounted beneath cradle 36 is operable transfer particulate matter from the hoppers 32 , 34 to the individual mini-hoppers 28 or directly to the openers 26 in a forced air stream.
[0028] As known in the art, central bulk fill hoppers, such as those described above, provide the convenience of a central fill location rather than having to fill the individual seed boxes. Also, the central fill hoppers have greater capacity than the seed boxes, which reduces the number of fill iterations that must be taken when planting. Simply mounting a central bulk fill assembly to a stack-fold planter, such as planter 12 , can create stability issues, especially when the stack-fold planter is in the transport position. In this regard, the present invention provides a mechanism for raising the bulk fill assembly 30 when the stack-fold planter 10 is in the folded, transport position. Raising the bulk assembly 30 provides greater stability during transport as well provides increased clearance between the bulk fill assembly 30 and the roadway.
[0029] Accordingly, the present invention provides a pair of hydraulic lift cylinders 70 and 72 for lifting the cradle 36 , and thus the bulk fill assembly 30 . Cylinder 70 is interconnected between forward knuckle 62 and a rearward knuckle 74 . As shown in FIG. 5 , the rearward knuckle 74 includes, or is coupled to, a mounting arm 76 that is coupled to axle 78 about which wheel 46 rotates. Cylinder 70 includes a ram 80 that is coupled to the rearward knuckle 74 whereas cylinder 70 is coupled to the forward knuckle 62 . In a similar fashion, cylinder 72 includes a ram (not shown) connected to a rearward knuckle 82 whereas the cylinder 72 is connected to the forward knuckle 64 . It will be appreciated that a mounting arm 84 is connected to, or formed with, the rearward knuckle 82 , and the mounting arm 84 is connected to an axle (not shown) about which wheel 48 rotates.
[0030] FIG. 6 shows the central bulk fill assembly 30 in the raised-for-transport position. The bulk fill assembly 30 is raised from the lower, field or working position by the actuation of cylinders 70 and 72 . In a preferred embodiment, the cylinders 70 , 72 are linked to the hydraulic system that raises and lowers the stack-fold planter 12 . Thus, the central bulk fill assembly 30 is automatically raised and lowered as the planter 12 is raised and lowered. It is contemplated however that the bulk fill assembly 30 could be raised and lowered independent of the stack-fold planter. Additionally, it is contemplated that a separate hydraulic system could be used to raise and lower the central bulk fill assembly 30 .
[0031] The following description details how the central bulk fill assembly 30 is raised and lowered. While reference will be made to cylinder 70 and its ram 80 , it should be noted that the other cylinder 72 and its ram operate similarly and in-tandem with cylinder 70 and ram 80 . In operation, the ram 80 is extended or retracted based on the pressure in cylinder 70 . When the ram 80 is extended, the force applied against the rearward knuckle 74 causes the forward knuckle 62 to elevate. Conversely, when the ram is retracted, the forward knuckle 74 is drawn downward resulting in lowering of the central bulk fill assembly 30 . It will be appreciated that the parallel linkages 50 , 52 maintain the lift arms at a consistent orientation throughout the range of motion provided by extension and retraction of the rams. In this regard, a substantially level central fill bulk assembly 30 is maintained during raising and lowering. Further, as shown by comparing the views of FIGS. 5 and 6 , the lift arms 62 , 64 remain above the parallel linkages throughout the range of vertical motion of the bulk fill assembly 30 .
[0032] Referring now to FIGS. 4 and 5 , a platform 86 is mounted to the Y-beam 66 and extends rearward therefrom beneath the bulk fill hoppers 32 , 34 . The platform 86 provides a standing area for a user to access the respective top hatches 88 , 90 for the hoppers 32 , 34 for inspecting the fill level of the hoppers 32 , 34 or add additional material to the hoppers 32 , 34 . Extending uprightly generally from a back edge of the platform 86 is a barrier 92 designed to prevent a user from falling off the back edge of the platform 86 .
[0033] As shown in FIG. 5 , even when the bulk fill assembly 30 is in the lowered, field position, the platform is substantially elevated above the field surface. Thus, to provide access to the platform, the present invention provides a stowable ladder 94 that when stowed is retained in a slot 95 formed between the bottom surface of platform 86 and a floor 97 that is mounted below the platform 86 . The ladder 94 may be slid rearwardly from the slot 95 and then lowered to a use position, as illustrated in FIG. 7 . It will be appreciated that the rearward end of the slot 95 includes catches 96 that retain the forward (top) end of the ladder 94 so that the ladder 94 is not completely removed from the slot 95 when the ladder 94 is moved to the use position. The catches 96 are shaped such that the ladder 94 , when it reaches it fully extended position, it may be pivoted or rotated downward so that the trailing (bottom) end engages the ground.
[0034] FIG. 8 is a detailed view of the stowable ladder and platform arrangement generally described above. When the ladder 94 is in the working, extended position ( FIG. 7 ), the ladder 94 may be stowed by lifting up at (or near) the ground engaging end of the ladder along pivot line 98 extending through catches 96 and then sliding the ladder toward the front of the central bulk fill assembly 30 as indicated by arrow 100 until the ladder 94 is fully seated in position in slot 97 beneath the platform 92 . It will therefore be appreciated that when the ladder 94 is in the stowed position, the ladder 94 does not interfere with access to the lower components of the central bulk fill assembly 30 , such as the air blower 68 for example.
[0035] It will be appreciated that the present invention provides a stack-fold implement having a central bulk system and thus the advantages typically associated with bulk fill systems, such as reducing filling intervals, longer seeding times, and greater efficiency. Additionally, the centralized hoppers provide the convenience of a central fill location that is generally clear of the openers whether the implement 12 is in a working position or a stacked, transport position. The placement of the bulk fill system rearward of the center section 18 also provides additional stability to the implement 12 when the implement is in the stacked position.
[0036] Many changes and modifications could be made to the invention without departing from the spirit thereof. The scope of these changes will become apparent from the appended claims. | 1a
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates in general to a treatment for a Plantar Fasciitis, acute ankle sprains, tendonitis, tendon ruptures, acute foot pain, or other conditions and in particular to a splint or boot for immobilizing the human foot and ankle. Still more particularly, the present invention relates to a night splint for stretching ankle tendons, which can be converted to a durable walking boot with minimal complexity.
2. Description of the Prior Art
In the area of orthotic splints, the prior art has generally evolved into two distinct designs, walking boots and splints.
Walking boots are generally study, heavy and designed to support the patients weight during walking or other ambulatory activities. Examples of walking boots may be seen in U.S. Pat. No. 5,611,773, U.S. Pat. No. 4,962,760 and U.S. Pat. No. 5,176,623. Each of these devices is designed to restrict the flexing of the human foot with respect to the lower leg and frequently such boots include adjustable hinge mounts so that the amount of Dorsi flexion or Plantar flexion may be accurately described and controlled.
Splints on the other hand are typically lightweight and designed to be worn while the patient sleeps or during other periods of extended inactivity. Examples of splints may be seen in U.S. Pat. No. 5,797,865, U.S. Pat. No. 6,146,350, U.S. Pat. No. 5,897,520 and U.S. Pat. No. 5,094,232. Each of these splints is lightweight and designed to be worn either with a conventional shoe or, alternatively, while the patient sleeps or during an extended period of inactivity.
This dichotomy between the two design philosophies has resulted in some difficulty for patients whose medical treatment requires that the movement of their foot or ankle be restricted during long periods of time, but who cannot sleep with a heavy durable walking splint in place or cannot walk while wearing a lightweight night splint. A similar problem had existed when the ankle is immobilized utilizing a plaster or fiberglass cast. Recognizing this difficulty, several inventors have attempted to provide cast protective devices, which could be slipped over the foot portion of a plaster or fiberglass cast to protect the cast while permitting the wearer some degree of mobility. Excellent examples of these devices may be seen in U.S. Pat. No. 3,802,424 and U.S. Pat. No. 4,005,704.
The desirability of a lightweight night splint which may be modified to permit the patient to become ambulatory is known in the art. U.S. Pat. No. 5,913,841, issued to William D. Lamont, discloses a medical boot which includes a lightweight night splint device and which includes a durable fabric material which may be temporarily attached to the bottom of the boot to permit some ambulation on the part of the patient. Similarly, U.S. Pat. No. 5,609,570 issued to the same inventor, discloses a boot, which may be wrapped around the night splint and patients ankle to permit the user to ambulate while wearing a night splint.
Upon reference to these last two patents, it should be apparent that while providing an excellent solution to the problem of ambulation while wearing a lightweight night splint, neither of these designs provides anywhere near the weight bearing durability of typical walking boot splints and consequently, it would be desirable to provide a method or system whereby a lightweight night splint may be efficiently converted to a walking boot without undue complexity.
SUMMARY OF THE INVENTION
It is therefore one object of the present invention to provide an improved treatment for Plantar Fasciitis, acute ankle sprains, tendonitis, tendon ruptures, acute foot pain, or other conditions.
It is another object of the present invention to provide an improved splint for immobilizing the human foot and ankle.
It is yet another object of the present invention to provide a splint for stretching ankle tendons during periods of inactivity, which can be converted to a walking boot with minimal complexity.
The foregoing objects are achieved as is now described. A frequent method of treating Plantar Fasciitis, acute ankle sprains, tendonitis, tendon ruptures, acute foot pain, or other conditions is a so-called night splint which may be utilized by a patient while sleeping, or during other periods of extended inactivity, to maintain a desired orientation between a patient's foot and lower leg, thus stretching ankle tendons. A night splint portion includes a thin, lightweight sole portion not suitable for walking or other weight bearing activities; however, a sturdy raised lip around the sole portion includes multiple mounting slots which temporarily mate with matching mounting tabs on a walking boot attachment which includes a sturdy, weight bearing sole so that a patient may temporarily convert the night splint to a walking boot.
BRIEF DESCRIPTION OF THE DRAWINGS
The novel features believed characteristic of the invention are set forth in the appended claims. The present invention itself, however, as well as a preferred mode of use, further objectives, and advantages thereof, will best be understood by reference to the following detailed description of a preferred embodiment when read in conjunction with the accompanying drawings, wherein:
FIG. 1 is a side pictorial view of the combination night splint and walking boot of the present invention;
FIG. 2 is a perspective view of the night splint portion of the combination night splint and walking boot of the present invention;
FIG. 3 is an exploded view of a rotatable hinge utilized in the combination night splint and walking boot of the present invention;
FIG. 4 is a cut-away side view of the rotatable hinge of FIG. 3, in a locked position;
FIG. 5 is a cut-away side view of the rotatable hinge of FIG. 3, in a pivoting position;
FIGS. 6A-6C are schematic views of the rotatable hinge of FIG. 3, demonstrating the range of adjustment possible;
FIG. 7 is a perspective view of the walking boot portion of the combination night splint and walking boot of the present invention;
FIG. 8 is an exploded view demonstrating the joining of the night splint portion and walking boot portion of the combination night splint and walking boot of the present invention; and
FIGS. 9 and 10 are partial views of the mounting slots and tabs utilized to join the night splint portions and walking boot portions of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
With reference now to the Figures and in particular with reference to FIG. 1, there is illustrated a side pictorial view of the combination night splint and walking boot 10 of the present invention. As illustrated, combination night splint and walking boot 10 is constructed of a lightweight material such as Titanium, Aluminum or Plastic, such as Nylon Polyurethane or Polyethylene and includes a leg brace 12 and an identical second leg brace 14 (not shown in this Figure). Mounted along leg brace 12 is a hook or loop fastener strip 16 and a similar strip is provided on the opposite leg brace. In this manner, a pair of hook or loop straps 20 and 22 may be wrapped around the lower leg of the patient and, when engaged with the hook or loop strip 16 and the second hook or loop strip, may be utilized to retain the pair of leg braces in a tight proximate position to the lower leg of the patient.
Mounting each leg brace 12 or 14 to combination night splint and walking boot 10 is a rotatable hinge 24 . A similar rotatable hinge 26 is also provided but not depicted in this Figure.
A foot support member 28 is provided and, as illustrated, is constructed utilizing a thin flat sole portion, which may be utilized to support the human foot. A walking boot attachment 30 is mounted to foot support member on 28 and includes a heel portion 32 , mid-foot portion 34 , and a toe portion 36 . As illustrated in FIG. 1, heel portion 32 and toe portion 36 are slightly inclined from the plane defined by mid-foot portion 34 in order to assist the patient in walking.
An instep strap 38 is illustrated which is attached to turnbuckles 40 and 42 (not shown in this Figure) and utilized to further restrain the human foot in close proximity to foot support member 28 . Finally, as illustrated in FIG. 1, a raised lip portion 44 is depicted. As illustrated, raised lip portion 44 forms a counter around the heel area of combination night splint and walking boot 10 and extends along each side of foot support member 28 , forming the mounting surface for turnbuckles 40 and 42 (not shown in this Figure).
Referring now to FIG. 2, there is depicted a perspective view of the night splint portion of the combination night splint and walking boot of the present invention. As now depicted, leg braces 12 and 14 extend upward along the lower leg of the patient and are mounted to foot support member 28 by means of rotatable hinges 24 and 26 .
As clearly illustrated herein, raised lip portion of 44 forms a counter around the heel area of foot support member 28 and extends along each side thereof, providing a mounting surface for turnbuckles 40 and 42 .
In accordance with an important feature of the present invention, raised lip portion 44 also serves to provide a plurality of mounting slots. Generally rectangular mounting slots 46 , 48 and 50 are depicted in FIG. 2; however, those ordinarily skilled in the art will appreciate, upon reference to the foregoing, that a greater or lesser number of slots maybe chosen.
With reference now to FIG. 3, there is depicted an exploded view of rotatable hinge 24 , which may be utilized in construction of the combination night splint and walking boot 10 of the present invention. Of course, rotatable hinge 26 is constructed in an identical manner. As depicted, a hinge socket 54 is integrally formed as part of raised lip portion 44 . Hinge socket 54 receives axle pin 56 through axle aperture 60 and a plurality of position pins 58 through a matching plurality of position pin apertures 62 .
Lock plate 64 is also illustrated in FIG. 3 . As depicted, lock plate 64 includes a lock plate axle aperture 66 and lock plate position pin apertures 68 . Each lock plate position pin 68 is aligned with a position pin aperture 62 within hinge socket 54 and receives a position pin 58 , thus prohibiting rotation of lock plate 64 .
An important feature of the rotatable hinge of the present invention is the provision of lock pins 70 . As depicted, two lock pins 70 are provided and, in a manner which will be explained in greater detail herein, these lock pins may be inserted into a selected lock pin aperture 80 to adjust the angular relationship between leg brace 12 and combination night splint and walking boot 10 .
Still referring to FIG. 3, spring 72 and axle pin cap 74 are also provided and are coaxially aligned with axle pin 56 to provide adjustment of rotatable hinge 24 in a manner which will be explained in greater detail herein. Leg brace 12 having hook or loop strip 16 attached thereto, terminates in a brace plate 78 which includes a plurality of lock pin apertures 80 and a brace plate axle aperture 82 . Axle pin cap 74 will protrude through brace plate axle aperture 82 and each lock pin 70 will be inserted into a selected one of lock pin apertures 80 to provide fixed angular adjustment as depicted below. Finally, a flexible cap 84 is provided and mounted conventionally to brace plate 78 to protect the mechanisms contained therein and provide means for adjusting rotatable hinge 24 , as explained below.
Referring now to FIG. 4, there is depicted a cut-away side view of rotatable hinge 24 of FIG. 3, in a locked position. As depicted herein, position pins 78 prevent rotation of lock plate 64 . As illustrated, lock pins 70 , mounted to lock plate 64 , are each inserted into a lock pin aperture 80 within brace plate 78 and consequently, leg brace 12 is prohibited from rotating with respect to the combination night splint and walking boot 10 of the present invention.
With reference now to FIG. 5, there is depicted a cut-away side view of rotatable hinge 24 of FIG. 3, in a pivoting position. As illustrated in this Figure, flexible cap 84 has been depressed inward in the direction indicated at arrow 86 . Axle pin cap 74 compresses spring 72 , pushing lock plate 64 further onto each position pin 58 . In this position, lock pins 70 are disengaged from lock pin apertures 80 within brace plate 78 . While flexible cap 84 remains depressed in the depicted position, leg brace 12 may be rotated with respect to combination night splint and walking boot 10 . In the depicted embodiment of the present invention, six lock pin apertures 80 are provided in both the upper and lower region of brace plate 78 and each one is located in order to permit ten (10°) degrees of Dorsi flexion or Plantar flexion of combination night splint and walking boot 10 with respect to leg brace 12 . In this manner, the health professional may select a particular orientation to be maintained between the patient's foot and lower leg in accordance with the treatment regimen, which is desired.
Referring now to FIGS. 6A-6C, there are depicted schematic views of rotatable hinge 24 of FIG. 3, demonstrating the aforementioned range of adjustment. As depicted, the positioning of lock pins 70 into selected lock pin apertures 80 may result in a ten (10°) degree Dorsi flexion or ten (10°) degree Plantar flexion. Similarly, in FIG. 6B, a twenty (20°) degree Dorsi flexion or twenty (20°) degree Plantar flexion may be obtained. Finally, as depicted in FIG. 6C, a thirty (30°) degree Dorsi flexion or thirty (30°) degree Plantar flexion may be selected, providing a wide range of treatment options to the health care professional.
With reference now to FIG. 7, there is depicted a perspective view of walking boot attachment 30 of the combination night splint and walking boot 10 of the present invention. As illustrated, walking boot attachment 30 is a sturdy, weight-bearing unit, which includes a heel portion 32 , a mid-foot portion 34 and a toe portion 36 . As described above, heel portion 32 and toe portion 36 are inclined slightly from the plane defined by mid-foot portion 34 to assist the patient in walking.
Still referring to FIG. 7, as depicted therein, walking boot attachment 30 includes a plurality of mounting tabs, 90 , 92 and 94 . In the depicted embodiment, each mounting tab 90 , 92 or 94 , includes a mounting tab slot, 96 , 98 and 100 . Further, each mounting tab includes a pair of mounting tab ears. Thus, mounting tab 90 includes mounting tab slot 96 and mounting tab ears 102 and 104 . Similarly, mounting tab 92 includes a mounting tab slot 98 and mounting tab ears 106 and 108 . Finally, mounting tab 94 includes a mounting tab slot 100 and mounting tab ears 110 and 112 . Mounting tabs 90 , 92 and 94 are preferably constructed of a sufficiently flexible material such that compression of each portion of the mounting tab toward the mounting tab slot will provide sufficient clearance so that the associated mounting tab ears may pass through an associated rectangular mounting tab slot and, once clear, may expand to form a temporary and efficient lock.
With reference now to FIGS. 9 and 10, there are illustrated partial views of the interaction between mounting slots and mounting tabs which may be utilized to join together the combination night splint and walking boot portions of the present invention. As illustrated in FIG. 9, mounting tab 92 has been compressed toward mounting tab slot 98 such that mounting tab ears 106 and 108 have passed through mounting slot 46 and thereafter expanded, forming a rigid bond between walking boot attachment 30 and foot support member 28 . Similarly, raised lip portion 44 in FIG. 10 forming the counter around the heel portion of foot support member 28 includes a mounting slot 50 which, in the matter described above, has accommodated mounting tab 94 .
Upon reference to the foregoing, those skilled in the art will appreciate that the inventor's herein have provided a lightweight night splint which may be rapidly and efficiently converted to a walking boot while maintaining a desired orientation between the patients foot and lower leg, permitting accommodation of sleep or large periods of inactivity and ambulation.
While the invention has been particularly shown and described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention. | 1a
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The present invention relates to a dosage form containing a biologically-active substance and formulated for oral administration, especially to ruminants. The dosage form contains an active-substance core comprising at least one biologically active substance and having a coating surrounding this core which coating effects a delayed release of the core after oral administration. The invention also relates to the use of this dosage form for the nourishment or veterinary care of ruminants and to a method for supplying ruminants with active substances.
BACKGROUND OF THE INVENTION
Frequently, additional biologically-active substances must be administered to animals raised and kept for the production of e.g. meat, milk, wool or eggs, e.g. for supplying them with amino acids supplements, vitamins or veterinarily active substances. This generally poses no problems in the case of monogastric animals because the active substances to be supplied to them can be quite simply administered orally, e.g. mixed into the feed as an additive or in the form of gelatin capsules containing the active substance. However, such simple methods generally fail in the case of ruminants because the active substances to be supplied are metabolized at least for the most part in the rumen by the rumen flora and, in any case, are available in a low amount for direct resorption in the following intestinal tract. If a delayed release of the active substance is desired in addition thereto, this poses problems even in monogastric animals, especially when a large dose must be administered, since the active substance is generally either bound to a matrix or is embedded in a matrix and the matrix can usually contain only a small amount of the active substance. Also, diffusion-controlled release of active substances is difficult to coordinate and is hardly suitable for administering large amounts of active substance. Also to be considered is the cost of preparing the dosage forms.
An almost limitless number of suggestions have already been made for solving these problems. They all have in common the fact that the active substance to be supplied is protected against premature release in the rumen or the stomach by embedding it in a matrix or by surrounding it with a coating. A variety of materials can be used for the matrix or the coating. However, none of the known suggested solutions is completely satisfactory because substances must be used as component for the protective materials which are either not legally acceptable for ruminant nutrition or at least not yet or are not readily available, require an expensive pretreatment or the particles prepared with their help tend to adhere during storage and/or are thermally and mechanically not sufficiently stable.
SUMMARY OF THE INVENTION
The object of the present invention is to make available an active-substance preparation which offers a slow-release effect with a broad protection of the active substance in the rumen or the stomach but releases the active substance in the ensuing intestinal tract, which can be produced in a simple and economic manner from as few substances as possible, which are physiologically completely compatible and which are thermally and mechanically stable. Further objects of the invention are to provide for the use of such a preparation to supply ruminants with the active substance.
These and other objects are achieved in a dosage form in which the active substance is enclosed in a coating which has rather thin areas and/or predetermined rupture sites which accelerate the delayed release vis-a-vis an essentially uniform coating.
The term "rupture sites" denotes such areas which result in the separation of entire coating parts as such or in the breaking apart of the active-substance preparation. This can occur e.g. in that an essentially capsule-shaped active-substance preparation breaks apart in the middle or that one or several coverings e.g. of a pellet peel off. The predetermined rupture sites are usually tapered areas or thinner areas, preferably in the form of an annulus. The encasing coating should consist of a material which is not oily but rather preferably brittle at the body temperature of the mammal to which the active-substance preparation is administered. An oily casing would re-cover the predetermined rupture sites in the coating as a consequence of the stomach or intestinal activity, so that the desired effect can not occur. Likewise, coatings which are soft or too elastic are poorly suited for the purposes of the invention, since they break open and release the active substance only with difficulty on account of their shock-absorbing property. On the other hand, the casing should be so stable that the active-substance preparation does not break apart during normal handling. This can also be achieved e.g. in that the active-substance core is not a loose powder but rather is a unitary object, so that minor damage to the coating even prior to oral administration is harmless and no active substance is lost before the administration as a result of damage and only a small opening remains after the oral administration from which the active substance is dissolved only slowly. A sufficient delay of the release of the active substance is also achieved.
The coating is generally built up from a film former. Naturally occurring or modified naturally occurring polymers or homo- and copolymers which can be produced according to customary known methods can be used as film formers. Such suitable polymers are e.g. cellulose esters, cellulose ethers, cellulose acrylates, poly(meth)acrylates, polyamides, polyesters and copolymers of e.g. acrylonitrile, an optionally substituted vinyl pyridine with e.g. styrene, ethylene, propylene, butadiene or esters and amides of methacrylic acid or acrylic acid. A softener such as, e.g., diethylphthalate, polyethylene glycol or a citric-acid ester or further adjuvants such as silica, talcum or alkali stearates or alkaline-earth stearates can optionally be added to the film former. The coating should be selected in such a manner that a peeling off which is not too rapid takes place. According to the invention, film formers can be used which do not permit any or only a very slight (<50%) release of the active substance with a uniform coating but the desired action takes place nevertheless through the predetermined rupture sites.
A coating based on a cellulose ether, preferably ethyl cellulose and in particular such a coating with an additional, inner, filled layer is quite particularly suitable.
The coating is preferably 1.5 to 30% by weight, relative to the weight of the active-substance core. It is advantageous in this instance if the film former is present, again in relation to the weight of the active-substance core, at 1 to 20% by weight and the adjuvant or filler at 0.5 to 10% by weight; a combination of both is the most favorable. The ratio between film former and filler should normally be in the range of 10:1 to 1:5 and a ratio between 5:1 to 1:2 is preferred.
Suitable fillers are especially metal carbonates, silicas, silicates, alginates, stearates, starches and rubbers. Such suitable fillers are e.g. magnesium-, calcium or sodium carbonate, precipitation silica, calcium-, aluminum- or sodium aluminum silicate, calcium-, sodium or aluminum alginate, sodium stearate, corn starch or gum arabic or a mixture of two or more of these substances. The particle size of the fillers is of little importance. The size should be, if possible, distinctly smaller than the layer thickness and is customarily in a range of 0.1-30 μm, preferably 0.7-10 μm.
Especially suitable coatings contain two layers, an inner one consisting of the total amount of the filler and 0.2 to 8% by weight film former, again in relation to the weight of the active-substance core, and an outer layer containing the remainder of preferably the same film former.
Such a coating is sufficiently brittle, so that it breaks up gradually after the oral administration, as a result of which the active substance is released gradually in a delayed fashion. The double coating based on a cellulose ether is also suitable for breaking up and releasing the active substance without the described predetermined rupture sites. Other favorable points, in this connection, are also the simple manufacture, the low material cost and the legal acceptability in accordance with nutrition and feed laws. The combination of this coating with the predetermined rupture sites which aid the break-up is especially advantageous.
The thinner areas, which can also be present in a continuous fashion as an area which is e.g. areal or preferably in the form of closed lines, especially circular lines, advantageously extend over at least 0.5% (areal percent) of the entire surface of the coating and as a rule more than at least 1%. Thin areas are especially suitable which constitute at least 2% of the entire surface of the coating and especially in the case of areal instead of linear thinner areas their area is approximately at least 5% of the entire surface. Normally, the areas of the thinner areas should not exceed 20% of the entire surface of the coating; particularly in the case of linear thinner areas, 10% of the entire surface is generally not exceeded. The thinner area should be at least 20% below the average layer thickness; at least 30% is preferable and especially at least 50%. On the other hand, the thinner area should not be too thin, as otherwise a break can occur too rapidly. It is generally advantageous if at least 10% of the average layer thickness is maintained. Basically, small-area, thinner areas in the layer thickness should be especially thin in order to reliably break open.
The thinner areas and/or predetermined rupture sites are preferably formed by edges. Such edges occur e.g. in pellets or tablets and the thinner areas and/or predetermined rupture sites are readily achieved in that the edges are not dulled before the coating but rather remain as sharp edges. The coating then takes place on the areas thicker than on the edge. Likewise, the entire coating must not be applied in too thick a manner as otherwise the release of the active-substance core will take place too slowly or not at all in spite of the formed thinner areas. 5 to 150 μm, especially 10 to 80 μm and especially preferably 20 to 60 μm were found to be the favorable average layer thicknesses. If the thinner areas and/or predetermined rupture sites are formed by edges, the adjacent areas forming the edges preferably form an angle of ≦120°, preferably ≦90° and especially ≦70°. An angle below 20° should not be used and angles above 45° are preferred. The areas adjoining the edge are preferably not too small, that is, they should have a length vertical to the edge of at least 0.05 mm, preferably at least 0.1 mm and especially at least 0.2 mm. It is advantageous if the edges do not exhibit too great a radius, that is, they should be sufficiently sharp-edged. An edge radius of ≦1 mm, preferably ≦0.7 mm and especially ≦0.5 mm is suitable. It is especially advantageous in this connection if the radius of the edge exhibits at the most the length of the areas adjacent to the edge vertical to the edge; in particular, the radius should be at the most 2/3 and in an especially favorable manner at the most one half of this length. Such edges, especially those with a very small radius, are sufficiently susceptible to mechanical actions and are especially thinly coated, so that the coating breaks open at these edges and the active substance is gradually released.
The successive release of the active substance should be regulated in such a manner for ruminants by the selection of the coating and the design of the coating that 6 hours (≈the average dwell time in the rumen) after oral administration, at the most 50%, preferably at the most 30% and especially at the most 20% has been released. On the other hand, after 24 hours after oral administration, at least 50% by weight, preferably at least 70% by weight and especially at least 80% by weight of the biologically active substance should have been released. It is advantageous if a part of the active substances had been released, even before 6 hours, since this serves e.g. to nourish rumen bacteria As a rule, a release of at least 2% by weight, preferably 5% by weight and especially 10% by weight of the biologically active substance is achieved with the coatings of the invention after 6 hours after the oral administration. In this respect, the coating of the invention is clearly superior to purely pH-dependent coatings since the latter generally release no active substance at all in the rumen and on the other hand they bring about a sudden release of the active substance. For applications other than in ruminants, the release of the active substance is generally adjusted in such a manner that after 2 hours after the oral ingestion, at the most 50% by weight, preferably at the most 30% by weight and especially at the most 20% by weight has been released. Then, after 8 hours, at least 40% by weight, preferably at least 50% by weight and especially preferably at least 75% by weight should have been released. Such values permit an essentially uniform supplying of the organism with the active substance with only two administrations per day. The preparations provided with the thinner areas and/or predetermined rupture sites of the invention generally deliver at least 20% more active substance thereby after the above-cited times than the preparations with an essentially uniformly thick coating, usually even more than 30 and in special instances more than 50% by weight is released.
The coating of the invention has the advantage that its properties can be adjusted in such a manner in accordance with its composition and/or design that the release of the active substance takes place largely independently of the pH of the particular medium or of the presence of enzymes or other breakdown-promoting substances entirely or partially in the areas of the gastrointestinal tract in which the availability of the active substance is desired. For example, it can be arranged that a slight part of the active substance is released in the rumen, as is desirable e.g. in the case of nicotinamide, and/or that the main amount of the active substance is available rapidly, or in a few instances with slow-release effect, in the small intestine, the actual resorption site for the active substance.
It is especially important that cellulose ether and the fillers have previously been used for a long time with success in animal feeding and are accepted without limitation by feed laws.
The designations, "active substance" and "biologically-active substance", as used herein, refer to animal feeds, nutrients and drugs [veterinary-active medications]. These include for example, proteins, amino acids and amino-acid derivatives, vitamins, carbohydrates, hormones and other (animal) medications. Examples of proteins are e.g. feather meal, fish meal, casein or potato protein; of amino acids and amino-acid derivatives: Methionine, lysine, threonine, tryptophane, N-acyl amino acids, hydroxy amino acids or their physiologically compatible (metal) salts or peptides; of vitamins: Vitamin A, vitamin A acetate, vitamin D, vitamin E, nicotinic acid or nicotinic-acid amide, the B vitamins or choline chloride; of carbohydrates: glucose, starch or saccharose; of hormones and (animal) drugs: estrogen, thyrotropin, antibiotics, anthelmintics or paraciticides. Of course, combinations of several such active substances can also be used.
The active substance or the active-substance combination is advantageously formed with a binder into pellets tablets or granulates and compressed using conventional compaction methods such as extrusion, tabletting, spray-, fluid-bed- or agitated granulation. The binder can be substances such as non-toxic rubbers, starch, gelatins, cellulose derivatives, alginates and similar known substances which are customarily used in food or fodder processing as binding, gelling, thickening or tabletting agents.
Other substances such as silicas, silicates, metal carbonates, metal phosphates or metal oxides and alkali-metal stearates can optionally be used as auxiliary flux agents, as lubricants, density regulators or adsorbents for liquid active substances.
The active-substance cores produced in this manner are subsequently encased in such a manner with the protective coating that they are brought into contact with a solution of the film former in which the filler is optionally suspended and the solvent is then evaporated. Suitable solvents can be found among the hydrocarbons, short-chain alcohols or ketones and are e.g. toluene, isopropyl alcohol, methanol, ethanol, acetone or mixtures of such solvents.
The film former, which is soluble therein, is advantageously a cellulose ether which is advantageously insoluble or slightly soluble in water or is a mixture of several such cellulose ethers, but preferably ethyl cellulose.
The filler is selected with advantage from the abovementioned substances. Of course, mixtures of such fillers can also be used. The filler has several advantageous effects: On the one hand, it renders the film former brittle, thus facilitating the breaking up of the coating; on the other hand, it acts like a sponge for the gastric juices (or other juices), which facilitates the breaking off or opening up of the coating, and finally, the filler layer permits the application of a thinner outer layer so that in particular the mechanical peeling off of the coating described above is facilitated. A coating with a high filler content through the entire coating is usually not suitable since the coating disintegrates too rapidly.
The known and customary methods, e.g. various fluid-bed and coating methods are suitable as coating method.
The production of the active-substance preparation in accordance with the invention takes place in a typical instance in such a manner that the active, substance is mixed with 5 to 95% by weight, preferably 10 to 20% by weight, relative to the weight of the active substance, of the binder or of a mixture of the binder and water or a saturated solution of the active substance in water and is pressed to tablets or pellets, or that the active substance is granulated together with the binder. The tablets or pellets should preferably be 0.5 to 2 mm×1 to 5 mm and the (angular) granulates 1 to 2 mm in size; however, they can also be larger or smaller. Pellets and tablets are especially preferred for this coating since the thin areas or predetermined rupture sites are also obtained with them in a simple manner.
After drying, the active-substance cores produced in this manner are first sprayed with the suspension of the filler in a solution of the film former and then with the pure solution of the film former. The coating constitutes 1.5 to 30% by weight, preferably 2.5 to 20% by weight and especially 4 to 14% by weight, relative to the weight of the active-substance core, and contains, again in relation to the weight of the active-substance core, 1 to 20% by weight, preferably 2 to 15% by weight and especially 3 to 10% by weight film former and 0.5 to 10% by weight, preferably 0.5 to 5% by weight and especially 1 to 4% by weight filler.
The coating is generally applied in such a manner that a 2 to 20% by weight, preferably 4 to 15% by weight solution of the film former is prepared in a suitable solvent or solvent mixture and is sprayed on in isolated and sequential steps in such a manner that the inner layer contains, again in relation to the weight of the active-substance core, 0.2 to 8% by weight, preferably 0.2 to 5% by weight and especially 0.5 to 3.5% by weight film former and the entire amount of filler. After the evaporation of the solvent or solvents from this first layer, the remainder of the filmformer solution is sprayed on in order to form a second layer and the solvent or solvents is (are) again evaporated.
If angular active-substance cores such as e.g. pellets or tablets are coated in this manner, then a coating is obtained which is distinctly thinner on the edges. The particle can then break open in the stomach or the intestine at these "weak points", even if film formers such as e.g. cellulose ether, which is partially on top, are used which are only slightly soluble or even non-soluble in the digestive juices. The coating process should naturally take place with caution so that the edges are not rounded off too much.
REFERENCE TESTS
The invention will be illustrated in more detail in the following examples and reference tests. All percent data indicates % by weight.
In order to estimate the protective action of the coating, an in-vitro test can be as a reference which simulates the conditions in the digestive system e.g. of a ruminant at least as regards the pH, the temperature and partially also the motion. To this end, the active-substance preparation produced is incubated in a shaking water bath at 37° C. in three different buffer solutions, one after the other, first for 6 hours in a citrate buffer produced by dissolving 72 g citric acid×1 H 2 O and 19.5 g NaOH in water and diluting with water to 1 liter with a pH of 5.5; then for 2 hours in an HCl/KCl buffer produced by diluting 250 ml 0.2M KCl solution and 65 ml 0.2M HCl solution with water to 1 liter with a pH of 2.0; and finally for 16 hours in a citrate buffer produced by dissolving 42 g citric acid×1 H 2 O and 23 g NaOH in water and diluting with water to 1 liter with a pH of 6.5. Depending on the time indicated, the undissolved component of the active substance in the particles is determined by HPLC and indicated relative to the 100 percent content before the test in the form a % after the incubation at pH 5.5./b % after the incubation at pH 2.0/c % after the incubation at pH 6.5.
It was found that the values obtained in this manner correlate well with results from in-vivo tests and yield a rapid and reliable estimate of the suitability of the tested particles, thereby reducing the need for in vivo testing.
BRIEF DESCRIPTION OF FIGURE OF DRAWING
The invention will be described in more detail by reference to the drawing in which:
FIG. 1 is an elevation view, in cross-section, along the longitudinal axis of a pellet coated according to the invention;
FIG. 2 is an enlarged view of a portion of FIG. 1 marked by broken lines; and
FIG. 3 is a view of the pellet of FIG. 1 with one circular edge broken open.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The surface of a pellet 1 with an active substance core 2 is completely covered by a coating 3. The coating 3 may include a filler 11, which is preferably in the inner layer near the active substance core 2. The end walls 4 of the pellet are concave, thus forming two circular edges 5 with the angle α (dotted lines in FIG. 2). In the area of these edges 5, the coating 3 is considerably thinner than in the other areas of the pellet 1, so that a predetermined rupture site 6 is formed. The formation of the predetermined rupture site 6 and the breaking open of said site is favored by the edges 5 which form an acute angle α with their adjacent areas (i.e., in the given example, the curved surface 7 and the corresponding end wall 4 of the pellet 1).
The angle α is determined by the curved surface 7 and the tangent of the end wall 4 to the edge 5.
Likewise, the radius r of the edge 5 and the length L of the areas 7 and 4 adjacent to the edge 5 (measured perpendicularly to the edge 5) are responsible for the function, that is the breaking open of the predetermined rupture site 6. The length L is measured up to the next considerable change of the corresponding area, i.e., for the given example in the case of the curved surface 7 up to the other edge and in the case of the end wall 4 up to the opposite part of the corresponding circular edge 4. If these lengths L are too small, the predetermined rupture site will be especially thickly coated, so that the desired effect cannot occur.
FIG. 3 shows the pellet of FIG. 1 where the endwall is broken open. At the end wall 4, the coating 3 is broken open like a lid my mechanical action or by partial dissolution of the coating 3 in the area of the predetermined rupture site 6, so that the active substance is released from the core in the area 10.
The following examples illustrate the invention.
EXAMPLE 1
3,600 g DL-methionine and 400 g of the sodium salt of carboxymethylcellulose are placed in a receiver and combined with intensive mixing with 870 g water. The mixture is pressed in an annular grind-and-mix press with 1.5 mm matrix bore to pellets which are cut to a length of approximately 2 mm and dried at 60° C.
100 g of these pellets are sprayed in a coating device, at first with a solution of 0.5 g ethyl cellulose in 25 ml ethanol in which 2.5 g sodium aluminum silicate (particle size 3.5 μm) are suspended. Then, a solution of 3.5 g ethyl cellulose in 95 ml ethanol is sprayed on. The particles coated in this manner are dried under reduced pressure at 60° C. Their methionine content, determined by bromatometric titration, is 83.6% and the undissolved portion of the methionine 75% /63% /18%.
EXAMPLE 2
100 g of the pellets produced according to Example 1 are coated as in Example 1 using a total of 4 g ethyl cellulose (inside 1 g, outside 3 g) and 1.5 g sodium aluminum silicate. The methionine content is 84.6% and the particular undissolved portion of the methionine 70% /56%/13 %.
EXAMPLE 3
100 g of the pellets produced according to Example 1 are coated as in Example 1 using a total of 5 g ethyl cellulose (inside 1.25 g, outside 3.75 g) and 2.5 g sodium aluminum silicate. The methionine content is 83.0 % and the particular undissolved portion of the methionine 77%/64%/21%.
EXAMPLE 4
100 g of the pellets produced according to Example 1 are coated as in Example 1 using a total of 8 g ethyl cellulose (inside 2 g, outside 6 g) and 5 g sodium aluminum silicate. The methionine content is 79.5% and the particular undissolved portion of the methionine 93%/87%/47%.
REFERENCE EXAMPLE 5
The pellets produced according to Example 1 are treated in such a manner in a customary apparatus suitable for this purpose, e.g. in a rounding device, that the edges and webs of the invention are ground off to a large extent. Then, 100 g of the pellets rounded in this manner are coated as in Example 1 using a total of 4 g ethyl cellulose (inside 0.5 g, outside 3.5 g) and 2 g sodium aluminum silicate. The methionine content is 84.8% and the undissolved portion of the methionine 94%/91%/74%.
This reference test shows that after the edges and webs have been ground off, thus eliminating predetermined rupture sites, by far the greatest part of the methionine still remains undissolved even after 24 hours.
EXAMPLE 6
100 g of the pellets produced according to Example 1 are coated as in Example 1 using a total of 5 g ethyl cellulose (inside 1.25 g, outside 3.75 g) and 2.5 g ammonium alginate as filler. The methionine content is 84.1% and the undissolved portion of the methionine 86%/76%/34%.
EXAMPLE 7
100 g of the pellets produced according to Example 1 are coated as in Example 1 using a total of 5 g ethyl cellulose (inside 1.25 g, outside 3.75 g) and 2.5 g magnesium carbonate as filler. The methionine content is 83.4% and the undissolved portion of the methionine 91%/82%/43%.
EXAMPLE 8
100 g of the pellets produced according to Example 1 are coated as in Example 1 using a total of 5 g ethyl cellulose (inside 1.25 g, outside 3.75 g) and 2.5 g starch as filler. The methionine content is 83.4% and the undissolved portion of the methionine 84%/75%/31%.
EXAMPLE 9
100 g of the pellets produced according to Example 1 are coated as in Example 1 using a total of 5 g ethyl cellulose (inside 1.25 g, outside 3.75 g) and 2.5 g gum arabic as filler. The methionine content is 83.8% and the undissolved portion of the methionine 91%/83%/40%.
EXAMPLE 10
100 g of the pellets produced according to Example 1 are coated as in Example 1 using a total of 5 g ethyl cellulose (inside 1.25 g, outside 3.75 g) and 2.5 g sodium stearate as filler. The methionine content is 82.9% and the undissolved portion of the methionine 78%/65% /18%.
EXAMPLE 11
The same method is used as in Example 1, but 400 g starch are used instead of the sodium salt of carboxymethylcellulose in the production of the active-substance pellets. 100 g of these pellets are coated as in Example 1 using a total of 5 g ethyl cellulose (inside 1.25 g, outside 3.75 g) and 2.5 g sodium aluminum silicate as filler. The methionine content is 84.2% and the undissolved portion of the methionine 80%/69%/29%.
EXAMPLE 12
The same method is used as in Example 1, but 360 g starch and 40 g sodium stearate are used instead of the sodium salt of carboxymethylcellulose in the production of the active-substance pellet.
100 g of these pellets are coated using a total of 3.5 g ethyl cellulose (inside 1 g, outside 2.5 g) and 2 g sodium aluminum silicate as filler. The methionine content is 85.5% and the undissolved portion of the methionine 66%/54%/8%.
EXAMPLE 13
100 g of the pellets produced according to Example 12 are coated using a total of 4 g ethyl cellulose (inside 1 g, outside 3 g) and 2 g sodium stearate as filler. The methionine content is 84.8% and the undissolved portion of the methionine 73%/63%/19%.
REFERENCE EXAMPLE 14
100 g of the pellets produced according to Example 1 are coated in only one layer with a solution of 7.5 g ethyl cellulose in 200 ml ethanol without using a filler. The methionine content is 83.4% and the particular undissolved portion of methionine 88%/81%/54%.
This reference test shows that, given a relatively thick and elastic coating of the active-substance core in one layer, the greatest part of the methionine remains undissolved even after a total of 24 hours.
EXAMPLE 15
100 g of the pellets produced according to Example 1 are coated in only 1 layer with a solution of 5 g ethyl cellulose in 400 ml ethanol in which 2.5 g sodium aluminum silicate are suspended. The methionine content is 83.1% and the particular undissolved portion of the methionine 36%/19%/0%.
This test shows in comparison to Example 3 that the coating with the same amount of ethyl cellulose and sodium aluminum silicate but in only one layer protects the methionine only to an insufficient extent from dissolution already under the conditions in the rumen.
On the other hand, this coating is suitable for non-ruminants since only 81% of the active substance has been released after 8 hours. The slow-release effect obtained brings about a uniform supplying of the organism with the active substance in 2 doses/day.
ANIMAL TESTS
The following investigations using animal tests demonstrate the superior action of the product of the invention. The rise of the methionine content in the blood plasma of milk cows was examined. Since all nutrients contained in milk and their precursors are supplied to the mammary gland with the blood stream, the methionine from a protected product must arrive there in the blood.
PRELIMINARY TEST
The extent of the rise of methionine in the blood plasma upon administration of defined amounts of protected methionine is tested in preliminary examinations in which methionine preparations are introduced directly into the abomasum after 6 hours pre-incubation in the rumen (simulation of the natural dwell time).
The product to be tested was sewn in portions of 25 g into nylon bags (30 μm pore size) and pre-incubated for 6 hours in the rumen of the test cows (3 animals) (max. 6-8 bags per animal). After having been removed, the bags were cleaned of fodder particles but not washed. The contents of all bags were pooled and weighed to determine the substance loss. The methionine content was determined in a specimen of the pre-incubated, pooled material, from which the methionine amount which disappeared during the 6 hours can be calculated at 17% by weight and the amount of rumenstable methionine at 83% by weight. A known product which was also tested (reference Example 17) was 100% stable in the rumen.
The pre-incubated material was then weighed into gelatin capsules which dissolve within a few minutes in the abomasum. The administration took place four times daily in the 3 animals through the rumen fistula directly into the abomasum. 25 g methionine per day was administered in this manner over a period of four days (day 1-4).
Day 0 served for obtaining the control parameters. On days 0, 3 and 4 blood samples were taken from the animals by means of puncturing the Vena jugularis at 1 P.M. and 4 P.M. The content of free methionine in the rumen was determined in these samples. There was a rise of the plasma methionine level of approximately 100% in the middle of days 3 and 4 in comparison to day 0.
EXAMPLE 16 AND REFERENCE EXAMPLE 17
In the test, the animals received (4 per product) 30.6 g DL-methionine in the form of pellets produced according to Example 12 which were coated using a total of 4% by weight ethyl cellulose relative to the weight of the active-substance core (inside 0.5%, outside 3.5%) and using 2% by weight sodium aluminum silicate as filler (Example 16) and received 25 g in the form of active-substance granulates which contain 50% by weight DL-methionine and obtain their protection from a coating with monocarboxylic acids with 14-22 atoms (reference Example 17). The animals received the above in a complete ration which consisted of 10% hay, 30% grass silage, 20% corn silage (together 15 kg dry mass/day) and 40% of a grain/coarse soya bean meal feed concentrate (6 kg dry mass/day).
Such products are known from European patent EP 0 037 478 and German DE patent 22 12 568 and are commercially obtainable.
The amounts were calculated in such a manner that, based on the rumen stability of the products measured in the preliminary test, approximately 25 g DL-MET should pass into the small intestine (83% stability for Example 16 and 100% for reference 17). The preparations were administered for 12 days (day 1-12). On days 0, 10, 12 and 14, blood samples were taken (Vena jugularis, 11.50 A.M. and 2.50 P.M.). The table shows the results of the measurements.
The methionine content rises in the blood plasma in both instances. The rise in Example 16 with 188% on day 10 is distinctly higher in comparison to reference 17 with 28%. On day 12, the last day of the oral administration, the corresponding values are +151% and +5%. Two days after discontinuation, the methionine content in the blood plasma has fallen back again to the starting level and in the reference treatment it is even 10% below the starting value.
The differences in the methionine content in the manure correspond to these findings. Whereas in the middle of days 10 and 12 0.074% methionine was found in the manure of the four cows in Example 16, 0.246% was found in reference 17.
__________________________________________________________________________The Influence of Protected Methionine Products on the Plasma MethionineLevel of Cows after aFeeding with Feed Concentrate (KF) (average of 4 cows and 2 times ofday) daily MET (g) in the Blood MET level (μmole/l) Rise of the Blooddaily MET small intestine Control No MET MET-Leveladministration (calculated from two values each (rel. increase in %)via the KF (g) preliminary test) Day 0 Day 10 Day 12 Day 14 Day 10 Day Day__________________________________________________________________________ 1430.6 25.4 8.3 ± 4.0 23.8 ± 8.8 20.8 ± 6.0 8.4 ± 5.8 188 151 125.0 25.0 13.4 ± 4.2 17.2 ± 4.8 14.1 ± 5.9 12.1 ± 4.5 28 5 -10__________________________________________________________________________ | 1a
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BACKGROUND OF THE INVENTION
This invention pertains to a catheter designed to couple radiofrequency (RF) energy to biological tissue surrounding the catheter tip. Typical application is in thermal ablation of cardiac tissue.
Percutaneous ablation is a therapeutic procedure used with increasing frequency for treatment of ventricular tachycardia. It works by destroying cardiac tissue responsible for the disease. For example, this subject is covered in Ablation in Cardiac Arrhythmias, G. Fontaine & M. M. Scheinman (Eds.), Futura Publishing Company, New York, 1987. A recent review of this field is given in a chapter by D. Newman, G. T. Evans, Jr., and M. M. Scheinman entitled "Catheter Ablation of Cardiac Arrhythmias" in the 1989 issue of Current Problems in Cardiology, Year Book Medical Publishers.
Currently, catheter ablation is performed by delivering a high voltage direct current pulse from a standard defibrillator through an electrode catheter designed for temporary pacing. Radiofrequency (RF) ablation using electrosurgical power units is in clinical investigation, as a safer ablation alternative to high voltage direct current pulses. Continuous, unmodulated RF output in the frequency range of 500 KHz to 1.2 MHz is typically used. (RF without qualifiers refers to the electromagnetic spectrum from 10 kHz to 100 GHz.) Laser energy is also being tested for catheter ablation of arrhythmias.
Some experimentation has been reported with the use of microwave energy for catheter ablation. U.S. Pat. No. 4,641,649 issued Feb. 10, 1987 to P. Walinski, A. Rosen and A. Greenspon describes a catheter consisting of a miniature coaxial line terminated in a protruding inner conductor antenna. This system operates at 925 MHz. Another microwave ablation catheter experiment has been reported by K. J. Beckman, & J. C. Lin et al, "Production of Reversible Atrio-Ventricular Block by Microwave Energy" abstracted in Circulation 76 (IV): IV-405, 1987. Technical details of a folded dipole applicator catheter used by Beckman have been described by J. C. Lin and Yu-jin Wang in "An Implantable Microwave Antenna for Interstitial Hyperthermia" in Proceedings of the IEEE, Vol. 75 (8), p. 1132, August, 1987. An earlier microwave applicator which fits into a blunt-ended mylar catheter has been described by B. E. Lyons, R. H. Britt, and J. W. Strohbehn in "Localized Hyperthermia in the Treatment of Malignant Brain Tumors Using an Interstitial Microwave Antenna Array", IEEE Trans on Biomedical Engineering, Vol. BME-31 (1), pp. 53-62, January, 1984.
A general geometrical requirement of catheter-based applicators is that they must be confined in slender cylindrical structure with a radius commensurate with the catheter diameter. In the discussion of catheter applicators which follows, it is convenient to adopt a cylindrical coordinate system with the z-axis coincident with the catheter axis and pointed toward the distal end. The radial component is at the direction normal to the z-axis and the circumferential component has a direction around the z-axis. Radius "r" is measured from the catheter axis. The catheter diameter is "a".
A common feature of all of the above RF catheters (the laser catheter which is an optical device will not be discussed further) is that the energy delivery is predominantly via an electric field (E-field) originating at the applicator's electrode/tissue interface. This class of catheter applicator will therefore be referred to as E-field applicators. Although the configurations of the E-field applicators described above vary, the E-field coupling causes a rapid decrease in current density and therefore tissue heating, as a function of distance from the electrode.
In order to represent the state of the art of RF heating catheters and to compare it with the preferred embodiment of this invention, a simplified E-field applicator is shown in FIG. 1A. Applicator electrode 10 is a wire immersed in a lossy dielectric medium which has electrical properties typical of muscle tissue. In spite of the simple geometry and low frequency approximation used in the description, FIG. 1 retains the salient feature of an E-field coupling.
In FIG. 1A, RF potential V14 is applied between applicator electrode 10 and a remote boundary 15 which corresponds to a neutral electrode applied to the skin. The exact location of boundary 15 is not important to the shape of the E-field near applicator electrode 10. Radial electric field E16 coincides with current density vector J r =σE r in the tissue, where σ is the conductivity of the tissue.
Continuity of current in a cylindrical geometry in FIG. 1 results in current density which decreases with the inverse square of the radius r. Therefore, corresponding electrical power dissipation resulting in heating of tissue decreases with the fourth power of a/r. Typically, an electrode radius is limited by practical catheter size to a maximum of 1 mm. In order to effectively ablate ventricular tachycardia (see Moran, J. M., Kehoe, R. F., Loeb, J. M., Lictenthal, P. R., Sanders, J. H. & Michaelis, L. L. "Extended endocardial Resection for the Treatment of Ventricular Tachycardia and Ventricular Fibrillation", Ann Thorac Surg 1982, 34: 538-43), it is desirable to heat tissue up to 10 mm from the catheter axis. In the applicator represented by electrode 10 in FIG. 1A, heat dissipation at the catheter surface is 10,000 times more intense than heat dissipation at a 10 mm radius.
In order to examine the effect of this wide range of heat dissipation, it is useful to divide the lossy medium in FIG. 1A into three cylindrical shells: first shell R11 adjacent to the applicator electrode 10, followed by shell R12, and R13 beginning at the 10 mm radius. Since the shells are traversed by the same current and the potential drop across the shells is additive, energy delivery can be represented by three resistances R11, R12, and R13 in FIG. 1B, connected in series with the source of RF potential V14.
A very steep heating gradient at the applicator electrode 10 tends to desiccate blood or tissue close to the electrode, increasing the resistivity of R11. This in turn further increases the relative power dissipation in R11 in comparison with R12 and R13, until effective impedance of the desiccated region R11 becomes, in effect, an open circuit shutting off the flow of RF power to the tissue beyond R11. This indeed is the problem of state-of-the-art RF ablation catheters which severely limits effective heat delivery to more distant tissue.
Insulation of the applicator electrode 10 from the tissue does not reduce the heat dissipation gradient: If the applicator electrode 10 is insulated from the lossy medium by a thin dielectric tube, the effect of the dielectric can be represented by capacitor (not shown) in series with the source of RF potential V14. Now the applicator must be operated at a frequency high enough so that the impedance of the sum of resistances R11 and R12 and R13 must be higher than the capacitive impedance of the dielectric tube. R11 still dominates the heat distribution.
Therefore in biomedical applications, there is a need for a catheter-compatible RF energy delivery system which dissipates heat more uniformly to a specified depth, thereby leading to a more accurately controlled and larger ablated region. It is also desirable to eliminate the effect of desiccation of tissue adjacent to the electrode on heat dissipation to surrounding tissue.
OBJECT OF THE INVENTION
Accordingly, the principal object of the invention is an RF energy applicator which is housed in a biomedical catheter, typically of 2 mm diameter. This applicator exhibits deeper and more uniform heat dissipation and is not subject to power reduction from desiccation of tissue in the proximity of the applicator, typical of state-of-the-art devices.
A further object of the invention is a cardiac ablation system which provides monitoring and control of RF power fed to the catheter and which also provides signal processing, monitoring and display of the intracardiac electrogram. In this application, the RF energy applicator is configured to allow recording of intracardiac electrograms in proximity to the catheter tip. This is important in order to accurately localize the cardiac tissue to be ablated.
A still further object of the invention is a localized hyperthermia system for cancer treatment, where the catheter with RF energy applicator offers adjustable depth of heating compatible with a tumor size. This system also provides monitoring and control of RF power fed to the catheter for proper thermal dosimetry.
Further advantages of the invention will become apparent from the consideration of the drawings and the ensuing description thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A shows the electric field (E-field) applicator represented by a conductor immersed in a lossy dielectric medium (state of the art).
FIG. 1B is an equivalent circuit of heat delivery of an E-field applicator (state of the art).
FIG. 2A shows a solenoidal applicator in the form of a helix immersed in a lossy dielectric medium.
FIG. 2B is an equivalent circuit of heat delivery of a solenoidal applicator.
FIG. 3 shows details of a catheter tip mounted solenoidal applicator with intracardiac electrogram monitoring capability.
FIG. 3A and FIG. 3B show magnified details of the circled portions of FIG. 3.
FIG. 4 is a block diagram of RF heating and intracardiac electrogram monitoring ablation catheter system.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIGS. 1A and 1B, which illustrate the problems inherent to state-of-the-art E-field applicators, have already been discussed in the Background section above.
FIG. 2 shows a conductor in the form of a helix 20 traversed by RF current I24. A helix radius in a catheter application is typically a=1 mm and maximum desired radius of tissue heating for cardiac ablation is R=10 mm. The resultant magnetic field typified by H21, H22, and H23 has primarily an axial (z) component and induces a transverse electric field E.sub.φ typified by E21, E22, and E23 (and a proportional current density not shown), primarily in the circumferential direction around the helix. The circumference of E22 corresponds to R.
At an operating frequency of 915 MHz, and within a cylinder of a radius of 10 mm, the magnitude of induced electric field E.sub.φ (and corresponding current density J=σE.sub.φ) decreases approximately as a/r, where a is the radius of the helix. The z component of electric field E z , which follows field lines similar to H 21 , H 22 and H 23 , decreases with radius r even more slowly than a/r. Hence the heating power dissipation decreases no faster than (a/r) 2 . For a typical catheter radius a=1 mm and desirable depth of heat penetration in ablation R=10 mm, the ratio of heat dissipation at the catheter wall to heat dissipation at R=10 mm is approximately 100:1. It should be noted that this is a major improvement over the ratio of heat dissipation for the E-field applicator which for the same conditions is 10,000:1.
With a solenoidal applicator, the effective heat dissipation radius R can be adjusted: R increases with decreasing frequency. For ablation of cardiac arrhythmias, ISM (industrial, scientific, and medical) frequencies of 915 MHz and 2450 MHz are of interest. For hyperthermia treatment of cancer, a wider gamut of frequencies is needed depending on the size of a tumor.
FIG. 2B shows an equivalent circuit of a helical heating applicator. Within a volume inside a radius of 10 mm, a circular induced electric field E 100 multiplied by the length of its circumference gives a potential around each cylindrical shell which is approximately equal. The shell of lossy medium adjacent to the helix, energized by E21, the shell at the intermediate distance energized by E22, and the shell corresponding to R=10 mm energized by E22, appear in FIG. 2B as parallel resistances R21, R22, and R23 respectively, exposed to the same potential. Current source I24 feeds the three resistances.
Now, if desiccation occurs adjacent to the helix, resistance R21 increases. This reduces power dissipation in R21 and increases power dissipation in resistances R22 and R23. In general then, as power is increased to a point of desiccation at a catheter surface, the heat delivered to a desiccated volume decreases in a solenoidal applicator while it increases in an E-field applicator. Thus, the solenoidal applicator is much less likely to cause excessive desiccation but even if desiccation occurs, it will not lead to a decrease in power dissipation in remote tissue at R=10 mm.
The helix in FIG. 2A is an example of a solenoidal applicator structure, characterized in general by current loop or loops and an electrical short as an end termination. Solenoidal applicator generates a magnetic field in the surrounding tissue. This magnetic field by induction generates in turn, an electric field and current which heats the tissue. In contrast, the E-field applicator has an electrical open end termination and the primary, rather than induced, electric field heats the tissue.
The preferred embodiment of the helical solenoidal applicator in an ablation catheter is shown in FIG. 3. Coaxial line 43 consists of a center conductor 44 (0.16 mm diameter), a dielectric 46 (1.35 mm outside diameter), a metal braid 45 and insulating sleeve 57 (1.8 mm outside diameter). Small diameter and flexible construction makes the coaxial line 43 suitable for a biomedical catheter application. Helical winding 50 is wound on a ceramic or ferrite core 51. A heat-shrunk TEFLON(TFE: Tetrafluoroethylene sleeve 53 covers the helical winding 50.
Distal end of the helical winding 50 is connected at distal peripheral terminal 58 to distal electrode 56 and to bypass capacitor 55. Bypass capacitor 55 is connected to braid 45 through metallized coating 52 on the inside of core 51. The function of the bypass capacitor 55 is to ground the RF energy. Thus during RF current flow through helical winding 50, distal electrode 56 has no RF voltage thereby preventing E-field heating. Distal electrode 56 in conjunction with a proximal ring electrode 47 picks up a cardiac electrogram voltage between them. The distance from the beginning of proximal ring electrode 47 to the end of the distal electrode 56 is 20 mm.
A number of turns on the helical winding 50 is chosen so that at an operating frequency of 915 MHz, the helix is somewhat short of being a quarter wavelength resonator. The proximal end of the helical winding 50 is connected to a variable tuning capacitor 48 at proximal peripheral terminal 49. Variable tuning capacitor 48 is moved with respect to neutral electrode 47 during manufacture for tuning to a precise quarter wavelength resonance. Details of the tuning capacitor 48 are shown magnified in FIG. 3A.
RF power is coupled into the helical resonator by connecting the center conductor 44 to the helical winding 50 at feed terminal 54. The connection at feed terminal 54 is shown magnified in FIG. 3B. The position of feed terminal 54 on the helix is selected for good match between the characteristic impedance of the line and the impedance of the resonator.
The choice of an axial quarter wavelength resonator is by no means unique. One could just as well select any multiplicity of quarter wavelengths e.g., half wavelength or full wavelength resonators.
In some applications, it may be desirable to distort the axisymetrical form of the induced E-field. This can be accomplished by partially covering a dielectric sleeve 53 with metal foil (not shown). Currents induced in such foil modify the shape of a heating pattern and so serve as an aperture antenna. An asymmetrical field pattern can also be accomplished by a loop antenna.
In cardiac ablation, it is highly desirable to be able to monitor intracardiac electrogram just before and after the application of heat. FIG. 4 shows a block diagram of a system which combines dosimetry control of the solenoidal heat delivery with monitoring of intracardiac electrograms.
The RF power is generated in an RF power source 41. The RF power is controlled and monitored in controller 42 which couples the RF power to the coaxial line 43 through capacitor 62, which for RF represents substantially a short-circuit.
The center conductor 44 is attached at feed terminal 54 to the helical winding 50 wound on a core 51. Quarter wavelength resonance tuning is accomplished by adjustment of variable tuning capacitor 48 connected to the helical winding 50 at proximal peripheral terminal 49. The RF ground is maintained by the bypass capacitor 55 connected to the distal electrode 56 and then to helical winding 50 at distal peripheral terminal 58.
Distal electrode 56 in conjunction with the proximal ring electrode 47 picks up the local intracardiac electrograms and feeds this electrogram signal through the coaxial line 43 to capacitor 62. Capacitor 62 represents a short circuit for the RF power and an open circuit for the much lower frequency band (typically 0.1 Hz to 100 Hz) associated with intracardiac electrogram activity. The electrogram signal appears therefore on lines 63 and 64 at the input to the low-pass filter 61.
Filter 61 has a high input impedance to the RF and hence has no effect on transmission of RF power between controller 42 and coaxial line 43. Filter 61 blocks the transmission of the RF power to switch 60 while allowing passage of the electrogram signal. Switch 60 is closed simultaneously with application of RF power, thus providing additional protection for monitor 59. Electrogram signal processing, display, and recording is accomplished by monitor 59. Standard existing equipment is suitable for application as monitor 59.
Solenoidal catheter applicator for hyperthermia treatment of tumors follows largely the same design as the one represented in FIG. 3 except that in this case, there is no need for the distal electrode 56 and the proximal ring electrode 47. Since the depth of heat penetration depends inversely on the square root of frequency, the frequency of operation and the helical winding design can be tailored to the required depth of penetration depending on tumor size.
While certain specific embodiments of improved RF heating applicator and systems have been disclosed in the foregoing description, it will be understood that various modifications within the scope of the invention may occur to those skilled in the art. Therefore it is intended that adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. | 1a
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CROSS-REFERENCE TO RELATED APPLICATIONS
This is a continuation of application Ser. No. 08/400,336 filed Mar. 8, 1995 now abandoned, which is a continuation-in-part of application Ser. No. 08/259,744 filed Jun. 14, 1994 now abandoned, which is a continuation of application Ser. No. 08/024,601 filed Mar. 1,1993 now abandoned.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates in general to athletic shoes, and in particular relates to athletic shoes for sports such as running, jogging and cross-training.
More particularly, the invention relates to athletic shoes having midsole portions which provide independent shock absorption of corresponding forces and concomitant gait control.
2. Description of the Related Art
Recent developments in the design of athletic shoes have led to relatively lightweight shoes with soles formed of materials selected for optimum cushioning and flexibility and with minimal sole wear. Despite these improvements in shoe design, many individuals continue to develop injuries which can be traced to foot problems and shortcomings in the design of the shoes they are wearing. Among these problems are Achilles tendonitis caused by physiological defects such as short Achilles and problems such as an unstable heel, inverted heel, weak arch and excessive use of toe flexers; metatarsal stress fracture caused by an unstable heel, pronatory abnormalities and forefoot problems; and runner's knee (chondromalacia) caused by conditions such as weak foot, forefoot varus, Morton's foot and pronatory foot influences including an unstable heel.
Among the solutions which have been employed to correct the foregoing problems are the use of orthotics that are prescribed for particular individuals. The orthotics are fitted within the heel cup of a shoe to control pronation throughout heel and forefoot contacts during the gait cycle. Certain shoes have been designed which incorporate a varus wedge which operate in a similar manner to orthotics for control of foot pronation. Other designs incorporate a flared sole construction resulting in a pyramid shaped midsole which has the objective of providing more stability for the shoe during rear foot impact.
Various attempts have been made to prevent overpronation or oversupination of the wearer's foot as the shoe strikes the ground. These include stiffening the heel counter, and upward extension of the midsole area to encompass at least a portion of the upper. In addition, new materials have been incorporated into shoe designs to increase strength.
All prior ideas and shoe designs have been attempts to stabilize the foot by increasing the structural strength of shoe. None of the prior shoe designs have controlled the wear on the shoe while simultaneously allowing for differences in the individual gaits and concomitant forces placed on the shoe by the individual's foot.
Despite various conventional improvements in shoe design, injuries continue to occur due to the fundamental flaw of not providing a mass produced shoe which can adjust to the needs of each individual wearer. The most frequently recurring problems are due to instability in the wearer's heel, arch and toe areas due to the inability of the shoe to adjust to the particular wearer's gait and corresponding varying forces. These features also tend to interfere with the natural gait of the wearer, e.g. by raising the level of the wearer's heel, or by accelerating pronation of the individual's foot during normal walking or running activity.
FIG. 1 illustrates a prior art conventional shoe 10 comprising an upper 12 and sole 18. During the initial heel strike phase of the running cycle the shoe is in the normal supinated position, as illustrated in FIG. 1, when viewed from behind for the right shoe of an individual. The maximum shock forces are absorbed by the sole and heel portions during the initial phase of heel strike. These forces, in conventional shoes, compress the outer rim of the sole at 16, which also tends to collapse or flex the upper heel wrap at 17 creating correlative forces shown by the arrows at 20 on the upper, at 22 on the heel wrap and at 24 on the sole. The correlative forces create abnormal shock absorption and stress on the sides of the shoe and the runner's foot. The corresponding result is an abnormal transfer of force upon the runner's foot during normal walking or running. This results in decreased stability and control for the runner's heel.
The feet of most runners strike the surface in a supinated position and tend to pronate, i.e. rotate toward the medial side, as they continue through the running cycle. Conventional shoes of the type shown in FIG. 1 do not provide adequate support for this type of motion. Certain prior art shoe designs have attempted to alleviate the foregoing problem by incorporating various grooves and channels within the outsole of the shoe. However, these grooves or channels are not sufficiently deep to permit the sole to independently react to shock absorption relative to the left lateral and right lateral portions of the sole and upper. The conventionally designed grooves, as shown in 23 of FIG. 1, do not allow the left and right lateral halves of the sole to independently react to the runner's foot when corresponding forces are placed on the runner's foot upon impact.
OBJECTS AND SUMMARY OF THE INVENTION
It is an object of the present invention to provide an athletic shoe which obviates the problems that arise from overpronation and oversupination.
It is another object to provide an athletic shoe which combines a rigid heel counter with a sole that is divided by a channel into lateral and medial compression elements so that there is independent absorption of shock forces between the lateral and medial portions of the runner's foot.
Another object of the present invention is to provide an athletic shoe which combines a rigid heel counter with a sole which is divided by a channel into lateral and medial compression elements. The compression elements independently react in relation to the runner's foot and keep the heel in proper alignment such that the body is in a more natural position to absorb shock.
The present invention in summary provides an athletic shoe having an upper with a rigid heel counter in combination with a sole which is divided into medial and lateral independent compression elements. The compression elements are separated by a deep channel which is spaced apart sufficiently to isolate the elements so that pronation movement of the shoe throughout the heel strike and loading phases is with low acceleration.
The foregoing and additional objects and features of the invention will appear from the following specification in which the embodiments have been set forth in detail in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a rear elevational view of a prior art athletic shoe shown in a supinated position following initial heel contact with a surface.
FIG. 2 is a side elevational view of an athletic shoe incorporating one embodiment of the invention.
FIG. 3 is a cross sectional view taken along the line 3--3 of FIG. 2.
FIG. 4 is a bottom plan view of the shoe of FIG. 2.
FIG. 5 is a rear elevational view of the present invention shown at a position just following initial heel contact with a surface.
FIG. 6 is a chart depicting the results of a heel strike motion study analysis for shoes of the present invention in relation to barefoot runners and to those wearing conventional athletic shoes.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 illustrates generally at 10 a prior art athletic shoe having an upper 12 mounted to a sole 18. The sole 18 is formed with a shallow longitudinal channel 23. The purpose of the channel 23 and sole 18 is to provide better traction and stability for the runner during normal and stressed gaits. FIG. 1 depicts the rear view of the right shoe worn by an individual at the heel strike phase when the foot is in a supinated position. The full gait cycle is from the heel strike phase to a loading phase at which the sole is flat on the surface, then to a pronation phase at which the shoe continues to rotate to the medial side, then to a forefoot phase, and then to a toe off phase.
At the time of initial heel contact in the supinated position, the lateral edge of the sole 18 is compressed at 16 and 17. This occurs as the impact force begins to be absorbed by the sole and is carried out through the shoe to the foot. The weight of the individual pressing down along the line above the point of impact creates a pressure which tends to collapse the upper at 20. Correlative forces 22 and 24 are thus exerted inward and downward forcing the medial portion of the right shoe to absorb a portion of the shock exerted on the lateral portions. This creates an unnatural absorption of shock on the runner's foot between the medial and lateral sides of the shoe and imparts an unnatural transfer of forces within the shoe. Similar conditions and results occur on the runner's left shoe (not shown) when it strikes a surface.
In the drawings FIGS. 2-5 illustrate generally at 26 an athletic shoe incorporating one preferred embodiment of the present invention. The shoe 26 is adapted for wearing on the user's right foot and comprises an upper 28 joined to a sole 29. The sole comprises a midsole 30 which is joined to an outsole 32. The midsole and outsole are formed of suitable synthetic polymer materials having properties of durability, flexibility and resiliency for cushioning the foot during the running cycle.
Upper 28 is slip lasted and comprises an outer lining 34, which can be of a suitable material such as leather or synthetic leather, an inner lining 36, which can be of a thin foam material of substantially 3 mm thickness, a foam insole 38 and a lasting board 40 which can be of a suitable stiff material having limited flexibility. The outer and inner linings, insole and lasting board extend substantially the entire length of the shoe. The heel portion of the shoe includes a rigid heel counter 42 for supporting and stabilizing the wearer's heel within the shoe. On the opposite medial and lateral sides of the shoe the heel counter is layered between outer liner 34 and inner liner 36.
A midsole wrap or support band 44 is provided for resisting flexing of the sides of the heel cup relative to the midsole. The support band extends around the sole's outer periphery at the juncture between the upper and midsole, and can either be formed integrally with the midsole as shown in FIG. 3 or it can be a separate piece secured as by fusion to the midsole during manufacture. The support band functions in the manner explained in U.S. Pat. No. 4,322,895 for Stabilized Athletic Shoe issued Apr. 6, 1982 to Stan Hockerson, the inventor of the present invention.
A longitudinally extending, upright channel 46 is formed through the midsole and outsole. The channel penetrates rearwardly through the peripheral rim 47 of the heel portion which is thereby divided into a pair of laterally adjacent compression elements 48 and 50. Channel 46 extends forwardly to a point 48 near the instep region 50 of the sole, as illustrated in FIG. 4. The upper edge of the channel extends to a point closely adjacent the lower portion of upper 28. This leaves only a thin connecting portion 52 which is sufficiently weak to allow substantially independent movement between the two compression elements. The interior sidewalls 54, 56 of the compression elements are spaced apart by a distance 58 (FIG. 4) which is sufficiently wide to isolate the compression elements from the motion of their interior sidewalls during heel strike of the sole onto a surface. This permits independent movement or reaction of the compression elements relative to each other. The width 58 is in the range of 1 mm to 10 mm, and preferably 3 mm. The channel 46 extends longitudinally only through the heel portion of the shoe to allow for independent absorption of forces upon the compression elements as the shoe begins to pronate, i.e. rotate toward the medial side, from the supinated position following initial heel contact as shown in FIG. 5.
It is an important feature of the present invention that the longitudinal channel 46 and compression elements 48 and 50 are in combination with the rigid heel counter 42 in the shoe's upper. Athletic shoes in the prior that are formed with sipes or slots in the soles, such as described in PCT patent publication no. WO 91/05491 dated May 2, 1991 to Ellis, do not include either rigid heel counters or rigid motion control devices. In the type of shoe exemplified by the Ellis patent a rigid heel counter or motion control device would significantly reduce flexibility in the frontal plane, which is an important aspect to shoes of that type. In the present invention the combination of the longitudinal channel, independent compression elements and rigid heel counter results in natural heel strike followed by control of the foot throughout the pronation and forefoot phases of motion.
The use and operation of the invention will be explained in relation to the runner's right shoe, and it is understood that a left shoe, which would be a mirror image of the illustrated shoe 26, would operate in a similar manner. For a typical runner, the runner's foot and shoe are in a supinated position at the time of heel strike such that the lateral edge of compression element 50 makes initial ground. Compression element 50 is then compressed to a greater extent along its lateral side, permitting the underlying portion of outsole 32 to smoothly move into flat contact with the ground as pronation begins. Because channel 46 extends up substantially the entire thickness of the midsole, the change in shape and movement of lateral compression element 50 is independent of that of compression element 48. This permits the runner's foot to make a more natural heel strike during the loading phase. As pronation movement continues the lateral edge of medial compression element 48 makes ground contact to segue into the loading phase, causing this element to also compress and move relative to the shoe into a shape permitting the underlying portion of outsole 32 to smoothly move into flat contact with the ground. The pronation phase then begins, afterwhich movement of the runner causes the weight to shift forward, moving the shoe into the forefoot phase followed by the toe off phase. Throughout the heel strike, loading and pronation phases the rigid heel counter 42 in combination with the action of the compression elements maintains substantially natural heel motion.
The invention obviates the problem in conventional running shoes of the acceleration of motion that occurs during pronation motion from the lateral to the medial side. The acceleration of pronation motion occurs in connection with conventional athletic shoes because the lateral and medial portions of the midsole and outsole at the heel are connected. Thus, compression motion on the lateral side causes the medial side to react and move.
The chart of FIG. 6 graphically shows the results of a motion study analysis which compared shoes of the present invention with conventional athletic shoes and barefoot running by measuring the differences in elapsed time from heel strike to the loading phase for different runners. The analysis was conducted using a machine adapted to measure the motion of points on the lateral and medial sides of the shoes, or of the runner's foot in the case of the barefoot tests. The abscissa of the chart ranks the individual runners, who were of different heights and weights. Three tests were conducted for each of the runners, one test with the runners wearing a pair of shoes according to the present invention, another test wearing a pair of conventional shoes, and another test running barefoot. The ordinant of the chart plots the time in seconds from heel strike to the loading phase. The line 60 plots the time for the prior art conventional shoes, the line 62 plots the time for the shoes incorporating the present invention, and the line 64 plots the time for barefoot runners. The results show that the shoes incorporating the present invention, because the time from heel strike to the loading phase is longer, accelerate less than that of the conventional shoes worn by the runners. The chart of FIG. 6 also shows that the shoes of the present invention come closer to the natural barefoot gait, which is the desirable condition.
While the foregoing embodiments are at present considered to be preferred it is understood that numerous variations and modifications may be made therein by those skilled in the art and it is intended to cover in the appended claims all such variations and modifications as fall within the true spirit and scope of the invention. | 1a
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This application is a division of application Ser. No. 447,423, filed Dec. 6, 1982, now U.S. Pat. No. 4,543,958, which application is a continuation-in-part of pending application Ser. No. 246,873 filed Mar. 23, 1981, which is a continuation-in-part of application Ser. No. 34,394, filed Apr. 30, 1979, and now U.S. Pat. No. 4,257,424, issued Mar. 24, 1981.
SUMMARY OF THE INVENTION
It is known in the prior art to produce highly efficient yet inexpensive medical electrodes by applying a layer or stripe of conductive paint such as a silver paint to a nonconductive plastic substrate, one portion of the paint layer being bridged to the skin of a subject under examination, such as a patient, by means of an electrolyte layer or sponge and another portion of the conductive paint remaining exposed for connection to peripheral equipment such as monitoring equipment, stimulating equipment or the like.
In the present invention, a stripe of conductive paint is applied to a substrate comprising integrally formed electrode segments partially separated by weakenings which allow individual electrode segments or groups of electrode segments to be severed from a larger supply. For convenient dispensing of the electrodes from the larger supply, the supply is stored as a roll of connected electrode segments in a protective housing or conditioner having a slot through which conditioned electrode segments may be sequentially removed.
In one embodiment, the protective housing confines a humidifying solution which moisturizes an atmosphere delivered through a ventilation opening to the electrode segments stored in the housing which are thereby provided with a sufficient moisture or humidity to preserve the tackiness and electrical conductivity of a polymeric film tailored to perform at such humidity as both an adhesive and an electrolyte, the humidified electrode segments being directly attachable to the skin of a subject without further preparation.
In another embodiment, the electrode conditioner carries in it a supply of activating fluid and a fluid application means which activates the electrode segments as they are removed, thus relieving the requirement for a controlled humidity environment.
BRIEF DESCRIPTION OF THE DRAWINGS
In the drawings:
FIG. 1 is a fragmentary perspective view of a strip of integrally connected medical electrodes in accordance with the present invention.
FIG. 1A is a greatly enlarged fragmentary section illustration taken along the line 1A--1A through the thickness of a portion of the strip of FIG. 1, where coated by a conductive adhesive composition.
FIG. 2 is a perspective view of a single medical electrode in accordance with this invention.
FIG. 3 is a cross-sectional view with exaggerated thickness taken substantially along the line 3--3 of FIG. 2.
FIG. 4 is a perspective view of a first embodiment of an electrode conditioner in accordance with the present invention, this figure illustrating a portion of a strip of electrodes and adjacent release paper projecting out of an exit opening of the conditioner.
FIG. 5 is an enlarged, partly exploded perspective view of the conditioner of FIG. 4.
FIG. 6 is a side elevational view of a portion of a second embodiment of an electrode conditioner in accordance with this invention.
FIG. 7 is a partly exploded fragmentary perspective illustration of a medical electrode of this invention and a cable connector for electrically connecting the electrode to peripheral equipment.
FIG. 8 is a longitudinal cross-sectional view of the cable conductor of FIG. 7 with the electrode connected thereto.
DETAILED DESCRIPTION
Referring to the drawings in greater detail, FIGS. 1, 1A, 2 and 3 illustrate a nonconductive substrate 10 which was initially an indefinitely long strip of uniform width and thickness. In the preferred embodiment of this invention, the substrate comprises a flexible and dimensionally stable sheet of plastic material such as polyethylene terephthalate which may have a thickness in the range of 1/2 mil (0.00127 cm) to 20 mils (0.0508 cm). Such substrate is sold under the trademark Mylar by the DuPont Chemical Corporation. As shown, the substrate has been shaped by suitable cutting dies so as to comprise an indefinite number of electrodes 12 each having a broad heel section 14 and a relatively narrow toe section 16, each electrode 12 having sloping shoulders 18 in the opposite side margins thereof where the side-to-side width of the electrodes is reduced from the width of the heel section 14 to the width of the toe section 16. The toe section of each of the electrodes 12 is integrally attached to the heel section of the next adjacent electrode 12 by a pair of webs 20 that are left intact as a part of the substrate 10 when perforations 22 are formed in the body of the substrate between the webs 20. The webs 20 thus preserve the integrity of the substrate 10 between adjacent electrodes 12 but provide only a weak connection between adjacent electrodes 12 such that the adjacent electrodes can be separated with relative ease.
Disposed centrally between the sides of the substrate 10 and extending longitudinally along the entire length of one face of the substrate is a stripe 24 of an electrically conductive paint which preferably comprises a plastic carrier loaded with metallic particles or flakes. A commercially available example of such paint is DuPont conductor composition No. 9793 available from the DuPont Chemical Corporation. For the purposes of this invention there is admixed to this commercially available paint a small quantity of silver chloride powder which will cause the stripe 24 to behave as a chlorided silver paint conductor. Alternatively, the chloriding can be induced by application to the paint in the presence of an electrolyte of an electrical chloriding current or by other techniques known in the art.
In the utilization of the present invention, the heel section 14 will be affixed to the skin of the subject or patient for purposes of exchanging electrical signals between the skin of the patient and the peripheral equipment. To allow an adequate transpiration to take place, the heel section is perforated as will be described.
Thus, the heel sections are perforated uniformly throughout by punching and/or melting to produce pores 11 extending through the thickness of the substrate in the heel sections 14. The pores 11 may be confined to the heel sections 14. However, it is also possible to distribute the pores 11 throughout the major surfaces of the substrate 10. By confining the pores 11 to the heel sections 14, however, irregularities at the side margins may be avoided and the tearing designed to occur between the heel sections 14 and the toe sections 16 of adjacent electrodes confined to weaknesses created by the perforations 22. Thus, it is possible to so distribute the pores 11 that these pores do not in themselves create weaknesses along which the substrate will tend to tear. Where indiscriminate tearing of the substrate poses no problem, the pores 11 may be distributed uniformly over the major areas of the substrate 10. Whether the pores 11 are distributed uniformly throughout the major areas of the substrate or confined to selected areas such as the heel sections 14, the pores, which may be approximately one-sixteenth of an inch in diameter (0.158 cm), may occupy approximately 50 percent of the surface area of the substrate 10 in those areas where the pores 11 are provided. The pores may be arranged in any pattern desired, examples being pores aligned in parallel rows or, if desired, pores aligned in rows with the pores in one row staggered with respect to pores in adjacent rows. The perforations 22 may be formed simultaneously as the pores 11 are formed. Referring to FIG. 1A pores 11 extending through the thickness of the substrate 10 are illustrated. In the preferred practice, the stripe 24 is applied to the substrate 10 after formation of the pores 11 and any of various screening techniques is employed to minimize loss of the paint through the pores 11 and perforations 22.
Traversing each of the heel sections 14 is a film 26 of a conductive adhesive which overlies the stripe 24 and extends laterally beyond the side edges of the stripe 24 to fully cross the width of the heel section 14.
In the preferred embodiment, the conductive adhesive may be applied to the substrate 10 before the side edges of the substrate have been cut to shape but may alternately be applied thereafter. In any event, it is preferred to apply the conductive adhesive film 26 after perforating the heel portions 14 so as to form the pores 11.
In one version, the conductive adhesive film 26 comprises a naturally occurring karaya gum which has blended therein an electrolyte which is derived from an aqueous salt solution. Such composition is available in sheet form from Lectec Corporation, 120 South Crosstown Circle, Eden Prairie, Minn. Various other conductive adhesive compositions could be used. Suitable compositions are described, for example, in the following U.S. patents: Marks et al., U.S. Pat. Nos. 3,357,930; Kater 3,993,049; Berg 4,066,078; and Cross et al., 4,141,366. Those familiar with the art will appreciate that the formulation of the composition will depend on the desired use of the electrode, i.e. whether for monitoring or stimulation.
In the preferred embodiment, the conductive adhesive comprises a synthetic polymer which is preferably a hydrophilic polymer blended with an aqueous electrolyte. A water based emulsion including an acrylic resin and a suitable plasticizer is the polymer of choice. The electrolyte of choice is sodium chloride. The blended polymer and aqueous electrolyte are applied to the substrate as a thin film which is then dried by heating, the dried film preferably having a thickhess in the range of 1 mil (0.00254 cm) to 4 mils (0.01016 cm).
In the practice of the present invention, the conductive adhesive, whether based on natural or synthetic resins, gums and the like, is tailored by known techniques to have a good ionic conductivity and adequate tackiness when equilibrated with an atmosphere whose relative humidity is in the range of approximately 30 percent relative humidity to approximately 60 percent relative humidity. This humidity range is found to be suitable for processing purposes. However, those skilled in the art will appreciate that both the ionic conductivity and tackiness can be satisfactory at substantially different humidity levels. The 30 to 60 percent range is preferred because in this range there is less of a tendency of the conductive adhesive film 26 to transfer to the skin of a patient. Thus, within the indicated humidity range the conductive adhesive film 26 will tend to stay with the electrode and separate cleanly from the skin of the patient when the electrode is removed. As will be described hereafter, the substrate 10 containing the electrodes 12 will be wound for storage in a conditioner and since such storage may occur over long periods of time, it is preferable to employ a release means such as a release paper 27 interleaved with the wound substrate. Alternatively a coating, not shown, of a release agent such as silicone or the like may be applied to that surface of the substrate 10 which is opposite the surface supporting the conductive adhesive films 26.
Those skilled in the art will recognize that each of the electrodes 12, prepared as described, contains the basic ingredients for a medical electrode such as may be employed in electrocardiograph monitoring. Thus, each electrode 12 comprises, as best shown in FIGS. 2 and 3, a substrate 10, an electrical conductor (the stripe 24) which is exposed at the toe section 16 for connection to peripheral instrumentation such as an electrocardiograph monitor, and an electrolyte (dispersed throughout the conductive adhesive film 26, such adhesive having been applied to the heel section 14 of the electrode 12). In the humidified condition above described, i.e. 30 percent to 60 percent relative humidity, the conductive adhesive has an adequate tackiness for attachment of the conductive adhesive film 26 to the skin of a subject and also has an adequate signal transmission capability for transmitting electrical signals between the skin and the conductive stripe 24 to operate as a medical electrode. What is required, however, is a means to sustain such electrode qualities during storage and shipment or, in the alternative, to restore such qualities at the time the electrode is to be used.
FIGS. 4 and 5 illustrate a conditioner generally designated 30 including means to activate or sustain the activation of electrodes to be dispensed or removed in accordance with the present invention. The conditioner 30 comprises a molded plastic housing generally designated 32 having, as viewed in FIGS. 4 and 5, a far side wall 34 and a near side wall 36. Spanning between the side walls 34 and 36 are housing body portions comprising a top housing portion 38 and a bottom housing portion 40 which integrally join with an arcuate rear wall 42. As shown in FIG. 5, the far side wall 34, the top housing portion 38, the bottom housing portion 40 and the rear wall 42 are all integrally formed in one piece, preferably of molded plastic that for convenience is referred to herein as a housing body member 44. The near side wall 36 prior to assembly of the conditioner is formed as a separate plate which, as a final step in the assembly of the conditioner 30, is permanently affixed to the housing body member 44 as will be described below.
The housing body member 44 is shaped to provide a generally cylindrical chamber 46 sized to receive a roll 48 of electrodes 12 connected as shown in FIG. 1 and wound on a hollow roller 50, mounted on an axle 51 which may be molded with and affixed to the far side wall 34 of the housing body member 44. A strip passageway 52 extends longitudinally of the housing body member 44 from the roll chamber 46 to an exit opening 54 at the front end of the dispenser located generally between the forwardmost end of the top housing portion 38 and the confronting surface of the bottom housing portion 40. The bottom housing portion 40 further includes a forwardly extending ledge 56 terminating at its forwardmost end with a separation edge 58 aligned generally with the exit opening 54 and provided with one or more teeth 59 for interfitting the perforations 22 between electrodes 12. Preferably the serially connected electrodes 12 are so wound to form the roll 48 that their toe sections 16 are all on the clockwise side of their heel sections 14 and the substrate 10 winds in the clockwise sense from its innermost convolution to its outermost convolution. Accordingly, one may engage the toe portion of an electrode lying on the ledge 56 and pull the electrode out of the conditioner 30 until the perforation 22 is engaged by the tooth 59 of the separation edge 58 without touching the conductive adhesive 26. As is apparent, the electrode 12 which has been fully pulled out of the conditioner 30 may be readily severed by pulling downwardly on the toe portion 16 to cause the webs 20 connected to the next adjacent electrode 12 to be severed. In those cases where a release paper 27 such as is shown in FIGS. 4 and 5 lies adjacent the electrodes 12, this release paper is also perforated in alignment with the perforations 22 so as to be torn away over the separation edge 58 along with the adjacent electrode or electrodes 12. The release paper is then readily separated by the nurse or attendant from the severed electrodes. The toe portion 16 of the adjacent and unsevered electrode 12 will then lie on the ledge 56 in a position convenient for its removal at a later time.
A pair of nip rollers comprising an upper roller 60 and a lower roller 62 are rotatably mounted on axles 64 and 66 respectively that may also be molded integrally with the far side wall 34 as part of the housing body member 44. The nip rollers 60 and 62 preferably are made from rubber or other resilient material and are so located with respect to one another that electrodes 12 and any adjacent release paper are squeezed therebetween as they are pulled from the conditioner 30. The surfaces of the nip rollers 60 and 62 accordingly meet on a line extending transversely through the center of the strip passageway 52. The nip rollers 60 and 62 are received within confronting sockets 68 and 70 in the housing top portion 38 and the housing body bottom portion 40 respectively of a size and shape to permit the nip rollers 60 and 62 to rotate but to lightly engage them and therefore substantially preclude an interchange between the atmosphere inside the conditioner 30 and the atmosphere outside the conditioner 30.
Disposed within the conditioner 30 is a compartment 72 having atmospheric communication to the chamber 46 through one or more vent passageways 74. The compartment 72 is partly filled by a constant humidity solution 76 formed from distilled water to which has been charged a suitable salt. The constant humidity solution 76 is selected using techniques well-known to those concerned with humidified atmospheres to maintain the air within the conditioner 30 at a substantially constant relative humidity at room temperatures in the range of 30 to 60 percent relative humidity, this being the relative humidity range discussed above for causing the conductive adhesive film 26 to be adequately tacky for adhesive attachment to the skin of the subject and also to serve as an acceptable electrolyte.
During assembly of the conditioner 30 after the vent passageway or passageways 74 have been formed such as with the assistance of suitable drills or cutters, the nip rollers 60 and 62 may be mounted on the axles 64 and 66 and the electrode roll 48, the electrodes 12 of which, together with any adjacent release paper, are already equilibrated with a 30 to 60 percent relative humidity atmosphere, mounted on the hollow roller 50 surrounding the axle 51 and threaded through the strip passageway 52 so that the toe section 16 of the free end of the strip of electrodes overlies the ledge 56. The constant humidity solution can then be poured into the compartment 72, with the housing body 44 resting on a horizontal table. The plate forming the side wall 36 is then fitted over the housing body member 44. For this purpose, it may have a stub axle 78 adapted to fit within the roller 50 and a pin 80 adapted to fit within an aperture 82 formed in the confronting face of the housing body member 44. The aperture 82 may desirably be provided with a bead or the like which receives the pin 80 with a snug fit. The stub axle 78 may likewise be snap fittedly received within the hollow roller 50. The side plate member is also preferably secured to the body member 44 by a hot melt or other adhesive to ensure that there is no interchange of air between the inside and the outside of the conditioner 30 and also to securely trap the constant humidity solution 76 within the compartment 72.
In the use of the conditioner 30, electrodes are drawn out of the exit opening 54 one at a time or in groups of two or more electrodes, as needed. Since, as described, the electrodes have been preconditioned before insertion into the conditioner 30 and can remain so conditioned for long periods while remaining in the conditioner 30, all electrodes removed from the conditioner 30 are ready for immediate application to the skin of a subject to be monitored or stimulated.
The dispenser ledge 56 with its tooth 59 is so spaced with respect to the nip rollers 60 and 62 that when the toe of one electrode 12 and any adjacent release paper rests on the ledge 56 to engage the tooth 59, the portion of its heel section coated by the adhesive film 26 and any adjacent release paper remains on the opposite side of the nip rollers 60 and 62. This means, for example, that on a given day one or more electrodes 12 can be removed from the conditioner and then on a following day, for example, the next electrode to be used, whose toe section is already projecting out of the exit opening, can be removed for use without its adhesive film 26 having lost its humidity conditioned state. This necessarily requires that the toe section and the uncoated portion of the heel section of each electrode and corresponding release paper be longer in longitudinal extension than the separation between the seal formed by the nip rollers 60 and 62 and the separation edge 58. As a convenience for gripping the conditioner 30, a through bore 84 extends through the lower housing portion 40. The bottom surface of the conditioner is preferably flat so that the conditioner will remain upright when placed on a horizontal surface.
Although the indicated size and shape of the conditioner 30 is unimportant to this invention, it is presently preferred that it be sized so as to be conveniently held in one hand to permit the tearing away of an electrode 12 and any adjacent release paper by the other hand. The modified conditioner 86 of FIG. 6 is similar in external appearance to the preferred embodiment of FIGS. 4 and 5, comprising a body member 88 similar to the housing body member 44 of FIGS. 4 and 5, and a sidewall plate (not shown) that may be similar to the previously described side wall 36 with adjustments having been made so that the side wall employed in the embodiment of FIG. 6 will have a pin such as the pin 80 appearing in FIG. 5 and will also have a stub axle such as the axle 78 appearing in FIG. 5 for engaging in the aperture 90 and in the roller 91 appearing in FIG. 6 so as to confine the various rollers exposed in FIG. 6, said side plate being secured to the body member 88 by a hot melt adhesive or the like not shown. What is different in the modification is that the compartment 72 which contained the constant humidity solution described in connection with the preferred embodiment has been eliminated and instead, near the exit end of the conditioner, there has been provided a solution chamber 92 which receives an activating solution 94. A cylindrical wiper roller 96 biased downwardly into the solution chamber 92 by a pressure roller 97 is frictionally rotated by the electrode segments which pass successively between the pressure roller 97 and the wiper roller 96, the wiper roller 96 being wetted by the fluid 94 as the wiper roller 96 rotates. The fluid wetting the roller 96 is carried upwardly as the roller rotates in the clockwise direction as viewed in FIG. 6 and partially transferred to that face of the electrode segment which is frictionally engaging and rotating the wiper roller 96.
It being desired that the faces of the electrode segments 12 to which the fluid 94 is transferred be the faces coated by the conductive adhesive film 26, the substrate 10 when wound for insertion into the conditioner of FIG. 4 is wound in a clockwise sense with the surface of the substrate 10 which bears the stripe 24 being curved concavely by the winding operation.
To increase the volume of fluid that may be transferred upwardly to the electrode segments 12, a second wetting roller 98 may be rotatably mounted in the chamber 92 below the first wiper roller 96. This second roller 98 is effective to continue the upward transfer of fluid to the electrode segments 12 even after the level of the fluid 94 in the chamber 92 is too low for direct wetting of the wiper roller 96.
While the drawings illustrate transfer rollers for conveying liquid from the chamber 92 to the confronting faces of the electrode segments 12, it will be appreciated that other devices such as capillary wicks and brushes are also suitable for this purpose.
In simplest form, the activating solution may be water which saturates the conductive adhesive contained in the film 26, so as to provide a surface which is tacky and which is also loaded with ions and thus is an effective electrolyte.
Referring to both of the conditioner mechanisms disclosed in FIGS. 4, 5 and 6, it can be appreciated that these conditioner mechanisms can be characterized as conditioners having included therein a preparation means which prepares the conductive adhesive films 26 for attachment to the skin of a patient. In the embodiment of FIGS. 4 and 5, the preparation means comprises the solution compartment 72 together with its constant humidity solution 76 and with the nip rollers 60 and 62 which, in combination, assures that the already conditioned adhesive films 26 remain sufficiently tacky and conductive for immediate use.
In the embodiment of FIG. 6, the preparation means comprises the solution chamber 92 together with its associated means for conveying the activating solution from its chamber 92 to the films 26 which pass successively over the chamber 92, this preparation means assuring that the conductive adhesive films 26, although they may have experienced some dry out during storage and shipment, will be adequately moist when applied to the skin of a subject to possess both a sufficient tackiness and a sufficient conductivity for accomplishing the monitoring or stimulating function.
In the embodiment of FIG. 6, it is desirable that a release paper 93 be rolled with the substrate 10 and this release paper is separated from the substrate 10 by means of a drop channel 95 molded into the body member 88 of the modified conditioner 86. The drop channel 95 is shaped at its mouth with a sharp edge which separates the release paper from the substrate 10 in advance of the wiper roller 96 so that the release paper will not block the wiping action of this roller. The release paper is, of course, tailored to separate readily from the substrate 10 and drops freely through the drop channel 95. The presence of the drop channel means that some moisture may escape from electrodes stored in the conditioner. However, the presence of the wiper roller 96 and the activating solution applied thereby to the electrodes assures in any event that the electrodes will be adequately conditioned for application to the skin of a patient when removed from the modified conditioner 86.
While the present invention has been described with reference primarily to the accomplishment of patient stimulation and signal monitoring functions, those skilled in the art will appreciate that the most immediate function accomplished with the present invention is the dispensing of electrodes readily attachable to the skin of a subject. If the toe section of the electrode is then attached to signal monitoring equipment, the electrode functions as a monitoring electrode. If the toe section is attached to a source of voltage for stimulation purposes, then the electrode functions as a stimulation electrode.
Referring to the cable connector 100 appearing in FIGS. 7 and 8, the cable connector comprises a plastic tray 102 having a longitudinally extending channel 104 formed in the upper face thereof. Integrally formed at the upper surface of the tray 102 is a hinge 106 which is one-piece with a cover member 108, the cover member 108 being rendered pivotal on the hinge 106 by the molding of a notch 110 lying under the hinge 106 as shown in FIG. 8.
The cover 108 is molded with outwardly projecting latches 112 which are formed integrally on stiffening ribs 114 extending along the opposite sides of the cover member 108. The tray 102 is formed with inwardly projecting latch retainers 116 which are sized and shaped to receive and then seize the latches 112 as the cover member 108 is pivoted downwardly to press the latches 112 into interfitting engagement with the latch retainers 116.
The cover member 108 is provided with an outwardly sloped lifting grip 118 to allow an operator to lift the cover member 108 against the seizing grip of the latch retainers 116 at times when it is desirable to lift the cover member 108 to the position shown in FIG. 7.
When the cover member is lifted, as shown, there is exposed in the channel 104 a rectangular metal plate 120 from which extends an integrally connected conductor 122. This conductor 122 extends rearwardly from the plate 120 through the rearward end of the tray 102 where the conductor is surrounded by an insulator 124 received in a protective sleeve 126 molded integrally to the tray 102. FIGS. 7 and 8 show the conductor 122 and the insulator 124 as having been broken off or otherwise terminated near the rear end of the tray 102. In actual practice, however, the conductor 122 and the surrounding insulator 124 may be indefinitely long, the purpose being to effect an electrical connection between the metal plate 120 and peripheral equipment such as a source of stimulating voltage or electrical monitoring apparatus. As evident in FIG. 7, the channel 104 is sized to receive the toe section 16 of any one of the electrode segments 12 but is too small in dimension to accept any of the heel sections 14. Thus, an operator may insert any one of the toe sections 16 into the channel 104 without difficulty and, with closure of the cover member 108, the exposed conductive stripe 24 extending along the toe section 16 will be pressed into intimate engagement with the metal plate 120. As the cover member 108 is closed, a rib 128 formed integrally on the lifting grip 118 seizingly engages the root of the section immediately adjacent the heel section 14.
The heel section 14 thus remains outside the tray 102 where it can be conveniently attached by means of the conductive adhesive layer 26 to the skin of a patient with the seizing engagement of the rib 128 against the root of the toe section 16 being effective to support the weight of the tray 102 and any dangling conductor 122 as the adhesive film 26 adheres to the skin of a patient.
When the conductive adhesive layer 26 has been appropriately conditioned either by the humidified environment of the conditioner 30, or by the activating solution of the modified conditioner 86, the electrode segments are immediately attachable to the skin. The conditioned electrode, when contacted to the metal plate 120 upon insertion into the cable connector 100, is immediately operative for its intended purpose whether for electrode monitoring or patient stimulation.
Although the preferred embodiments of the present invention have been described, it will be understood that various changes may be made within the scope of the appended claims. | 1a
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TECHNICAL FIELD
This invention is a pharmaceutical composition that inhibits the growth of cancers and tumors in mammals, particularly in human and warm blooded animals. The composition contains a 1,3-bis-triazolyl-2-propanol derivative.
BACKGROUND OF THE INVENTION
Cancers are the leading cause of death in animals and humans. The exact cause of cancer is not known, but links between certain activities such as smoking or exposure to carcinogens and the incidence of certain types of cancers and tumors has been shown by a number of researchers.
Many types of chemotherapeutic agents have been shown to be effective against cancers and tumor cells, but not all types of cancers and tumors respond to these agents. Unfortunately, many of these agents also destroy normal cells. The exact mechanism for the action of these chemotherapeutic agents are not always known.
Despite advances in the field of cancer treatment the leading therapies to date are surgery, radiation and chemotherapy. Chemotherapeutic approaches are said to fight cancers that are metastasized or ones that are particularly aggressive. Such cytocidal or cytostatic agents work best on cancers with large growth factors, i.e., ones whose cells are rapidly dividing. To date, hormones, in particular estrogen, progesterone and testosterone, and some antibiotics produced by a variety of microbes, alkylating agents, and anti-metabolites form the bulk of therapies available to oncologists. Ideally cytotoxic agents that have specificity for cancer and tumor cells while not affecting normal cells would be extremely desirable. Unfortunately, none have been found and instead agents which target especially rapidly dividing cells (both tumor and normal) have been used.
Clearly, the development of materials that would target tumor cells due to some unique specificity for them would be a breakthrough. Alternatively, materials that were cytotoxic to tumor cells while exerting mild effects on normal cells would be desirable. Therefore, it is an object of this invention to provide a pharmaceutical composition that is effective in inhibiting the growth of tumors and cancers in mammals with mild or no effects on normal cells.
More specifically, it is an object of this invention to provide an anti-cancer composition comprising a pharmaceutical carrier and a 1,3-bis-triazolyl-2-propanol derivative as defined herein along with a method for treating such cancers.
These and other objects will become evident from the following detailed description of this inventions.
SUMMARY OF THE INVENTION
A pharmaceutical composition for treatment of mammals, and in particular, warm blooded animals and humans, comprising a pharmaceutical carrier and an effective amount anti-cancer compound selected from the group consisting of: ##STR1## wherein R 1 is an optionally substituted alkyl, cycloalkyl (e.g. cyclopentyl or cyclohexyl), aryl or haloaryl (e.g. phenyl or 2,4-dichlorophenyl) or aralkyl (e.g., benzyl); and salts and metal complexes and ethers or esters thereof, and the non-toxic, pharmaceutically acceptable acid addition salts with both organic and inorganic acids. Specifically, such his triazole derivatives as 2-(2,4-dichlorophenyl)-1,3-bis(1H-1,2,4-triazole-1-yl)propan-2-ol and its corresponding 2- and 4- chlorophenyl analogs and 2,4-diflourophenyl analogs are claimed.
These compositions can be used to inhibit the growth of cancers, leukemia and other tumors in humans or animals by administration of an effective amount either orally, rectally, topically or parenterally, intravenously or by injection into the tumor. These compositions do not significantly affect healthy cells as compared to adriamycin which has a detrimental effect on healthy cells.
These compositions are also effective against viruses. Therefore it is an object of this invention to provide a composition effective against HIV, herpes, influenza, rhinoviruses and the like.
DETAILED DESCRIPTION OF THE INVENTION
A. Definitions
As used herein, the term "comprising" means various components can be conjointly employed in the pharmaceutical composition of this invention. Accordingly, the terms "consisting essentially of" and "consisting of" are embodied in the term comprising.
As used herein, a "pharmaceutically acceptable" component is one that is suitable for use with humans and/or animals without undue adverse side effects (such as toxicity, irritation, and allergic response) commensurate with a reasonable benefit/risk ratio.
As used herein, the term "safe and effective amount" refers to the quantity of a component which is sufficient to yield a desired therapeutic response without undue adverse side effects (such as toxicity, irritation, or allergic response) commensurate with a reasonable benefit/risk ratio when used in the manner of this invention. The specific "safe and effective amount" will, obviously, vary with such factors as the particular condition being treated, the physical condition of the patient, the type of mammal being treated, the duration of the treatment, the nature of concurrent therapy (if any), and the specific formulations employed and the structure of the compounds or its derivatives.
As used herein, a "pharmaceutical addition salts" is salt of the anti-cancer compound with an organic or inorganic acid. These preferred acid addition salts are chlorides, bromides, sulfates, nitrates, phosphates, sulfonates, formates, tartrates, maleates, malates, citrates, benzoates, salicylates, ascorbates, and the like.
As used herein, a "pharmaceutical carrier" is a pharmaceutically acceptable solvent, suspending agent or vehicle for delivering the anti-cancer agent to the animal or human. The carrier may be liquid or solid and is selected with the planned manner of administration in mind.
As used herein, "cancer" refers to all types of cancers or neoplasm or malignant tumors, including leukemia, found in mammals.
As used herein, the "anti-cancer compounds" are the 1,3-bis-triazolyl-2-propanols, and their salts. The exact 1,3-bis-triazolyl-2-propanols are described in detail below. The preferred materials are the products sold under the names "fluconazole®" by Pfizer.
As used herein, "viruses" includes viruses which cause diseases (vital infection) in man and other warm blooded animals such as HIV virus, herpes, influenza and rhinoviruses.
B. THE ANTI-CANCER COMPONDS
The anti-cancer compounds are 1,3-bis-triazolyl-2-propanol derivatives which are known for their antifungal activities. They are systemic fungicides used to prevent and eradicate fungi. The compounds have the following structure: ##STR2## wherein R 1 is an optionally substituted alkyl, cycloalkyl (e.g. cyclopentyl or cyclohexyl), aryl or haloaryl (e.g. phenyl or 2,4-dichlorophenyl) or aralkyl (e.g., benzyl); and salts and metal complexes and ethers or esters thereof, and the non-toxic, pharmaceutically acceptable acid addition salts with both organic and inorganic acids. Specifically, such bis triazole derivatives as 2-(2,4-dichloropheyl)-1,3-bis(1H-1,2,4-triazole-1-yl)propan-2-ol and its corresponding 2- and 4- chlorophenyl analogs and 2,4-diflourophenyl analogs are useful herein. Preferably the composition is 2-(2,4-difluorophenyl)1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol and its pharmaceutically acceptable acid addition salts with both organic and inorganic acids.
These compounds are prepared according to the method described in U.S. Pat. No. 4,404,216 issued to Richardson, Sep. 13, 1983 and British Patent Application No. 2,078,719A published Jan. 13, 1982 and European patent application No. 44,605 published Jan. 27, 1982 (both assigned to Imperial Chemical Industries Ltd).
It is believed that these particular fungicides have the capability of reducing tumors or decreasing their growth significantly because of their ability to inhibit the synthesis of sterols.
C. DOSAGE
Any suitable dosage may be given in the method of the invention. The type of compound and the carrier and the amount will vary widely depending on the species of the warm blooded animal or human, body weight, and tumor, virus, cancer or disease being treated. Generally a dosage of between about 2 milligrams (mg) per kilogram (kg) of body weight and about 400 mg per kg of body weight is suitable. Preferably from 15 mg to about 150 mg/kg of body weight is used. Generally, the dosage in man is lower than for small warm blooded mammals such as mice. A dosage unit may comprise a single compound or mixtures thereof with other compounds or other cancer inhibiting compounds. The dosage unit can also comprise diluents, extenders, carriers and the like. The unit may be in solid or gel form such as pills, tablets, capsules and the like or in liquid form suitable for oral, rectal, topical, intravenous injection or parenteral administration or injection into or around the tumor.
D. DOSAGE DELIVERY FORMS
The anti-cancer compounds are typically mixed with a pharmaceutically acceptable carrier. This carrier can be a solid or liquid and the type is generally chosen based on the type of administration being used. The active agent can be coadministered in the form of a tablet or capsule, as an agglomerated powder or in a liquid form. Examples of suitable solid carriers include lactose, sucrose, gelatin and agar. Capsule or tablets can be easily formulated and can be made easy to swallow or chew; other solid forms include granules, and bulk powders. Tablets may contain suitable binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, flow-inducing agents, and melting agents. Examples of suitable liquid dosage forms include solutions or suspensions in water, pharmaceutically acceptable fats and oils, alcohols or other organic solvents, including esters, emulsions, syrups or elixirs, suspensions, solutions and/or suspensions reconstituted from non-effervescent granules and effervescent preparations reconstituted from effervescent granules. Such liquid dosage forms may contain, for example, suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweeteners, thickeners, and melting agents. Oral dosage forms optionally contain flavorants and coloring agents. Parenteral and intravenous forms would also include minerals and other materials to make them compatible with the type of injection or delivery system chosen.
Specific examples of pharmaceutical acceptable carriers and excipients that may be used to formulate oral dosage forms of the present invention are described in U.S. Pat. No. 3,903,297 to Robert, issued Sep. 2, 1975. Techniques and compositions for making dosage forms useful in the present invention are described in the following references: 7 Modem Pharmaceutics, Chapters 9 and 10 (Banker & Rhodes, Editors, 1979); Lieberman et at., Pharmaceutical Dosage Forms: Tablets (1981); and Ansel, Introduction to Pharmaceutical Dosage Forms 2nd Edition (1976).
E. METHOD OF TREATMENT
The method of treatment can be any suitable method which is effective in the treatment of the particular cancer or tumor type or virus that is being treated. Treatment may be oral, rectal, topical, parenteral or intravenous administration or by injection into the tumor and the like. The method of applying an effective amount also varies depending on the tumor being treated. It is believed that parenteral treatment by intravenous, subcutaneous, or intramuscular application of the 1,3-bis-triazolyl-2-propanol compounds, formulated with an appropriate carrier, additional cancer inhibiting compound or compounds or diluent to facilitate application will be the preferred method of administering the compounds to warm blooded animals. | 1a
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This application claims priority to U.S. Provisional Application No. 61/443,063 filed on Feb. 15, 2011, the entire contents of which are specifically incorporated herein by reference without disclaimer.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to transgenic fish, particularly purple fluorescent transgenic fish.
2. Description of Related Art
Transgenic technology involves the transfer of a foreign gene into a host organism enabling the host to acquire a new and inheritable trait. The technique was first developed in mice by Gordon et al. (1980). They injected foreign DNA into fertilized eggs and found that some of the mice developed from the injected eggs retained the foreign DNA. Applying the same technique, Palmiter et al. (1982) introduced a chimeric gene containing a rat growth hormone gene under a mouse heavy metal-inducible gene promoter and generated the first batch of genetically engineered mice, which were almost twice as large as non-transgenic siblings.
In addition to the stimulation of somatic growth for increasing the gross production of animal husbandry and aquaculture, transgenic technology also has many other potential applications. First, transgenic animals can be used as bioreactors to produce commercially useful compounds by expression of a useful foreign gene in milk or in blood. Many pharmaceutically useful protein factors have been expressed in this way. For example, human 1-antitrypsin, which is commonly used to treat emphysema, has been expressed at a concentration as high as 35 mg/mL (10% of milk proteins) in the milk of transgenic sheep (Wright et al., 1991). Similarly, the transgenic technique can also be used to improve the nutritional value of milk by selectively increasing the levels of certain valuable proteins such as caseins and by supplementing certain new and useful proteins such as lysozyme for antimicrobial activity (Maga and Murray, 1995). Second, transgenic mice have been widely used in medical research, particularly in the generation of transgenic animal models for human disease studies (Lathe and Mullins, 1993). More recently, it has been proposed to use transgenic pigs as organ donors for xenotransplantation by expressing human regulators of complement activation to prevent hyperacute rejection during organ transplantation (Cozzi and White, 1995). The development of disease resistant animals has also been tested in transgenic mice (e.g. Chen et al., 1988).
Fish are also an intensive research subject of transgenic studies. There are many ways of introducing a foreign gene into fish, including: microinjection (e.g., Zhu et al., 1985; Du et al., 1992), electroporation (Powers et al., 1992), sperm-mediated gene transfer (Khoo et al., 1992; Sin et al., 1993), gene bombardment or gene gun (Zelenin et al., 1991), liposome-mediated gene transfer (Szelei et al., 1994), and the direct injection of DNA into muscle tissue (Xu et al., 1999). The first transgenic fish report was published by Zhu et al., (1985) using a chimeric gene construct consisting of a mouse metallothionein gene promoter and a human growth hormone gene. Most of the early transgenic fish studies have concentrated on growth hormone gene transfer with an aim of generating fast growing fish. While a majority of early attempts used heterologous growth hormone genes and promoters and failed to produce these fish (e.g. Chourrout et al., 1986; Penman et al., 1990; Brem et al., 1988; Gross et al., 1992), enhanced growth of transgenic fish has been demonstrated in several fish species including Atlantic salmon, several species of Pacific salmons, and loach (e.g. Du et al., 1992; Delvin et al., 1994, 1995; Tsai et al., 1995).
The zebrafish, Danio rerio , is a model organism for vertebrate developmental biology. As an experimental model, the zebrafish offers several major advantages such as easy availability of eggs and embryos, tissue clarity throughout embryogenesis, external development, short generation time, and easy maintenance of both the adult and the young. Transgenic zebrafish have been used as an experimental tool in zebrafish developmental biology. However, for the ornamental fish industry the dark striped pigmentation of the adult zebrafish does not aid in the efficient display of the various colors that are currently available on the market. More recently, Lamason et al. (2005) in their report showed that the Golden zebrafish carry a recessive mutation in the slc24a5 gene, a putative cation exchanger, and have diminished number, size, and density of melanosomes, which are the pigmented organelles of the melanocytes and hence are lightly pigmented as compared to the wild type zebrafish. The availability of such fish having modified pigmentation for transgenesis with fluorescent proteins would result in better products for the ornamental fish industry due to better visualization of the various colors.
Green fluorescent protein (GFP) is a useful tool in the investigation of various cellular processes. The GFP gene was isolated from the jelly-fish Aqueous victoria . More recently, various other new fluorescent protein genes have been isolated. For example, fluorescent proteins genes called DsRed (a red fluorescent protein gene), ZsGreen (a green fluorescent protein gene), and ZsYellow (a yellow fluorescent protein gene) have been isolated from the Anthozoa class of coral reefs (Matz et al., 1999; Wall et al., 2000). The novel fluorescent proteins encoded by these genes share 26-30% identity with GFP (Miyawaki, 2002).
Coral reef fluorescent proteins have broad application in research and development. The red fluorescent protein, DsRed, has been used as a reporter in transgenic studies involving various animal model systems: for example, filamentous fungi (Eckert et al., 2005, Mikkelsen et al., 2003); ascidian (Zeller et al., 2006); zebrafish (Zhu et al., 2005, Zhu and Zon, 2004, Gong et al., 2003, Finley et al., 2001); xenopus (Werdien et al., 2001); insect (Cho et al., 2006, Handler and Harrell, 2001, Horn et al., 2002); drosophila (Barolo et al., 2004); silkworm (Royer et al., 2005); mouse (Schmid et al., 2006, Vintersten et al., 2004); rat (Sato et al., 2003); and plants (Wenek et al., 2003). It has also been used as a marker in imaging studies in stem cells (Tolar et al., 2005, Long et al., 2005) and mouse (Long et al., 2005, Hadjantonakis et al., 2003). Green fluorescent protein, ZsGreen, has been used as a transformation marker in insects (Sarkar et al., 2006), knock-in mouse model for the study of KIT expressing cells (Wouters et al., 2005), and as reporters for plant transformation (Wenck et al., 2003). Yellow fluorescent protein, ZsYellow, has been used as a reporter for plant transformation (Wenck et al., 2003) and for visualizing fungal pathogens (Bourett et al., 2002).
Fluorescent proteins that produce a purple fluorescent color have also been developed. For example, the fluorescent protein called FP635 (also called TurboFP635 or Katushka) is a far-red fluorescent protein that exhibits a bright fluorescent color and is useful for visualizing living tissues (Shcherbo et al., 2007). FP635 was derived by targeted and random mutagenesis of a bright red fluorescent protein from the sea anemone Entacmaea quadricolor that is called eqFP578 (Shcherbo et al., 2007).
SUMMARY OF THE INVENTION
In certain embodiments, the present invention concerns making recombinant constructs and transgenic fluorescent fish and providing such fish to the ornamental fish industry.
The term “recombinant construct” is used to mean recombinant DNA constructs having sequences that do not occur in nature or exist in a form that does not occur in nature or exist in association with other materials that do not occur in nature. The term “transgenic” has historically been used in many contexts with various meanings. In the embodiments of this invention, transgenic is understood to mean that genetic material has been artificially introduced into the genome of an organism. An organism incorporating such genetic material, or progeny to which this genetic material was passed, would be considered a transgenic organism. A gene that is artificially introduced into the genome of an organism is referred to herein as a transgene.
Specific embodiments of the invention are directed to methods of making transgenic fluorescent fish having one or more chromosomally integrated expression cassettes that encode a fluorescent protein. In some embodiments, the provided fluorescent fish are fertile transgenic fluorescent fish. In a particular embodiment, the fish for use with the disclosed constructs and methods is the Golden zebrafish. Zebrafish skin color is determined by pigment cells in their skin, which contain pigment granules called melanosomes (black or brown color), xanthosomes (yellow color), erythrosomes (orange or red color), or iridosomes (iridescent colors, including white color). The number, size, and density of the pigment granules per pigment cell influence the color of the fish skin. Golden zebrafish have diminished number, size, and density of melanosomes and hence have lighter skin when compared to the wild type zebrafish. Golden zebrafish have a mutation in slc24a5 gene, rendering the fish skin lighter or less pigmented (Lamason et al., 2005).
In certain aspects, methods of making transgenic fluorescent fish are provided. Transgenic expression cassettes that may be used to make transgenic fluorescent fish may include a set of transcriptional regulatory motifs such as a promoter—which may be from the host species (herein referred to as a homologous promoter) or from another species (herein referred to as a heterologous promoter)—heterologous genes that may code for a fluorescent protein, and an appropriate RNA-processing and/or translational enhancing motif. The term “promoter” as used herein refers to the DNA elements that direct and regulate transcription. For instance, the zebrafish fast skeletal muscle myosin light chain promoter and carp β-actin promoter may be used according to the invention. In certain specific embodiments, there are provided methods to use multiple vectors or multiple copies of a transgene to express at least one fluorescent protein in order to enhance expression.
The steps involved in making the transgenic fish may also involve introduction (e.g., by injection) of the transgenic expression cassette into the zebrafish embryos or zebrafish embryonic stem cells. Embryos, fry, or fish that express the transgene may then be selected. For example, fish that express a fluorescence transgene may be selected by exposing the fish to light of appropriate wavelength and/or by visibly inspecting the fish and observing the expression of the transgene.
In certain embodiments there are provided transgenic fluorescent zebrafish comprising specific transgenic integration events. These fish are of particular interest because, for example, they embody an aesthetically pleasing level of protein fluorescence. Thus, in some specific embodiments, there is provided a transgenic zebrafish comprising a chromosomally integrated expression cassette encoding an FP635 fluorescent protein, wherein the zebrafish comprises the “Purple zebrafish 1 transformation event,” sperm comprising the Purple zebrafish 1 transformation event having been deposited as ECACC accession no. 11012801. Eggs, sperm and embryos comprising these specific transgenic events are also included as part of the invention.
In certain aspects, the transgenic zebrafish comprising the Purple zebrafish 1 transformation event is further defined as a fertile, transgenic zebrafish. In other certain aspects, the transgenic zebrafish is further defined as a transgenic Golden zebrafish. The transgenic zebrafish comprising the Purple zebrafish 1 transformation event, may be homozygous or heterozygous (including, for example, hemizygous) for the integrated expression cassette. Homozygous fish bred with fish lacking an expression cassette (e.g., Golden zebrafish) will in nearly all cases produce 100% heterozygous offspring.
Transgenic fish described herein may emit far-red or purple fluorescence and hence will be unique and attractive to the ornamental fish industry. Thus, also disclosed herein are methods of providing a fluorescent transgenic zebrafish to the ornamental fish market, comprising obtaining a transgenic fish comprising the Purple zebrafish 1 transformation event, and distributing the fish to the ornamental fish market. In some embodiments, the fish are distributed by a grower to a commercial distributor. In other embodiments, the fish are distributed by a grower or a commercial distributor to a retailer for sale to the public. In one such embodiment, the fish may also be sold by the grower or commercial distributor to a regional wholesale distributor, who will then sell to a retailer for sale to the public. The retailer may be a multi-product retailer having an ornamental fish department. The fluorescent transgenic fish are also useful for the development of a biosensor system and as research models for embryonic studies such as cell lineage, cell migration, cell and nuclear transplantation, cell-cell interaction in vivo, etc.
Also provided are methods for producing a transgenic zebrafish comprising: (a) obtaining a zebrafish comprising a chromosomally integrated expression cassette encoding an FP635 fluorescent protein, wherein the zebrafish comprises the Purple zebrafish 1 transformation event, sperm comprising the Purple zebrafish 1 transformation event having been deposited as ECACC accession no. 11012801; and (b) breeding the obtained zebrafish with a second zebrafish to provide a transgenic zebrafish comprising the Purple zebrafish 1 transformation event. The second zebrafish may be a transgenic zebrafish or a non-transgenic zebrafish.
In further embodiments, also provided are methods of producing a transgenic organism, the method comprising using sperm comprising the Purple zebrafish 1 transformation, such sperm having been deposited as ECACC accession no. 11012801, to produce transgenic offspring. Such offspring may be, for example, a zebrafish, a species of the Danio genus, a fish species related to zebrafish, or another fish species. In some aspects, the fish may be produced using in vitro fertilization techniques known in the art or described herein.
Embodiments discussed in the context of a method and/or composition of the invention may be employed with respect to any other method or composition described herein. Thus, an embodiment pertaining to one method or composition may be applied to other methods and compositions of the invention as well.
As used herein the terms “encode” or “encoding” with reference to a nucleic acid are used to make the invention readily understandable by the skilled artisan; however, these terms may be used interchangeably with “comprise” or “comprising” respectively.
As used herein the specification, “a” or “an” may mean one or more. As used herein in the claim(s), when used in conjunction with the word “comprising,” the words “a” or “an” may mean one or more than one.
The use of the term “or” in the claims is used to mean “and/or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and/or.” As used herein “another” may mean at least a second or more.
Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, or the variation that exists among the study subjects.
As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.
Any embodiment of any of the present methods and compositions may consist of or consist essentially of—rather than comprise/include/contain/have—the described features and/or steps. Thus, in any of the claims, the term “consisting of” or “consisting essentially of” may be substituted for any of the open-ended linking verbs recited above, in order to change the scope of a given claim from what it would otherwise be using the open-ended linking verb.
Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
DETAILED DESCRIPTION OF THE INVENTION
Transgenic Fish
In some aspects, the invention regards transgenic fish. Methods of making transgenic fish are described in, for example, U.S. Pat. Nos. 7,135,613; 7,700,825; 7,834,239, each of which is incorporated by reference in its entirety.
It is preferred that fish belonging to species and varieties of fish of commercial value, particularly commercial value within the ornamental fish industry, be used. Such fish include but are not limited to catfish, zebrafish, medaka, carp, tilapia, goldfish, tetras, barbs, sharks (family cyprinidae), angelfish, loach, koi, glassfish, catfish, discus, eel, tetra, goby, gourami, guppy, Xiphophorus , hatchet fish, Molly fish, or pangasius. A particular fish for use in the context of the invention is zebrafish, Danio rerio . Zebrafish are increasingly popular ornamental animals and would be of added commercial value in various colors. Zebrafish embryos are easily accessible and nearly transparent. A fish that is of particular use with the disclosed constructs and methods is the Golden Zebrafish. Zebrafish skin color is determined by pigment cells in their skin, which contain pigment granules called melanosomes. The number, size, and density of the melanosomes per pigment cell influence the color of the fish skin. Golden zebrafish have diminished number, size, and density of melanosomes and hence have lighter skin when compared to the wild type zebrafish. Golden zebrafish have a mutation in the slc24a5 gene, which codes for a putative cation exchanger localized to intracellular membrane, thus rendering the fish skin lighter or less pigmented (Lamason et al., 2005).
Fertilization from Frozen Sperm
Fish sperm freezing methods are well-known in the art; see, e.g., Walker and Streisinger (1983) and Draper and Moens (2007), both of which are incorporated herein by reference in their entireties. To obtain transgenic fish disclosed herein, frozen zebrafish sperm may be used to fertilize eggs, as described in Draper and Moens (2007).
Eggs are collected as described in Draper and Moens (2007). Briefly, two females are placed in tricaine solution at 16 mg/100 mL water. After gill movement has slowed, one of the fish is removed and rinsed in water. The fish is placed on a paper towel to dry briefly and then transferred to a small plastic dish. With slightly damp fingers, one finger is placed on the dorsal side of the fish. The eggs are removed by gently pressing on the ventral side of the fish, starting just behind the pectoral fins and moving toward the tail.
The eggs from the female zebrafish are squeezed into a 35 mm plastic Petri dish. The sperm are thawed at 33° C. in a water bath for 8-10 sec. 70 μl room temperature Hanks solution is added to the vial and mixed. The eggs are then immediately added to the vial and gently mixed. The sperm and eggs are activated by adding 750 μl of fish water and mixing. The mixture is incubated for 5 min at room temperature. The dish is then filled with fish water and incubated at 28° C. After 2-3 hrs, fertile embryos are transferred to small dishes where they are further cultured.
Parichy and Johnson, 2001, which is incorporated by reference in its entirety, provides additional examples regarding in vitro fertilization.
The invention further encompasses progeny of a transgenic fish containing the Purple zebrafish 1 integration event, as well as such transgenic fish derived from a transgenic fish egg, sperm cell, embryo, or other cell containing a genomically integrated transgenic construct. “Progeny,” as the term is used herein, can result from breeding two transgenic fish of the invention, or from breeding a first transgenic fish of the invention to a second fish that is not a transgenic fish of the invention. In the latter case, the second fish can, for example, be a wild-type fish, a specialized strain of fish, a mutant fish, or another transgenic fish. The hybrid progeny of these matings have the benefits of the transgene for fluorescence combined with the benefits derived from these other lineages.
The simplest way to identify fish containing the Purple zebrafish 1 transformation event is by visual inspection, as the fish in question would be purple colored and immediately distinguishable from non-transgenic fish.
EXAMPLES
The invention will now be further described with reference to the following examples. These examples are intended to be merely illustrative of the invention and are not intended to limit or restrict the scope of the invention in any way and should not be construed as providing conditions, parameters, reagents, or starting materials that must be utilized exclusively in order to practice the art of the present invention.
Example 1
Purple Transgenic Zebrafish
Transgenic fish exhibiting a purple color are provided. The FP635 fluorescent protein open reading frame was acquired from Evrogen, JSC as the pTurboFP635-N plasmid, which is commercially available (Cat. No. FP722). This protein was derived from TurboRFP, which is a modified version of the red fluorescent protein eqFP578 from Entacmaea quadricolor . The FP635 protein was introduced into an expression cassette. The expression cassette sequence was verified using restriction endonucleases and by sequencing of the completed cassette. To make the transgenic fish, the constructs were purified by conventional methods and introduced into founder fish.
The specific transgenic events embodied in these fish are designated Purple zebrafish 1. Sperm from these fish may be used to fertilize zebrafish eggs, using methods known to those of ordinary skill in the art and methods described herein, and thereby breed transgenic zebrafish that comprise these specific transgenic integration events. Sperm from this line is deposited at the European Collection of Cell Cultures (ECACC), Porton Down, Salisbury, SP4 OJG, United Kingdom, on Jan. 28, 2011, under the provisions of the Budapest Treaty as “Purple zebrafish 1” (accession no. 11012801; cell line ZEBRAFISH 2011.1 PZF001).
The fluorescent transgenic fish have use as ornamental fish in the market. Stably expressing transgenic lines can be developed by breeding a transgenic individual with a wild-type fish, mutant fish, or another transgenic fish. The desired transgenic fish can be distinguished from non-transgenic fish by observing the fish in white light, sunlight, ultraviolet light, blue light, or any other useful lighting condition that allows visualization of the purple color of the transgenic fish.
The fluorescent transgenic fish should also be valuable in the market for scientific research tools because they can be used for embryonic studies such as tracing cell lineage and cell migration. Additionally, these fish can be used to mark cells in genetic mosaic experiments and in fish cancer models.
All of the compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the methods described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents that are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope, and concept of the invention as defined by the appended claims.
REFERENCES
The following references, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference.
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BACKGROUND OF THE INVENTION
This invention concerns game pucks, particularly non-ice hockey pucks. The puck of the invention has a series of runners that engage the play surface, the runners being replaceable and interchangeable by hand, without tools.
Non-ice hockey pucks are typically used on streets or courts, some of which have rough surfaces which can wear down the plastic puck surfaces rather quickly. Eventually the entire puck must be replaced.
It would be desirable to have a puck in which a puck body, the main component and bulk of the puck, is long-lasting and nearly indestructible, but with runner elements that actually contact the playing surface, with these elements of any desired low-friction material, and being relatively inexpensive and easily replaced by hand.
SUMMARY OF THE INVENTION
The current invention achieves this purpose with a puck body of highly durable plastic, the puck body comprising an outer peripheral annulus providing a peripheral striking surface, and a central hub or core and a series of spokes connecting the central hub to the peripheral annulus. The puck body preferably is injection-molded of a hard, durable plastic such as PVC. It can also be formed of TPR (thermo plastic resin), PU (polyurethane), plasticized carbon fiber or vulcanized rubber.
To this puck body are secured a series of removable/replaceable runners, positioned at both opposed surface-engaging sides of the puck. The runners on each side of the puck can provide either a substantially contiguous ring for play surface engagement, or an interrupted series of circumferentially spaced apart runners for less contact area and lower friction with a play surface.
The runners are attached to the puck body in a unique way. Each runner has a glider head that actually contacts the play surface, and a leg curving down from the glider head to extend generally at a right angle to the glider head and gliding surface of the runner. The leg has a distal or inner end adjacent to which is a hook that is positioned to snap over and engage a ledge formed in the inner wall of the peripheral annulus of the puck body. The runner is of integrally molded plastic, such as a hard nylon plastic, and the leg possesses a springing elasticity so as to be capable of deflection when the runner is pushed into position on the peripheral annulus, to the extent that the hook snaps over the ledge and locks the runner in place on the puck body. In a preferred embodiment, replaceable runners are assembled onto both sides of the puck, generally opposite one another and with the legs positioned side by side in openings of the puck body between the spokes. Here, the hooks of the two runner legs latch onto adjacent but oppositely-directed ledges.
Although the runners are securely retained on the puck body and will not release during play, they are easily removed by hand when desired. On the opposite side of the puck from a runner's glider head, the tail end of the leg has a release tooth that can be engaged with a fingernail or with a narrow object such as a ballpoint pen. Engaging this tooth and pressing inwardly toward the hub will quickly release the hook from the ledge causing the runner to be ejected from the puck body.
Preferably the runner includes a positioning shank depending from the underside of the glider head, this shank being positioned to engage in a slot of the peripheral annulus so as to hold the glider head in proper position as the runner is pushed, the leg is deflected and the hook is caused to snap over the ledge.
The invention allows worn or broken runners to be quickly and easily replaced, as well as interchangeability of runners to provide runners of different size or play characteristics. This is easily achieved by hand, without tools. These and other objects, advantages and features of the invention will be apparent from the following description of a preferred embodiment, considered along with the accompanying drawings.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view showing a non-ice game puck in accordance with an embodiment of the invention.
FIG. 2 is a perspective view showing the hockey puck with different runners.
FIG. 3 is a schematic, exploded perspective view indicating assembly of runners into the hockey puck body of the invention.
FIG. 4 is a sectional elevation view indicating assembly of a runner into the puck body.
FIGS. 5 and 6 are perspective views indicating a puck body but with different runners assembled into the bodies, forming different glider configurations.
FIG. 7 is a side elevation view showing the assembled puck of FIG. 5 .
DESCRIPTION OF PREFERRED EMBODIMENTS
In the drawings, FIG. 1 shows a game puck 10 of the invention, particularly a hockey puck for non-ice surfaces. The puck includes a puck body 12 that is comprised of a center hub or core 14 , a plurality of radially-extending spokes 16 (five are shown here) that extend preferably integrally from the hub 14 , and a peripheral annulus 18 that is connected, preferably integrally, to the spokes 16 . This leaves a series of openings indicated at 20 , equal to the number of spokes, an opening being positioned between each pair of adjacent spokes. The outside of the puck body presents a peripheral surface 21 , slightly rounded as shown, for striking.
A series of runners 22 are fitted onto the peripheral annulus 18 to present a low-friction surface to engage against the play surface (floor, street, etc.), each runner 22 having a leg 24 extending down into the opening between adjacent spokes. The runners 22 are fitted into the puck body 12 from both sides, and distal or inner or tail ends 26 of some of the runners inserted from the opposite side are seen in FIG. 1 .
In FIG. 1 the runners 22 have glider heads 22 a of limited surface area, i.e. limited area for contact with the play surface. These are for smooth surfaces and allow for less friction. FIG. 2 , on the other hand, shows a puck 10 a which has the same puck body 12 but with different runners 30 , each having glider heads 30 a of larger surface area, so that the series of glider heads 30 a on a side of the puck preferably present a substantially continuous ring as shown. These can be considered training gliders, in that they can be used on coarse surfaces such as streets or concrete and provide a good puck for training, with the runners easily replaced when worn or broken. The hard nylon plastic used in both cases is a low friction material with good wear characteristics. Other plastics could be used.
FIGS. 5 and 6 show the pucks 10 and 10 a of FIGS. 1 and 2 , along with the respective runners 22 and 30 used in those pucks, the puck body 12 being the same in both cases.
FIGS. 3 and 4 , both exploded views, show the configuration of the runners and demonstrate the assembly and securing of runners into the puck body 12 . In this case the runners 22 with smaller glider head 22 a are shown, as in FIG. 1 .
Each runner has the glider head 22 a , a leg 24 extending down from the glider head, preferably on a curve as shown, toward a distal or inner end 26 which, as explained below, also constitutes a finger tab. In addition, the leg has a hook 32 for securing the runner 22 into the puck body. Also preferably included in the integrally, unitarily molded runner 22 is an anchoring shank 34 as seen in the drawings. As indicated in FIG. 3 , the runners 22 are inserted from both sides, and in doing so the legs 24 become positioned side by side (but inverted in orientation), and this is illustrated in FIG. 1 where the leg inner or tail ends 26 inserted from the opposite side are visible, each being directly alongside a leg of the runner 22 at the illustrated top side.
The runner body 22 , in the peripheral annulus 18 , preferably includes a series of slots or cavities 36 as shown in FIGS. 3 and 4 , positioned to receive the anchoring shanks 34 of the runners. On assembly of a runner 22 down into the puck body 12 , as particularly illustrated in FIG. 4 , the anchoring shank 34 (which may be tapered as shown) is engaged into a corresponding slot 36 of the puck body, as the leg 24 is inserted down into the space 20 between spokes. As shown, the leg 24 preferably is shaped essentially complementarily to the corresponding surface of the peripheral annulus, that shape comprising a deflection ramp 38 (preferably curved) which is engaged by a lower or distal end of the leg as the runner is pushed in. With the anchoring shank 34 in the slot 36 , further advancement of the runner leg down into the puck body bends and deflects the leg 24 somewhat, until the hook 32 clears a ledge 40 at the bottom end of the deflection ramp, whereupon the hook 32 snaps into place, locking the runner firmly in place on the puck body with the glider head 22 a against the top of the peripheral annulus as viewed in FIG. 4 . Note that the puck body preferably has top/bottom symmetry, with deflection ramps 38 and ledges 40 side by side (and inverted) in each space 20 , but FIG. 4 is a sectional view as cut through one of the ledges 40 . When all runners 22 have been snapped into both sides of the puck body, the puck 10 appears as in FIG. 1 .
When a worn or broken runner is to be removed and replaced, or to interchange the type of runner to be used on a puck body, the finger tab 26 of a runner, i.e. the runner's tail or distal end, is accessible from the side of the puck opposite the runner's glider head. Thus, as can be envisioned from FIG. 1 and also FIG. 4 , one can engage the finger tab 26 and deflect it radially inwardly toward the hub or core, thus releasing the hook from the ledge. In lieu of a finger tip, a narrow object such as a pen or pencil can be used. Releasing the hook tends to pop the runner out from the opposite side of the puck body because of the spring action of the runner leg.
FIG. 7 is a side view showing the puck 10 of the invention, i.e. the configuration shown in FIG. 1 . The glider heads 22 a of the runners are shown as protruding upwardly (and downwardly) from the peripheral annulus of the puck body, these providing the contact area for engaging with a floor or other play surface.
The puck body and the runners are efficiently made by injection molding. Runners can be of any desired color which can be different from that of the puck body. If desired the puck body can carry a central decorative hub insert (which could be co-molded), and this can match the runner color. The size of the puck is about 3 inches outside diameter (+/−10%), and about 1⅛ inches in height (+/−10%), including the runners, generally the size of a standard puck.
The above described preferred embodiments are intended to illustrate the principles of the invention, but not to limit its scope. Other embodiments and variations to these preferred embodiments will be apparent to those skilled in the art and may be made without departing from the spirit and scope of the invention as defined in the following claims. | 1a
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RELATED APPLICATION
This application is a continuation of copending patent application Ser. No. 06/922,041, filed Oct. 21, 1986, and entitled "METHOD AND APPARATUS FOR ADJUSTING A BASKETBALL GOAL," invented by Stephen F. Nye, now U.S. Letters Pat. No. 4,781,375, issued Nov. 1, 1988. That application is incorporated herein by specific reference.
BACKGROUND
1. Field of the Invention
The present invention relates to a method and apparatus for adjusting the height of a basketball goal.
2. The Background of the Invention
Because of the popularity of the sport of basketball, particularly in the United States, many people, especially families, mount a basketball goal on their property. This allows them to have ready access to a basketball goal to enjoy the sport of basketball.
Children, however, frequently find it frustrating to learn how to play basketball because the standard height of a basketball goal is ten feet and it is often difficult for children to throw the basketball that high. Thus, many families with small children find it desirable to install a basketball goal at a height which is much lower than the standard height. Indeed, families with many small children may be forced to sacrifice having a basketball goal at the standard height, which is suitable for adults, so that the children may more easily develop their basketball skills and more fully enjoy the game.
Although many small children have the ability to throw the basketball through the goal, this is usually only accomplished by exerting extreme effort, often at the expense of proper form. Many people never develop proper shooting form because, as small children, they developed an incorrect form because that was the only way they could throw the basketball high enough to reach the basket. Hence, another advantage of having a basketball goal at a lower height is that smaller children may learn proper basketball skills and practice shooting the basketball with correct form. Thus, the child does not have to relearn skills as he becomes stronger.
It will be appreciated by anyone with a knowledge of the sport of basketball that one of the most envied abilities associated with the sport is the ability to "dunk" the basketball. One dunks the basketball by throwing the basketball into the basketball goal from a position above the rim of the goal. Obviously, one must be extremely tall and/or possess an extraordinary leaping ability in order to position himself high enough to be able to dunk the basketball.
While many people are able to develop excellent basketball skills, it will be appreciated that very few people have the natural leaping ability and/or height to be able to dunk the basketball. So that one may be able to develop skills and practice different styles of dunking the basketball, it is often desirable to place the basketball goal at a height somewhat lower than the standard height. However, it is not usually practical to permanently mount a basketball goal at a lower height simply for the purpose of dunking the basketball. It is also not practical to have two basketball goals, one at the standard height and one at a lower height. Hence, most basketball goals are simply mounted at the standard height.
Because of the reasons mentioned above, many attempts have been made to design a basketball goal which is adjustable to several different heights. One design of an adjustable basketball goal employs a flexible cable, and a pulley which can be operated to raise or lower the goal to the desired height. The goal is then affixed at that height by tying off the cable. Disadvantages to this type of design are that adjustment is very slow and the cable often experiences a short life span because of its constant exposure to the weather. Thus, because of the extreme amount of tension placed on the cable when the basketball goal is being used, especially when one dunks the basketball or hangs on the rim of the basketball goal, the cable could break. As the cable continually becomes weaker due to its constant exposure to a variety of weather conditions, the amount of tension required to break the cable gradually decreases until the actions of someone playing basketball are enough to cause the cable to break. When the cable does break, the break is usually caused by the actions of people using the goal. These people are endangered, and serious injury could result if they are in the path of the goal when the cable breaks should the goal fall to its lowest position.
Another design for an adjustable goal employs pivotally mounted parallel bars which connect the basketball backboard to a rigid mounting device such as a pole. The parallel bars combine with the basketball backboard and the rigid mounting device to form a parallelogram. Since the bars are pivotally mounted, they allow the backboard of the basketball goal to move to several different heights, while remaining vertically disposed. Typically, once the basketball goal is at the desired height, it is secured in place by tightening one or more bolts which "lock" the parallelogram in place.
One of the disadvantages of this device is that whenever one desires to adjust the basketball goal, it requires the use of a ladder or similar device to enable one to reach the one or more bolts which must be loosened to "unlock" the basketball goal. This is complicated by the fact that when the bolt or bolts are loosened, the person adjusting the goal must support the entire weight of the goal until the goal has been set to the desired height and the bolt or bolts are tightened again. This can be both a strenuous and a dangerous task and may be impossible physically for many small children to perform. This is an unfortunate disadvantage because it is usually small children who have the greatest need for lowering the basketball goal. Yet another significant disadvantage of this type of design is that if the bolt or bolts become loosened through vibration or other means while the basketball goal is in use, the goal will fall to its lowest position, striking whomever may be in its path.
Yet another design for an adjustable basketball goal employs the same parallelogrammatical structure as the previously discussed design except a telescoping ratchet mechanism is employed, rather than bolt or bolts, to secure the basketball goal in the desired position. As the goal is raised, a hinged pawl on one member engages a row of apertures in a second telescoping member, seriatim in a ratchet-like fashion. The configuration of the pawl permits the goal to be raised by applying an upward force to the basketball backboard, but the pawl will engage one of the apertures preventing downward movement if the upward force is removed. When the desired height is reached, the upward force is released and the pawl engages the aperture to which it is aligned preventing the goal from falling due to its own weight. From any of the intermediate height positions, the goal can be raised to a higher position, but it cannot be lowered to a lower position without neutralizing the pawl because the pawl will engage the nearest aperture preventing downward movement. To neutralize the pawl, the goal must be raised to its highest position, a position higher than the highest usable level for the goal, where the pawl engages an ear which cocks the pawl into a neutral position. With the pawl so neutralized, the basketball goal may be lowered because the pawl will not engage any apertures during the descent of the goal. As the goal reaches its lowest position, the pawl engages another ear which releases or trips the pawl back to its original, active position where it may again engage any of the apertures and secure the goal at the desired height.
One disadvantage of this design is that in order to lower the basketball goal one level, the goal must first be raised to its highest position where the pawl is neutralized before the basketball goal may be lowered. Then, the goal must be lowered to its lowest position in order to trigger and activate the pawl so that it may engage again the apertures. Finally, the basketball goal is raised to the desired position and the pawl secures that position by resting within the aperture corresponding to the desired height. If, however, the basketball goal is inadvertently raised one position too high, the pawl will not permit lowering the goal and it must again be raised to the extreme uppermost position to neutralize the pawl. The goal is then lowered to the extreme lowest position in order to activate the pawl so that the user can once again attempt to position the pawl to engage the desired aperture.
Because the pawl is neutralized only at the extreme uppermost position, this gives rise to another significant and possibly dangerous disadvantage. If, when the goal is at its highest usable level, a person dunks the basketball and momentarily hangs on the rim of the basket, the entire goal will spring upwardly upon release of the rim. If this upward force is substantial, the goal may spring upwardly causing the pawl to strike the ear which cocks the pawl into the neutral position. Neutralizing the pawl permits the basketball goal to crash to its lowest position, possibly injuring persons involved in the basketball game.
In order to reduce the danger in the potentially dangerous crashing of the basketball goal, a fluid cylinder has been used to prevent the basketball goal from rapidly falling when the pawl is neutralized. However, the fluid cylinder introduces a delay into the time it takes the basketball goal to be adjusted to the desired height because the assent and descent speed is retarded by the fluid cylinder. Additionally, the fluid cylinder does not prevent the pawl from being cocked into its neutral position under the conditions just described, nor does it obviate the necessity of having to readjust the height of the basketball goal when the pawl is neutralized and the basketball goal descends to its lowest height. Further, because the fluid cylinder is a separate accessory from the ratchet mechanism, the user may choose not to install it or the user may remove it if it becomes damaged or broken.
As an added precaution to reduce the potential for injury, a safety locking mechanism employing a tightening bolt has also been used to rigidly secure the height of the goal having adjustability provided by the ratchet mechanism described above. However, the basketball goal is often used without tightening the bolt to lock the ratchet mechanism in place because tightening the bolt would require employing a ladder to enable the user to reach the bolt. Furthermore, the bolt typically is at a height higher than the rim of the basket; hence, the higher the basketball goal is placed, the less likelihood there is that the user of the goal will be able to reach the bolt in order to secure the goal. Consequently, when the goal is at the standard height of ten feet, the bolt is positioned over ten feet high. Thus, the locking mechanism is least likely to be employed when the basketball goal is set at the highest usable level. It is at this level that it is critical to employ the locking mechanism to prevent the pawl from becoming neutralized inadvertently and the basketball goal from crashing to its lowest position.
It will be appreciated, therefore, that what is needed in the art are methods and apparatus for adjusting the height of a basketball goal which do not pose a danger to those who may use the device, are easily adjustable from one height to another without employing a ladder or similar device, and are durable and able to withstand constant exposure to a variety of weather conditions.
BRIEF SUMMARY AND OBJECTS OF THE INVENTION
The present invention includes novel methods and apparatus for adjusting a basketball goal. The invention uses a parallelogrammatic structure to facilitate the adjustability of the basketball goal. The present invention has an adjustable telescopic support comprising two telescoping cylindrical members which can be selectively secured with respect to each other whereby a person of any height, without the use of a ladder or similar device, may adjust the height of the basketball goal. Further, the present invention does not permit the basketball goal to crash to its lowest position either when the basketball goal is in use or when it is being adjusted.
The apparatus of the present invention utilizes a deformable parallelogrammatic structure comprising upper and lower support members pivotally mounted at one end to a vertically disposed rigid support, such as a pole or a wall, and at the other end to a mounting plate upon which a basketball backboard may be mounted. The parallelogrammatic structure is deformable in that each vertex for the structure is a pivot joint which allows the structure to change its shape while maintaining the characteristics of a parallelogram. Because of the nature of a parallelogram, the mounting plate upon which the upper and lower support members are pivotally mounted maintains a vertical disposition as it moves through an arc from its lowest position to its highest position as a consequence of the rigid support opposite the mounting plate being vertically disposed. In this manner, the basketball goal may be affixed to the mounting plate and the mounting plate will maintain the backboard vertical and the rim horizontal as the goal is adjusted up and down as desired.
The mounting plate is securely disposed in a selected position by means of the adjustable telescopic support which comprises two cylindrical members, one fitting concentrically within the other in a telescoping fashion. Preferably, the outer cylinder is pivotally mounted to the upper support member at or near the rigid support. The inner cylinder is pivotally mounted to the lower support member at or near the mounting plate, such that the two telescoping cylindrical members form substantially a diagonal to the parallelogram. The adjustable telescopic support is capable of adjusting its length to correspond to the length of a diagonal of a parallelogram as the mounting plate side of the parallelogrammatic structure is raised or lowered.
The inner cylinder has a longitudinal slot on its underneath side. The slot has several notches, each disposed in spaced relationship to the others along one side of the slot. A post is firmly mounted to the inside of the outer cylinder and the two cylinders are concentrically connected such that the post slidably engages the slot as the inner cylinder slides in and out of the outer cylinder in a telescoping fashion. The notches are configured to receive the post and secure it from movement within the slot when a downward force (such as the force of gravity) is applied at the mounting plate, while permitting release from the notch and movement within the slot when a sufficient upward force is applied at the mounting plate. The inner cylinder is biased, as is further explained below, such that whenever a notch is aligned with the post, the notch will receive the post. In this manner, the post will not release from the notch within which it is disposed and allow the basketball goal to crash down to its lowest position. Disengagement of the post from such notch is accomplished by either a sufficient upward force applied at the mounting plate or by actuating a latching mechanism.
The latching mechanism, when actuated, causes the inner cylinder to rotate about its longitudinal axis. This rotating movement causes the post to disengage the notch within which it is disposed and positions the post for longitudinal sliding movement within the slot. Although the latching mechanism can be connected in a fashion to rotate either the inner or the outer cylinder, for the purposes of this brief summary of the invention the latching mechanism will cause rotation of the inner cylinder. The latching mechanism comprises a lever plate with a release cup disposed at one end and a catch at the other end. The lever plate is pivotally mounted on brackets near the nontelescoping end of the inner cylinder. The catch engages a rocker arm secured to the end of the inner cylinder.
The inner cylinder is pivotally mounted such that it is capable of a certain degree of rotation about its longitudinal axis which is accomplished by depressing the release cup. As the release cup is depressed, the catch at the opposite end of the lever plate engages one end of the rocker arm which transfers force from the depression of the release cup to the rocker arm thereby causing the inner cylinder to rotate. The rotation of the inner cylinder moves the notches relative to the post to align the slot with the post thereby permitting the inner cylinder to slide freely inside the outer cylinder. The lever plate is biased so that when the depressing force to the release cup is removed, the inner cylinder rotates back to its original position thereby forcing the inner cylinder to rotate such that the post may engage a notch.
When it is desired to lower the height of the basketball goal, a long rod or similar implement may be used to depress the release cup. Depressing the release cup rotates the inner cylinder and disengages the post from the notch, allowing the goal to freely move up or down while the post slides along the slot. When the goal has been lowered to the desired height, the rod is removed from the release cup causing the inner cylinder to rotate such that the post engages the notch corresponding to that particular height. Because the lever plate is biased, it will return to its nondepressed position upon removal of the rod causing the inner cylinder to rotate back to a position for securely receiving the post in a notch. This consequent rotation occurs to prevent the force of gravity from causing the basketball goal to fall beyond the next lower height because the post engages the notch corresponding to that next lower height. Thus, the latching mechanism acts as an added safety feature in that inadvertent actuation of this latching mechanism or rapid removal of the depressing force to the release cup causes the basketball goal to fall only to the next lower position and not crash to the lowest position.
In raising the basketball goal to a selected height from among various predetermined heights, the rod is placed in a guide which is located near the mounting plate. The guide merely serves to provide a place close to the mounting plate where an upward force may be applied without the rod slipping. After placing the rod in the guide, a force sufficient to raise the goal is applied to the goal via the rod. Because of the configuration of the notches, as the basketball goal is raised, the inner cylinder is forced to rotate as the post slides out of the notch and into the slot so that the goal may be advanced to the next higher position. The side of the slot which has the notches remains biased against the post so that when the goal is raised to the position where the next notch is aligned with the post, the inner cylinder, acting under the biasing force of a spring or the like, immediately engages the notch with which it is aligned. Consequently, as each notch is encountered, the post engages the notch and the goal will rest at the predetermined height corresponding to that notch. As a continued upward force is applied, the post will disengage the notch within which it is resting and then advance to the next notch and each successive notch until the desired height is obtained.
An alternative method of raising the goal is to follow substantially the same procedure explained above for lowering the goal; that is, depressing the release cup with the rod, raising the goal to the desired height, and rapidly withdrawing the rod from the release cup. Because the goal can freely move up or down when the release cup is depressed, care must be taken to remove the rod from the release cup while not allowing the goal to drop below the desired height. When the rod is removed from the release cup, the lever plate immediately returns to its nondepressed position under the biasing force of the spring. This, in turn, forces the inner cylinder to rotate and engage the post with which the notch in the inner cylinder is aligned.
The backboard of the basketball goal is secured to the mounting plate such that it extends below the mounting plate to act substantially as a shield for the release cup. This prevents an errant basketball from depressing the release cup during normal play. Even if the release cup is inadvertently hit with the ball, the biased release cup is only momentarily depressed and the basketball goal will drop, if at all, only one position.
It is, therefore, a primary object of the present invention to provide an apparatus for adjusting a basketball goal in such a way that the adjustable telescopic support does not become completely disengaged when a force is applied to the basketball goal and then suddenly released, such as is often the case when the basketball is dunked.
It is a further object of the present invention to provide such methods and apparatus so that the basketball goal may be adjusted from one level to the next without having to perform complicated maneuvers.
It is an additional object of the present invention to provide an apparatus wherein normal use of the basketball goal will not cause the adjustable telescopic support to become disengaged resulting in the basketball goal falling to its lowest position.
It is a further object of the present invention to provide such methods and apparatus wherein the basketball goal may be adjusted without the use of a ladder or similar device.
Another object of the present invention is to provide an apparatus for adjusting the height of a basketball goal that is durable and resistant to a variety of changing weather conditions.
Still another object of the present invention is to provide an adjustable basketball goal that is easily adjustable and poses no danger to those who are adjusting the basketball goal or those who are playing basketball with the goal.
Other objects of the present invention may become apparent by reference to the drawings, the detailed description of the invention and the claims set forth herein.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a parallelogrammatic structure utilizing the present invention and having a basketball goal mounted thereon and disposed so that the basketball goal is at its highest usable position. The phantom lines show the structure of the present invention as it would appear in its lowered position.
FIG. 2 is a cross-sectional view taken along line 2--2 of FIG. 1.
FIG. 3 is a perspective view of the present invention showing portions of the adjustable telescopic support broken away to more fully illustrate the construction and operation of its various parts, which also demonstrates an alternative means of mounting the parallelogrammatic structure to a rigid support.
FIG. 4 is a perspective view of a portion of the present invention wherein the lever plate has been actuated, thus illustrating the rotating relationship between the two cylinders, with portions broken away to more fully illustrate the operation of the various parts.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention is directed to an apparatus for adjusting the height at which a basketball goal is set. The apparatus is designed to enable any person, including smaller children, to quickly and safely adjust the height of a basketball goal, and to prevent the inadvertent and undesirable crashing of the goal down to its lowest height.
Reference is now made to the figures wherein like parts are referenced by like numerals throughout. With particular reference to FIG. 1, an adjustable support system of the present invention is generally designated 10. The adjustable support system 10 comprises a deformable parallelogrammatic structure which is pivotally connected to a rigid support 12 on one side of the structure and to a conventional basketball goal 14 on the other side. As shown in FIG. 1, the adjustable support system 10 may be connected directly to the rigid support 12 by means of hinge bolts 15. The adjustable support system 10 may be connected to the rigid support 12 by any of several methods, which are more fully discussed below, so long as the adjustable support system 10 is pivotally connected to the rigid support 12.
As can best be seen in FIGS. 1 and 2, the adjustable support system 10 comprises an upper support 16, and a lower support 18. The upper and lower supports 16 and 18 may be comprised of two spaced structural pieces. The two structural pieces may be braced by means of a bracing member 19. It will be appreciated that these structural members may comprise any configuration sufficient to satisfy the structural limitations necessitated by the present invention. As seen in FIG. 2, the upper support 16 and the lower support 18 are pivotally mounted to a mounting plate 20 via pivot pins 22 on one end and pivotally mounted to the rigid support 12 via hinge bolts 15 at the other end. Upper support 16 and lower support 18 must be mounted so that they remain substantially parallel to each other as they pivot, changing the general configuration of the parallelogram defined by the rigid support 12, the upper support 16, the lower support 18 and the mounting plate 20. In this manner, as the configuration of the so-defined parallelogram changes with the raising or lowering of the mounting plate 20, the configuration remains a parallelogram and the mounting plate 20 remains vertically disposed because the rigid support 12 is vertically disposed.
Although the presently preferred embodiment of the present invention employs the use of mounting plate 20, the upper support 16 and lower support 18 may be mounted directly to the basketball goal 14. Instead of mounting the basketball goal 14 directly to the rigid support 12, as would be done in the absence of the present invention, for ease of construction, the basketball goal 14 is mounted to the mounting plate 20. The basketball goal 14 may be of the type conventionally known in the art, comprising a backboard 21 and a rim or hoop 23.
The adjustable support system 10 further comprises an adjustable telescopic support 24 which is pivotally connected to form substantially a diagonal in the so-defined parallelogram. While it is preferred that the telescopic support 24 be connected near the point where the lower support 18 is connected to the mounting plate 20 on one end and connected near the point where the upper support 16 is connected to the rigid support 12 at the other end, the present invention will also function with telescopic support 24 forming the other diagonal; that is, mounted at one end near where the upper support 16 is mounted to the mounting plate 20 and at the other end near where the lower support 18 is mounted to the rigid support 12.
As illustrated in the drawings, it is presently preferred that one end of the telescopic support 24 be pivotally mounted to the mounting plate 20 utilizing the lower pivot pin 22 to which the lower support 18 is mounted. It is also presently preferred that the opposite end of the telescopic support 24 be pivotally mounted to the upper support 16 utilizing a hinge pin 25 offset a short distance from where the upper support 16 is mounted to the rigid support 12. This configuration is designed to maximize the amount the basketball goal 14 may be raised and lowered while minimizing stress on the structure. Although the telescopic support 24 may be connected directly to the rigid support 12, the rigid support 12 would have to be modified so that the body of the telescopic support 24 would not collide with the rigid support 12 as the basketball goal 14 is raised or lowered. It will be appreciated by one skilled in the art that the adjustable support system 10 may function with the telescopic support 24 mounted at different positions along the parallelogrammatic structure. However, it is presently believed that the configuration illustrated in FIG. 2 is the most efficient configuration for accomplishing the objectives of the present invention.
Referring now to FIG. 3, the different components which comprise the telescopic support 24 will be explained. The telescopic support 24 comprises an outer cylinder 26 and an inner cylinder 28. In the presently preferred embodiment of the invention, the outer cylinder 26, as described above, is pivotally mounted at one end to the upper support 16. The other end of the outer cylinder member 26 acts as a sleeve in which one end of the inner cylinder 28 is inserted for slidable engagement. The other end of the inner cylinder 28 is pivotally mounted to the mounting plate 20 in a manner similar to the way the lower support member 18 is pivotally mounted, and preferably to the same pivot pin 22. In order to permit limited rotation of the inner cylinder 28 about its longitudinal axis, elongated bores 30 (shown in FIG. 4) are provided on opposite sides of the inner cylinder 28 near its mounted end. The pivot pin 22 extends through each of the elongated bores 30. A sleeve 31 is also provided which is a short piece of cylindrical tubing disposed within the inner cylinder 28 at its pivot end to maintain the concentric disposition of the inner cylinder 28 with respect to the outer cylinder 26.
It will be appreciated that the present invention will function regardless of whether the telescopic support 24 is mounted as shown in FIG. 3 with the outer cylinder 26 in the higher position or whether the telescopic support 24 is positioned with the inner cylinder 28 mounted in the higher position. However, it is presently preferred that the outer cylinder 26 be mounted in the higher position as illustrated in FIG. 3. In this manner, the telescopic support 24 is disposed such that it angles downward from its pivotally mounted end to the end that slidably engages the inner cylinder 28. Hence, precipitation in the form of rain, snow or the like is virtually prevented from entering the interior of the telescopic support 24 through the small space between the outer cylinder 26 and the inner cylinder 28 where they meet in slidable engagement.
The inner cylinder 28 has a slot 34 which extends substantially longitudinally along the inner cylinder 28. A plurality of notches 36 are provided spaced along one side of the slot 34. The outer cylinder 26 is provided with a post 32 affixed to the inside of the outer cylinder 26 such that the post 32 slides freely within the slot 34 of the inner cylinder 28 as the telescopic support 24 is extended and contracted. It will also be appreciated that it is possible to configure the telescopic support 24 such that post 32 is affixed to the inner cylinder 28 with slot 34 in the outer cylinder 26. With either configuration, in order to reduce the amount of exposure to the elements, it is presently preferred that the slot 34 and the post 32 be placed on the underside of the telescopic support 24.
As illustrated in FIG. 4, the notches 36 in the side of the slot 34 should be configured to have a bevelled side 37 and a stop side 38. The stop side 38 is substantially perpendicular to the side of the slot 34 or may have a slightly concave curvature so that when a downward force (e.g., gravity) is applied to the basketball goal 14 placing tension on the telescopic support 24 to extend its length, the post 32 engages the stop side 38 of a notch 36 and rests there which prevents the telescopic support 24 from lengthening. The bevelled side 37 of the notches 36 are configured so that when an upward force is applied to the basketball goal 14 which causes a compression force on the telescopic support 24, the post 32 is pushed against and advances along the bevelled side 37 of the notch 36 causing the inner cylinder 28 to rotate. As the post 32 exits the notch 36, it aligns with the slot 34 in slidable engagement thereby permitting the telescopic support 24 to contract.
A latching mechanism, generally designated as 40, is provided to initiate rotation of the inner cylinder 28 which releases the post 32 from the notch 36 it occupies. When the inner cylinder 28 rotates sufficiently to position the post 32 in the slot 34, the basketball goal 14 may be raised or lowered as the post 32 freely slides within the slot 34.
The latching mechanism 40 preferably comprises a lever plate 41 having a release cup 42 and brackets 43 used for pivotally mounting the lever plate 41. The brackets 43 are preferably mounted to the lower pivot pin 22 such that the mounting acts as a fulcrum for the lever plate 41. In this manner, a force applied at the release cup 42 will depress that end of the lever plate 41 causing the opposite end to move correspondingly in the opposite direction.
To transfer the depressing force applied at the release cup into rotation of the inner cylinder 28, a rocker arm 44 is provided which is disposed at the pivoting end of the inner cylinder 28. A portion of the rocker arm 44 extends beyond the circumference of the inner cylinder 28 and is disposed to engage the lever plate 41 at a catch 45. The catch 45 is designed to transfer force applied at the release cup 42 end of the lever plate 41 to the extended portion of the rocker arm 44. As can best be seen in FIG. 4, a force applied at the release cup 42 in the direction of arrow A depresses that end of lever plate 41. Correspondingly, the opposite end of lever plate 41 moves in the opposite direction of arrow A, and the catch 45 which is disposed at that opposite end exerts a force on the captured extended end of the rocker arm 44. That consequent force translates into rotation of the inner cylinder 28, to the extent permitted by elongated bores 30, in the direction of arrow B.
To return the release cup 42 to its nondepressed position once the force is removed, latch springs 46 are provided which are connected to the catch 45 end of the lever plate 41 and to the mounting plate 20. Such latch springs 46 provide the biasing which also causes the inner cylinder 28 to rotate back to the position at which the post 32 will rest within a notch 36.
Although two latch springs 46 are shown in the drawings, it should be understood that one or more such latch springs 46 or any appropriate type of biasing member, such as elastic or the like, can be used. By using one latch spring 46 the tension applied to the lever plate is less than using two such latch springs 46. Conversely, by using more than two latch springs 46, the tension can be increased. The presently preferred embodiment of the invention, as illustrated, also includes rows of spaced holes 48 to which the latch springs 46 may be anchored. This provides a method by which the tension in the latch springs may be adjusted by increasing or decreasing the length to which the latch springs 46 are stretched. The number of latch springs 46 and the number of rows of holes 48 is not critical so long as whatever biasing means is used has sufficient strength to return the lever plate 41 to its nondepressed position.
Within the telescopic support 24, a counterbalance spring 50 is provided which extends between and is anchored to the lower pivot pin 22 and the hinge pin 25. The counterbalance spring 50 (shown only in FIG. 2) reduces the force which must be applied to the basketball goal 14 in order to adjust the length of the telescopic support 24. Although the counterbalance spring 50 may be disposed outside the telescopic support 24 and still function to reduce the force needed to adjust the basketball goal 14, it is preferred that it be disposed within the telescopic support 24 where it is shielded from the elements and where the danger of pinching a user is eliminated.
Although the apparatus shown in FIGS. 1 and 2 and shows the basketball goal 14 as it might be newly constructed, the present invention may also be retrofit to an existing basketball pole. This can be done in at least two ways. First, as shown best in FIG. 1, the upper support 16 and the lower support 18 may be pivotally mounted by means of hinge bolts 15 to the existing pole. Alternatively, as shown in FIG. 3, the upper support 16 and the lower support 18 may be pivotally mounted to a rigid support plate 58 which is in turn secured to the existing pole by means of U-bolts 60 and a saddle clamp 62 or any other method commonly known by which the rigid support plate 58 may be rigidly secured to an existing pole. The rigid support plate 58 provides an additional advantage that it can be used to correct an improperly installed basketball pole. It is not uncommon for a basketball pole to be installed, particularly when a nonadjustable goal is used, where the pole is set too deep or it is turned such that the backboard 21 does not squarely address the playing area. With the rigid support plate 58, the basketball goal 14 can be raised or lowered with respect to the pole 12 by minute increments. Also, the angle at which the backboard 21 addresses the playing area may be adjusted. A further advantage of the rigid support plate 58 is that it can also be used to mount the present invention against a wall or other permanent wall-like structure. Thus, the present invention is not limited to use with a pole.
Operation of the present invention is quick and easy. The method employed to adjust the present invention depends on whether it is desired to raise or lower the basketball goal 14. To lower the height of the basketball goal 14, a long rod 65 is used to engage and depress the release cup 42. As the release cup 42 is depressed by pushing it in the direction shown by arrow A, as illustrated in FIG. 4, the lever plate 41 rocks on its fulcrum mounting causing the catch 45 to engage and to move the extended end of rocker arm 44 in the direction of arrow B. This forces the inner cylinder 28 to also rotate in the direction as is shown by arrow B. As the inner cylinder 28 rotates, because the outer cylinder 26 remains stationary from rotation about its longitudinal axis, the rotation of the inner cylinder 28 disengages the post 32 from the notch 36 and places the post 32 within the slot 34 of the inner cylinder 28. Compare FIGS. 3 and 4. In this position, the inner cylinder 28 is free to slide within the outer cylinder 26 in a telescoping fashion without the post 32 engaging any notches 36.
When the inner cylinder 28 is rotated to the position illustrated in FIG. 4, the basketball goal 14 may freely be lowered to the desired height. This is done by lowering the rod 65 while ensuring that the release cup 42 remains depressed. The speed at which the basketball goal 14 may be lowered while maintaining the release cup 42 in a depressed position is controlled by manipulation of the rod 65, friction in the pivotal joints, and the tension in the counterbalance spring 50. If the rod 65 is quickly removed from contact with the release cup 42 before the basketball goal 14 has been fully lowered, the release cup 42 will return to its nondepressed position, causing the inner cylinder 28 to rotate such that one of the notches 36 engages the post 32. This halts the continued descent of the basketball goal 14. Thus, in lowering the goal 14 to a desired position, the rod 65 can be quickly removed from the release cup 42 when the goal 14 is just above the desired height. The lever plate 41 under tension from the latch springs 46 then returns to its biased passive position and the inner cylinder 28 is forced to rotate in the opposite direction of arrow B thereby returning a notch 36 for secure engagement with the post 32 without allowing the goal 14 to drop to a lower height.
An alternative method for lowering the height of the basketball goal 14 involves depressing the release cup 42 portion of lever plate 41 so that the post 32 disengages the notch 36 and is positioned in slot 34. The goal 14 is then lowered to the lowest height permitted by the telescopic support 24 where the rod 65 used to depress the release cup 42 can be removed. The goal 14 is then raised to the desired height in a manner described hereinafter.
To raise the height of the basketball goal 14, an upward force sufficient to overcome gravity and minor frictional resistance is applied to the basketball goal 14. It should be appreciated that the force which must be applied to raise the basketball goal 14 may be applied at virtually any point on the basketball goal 14 or the adjustable support system 10. However, the greater the horizontal distance between where the force is applied and where the upper support 16 and the lower support 18 are pivotally mounted to the rigid support 12, the lesser the force required to raise the basketball goal 14. For this purpose, it is preferred that a guide loop 70 is positioned on the underside of the brace portion 72 of the basketball rim 23, as shown in FIG. 1. This guide loop 70 provides a holder for the end of a rod 65 used to apply the upward force (see arrow C) to the basketball goal 14. The guide loop 70, like the release cup 42, holds the end of the rod 65 to prevent slipping so that the force is applied to the desired area.
With the preferred embodiment of this invention, raising the goal 14 causes the telescopic support 24 to contract in length. This contraction of the telescopic support 24 forces the post 32 against the bevelled side 37 of whichever notch 36 within which the post 32 is positioned. As this force of such contraction overcomes the biasing of the inner cylinder 28 by sliding movement of the bevelled side 37 against the post 32, the inner cylinder 28 rotates in the direction of arrow B (as illustrated in FIG. 4). The post 32 disengages the notch 36 and advances within the slot 34 to the next notch 36 which is then engaged by the post 32 due to the biasing of the inner cylinder 28. A continued upward force causing further contraction of the telescopic support 24 causes the post 32 to disengage a notch 36, advance along the slot 34, and engage the next adjacent notch 36, until the desired height of the basketball goal 14 is obtained.
Referring now to FIGS. 3 and 4, it is also possible to raise the basketball goal 14 by depressing release cup 42 with a stick or a pole as is described above for lowering the basketball goal 14. As the release cup 42 is depressed, the resultant rotation of the inner cylinder 28 frees the post 32 from the notch 36. A continued upward lifting force on the release cup 42 advances the post 32 along the slot 34. As the post 32 aligns with the notch 36 corresponding to the desired height of the basketball goal 14, the rod 65 is quickly removed from the release cup 42 and the latch springs 46 cause rotation of the inner cylinder 28 which positions the post 32 in secure engagement with notch 36 before the force of gravity causes the basketball goal 14 to fall to a lower position. If the post 32 does not engage the desired notch 36, it will merely slide along the slot 34 until it engages the next notch 36. In no case will the present invention allow the basketball goal 14 to fall more than the height corresponding to the movement of the post 32 from one notch 36 to the next notch 36.
Consequently, an inadvertent striking of the release cup 42 with a basketball or other object, thereby temporarily depressing the release cup 42, causes only momentary rotation of the inner cylinder 28. Thus, if the post 32 does become disengaged from the notch 36, the telescopic support 24 will only expand until the post 32 comes into contact with the next notch 36. The biasing of the inner cylinder 28 causes a return rotation that positions the post 32 in the next notch 36 and prevents further descent of the basketball goal 14.
To facilitate the efficient operation of the adjustable support system 10 and reduce the effort needed to adjust the height of the basketball goal 14, bushings and spacers 75 made of friction reducing materials such as galvanized steel or polymers may be used at the pivoting connections described above. Such bushings and spacers reduce friction an increase the life of the system 10.
Further, although the present invention is shown as used with a basketball goal 14, as illustrated in FIGS. 1 and 2, it will be appreciated that the present invention may be used in any application such as volleyball nets, etc. wherein it is desired to adjust the height of an object to predetermined heights when to do so presents at least some of the problems the present invention is designed to overcome.
From the foregoing, it will be appreciated that the present invention provides a method and apparatus for quickly and safely adjusting a basketball goal or other object while avoiding the problems inherent in other adjustable basketball standards. The present invention avoids the significant safety hazards encountered by others, such as the possibility that the basketball goal may fall to its lowest position when the basketball is dunked. The present invention may be adjusted to various predetermined heights without having to perform complicated or dangerous maneuvers and adjustments may be accomplished without the use of a ladder or similar device.
It should be appreciated that the apparatus and methods of the present invention are capable of being incorporated in the form of a variety of embodiments, only a few of which have been illustrated and described above. The invention may be embodied in other forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive and the scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope. | 1a
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[0001] This application claims the benefit of the filing date of provisional application having Ser. No. 60/685,640, which was filed on May 27, 2005 and U.S. pending patent application Ser. No. 10/746,674, which was filed on Dec. 24, 2003.
FIELD OF THE INVENTION
[0002] The present invention relates to further improvements in dental implant structures, and in particular to adjustable and/or modular, removably secured dentures and dental bridges, i.e., oral, or dental prosthetics. A detailed background for this invention is provided in related International Publication number WO 02/28304 A2, published on 11 Apr. 2002 (hereinafter the “Prior Case) and number WO2004/060189 A3, (hereinafter the “Prior Case 11”), by the same inventor and applicant, the complete disclosures of which are incorporated herein by reference, including the specification and drawings.
BACKGROUND OF THE INVENTION
[0003] As shown in FIG. 1 of the Prior Cases, it is well known to firmly attach dentures to hard dental tissue, such as the jawbone 14 or tooth stubs by an implanted support, via prosthetic dental bridges 10 ; foundations 12 for such bridges 10 are known . In particular, the dental bridge 10 may be securely mounted to implanted screw posts 16 , or other known securing mechanisms. Such foundations 12 are also described, for example, in U.S. Pat. Nos. 5,575,651 and 5,788,492. Other, more readily removable, dentures secured to implanted supports are shown, for example in U.S. Pat. Nos. 5,567,155 and 3,514,858.
[0004] The use of relatively slender implants to support foundations, described in the first two patents identified above, and in the Prior Cases, were originally considered suitable primarily as short term devices for use until the larger, “permanent” implants healed. One aspect of the present invention continues the earlier development and further understanding that the slim implants can be used for substantially permanent, but removable denture prostheses of various types. The devices and procedures of the present invention avoid many of the problems of earlier systems when worn for extended periods, which included the lack of capability for easy removal and replacement, and potential irritation to the patient because of the difficulty of obtaining a proper fit to the jawbone and opposing teeth and gums, or to soft dental tissue.
[0005] Thus, a need continued to exist for a system which would permit the placement of a long-lasting dental prosthesis in a patient's mouth by chairside techniques available to the family dentist. Such a system should provide components for mounting such prosthesis, which can be firmly secured to the hard dental tissue, such as the jawbone, in a relatively short time, but which can be adjusted or removed to be prophylactically cleaned or repaired at a later date, and which are readily adaptable to the natural variations in the size and shape of ridges in jaw bones, so as to provide for more comfortable use of any dentures secured on such components, and which allows for multiple fittings and adjustments without damage to even the slender implants.
SUMMARY OF THE INVENTION
[0006] In accordance with a first aspect of the present invention, The existing or new denture prosthesis can be retrofitted with the advantageous system of this invention. The prosthesis can be removed from the mouth by the patient to be prophylactically cleaned daily, but is primarily is intended for fitting or refitting of the prosthesis without damage to the implant posts, by the dentist.
[0007] The improvement of this invention is to be primarily used in denture systems comprising anchoring implants and indexing guide pins that are permanently implanted, bi-laterally, at the most posterior parts of the jaw. The channel forming the concave underside of a full, or partial, denture, for either the upper or lower jaw, can be lined with a resilient material, covering the hard denture form, and thus more effectively maintain the denture in the correct position while cushioning the patient's dental ridge. Such a denture lining is intended to provide for an improved grip on implants, and can be readily resurfaced.
[0008] A chairside prosthesis foundation is also provided for securing to a plurality of anchored dental implants, in accordance with the Prior Cases. Each implant useful in that situation has an intermediate platform portion and an interconnectable top distal from the, preferably threaded, implanted portion. The foundation can comprise modular components, which can be supported by the intermediate implant platforms, but which can be locked together by being encased in a resin, in a permanent relative juxtaposition. The locked together components can be removably connected to the implants, to enable subsequent adjustment of the prosthesis to fit a range of jaw ridge sizes or for cleaning or repair. As explained in the Prior Cases, such modular components are secured in the jaw efficiently and relatively easily, and can be adjusted at a later date, to conform to the many variations in the size or shape of ridges in the jaw, rendering the prostheses more comfortable to the wearer. As also explained in the Prior Cases, the modular components can be interconnected while secured to the implants and are then reinforced and locked together by being encased by a cured, or hardened, resin composition, such as any of the self-curing dental resins well known to dentists.
[0009] Both types of foundations, each referred to as a “splint”, provides a base upon which tooth forms/synthetic teeth can be supported. When the screw shafts are implanted, temporary tooth forms can be created at chairside by a dentist, once a splint is in place, to provide a patient with a prompt replacement of missing teeth, which are firmly but replaceably connected to the implants. Immediately after placing the implants, the splint serves to index the implanted screws so that they are maintained in position without movement, to aid in the healing process with the jawbone, by allowing the bone to firmly grow around the implants.
[0010] In one embodiment, shown in the Prior Case and Prior Case II, each implant shaft has a polygonal top driving portion, engaging an indexing member which fits around and is held in a desired juxtaposition by the polygonal top. The preferred indexing member has paired arms extending outwardly therefrom, forming slots there between. Connecting bars, or flexible bands, extend through the slots on each indexing member from the first of a series of such implants to the last of the series, thus interconnecting the indexing members and thus anchoring the group of implanted screws together, to support each other in the desired juxtaposition. Each indexing member is in turn releasably secured to its respective implant shaft by a locking cap. To further enhance the rigidity and support provided by the overall splint structure, the bars and the indexing members are encased in a resinous material, thus forming a unitary rigid structure, which can be separated as a unit from the series of implants.
[0011] In accordance with the improvement of the present invention, by forming the locking caps from a material which is relatively soft compound to the implant posts, and non-adherent to the encasing dental resin, such as silicone or other polymeric non-adherent material, such as the polyacetal Delrin, the locking cap can be readily and safely unscrewed from the implant, so that the foundation splint structure can be removed from the implants, once the implants are firmly set, i.e., fully healed to the bone, or earlier, if necessary. Any of the temporary or longer term dentures can be thus supported on, and connected to the splint. The retaining implants as improved by this invention, preferably have a spheroidal head or an ovoidal head, extending above the gum line, and a platform substantially at the gum line and connected to the spheroidal or ovoidal head by a slender neck. A spheroidal head is one having a generally circular shape from a top view, and an ovoidal head is one having a generally elongated, or ellipsoidal, shape from a top view.
[0012] The ovoidal head allows a secure fit for dentures for use on patients having very narrow, so-called “knife-edge”, gum ridges. The concavity on the inner surface of the dentures for such patients must be molded to have an especially narrow opening in order to obtain a firm fit over such narrow gum ridges. The use of the ovoidal head on the implants permits firm and secure fitting for even the narrowest ridge, by aligning the major axis of the ovoidial head with the ridge. Alternatively, a denture for a wider ridge may be equally firmly supported by aligning the ovoidal head transversely, or perpendicularly, to the gum ridge. This allows the ovoidal head to extend fully across even the widest denture concavity and provide the required firm support. The widest dentures would be supported by aligning the major axis perpendicularly to the gum ridge, thus, the ovoidal head provides the most versatile use covering a wide range of denture sizes.
[0013] In accordance with the invention, damage during removal of the locking caps is further eased, while lessening the possibility of unduly stressing or damaging the implant foundation, during the initial fitting period. In this invention, the non-adherent locking cap is formed of a polymer and has a skirt portion at one end, and a dome-shaped portion at another end, having a spheroidal or ovoidal shape. The skirt portion is preferably an annulus, concentric with the dome portion, and having an internal diameter sufficient to surround any elements secured on the intermediate platform, but not greater than that of the platform diameter, so that the skirt bottom presses against the top surface of the platform. Preferably, a non-circular or polygonal, top driving portion is supported on the platform and in turn supports the threaded connector. Most preferably, at best, two elongated circumferential apertures are provided through the skirt, with relatively narrow skirt wall portions separating the two apertures. The apertures are preferably symmetrical about the circumference. These non-adherent locking caps are especially useful during the initial fitting period, when the fittings and these caps must be removed from the implants several times.
[0014] The locking cap is threadedly secured to the interconnectable top of the implant. When fitting the locking cap onto an implant, the externally threaded interconnectable top mates with the internal threaded portion of the cap. To reduce the chances of unintentional loosening of the cap, the cap is locked in place using a curable resin, which is inserted into the internal space within the skirt annulus in the locking cap. The resin is preferably one that will cure and harden quickly after the cap is screwed onto the implant, and is non-adherent to the locking cap. This hardened resin, portions of which extend into the apertures, will further secure the locking cap from rotational movement, which might otherwise cause it to loosen by surrounding, for example, the polygonal driving portion. The resin can be selected from among common curable dental resins, such as a polyacrylic or an epoxy polymer. When the locking cap is to be removed, the usual torque level is applied by the driving tool; the hardened resin in the apertures will tear the narrow strips of polymer forming the intermediate strips between the apertures, when the torque is applied to the caps. These resins may be auto-curing or light-curing, both of which are commonly used in dentistry. Generally, these are non-adherent to many dental polymers, such as Delrin.
[0015] By providing cured resin through the apertures, the cap is locked in place, but the cap can be readily torn at the ends of the apertures, under applied torque, thus, removing the lock without dislodging or moving the implant part before healing is complete. The material between the apertures can be made more likely to split in response to an applied torque by reducing the cross-sectional thickness of the material at those intermediate portions. Preferably the apertures extend, in toto, at least about 50% of the circumference, and most preferably at least about 80% of the circumference. To avoid extrusion of the resin beyond the apertures, before hardening, a thin, non adherent sleeve can be placed over the apertures and around the skirt portion. The sleeve can hold the resin in place during curing. The sleeve is most preferably non-adherent to the resin filling in the cap, such as a silicone, and also can have a slight elasticity to improve holding and simplify removal after hardening.
[0016] In use, an auto-cure or light-cure resin is inserted into the inner cup of the skirt of the locking cap. The cap is firmly tightened in place utilizing a U-shaped driver which fits within the aperture in the locking cap. Preferably, the apertures extend around and down the sides of the cap, and the U-shaped driver can conform to the downwardly extending side slots. Alternatively, a standard straight or cruciform slot across the top of the dome is provided, to allow a screwdriver to be used, or a polygonal indentation, for use, for example by an Allen wrench-type of driver. As the cap is screwed down, any excess curable resin material is forced outwardly, or upwardly, out of the cap, and can be easily wiped away before the resin hardens. A silicone sleeve placed around the apertures can be removed after the resin hardens.
[0017] The locking cap thus is held against rotation by the hardened resin surrounding the polygonal driver part on the implant and extending into the apertures of the skirt portion. The lower skirt portion, between the apertures, can be lifted out, or broken-up when exposed.
[0018] When it is desired to remove the cap, by applying sufficient torque to the caps e.g. with the U-shaped driver in matching slots, the hardened resin in the skirt will fracture the skirt wall portions, separating the apertures allowing, and the internally threaded portion of the cap and the skirt will separate at the apertures, allowing it to be easily unscrewed from the implant.
[0019] During the healing period, an interim prosthesis lined with the silicone material serves to lock the implants in place while providing an interim tooth replacement for the patient. That interim prosthesis will be removed once healing is complete. This procedure may need to be repeated a number of times during the healing, and the following trials and fittings of the final customized prosthesis. This final prosthesis can be constructed with the components described in, for example, U.S. Pat. No. 6,685,473 B2. After removal of the cap with the separated bottom section, a new cap must be secured in place in the same manner, when the interim prosthesis is replaced after the fitting.
[0020] The non-adhesive locking cap of this invention, is especially useful during the repeated fitting operations, because it is far less likely to stress or damage the thread of the, e.g., titanium, implant when being installed onto the implant, or being removed therefrom.
[0021] In a preferred embodiment, a central opening extends through the cap, regardless of the shape of the head, so that it is open at both ends; this permits excess resin to escape out the top, as the cap is being screwed down, while being held in place onto the threaded portion. This central opening can be provided regardless of the shape of the cap head.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1 illustrates, on a jaw model, a series of indexing and holding implants having the desired spheroidal head of this invention and banded necks;
[0023] FIG. 1 a illustrates, on the jaw model of FIG. 1 , a series of indexing and holding implants having the desired spheroidal head of this invention without the neck bands;
[0024] FIG. 2 illustrates, the jaw model of FIG. 1 with insert covers over the indexing implants;
[0025] FIG. 3 illustrates, the jaw model of FIG. 1 ; wherein the holding implants are covered by a half sheath;
[0026] FIG. 4 illustrates a detailed perspective view of the half sheath shown in FIG. 3 ;
[0027] FIG. 5 illustrates a top plan view of the spheroidal head of the holding implants of FIG. 1 ;
[0028] FIG. 6 illustrates, the jaw model of FIG. 3 , wherein the holding implants are covered by a half sheath which is in turn covered by a metal reinforcing frame;
[0029] FIG. 7 illustrates an elevation view of a spheroidal-headed implant for the present invention, as shown in FIG. 1 ;
[0030] FIG. 8 illustrates a front view of a splint being applied to the jaw, over the holding implants; and
[0031] FIGS. 9 A-I illustrate the procedure for forming a completed splint or dental prosthetic bridge in accordance with the present invention.
[0032] FIG. 10 illustrates a locking screw cap made of a structural, nonadherent polymer, such as the polyacetal Delrin, to secure the prosthesis to the implant;
[0033] FIG. 11 illustrates a single tooth prosthesis anchored to an implant;
[0034] FIG. 12 illustrates the skeleton of a prosthesis foundation which is threadedly connected to the implants;
[0035] FIG. 13 is an exploded perspective view of a threaded dental implant and internally threaded upper locking cap.
[0036] FIG. 14 is a perspective view of a threaded implant wherein the cap is threadedly connected to the implant and is in the process of being secured thereto utilizing a curable resin.
[0037] FIG. 15 is an elevational view of a spheroidal headed locking cap.
[0038] FIG. 16 is a partial cut away view of the locking cap of FIG. 15 , taken along lines 16 - 16 .
[0039] FIG. 17 is a top plan view of the spheroidal headed locking cap.
[0040] FIG. 18 A-C are elevational front and side views, respectively, and a top view, of an ovoidal locking cap.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0041] As described herein, the various rigid structural components shown in the drawings are fabricated from, for example, titanium, stainless steel, and/or any other suitable dental implant material which can withstand functional loads and support crowns, bridge segments, or the complete replacement of teeth with tooth forms/synthetic teeth/artificial teeth.
[0042] A model of a patient's jaw ridge R is shown in FIGS. 1 and 1 a , including implanted into the jawbone ridge a pair of the guide, or indexing, pins 2 in the posterior-most portions of the model, and a series of implant screw type retention pins 5 . Each of the retention pins in this embodiment, has a flattened dome-shaped, or spheroidal, head 9 , and a narrower neck 10 and threaded shank 20 , extending into the jawbone. Intermediate the shank and neck is a flange 22 having a distally facing platform 22 A. The combination of the neck 10 and head 9 provides an undercut surface for retention and the platform 22 A a firm support for the denture. In addition, closely surrounding the neck 10 there may be employed a removable elastic band 7 , which can be utilized to vary the degree of any undercut effect by reducing or increasing the effective diameter of the shank to the needs of the patient.
[0043] The spheroidal or ovoidal headed implant caps can be used for a single tooth prosthesis ( FIG. 11 ) or as part of a bridge denture, with other such implants. As shown specifically in FIG. 12 , and described more fully in the context of the Prior Case, another preferred embodiment of the holding implant screw 94 , 18 has, at one end, a relatively long self-tapping threaded shaft 20 . In use, an opening is made through any soft dental tissue, e.g., gums, overlying the jawbone, and the implant screw 18 is screwed into the hard dental tissue. The implant screw 18 has various advantageous features, such as a flange having a flat surface 22 A on a first side adjacent to which modular components are positioned and supported, and having a tapered smooth portion 22 B on a second side facing the dental tissue from which the threaded shaft 20 extends. The threads preferably do not extend the full length of the shaft 20 , such that a substantially smooth, unthreaded portion is preferably present immediately adjacent the tapered portion 22 B. In addition, this embodiment of the implant screw 18 includes a driving portion 24 which, in this example, is a flat polygonal extension, having a rectangular longitudinal cross-section. The driving portion 24 is adapted to engage a tool, such as a socket wrench bit. This is more fully set out in the Prior Case, incorporated herein. It is understood that the driving portion need not be in the specific shape shown, and may be polygonal concavity or extension, to engage compatible tools known in the art.
[0044] The preferred embodiment of the slender holding implant screw 94 , as shown in FIG. 13 , includes at the protruding longitudinal end, prosthesis connecting member 26 , for attaching modular prosthesis components thereto. As shown, the prosthesis connecting member 26 is externally threaded for receiving an internally threaded cap 109 ; for removably but rigidly connecting the implant screw to the splint.
[0045] As shown specifically in FIG. 13 , and described more fully in the “Prior Case”, a preferred embodiment of the implant screw 8 has at one end a relatively long self-tapping threaded shaft 20 and an adjacent shorter smooth cylindrical shaft 21 . A flange 22 is provided longitudinally adjacent the smooth portion of the shaft 21 , distal of the threaded portion, and includes a smooth tapered portion immediately adjacent the shaft flowing outwardly to a flat surface substantially perpendicular to the axis of the shaft and facing away from the shaft. A driving portion having a substantially polygonal cross-section extends longitudinally from the flat flange surface portion 22 . An externally threaded prosthesis connecting member 26 extends axially from the driving portion 24 in a direction away from the shaft 20 . The non-adherent locking screw cap 109 of this invention is shown in a position in FIG. 13 adjacent the threaded connector 26 , and in FIG. 14 screwed onto the threaded connector 26 .
[0046] The locking cap 109 comprises an annular, open-ended skirt portion 129 , having a generally cylindrical outer circumferential surface. A pair of circumferential apertures 110 are formed therethrough, so as to extend completely through the wall of the skirt 129 .
[0047] At the distal end of the locking cap 109 is a substantially spheroidal head portion 119 having radial, transversely extending slots 120 formed at diametrically opposed edges of the circumference of the spheroidal head. A narrower neck portion 116 is located intermediate the top of the skirt portion 129 which is defined by a relatively flat surface 121 , and the spheroidal head 119 . A central opening, defined by an internally threaded wall surface 115 extends completely through the spheroid head 119 and the neck portion 116 , to the interior of the skirt portion.
[0048] An alternative locking cap 209 is shown in FIGS. 18 A-C. At the distal end of the locking cap 209 is a substantially ovoidal head portion 219 having slots 120 preferably extending along the major circumference of the ovoidal head, as shown. The remaining aspects of this cap are as described above.
[0049] The locking caps 109 , 209 of this invention are preferably molded from a polymer of the types commonly used for placement in the mouth, by dentists, such as the polyacetal resin Delrin, utilizing either co-polymer grades or homo-polymer grades. Other useful materials include dental grades of nylon or polysulfone. Other suitable dental resins having the desired mechanical strength may also be utilized.
[0050] The relatively soft locking cap 109 made of a polymeric material is preferably used at least during the preliminary period after the implant is first affixed, when it is desired to provide an immediate replacement or splint to both hold a plurality of such implants in place and to provide the patient with at least an immediate replacement for the missing teeth, even though it is not one that may be maintained on a permanent basis. After the implants and bone have healed and become firmly secured, the permanent prosthesis can then be fitted. As the fitting of a permanent prosthesis often requires several trials, when the prosthesis must be removed, refitted and replaced, the use of a hard metal cap during this period could result in some damage to the metal implants. By utilizing the relatively soft resin cap, the likelihood of any damage occurring to the implant, from a cross threading or the like, is greatly reduced, if not wholly eliminated.
[0051] To further enhance the effectiveness of these caps, and to avoid their coming loose during this period, the caps can be initially filled with a curable dental resin in the cup formed by the skirt, preferably of the auto-cure or light cure type, and the cap is then applied to the threaded top portion of the implant and screwed down, while the excess resin from the skirt portion is squeezed out the top of the cap through the opening defined by the surface 115 .
[0052] As noted, the apertures 10 can be covered by a removable silicone sleeve 130 during curing, having sufficient elasticity to be able to be readily removed after the resin is set, if desired. The dental resin is generally not adherent to the silicone so the resin does not interfere with the removal of the sleeve. Any excess uncured resin which exudes from the top of the cap during the process of its being screwed on to the implant can be readily wiped-off before it hardens.
[0053] When the resin in the skirt is hardened, it surrounds the polygonal drive member 24 and extends into the apertures. This prevents inadvertent rotation of the cap when subjected to various stresses in the mouth. However, when the cap and resin are subjected to torque by the application of e.g., the U-shaped driver, on the slots 120 , 220 , the hardened resin in the apertures will press against the narrow portions 117 separating the apertures; these narrow portions in the skirt 117 are relatively weak, so that when torque is applied to the head of the resin cap the narrow portions with rupture. The cured dental resin, within the apertures of the skirt, pressing against these narrow portions between the apertures, will cause them to rupture upon the application of a reasonable torsional force, e.g. by utilizing a “U” shaped driver in the opposing slots 120 , 220 . The intermediate wall portions 117 can be further weakened by machining out some material so they are not as thick in cross-section as the remaining portion of the skirt wall 129 . The top portion of the cap can be removed when it is unscrewed. The lower skirt surrounding the driving portion 24 can be readily lifted out and removed, exposing the exposed threaded connection 26 , for attaching a new cap when the prosthesis is replaced by the dentist. This process can be repeated several times as needed during the trials and fittings of a customized prosthesis, without likelihood that the implant will be damaged.
[0054] Prior to initially forming the splint, of whichever form, a mold of the mouth showing the locations of the upper ends of the implants and their shape, together with any indexing element 80 present on each implant, is made using the usual dental impression material. A denture prosthesis can be prepared from this mold, by known procedures, which will locate the implant tops extending through the dental prosthesis. The concavity formed by the posterior indexing implants should be expanded to a larger opening to leave room for the jacket insert to be attached to the denture. This initial foundation, formed from a relatively hard dental resin, is then treated to remove material from the concave portion formed around the jaw ridge, to permit the molding and/or insertion of a softer more resilient dental resin liner, if desired.
[0055] This is not a part of this invention and merely provides the context for its use. This context is described more fully in a prior published application by the applicant (U.S. Patent Publication 2004/0166476-A1).
[0056] The use of the caps of this invention does not interfere with conventional molding techniques for dentures and, thus, allows dentists and dental laboratories to continue with their usual practice when forming a permanent denture prosthesis.
[0057] The above disclosure sets forth preferred embodiments of the present invention. Only the following claims fully define the invention: | 1a
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention is directed to a display frame which may alternatively be mounted in either a horizontal display configuration or a vertical display configuration, including a base having a front face suitable for presentation of graphic or textual information, and which frame suggests the illusion of depth of a displayed image object.
[0003] 2. Objects and Summary of the Invention
[0004] The present invention is directed to a display frame including curved front and rear walls, a viewing aperture and a base having a front surface suitable for display of textual or graphic information. The orientation of the display frame upon the base may be alternated between vertical and horizontal display formats by means of removable mounting pegs which attach to the walls of the display frame at predetermined locations.
[0005] It is an object of the present invention to provide a display frame removably mounted to a base for easily alternating the orientation of the frame with respect to the base between a horizontal display format and a vertical display format.
[0006] It is a further object of the invention to provide a display frame which suggests the illusion of depth of a displayed image.
[0007] It is a further object of the present invention to provide a base having a substantially upright broad front face suitable for presentation of graphic or textual information.
[0008] It is a further object of the present invention to provide a simply constructed, frame for display of various popular size photographs and similarly sized images.
[0009] It is a further object of the present invention to provide a display frame and base which are relatively inexpensive to fabricate.
[0010] It is a further object of the present invention to provide an inexpensive display frame and base suitable for use as advertising and mass marketing vehicles.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] [0011]FIG. 1 is a front perspective view of a first preferred embodiment of the present invention in the horizontal display format configuration.
[0012] [0012]FIG. 2 is a front perspective view of a second preferred embodiment the present invention in the vertical display format configuration.
[0013] [0013]FIG. 3 is a side view of a first preferred embodiment the present invention in the horizontal display format configuration.
[0014] [0014]FIG. 4 is a side view of a second preferred embodiment the present invention in the vertical display format configuration.
[0015] [0015]FIG. 5 is a rear perspective view of a second preferred embodiment the present invention in the vertical display format configuration.
[0016] [0016]FIG. 6 is a rear perspective view of a preferred embodiment of the base of the present invention.
[0017] [0017]FIG. 7 is a perspective detail view of the vertical display configuration mounting peg of the present invention.
[0018] [0018]FIG. 8 is a perspective detail view of the horizontal display configuration mounting peg of the present invention.
[0019] [0019]FIG. 9 is a top view of a preferred embodiment of the base of the present invention.
[0020] [0020]FIG. 10A is a front view of a first preferred embodiment of the present invention in the horizontal display format configuration.
[0021] [0021]FIG. 10B is a front view of a second preferred embodiment of the present invention in the vertical display format configuration.
[0022] [0022]FIG. 11 is a cross-sectional view of the FIG. 10A embodiment taken along line 11 - 11 of FIG. 10A.
[0023] [0023]FIG. 12 is a cross-sectional view of the FIG. 10B embodiment taken along line 12 - 12 of FIG. 10B.
DESCRIPTION OF PREFERRED EMBODIMENTS
[0024] Referring to FIGS. 1 through 12, preferred embodiments of the present invention will be described.
[0025] With respect to FIG. 1 a front perspective view of a first preferred embodiment of the present 3D Illusion Frame 10 invention is shown in a horizontal display configuration. The display frame housing 20 includes a curved front wall 22 which surrounds a viewing aperture 28 through which an image object 90 may be viewed. Joined to front wall 22 along one edge is a first rear wall 24 , and joined to wall 22 along an opposite edge is a second rear wall 26 . Display frame housing 20 is supported upon base 30 by two mounting pegs 70 . Base 30 includes a front surface 32 upon which textual or graphic material 40 may optionally be displayed. Front surface 32 extends substantially across the width of base 30 , and forms a predetermined acute angle from the vertical, which tilts front surface 32 a predetermined angle away from a viewer facing the front wall 22 of display frame housing 20 .
[0026] Display frame housing 20 may alternatively be repositioned in a vertical display configuration, as shown in FIG. 2. The display frame housing 20 may easily be reconfigured between horizontal and vertical configuration, as will be discussed below.
[0027] Referring to FIGS. 1, 3, 6 , 8 , 9 , 10 A and 11 , a first embodiment of the 3D Illusion Frame 10 includes display frame 20 in a horizontal configuration removably attached to base 30 by two first mounting pegs 70 . With particular reference to FIG. 8, pegs 70 include an upper portion 74 of predetermined diameter and a lower portion 76 having a predetermined diameter smaller than the diameter of portion 74 , and further having a different predetermined cross-sectional shape and size. A shoulder 72 is formed at the junction of upper portion 74 and lower portion 76 of peg 70 . Upper portion 74 of peg 70 includes projection 80 which forms curved mating surface 84 . The curvature of surface 84 is adapted to be complimentary to the shape or curvature of the outer surface 50 of the second rear wall 26 of display frame 20 . Pin 86 extends from mating surface 84 and is adapted to snugly, but removably engage positioning holes 36 , 38 formed in wall 26 . The upper portion 74 of peg 70 includes lip 82 and groove 88 which are adapted to removably engage the edge of wall 26 . Display frame 20 is assembled to first mounting pegs 70 by placing the edge of rear wall 26 into groove 88 and rotating display frame 20 about the edge of wall 26 relative to peg 70 so as to engage pin 86 in one of the positioning holes 36 , 38 . By reversing this operation, frame 20 may be disassembled from first mounting pegs 70 . Pin 86 and positioning holes 36 , 38 have complimentary shape and size to engage snugly, but removably.
[0028] Further referring to FIGS. 1, 3, 6 , 8 , 9 , 10 A and 11 , the lower portion 76 of each of first mounting pegs 70 is received in sockets 54 , 56 formed in the top surface 34 of base 30 . Sockets 54 , 56 are adapted to be complimentary to the shape and size of lower portion 76 of each peg 70 . Each of pegs 70 is inserted into sockets 54 , 56 until peg shoulder 72 contacts the top surface 34 of base 30 . The intersection of the long axis of first mounting peg 70 and the chord of the curvature of mating surface 84 forms a first predetermined acute angle, and when inserted into base 30 , the long axis of peg 70 forms a second predetermined acute angle from the vertical, which angles together tilt the display frame 20 a third predetermined angle away from a viewer facing its front wall 22 .
[0029] Referring to FIGS. 2, 4, 5 , 6 , 7 , 9 , 10 B and 12 , a second embodiment of the 3D Illusion Frame 10 includes display frame 20 placed in a vertical configuration, and removably attached to base 30 by two second mounting pegs 58 . With particular reference to FIG. 7, each second mounting peg 58 includes an upper portion 62 of predetermined diameter, preferably of a cylindrical shape, and a lower portion 64 having a predetermined diameter smaller than that of portion 62 and further having a different predetermined cross-sectional shape and size. A shoulder 60 is formed at the junction of upper portion 62 and lower portion 64 of peg 58 . Upper portion 62 of each second mounting peg 58 includes slot 66 having floor 68 which is adapted to compliment the shape and thickness of the first rear wall 24 and the second rear wall 26 of display frame 20 in order to receive either of these two rear walls. Slot 66 of peg 58 is sized and configured to snugly, but removably engage the first inner surface 46 , second inner surface 48 , first outer surface 50 , and second outer surface 52 of rear walls 24 , 26 , respectively. Display frame housing 20 is mounted on second pegs 58 by inserting a curved edge of rear wall 24 or rear wall 26 into slot 66 until the floor 68 is contacted. By reversing this operation, frame 20 may be disassembled from second mounting pegs 58 .
[0030] Further referring to FIGS. 2, 4, 5 , 6 , 7 , 9 , 10 B and 12 , the lower portion 64 of each of second mounting pegs 58 is received in sockets 54 , 56 formed in the top surface 34 of base 30 . Sockets 54 , 56 are adapted to conform to the shape and size of lower portion 64 of peg 58 , which is admitted into either of sockets 54 , 56 until peg shoulder 60 contacts the top surface 34 of base 30 . When inserted into base 30 , the long axis of each peg 58 forms a predetermined acute angle from the vertical, which tilts the display frame 20 a predetermined angle away from a viewer facing its front wall 22 .
[0031] Referring to FIGS. 11 and 12, display frame 20 includes an image object 90 , typically a photograph or graphic selected by the user. Optionally, the image object 90 may be enclosed in a transparent or translucent holder having a front leaf 92 and a rear leaf 94 . With particular reference to FIG. 11, the image object 90 may be positioned in a forward position within frame 20 so as to essentially conform with the inner surface 42 of front wall 22 . Alternatively, and with particular reference to FIG. 12, the image object 90 may be positioned in a rearward position within frame 20 so as to essentially conform with the inner surfaces 46 , 48 of rear walls 24 , 26 , respectively. When viewed through viewing aperture 28 with the image object 90 in a rearward position within frame 20 a visual suggestion of depth may be perceived. As has been described herein, the display frame 20 may be positioned on base 30 to display an image object 90 in either a horizontal format or a vertical format at the discretion of the user, and the display frame 20 may easily be alternated between the horizontal format configuration or the vertical format configuration as required by the format of the image object 90 .
[0032] The 3D Illusion Frame 10 is preferably fabricated of plastic, however any material having the required strength and rigidity may be used.
[0033] It will be understood by one skilled in the art that sockets 54 , 56 and lower portion 76 of first mounting peg 70 , and the lower portion 64 of second mounting peg 58 , may each be keyed so as to admit mounting pegs 58 , 70 in only selected orientations. It will also be understood by one skilled in the art that second mounting peg 58 and first mounting peg 70 may be fabricated as a single integrated structure combining both functions of supporting display frame 20 in the horizontal and in the vertical orientations, and further that the two peg mounting configuration may be replaced by a single structure. It will further be understood by one skilled in the art that walls 22 , 24 , 26 need not be curved, but may be planar, and that walls 24 , 26 may be extended to form a single wall. It will additionally be appreciated by one skilled in the art that walls 22 , 24 and walls 22 , 26 need not be joined along a common edge, but may each be joined to an intervening structure to increase the distance between walls 22 , 24 and walls 22 , 26 , respectively.
[0034] It will be understood that certain features and sub-combinations are of utility and may be employed without reference to other features and sub-combinations as they are outlined within the description above and within the claims appended hereto. While the preferred embodiments and application of the invention have been described, it is apparent to those skilled in the art that the objects and features of the present invention are only limited as set forth in the claims appended hereto. | 1a
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FIELD OF THE INVENTION
[0001] The present invention relates to wireless transmission of messages, and more particularly, to wireless transmission of messages between a local communication unit operated by an animal handler and a remote communication unit worn by the animal.
BACKGROUND OF THE INVENTION
[0002] Throughout human history, animals have played important roles in peoples' lives. Besides their obvious use as food, animals have provided labor, transportation, companionship, and have assisted humans in hunting and herding. One important role that animals play in modern society involves search-and-rescue operations. Animals, primarily dogs, can often enter into places that are too remote, rugged, or dangerous for a human rescuer. A dog's keen senses of smell and hearing are invaluable in aiding to locate trapped, injured or lost victims. However, once a dog does find a such a victim, there is a limit as to how much information can be communicated to or from the victim. It would be useful to have a way to communicate information to a victim, and also have a way for victims to communicate information back to the human rescuers, so that the human rescuers can be advised of and prepared to handle medical or other conditions, or be warned of dangers or other issues related to the rescue. Providing information, instructions or simply comfort to the victim in these situations can be very important.
[0003] In more casual applications, it will be appreciated that animals are helpful in initiating contact and conversation between people. Pets such as dogs are, unlike their owners, typically uninhibited about approaching other people, or other pets and their owners. In addition, people are generally initially more receptive to strange or unknown animals than they are to strange or unknown people. Thus owners can rely on a pet to “break the ice” with a stranger, gaining an entrée so that the owner can then initiate an interaction with the stranger.
[0004] Thus it would be useful to exploit these unique abilities of animals to facilitate tasks such as search and rescue, or mere social interaction.
SUMMARY OF THE INVENTION
[0005] In accordance with the invention, there is provided a communication system that includes a local communication unit and a remote communication unit in wireless communication with each other. The remote communication unit is configured to be mountable to an animal and to present to the animal or to a person in the vicinity of said animal an action that is initiated at the local communication unit.
[0006] Further in accordance with the invention, there is provided a remote communication unit configured for wireless communication with a local communication unit. The remote communication unit includes a mounting portion for mounting the remote communication unit to an animal, a communication circuit configured to receive signals from the local communication unit, and at least one transducer for presenting information to the animal or to a person in the vicinity of the animal in response to the received signals.
[0007] Further in accordance with the invention, there is provided a local communication unit configured for wireless communication with a remote communication unit adapted for mounting to an animal. The local communication unit includes an input device through which an operator initiates an activity at the remote communication unit, and a communication circuit configured to send signals associated with the activity to the remote communication unit.
[0008] Further in accordance with the invention, there is disclosed a communication method including initiating a message at a first location, and presenting the message at a second location using a transducer mounted to an animal.
[0009] Further in accordance with the invention, there is disclosed a communication system that includes a means for initiating a message at a first location, and means for presenting the message at a second location using a transducer mounted to an animal.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The accompanying drawings, which are incorporated into and constitute a part of this specification, illustrate one or more embodiments of the present invention and, together with the detailed description, serve to explain the principles and implementations of the invention.
[0011] FIG. 1 is a diagrammatic view of a system in accordance with the invention, including a local and remote communications units which are shown mounted on a collar;
[0012] FIG. 2 is a block diagram showing some details of a remote communications unit in accordance with the invention;
[0013] FIG. 3 is a diagrammatic view a system in accordance with a further aspect of the invention; and
[0014] FIG. 4 is a front elevational view of a local handheld communications unit in accordance with the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0015] Embodiments of the present invention are described herein in the context of a method and apparatus for wireless transmission using device worn by an animal. Those of ordinary skill in the art will realize that the following detailed description of the present invention is illustrative only and is not intended to be in any way limiting. Other embodiments of the present invention will readily suggest themselves to such skilled persons having the benefit of this disclosure. Reference will now be made in detail to implementations of the present invention as illustrated in the accompanying drawings. The same reference indicators will be used throughout the drawings and the following detailed description to refer to the same or like parts.
[0016] In the interest of clarity, not all of the routine features of the implementations described herein are shown and described. It will, of course, be appreciated that in the development of any such actual implementation, numerous implementation-specific decisions must be made in order to achieve the developer's specific goals, such as compliance with governmental or application- and business-related constraints, and that these specific goals will vary from one implementation to another and from one developer to another. In accordance with the invention, a system 100 for effecting communication between an operator or handler and an animal is shown in FIG. 1 . The term “handler” will be used to not only include the standard definition of an animal handler, but will also include pet owners and others who are interacting with the disclosed invention. System 100 includes a handheld wireless local communication unit 101 having a microphone 102 for voice pick-up, a push-to-talk switch 104 , and an antenna 106 . The handheld wireless local communication unit 101 is shown as a standalone unit, but it will appreciated that its functionality can instead be integrated into other devices. Standard circuitry and other components (not shown) are provided to enable the operator or handler to communicate message wirelessly from local communication unit 101 to a remote communication unit 108 disposed on collar 110 . The operator speaks into microphone 102 , which converts the operator's voice to electrical signals. In accordance with standard practice, these are then amplified and converted to RF (radio frequency) signals which are transmitted by antenna 106 , typically in modulated form. The RF transmissions may be terrestrial or satellite transmissions, and are conducted consistent with existing regulatory constraints. The frequencies and applications of the wireless transmission are preferably different from those used in cellular communication. Thus reliance on the cellular infrastructure is preferably avoided, particularly in applications involving emergency/rescue situations in which, for example due to remoteness, cellular reception may be compromised. This may not always be the case, and it is contemplated that in other situations and applications, cellular networks can provide an expedient means for the signal transmission.
[0017] Prior to speaking, the operator can depress switch 104 to activate the circuitry. Alternatively, voice activation circuitry (not shown) can be employed in lieu of switch 104 for purposes of convenient operation and/or battery power conservation. The RF signals (denoted at 112 ) representative of the operator's voice are emitted substantially in real-time by antenna 106 and received by remote unit 108 . It will be appreciated that while explained primarily in terms of the operator's voice, other signals and information can also be conveyed wirelessly and in substantially the same manner, including signals designed to trigger different types of alarms or pre-recorded messages stored and/or generated by either local unit 101 or remote unit 108 .
[0018] Remote communication unit 108 is detachably mounted to collar 110 , which is configured to be worn by an animal, for example around the neck of a dog. A mounting portion ( FIG. 3 ) is provided, for example in the form of loops though which the collar 110 passes, or complementary disengageable snaps provided on both the unit 108 and collar 110 , or Velcro™, buttons, straps, ore other means of detachably coupling the two components. While described in terms of attachment to a collar, it will also be appreciated that communication unit configurations, for example those consistent with attachment to and/or integration with harnesses, backpacks, saddles, headbands, ear clips, body bands, leg bands, chest plates, saddle bags pouches and so forth, are of course possible, and would be designed to comfortably and securely conform to the size, anatomy and disposition of the animal. In addition, the remote unit 108 could be built into a bag or other attachment (not shown) so that it can be attached to an existing collar, harness, or saddle. Further, unit 108 may be built into a headphone, earplug, or implant, and may be permanently attached, removably attached or integrated into a collar, harness, saddle or the like.
[0019] Antenna 114 receives RF signals 112 , which are then conveyed to appropriate circuitry ( 115 , FIG. 2 ) which amplifies (and demodulates) them, for, in the case of voice signals, conversion into audible signals by speaker (or loudspeaker) 116 . The converted audible message can then be heard by the animal wearing the device, or by people and/or animals in the vicinity thereof. It is contemplated that the volume from speaker 116 can be controlled and can alternatively be made sufficiently low to be audible exclusively to the animal, so that system 100 can be operated to provide commands to the animal to which people or other animals in the vicinity may not be privy. Alternative methods for accomplishing this is using speakers (not shown) implanted in the animal's ear canal or other locations, headphones placed over the animal's ears, ear phones, ear clips, and so forth. The volume and location of speaker 116 and remote unit 108 are also managed so as to avoid interference from ambient noise, by for example disposing the speaker close to the wearing animal's ear. Volume control of speaker 116 can be effected remotely from unit 101 , or locally, using a suitable knob (not shown) located on unit 108 .
[0020] While the various components of remote communication unit 108 are shown as being integrated into the same device and sharing a common housing, this is optional, and it is contemplated that these components can be separated out, for example a separate power pack (not shown) disposed elsewhere in the collar 110 for better accessibility, an antenna 114 that is located, either fixed or adjustable, in a more prominent location for improved signal reception, a speaker disposed closer to the animal's ear, and so forth.
[0021] The system of the invention can optionally be provided with other features, as described with reference to FIG. 2 , which is a block diagram of a remote communication unit 200 similar to unit 108 . An information acquisition portion 202 and an information presentation portion 204 are each coupled to an antenna 206 by way of a diplexer circuit 208 . Information acquisition portion 202 includes a GPS (global positioning system) receiver 210 , camera 212 , and microphone 214 . These devices gather information from the surroundings of communication unit 200 and convey this information wirelessly to local communication such as unit 101 described above, transmission circuit 216 . Specifically, position information indicative of the location of unit 200 is acquired by GPS receiver 210 and communicated to the handler at the local communication unit. Such location information can have obvious advantages, for example when worn by rescue dogs. Video information, which may be still or moving footage, is obtained by camera 212 , and sound information is obtained by microphone 214 . The video and sound information are also communicated to the handler at the local unit.
[0022] Information presentation unit 204 is serves to present information at remote unit 200 . Such information can be live (real-time) or pre-recorded voice messages presented by speaker 218 . Live messages are provided by a person such as the handler speaking into the microphone of the local communication unit, which transmits these wirelessly to remote unit 200 . Antenna 206 receives the wireless RF signals, which are suitably conditioned/filtered by diplexer 208 and forwarded to receiver circuit module 220 and on to speaker 218 for re-conversion to sound signals. Pre-recorded messages that originate at the local communication unit, which would be configured to store such messages in any known medium, for example in a magnetic, optical or electronic (RAM/ROM/EPROM/flash memory) form, are similarly wirelessly transmitted for presentation at remote unit 200 by speaker 218 . Alternatively, similar storage can be provided by a storage device 222 disposed in remote unit 200 , and the message can be read from the storage device at the instigation of an action, such as the press of a button, at the local unit. A synthesizer module 224 can optionally be provided upstream of speaker 218 in order to alter the sounds or voices from the speaker. For instance, if the collar on which remote communication unit 200 is to be worn by a large dog, the voice synthesizer module 224 can operate to modify the voice message so that the voice was played deeper or gruffer in tone, as if the large dog itself were speaking. Similarly, if the collar 110 was being worn be a small dog, the voice synthesizer module could modify the voice message so that the voice was played higher in pitch and softer in tone. Control of the synthesizer tone, pitch and other parameters can be conducted remotely via the local communication unit, or it can be conducted using input devices such as knobs, switches and so forth provided on unit 200 . It will be noted that both the live and pre-recorded messages can be passed through the synthesizer 224 . It will also be noted that sounds presented by speaker 218 , or by other such transducers (not shown), are not restricted voice messages. Instead (or in addition), tones can be presented, which the hearer, including the wearing animal, can interpret based on pre-agreed conditions or training. Such tones can be useful in order to maintain secrecy of communication, as others within hearing range may not be privy to their meaning, which can be useful in some situations.
[0023] In addition to audible signals, visual messages and signals can be presented by presentation unit 204 . For example, a bank of LEDs 226 can be provided, and patterns of these LEDs can be activated depending on the message intended to be conveyed. Activation of the LEDs, or other visual transducers such as incandescent lights and so forth, can be conducted remotely by the handler at the local communication unit. Other forms of signaling can be achieved using a vibration transducer 228 to provide vibrations of pre-selected frequencies, amplitudes, and so forth to which the wearing animal can be trained to respond.
[0024] It will be appreciated that FIG. 2 is a high-level diagrammatical illustration of one manner of implementing the various features and functionalities of the system 100 of the invention, and that other implementations are also possible. For instance, the GPS receiver 210 , camera 212 and microphone 214 , or other devices could each be provided with its own dedicated transmitter (not shown). In addition, transmission of signals from GPS receiver 210 , camera 212 and microphone 214 can be conducted in real-time, at distinct intervals. Additionally, the system can be configured so that the GPS receiver 210 , camera 212 and microphone 214 or other devices do not transmit their detected information, and instead store it for later review, using a storage device such as storage device 222 , or they can both transmit and store this information.
[0025] FIG. 3 shows a system 300 in accordance with a further aspect of the invention. A handheld wireless local communication unit 302 is in RF communication with a suite of remote units mounted to collar 304 . The remote units include a transceiver unit 306 configured to receive and transmit RF signals 308 . These signals correspond to voice, tone and other signaling information being transmitted from the handler or operator at local communication unit 302 , for example voice commands for the animal wearing the transceiver unit 306 , or voice messages to a rescuee that the wearing animal has reached, consistent with the description above. They can also correspond to electronic commands transmitted from the local communication unit 302 to the transceiver unit 306 to cause the transceiver unit to issue tones or other types of signals of an audible, visible, or tactile (for example vibrations, mild electric shock, and so forth) or other sensory nature. Such electronic commands are triggered by the handler, for example when the handler presses an associated button on the local communication unit 302 or otherwise performs a particular action which triggers the desired response at the transceiver unit 306 . They may also be triggered at the unit 306 , for example by rescuee reached by the wearing animal, in which case the rescuee can press a button provided on the unit 306 to hear a pre-recorded message. For audible signals, including voice, one or more speakers such as speaker 310 is provided. Other sensory outputs are provided by other known types of transducers (LEDs for light, electrodes for electric shock, mechanical vibrators for vibrational signals, and so forth). It will be appreciated that the term “transducer” as used herein refers to any device that converts an electrical signal to a non-electrical signals, and vice versa. Other components of transceiver unit 306 are antenna 312 for receiving the RF signals 308 from local communication unit 302 , and suitable circuitry (not shown) for converting and processing said received signals such proper triggering of audible, visible and other transducers is performed. A microphone 314 is also provided for detecting sounds from the environment of transducer unit 306 , which sounds are then processed for transmission back to local communication unit 302 as described above. Although speaker 310 and microphone 314 are shown as part of one package, it will be appreciated that separate packages for these two components are possible.
[0026] The suite of remote units mounted to collar 304 and in communication with local communication unit 302 also includes GPS locator unit 316 and video camera unit 318 disposed in a different location on collar 304 . GPS locator unit 316 can transmit location information to the handheld local communication unit 302 via antenna 319 . Similarly, video camera unit 318 can transmit video information to the handheld local communication unit 302 via antenna 320 . A mounting portion 321 is provided, which, as shown, consists of loops though which the collar 304 passes. Alternatively, complementary disengageable snaps (not shown) can be provided on both the unit 318 and collar 304 . Velcro™, buttons, straps, and other means may also be provided as the mounting portion. As discussed above, it is contemplated that camera unit 318 and/or GPS locator unit 316 can be in communication with transceiver unit 306 , either through direct wiring or wirelessly, such that they rely on some of the circuitry of transceiver unit 306 to effect communication with local communication unit 302 . It is also contemplated that camera unit 318 and/or GPS locator unit 316 can be in the same package, and can be configured to store data for later review rather than, or in addition to, transmitting the data to local communication unit 302 .
[0027] In FIG. 4 , a handheld local communication unit 400 , such as unit 302 , is shown in greater detail. Antenna 402 receives RF signals from the suite of remote communication units worn by the animal. These signals are converted to electrical signals and processed for presentation to the operator. In the case of audio signals, they are presented as sounds by speaker 404 . Similarly, visual information is presented on a display 406 , for example configured to display video scenes from camera unit 318 , and/or visual indications of location from GPS locator 316 , and/or various other information such as status information, power information, and indications of inputs entered by the operator at the local communication unit 400 . The information provided may be simple in nature, or it may include sophisticated displays of myriad information, such as images superimposed on a moving map, floor plan, schematic or other graphical device indicating where the moving animal is or has been relative to its environment. Multiple displays can also be used, each dedicated to a specific set of information, such as for video scenes from camera unit 318 , status information, and so forth. Controls (not shown) may be provided to adjust the display parameters, such as brightness, power-down duration, and so on. Similar controls (not shown) can be provided to adjust the view provided from the camera unit 318 , such as zoom, focus, and so forth. In input jack 408 is provided for connecting a headset (not shown), and at least one knob 410 can be provided for volume control of the headset and/or speaker 404 . A microphone 409 is also provided for sound pick-up.
[0028] There are numerous applications for the system, devices and methods of the invention in addition to those described above. These include use for sending training or directional commands to a wearing animal. The system could also be used to warn people to stay back from the animal wearing the device. In the case of an animal being used as a companion animal to a person, the device could be used to send encouraging words to the person. Further, such a device could be used to provide mobility to Alzheimer's sufferers and others with serious disabilities. Such a disabled person could safely go for a walk with a dog fitted with the disclosed invention, because the disabled person would always be in voice contact with caregivers, and the caregivers would be able to track the location of the disabled person. Caregivers who take pets to retirement homes to comfort the lonely could provide additional cheer with a dog that not only offered something for the individual to pet but spoke to the individual by name. This would provide greater personal interaction, which would provide a greater sense of comfort to the recipient. Other applications include monitoring and interaction with elderly independent live-alones, companionship and monitoring capability for Alzheimer patients on walks.
[0029] In addition to the search and rescue, novelty caregiver and companionship applications of the invention, it is also contemplated that the invention can be used for security and patrol. As in the other applications, the invention, by way of the remote communication unit with the accompanying video, audio and locative and other information acquisition features provided, enables the handler at the local communication unit to know where the wearing animal is and to see and hear the surroundings of the animal where the animal is and what the animal is seeing and hearing, enabling a more interactive experience with the animal. Such an interaction is enhanced when coupled with the handler's ability to send commands to the animal, such as in which direction to travel, how far to travel, to move towards or away from objects of interest or potential harm, approach certain people, avoid others, and so forth. Specifically, the invention could greatly expand security and patrolling options such as in fenced-in equipment storage yards, warehouses or large areas that need to be patrolled or secured. A dog as the wearing animal for instance could cover the terrain much faster and, depending upon the equipment being used, provide real-time feedback to the handler, thus allowing the handler to limit those areas or situations which would deserve a closer inspection. Further, through voice commands the handler can direct the dog to specific locations prior to the handler having to inspect these areas himself. Such applications would in essence reduce the number of false alarms or unnecessary investigations because areas could be patrolled by the dog.
[0030] It will also be appreciate that the search and rescue applications of the invention include wilderness search and rescue, disaster search and rescue, and buildings search and rescue and/or evacuation. Using the invention, ground could be covered much faster, areas could be reviewed remotely and the dog or wearing animal can be given specific commands to search certain areas. This enables a dog to be handled in areas not visible to the handler, in the dark and over distances or in high sound ambient situations where hand-signals or yelling commands to the dog are ineffective. The invention, when using the preferred non-cellular type of wireless communication, is particularly useful in search and rescue situations in wilderness because of the potential absence of cell phone coverage or in disaster situations where cell phones may be inoperable and consequently would be useless as a means of telemetry to and from the dog.
[0031] An example of a novelty application of the invention is as follows: A pet owner could talk into his local communication unit and his voice would be heard from the speaker on his pet's collar giving the impression the pet is speaking. As entertainment for children, adults or a party gag this interaction with the pet allows the owner to fantasize how his pet (or how THE OWNER) would talk to other people. The owner becomes a “Pettriloquist,” talking to others through his pet.
[0032] This would prove a significant icebreaker providing liberties that one could take with others, for example of the opposite sex, at the dog-park, coffee house or any setting, and not be perceived as offensive. A pet owner could also at a distance have a conversation through the pet with someone else. The voice synthesizer of the invention could modify the owner's voice to a breed-specific selection. For instance, the owner's voice would be masked big and burly for a Saint Bernard or soft and squeaky for a Pekinese. The situations where individuals could derive amusement from being a “Pettriloquist” is limited only by ones imagination, for example, a four member family with three dogs singing Happy Birthday to mom. Of course the invention is not limited to dogs and is equally applicable to other domesticated animals, such as cats, potbellied pigs and horses.
[0033] While embodiments and applications of this invention have been shown and described, it would be apparent to those skilled in the art having the benefit of this disclosure that many more modifications than mentioned above are possible without departing from the inventive concepts herein. The invention, therefore, is not to be restricted except in the spirit of the appended claims. | 1a
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RELATED APPLICATION
[0001] This application is a continuation of provisional U.S. patent application 60/271,090, filed Feb. 23, 2001.
FIELD OF THE INVENTION
[0002] This invention generally relates to sensors. More particularly, it relates to a system for making measurements concerning posture, orientation, and movement. Even more particularly, it relates to a system for measuring posture or repetitive motion and providing feedback.
BACKGROUND OF THE INVENTION
[0003] The range of motion of a joint of the body may be restricted as a result of injury. Range of motion can increase with therapy, exercise, and healing. Measurement of range of motion is important in evaluating the extent of injury and progress toward healing.
[0004] On the other hand treatment of various injuries may require temporary restriction in the range of movement, and devices such as casts, braces, elastic bandages, and corsets have been used to provide such temporary restraint. Some of these devices and some ergonomic chairs have also been used to promote a more erect posture.
[0005] Electronic sensors have been developed to measure angles between body segments and to measure range of motion of various joints, as described in commonly assigned U.S. patent application, Ser. No. 08/990,912 to Arms, (“the '912 patent application”), filed on Dec. 15, 1997, and incorporated herein by reference. The '912 patent application describes a pair of housings that contain a pair of inclinometer board assemblies and the cable and plugs for their connection. The inclinometer board assemblies each include pairs of accelerometers oriented orthogonal to each other, a/d converters, a multiplexer, a voltage regulator, and a microprocessor. The microprocessor computes the angle of each inclinometer housing with respect to the other.
[0006] Commonly assigned U.S. patent application, Ser. No. 09/457,493 to Arms, (“the '493 patent application”), filed on Dec. 8, 1999, and incorporated herein by reference discloses an inclinometer that includes three orthogonal accelerometers and three orthogonal magnetometers used to measure earth's gravitational and magnetic field vectors from which pitch, roll, and yaw (compass heading) are calculated. Low pass filters are provided to minimize effects due to inertial inputs to the accelerometers that might interfere with accuracy. The invention also provides a digital network to allow multiple devices to be wired together on a single bus, a feature useful for applications, such as posture monitoring.
[0007] Mechanical and electronic sensors have been developed to measure range of motion, as described in U.S. Pat. No. 4,665,928 to Linial et al. Other devices, such as those described in U.S. Pat. Nos. 4,958,145 to Morris, 5,089,808 to Amirdash, and 5,128,655 to Shore use measurement devices that detect whether an incline angle has been exceeded and provide an alarm when the user exceeds that prescribed angle.
[0008] Restraint on the extent of movement with the ability to perform exercises within a prescribed range is provided in U.S. Pat. No. 5,823,975 to Stark, et al. An orthopaedic restraining device is provided which provides restraint while permitting a range of exercise during rehabilitation. A communications device is included to provide feedback to the prescribing physician so the physician can evaluate the patient's progress in regard to the exercise the physician prescribed. The device is equipped to summon the patient to perform exercise with a visual alarm or a vibrator, to verify that torque used for the exercise is within a prescribed limit, to provide choices of torque and repetitions for each exercise, and otherwise give the patient immediate feedback respecting exercise. For example, the control program calculates the work or energy exerted by the patient and displays the energy exerted as a percentage of the targeted energy amount.
[0009] U.S. Pat. No. 5,593,431, to Sheldon, “the '431 patent,” determines the physical posture of a patient's body in relation to earth's gravitational field. A device with two or three DC accelerometers having sensitive axes mounted orthogonally within an implantable housing is adapted to be implanted with the sensitive axes generally aligned with the patient's body axes. The activity and body position signals from these sensors may be stored and/or used to monitor and effect the delivery of a therapy to the patient, e.g. by controlling the pacing rate of a rate responsive pacemaker. The device provides a multi-axis, solid state position and activity sensor operable along at least two orthogonal axes to distinguish the posture or positional attitude of the patient at rest and at levels of exercise.
[0010] However, the present inventors found that while the device of the '431 patent can distinguish various lying down positions from each other and from standing, the device cannot distinguish between various upright positions. For example, the device of the '431 patent cannot distinguish sitting from standing positions of the patient. Thus, a better system for monitoring is needed that provides improved ability to distinguish posture and activity in upright positions, and this solution is provided by the following invention.
SUMMARY OF THE INVENTION
[0011] It is therefore an object of the present invention to provide a device that can distinguish lying down, sitting and standing positions of a user;
[0012] It is a further object of the present invention to provide a device that distinguishes various postures within the sitting position;
[0013] It is a further object of the present invention to provide a device that recognizes too much time in a kyphotic posture and prompts the user to spend more time in lordosis.
[0014] It is a further object of the present invention to provide notice or instruction indicating too much time in a fixed position or too much time with little activity;
[0015] It is a further object of the present invention to provide notice or instruction indicating repetitive activity that can cause repetitive stress injury;
[0016] It is a feature of the present invention to provide a plurality of sensors extending on each side of a hip joint to distinguish lying, sitting and standing positions;
[0017] It is a feature of the present invention to provide a plurality of sensors, a processor, a storage device, and a feedback mechanism, wherein the sensors provide a dc response to detect inactivity or too little activity;
[0018] It is an advantage of the present invention that the device provides warning of too much time in a kyphotic posture;
[0019] It is an advantage of the present invention that the device provides warning of too little activity or repetitive activity that can cause repetitive stress injury.
[0020] These and other objects, features, and advantages of the invention are accomplished by a device for attaching to a living subject, comprising a sensor, a processor, and a storage device. The sensor comprises an acceleration measurement device. Data from the sensor is processed in the processor and stored in the storage device for determining when a person is in a sitting position and for determining body posture in the sitting position.
[0021] Another aspect of the invention is accomplished by a device comprising a sensor, a processor, a storage device, and a feedback notifier. Data from the sensor is processed in the processor to provide an output. The output is stored in the storage device as a function of time. Multiple points of the time dependent output stored in the storage device are processed in the processor. The processor directs the feedback notifier to provide information or instruction in response to the time dependent output indicating too little activity or indicating repetitive activity that can cause repetitive stress injury.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] The foregoing and other objects, features, and advantages of the invention will be apparent from the following detailed description of the invention, as illustrated in the accompanying drawings, in which:
[0023] [0023]FIG. 1 is a block diagram of the sensor unit of the present invention;
[0024] [0024]FIG. 2 a is a three dimensional sensor unit of the present invention;
[0025] [0025]FIG. 3 is a three dimensional sensor unit of the present invention showing rotation around the orthogonal axis including the direction of the gravity vector;
[0026] [0026]FIG. 4 a are equations to used calculate the accelerations and the angular positions of the sensor;
[0027] [0027]FIG. 4 b show the accelerometers and magnetometers as they are ideally positioned along orthogonal axis and rotations around those axes;
[0028] [0028]FIG. 4 c are equations to used calculate the components of earth's magnetic field and the rotation of the sensor about the z axis;
[0029] [0029]FIGS. 5 a and 5 b are flow charts showing two embodiments of the steps in the program run in the microprocessor of the apparatus;
[0030] [0030]FIG. 6 is a three dimensional view of a person using a wire connected apparatus of the present invention;
[0031] [0031]FIG. 7 is a three dimensional view of a person using a wireless apparatus of the present invention;
[0032] [0032]FIG. 8 is a block diagram of a wireless apparatus of the present invention; and
[0033] [0033]FIG. 9 is a three dimensional view of a person using a wireless apparatus of the present invention having multiple sensor systems and a wrist mounted remote processing unit.
DETAILED DESCRIPTION OF THE INVENTION
[0034] The present inventors recognized that available accelerometer based posture monitors could not distinguish between lying down and each upright position of sitting and standing. The '431 patent, for example, distinguishes among several lying down positions but has no mechanism to distinguish sitting from standing. In addition, the present inventors recognized that physical discomfort and medical problems arising from posture and repetitive movements can be prevented with appropriate characterization and feedback.. They recognized a common solution for a variety of problems, such as (a) extended time in a single position; (b) extended time sitting in a slouching posture (kyphosis) as opposed to sitting in an erect posture (lordosis); and (c) repetitive stressful movements, such as may be found on some manufacturing lines, while typing for an extended period of time without proper wrist support, or while working all day at a job lifting boxes.
[0035] The present inventors designed a miniature electronic device that records position and posture within that position data over time, senses the circumstances that could lead to physical problems by analysing position and posture data over time, and signals the user to take action to avoid injury. The same equipment can also be used during physical therapy to monitor movements and exercises to ensure that a prescribed range of motion is not exceeded and to encourage proper performance of prescribed exercises. It can also be used to analyse movement during participation in physical activity, such as a sport involving a swing, to improve performance.
[0036] In one embodiment, the present invention networks a pair of angular position sensors, one on each side of the hip joint, to distinguish lying down, sitting, and standing positions. In another embodiment, the present invention repeatedly records position and/or posture data over time. Feedback is provided when a condition is met, such as position remains constant for too long a period of time or posture is kyphotic for too long a period of time. Feedback can also be provided if a repetitive stressful movement is repeated too many times or if a desired range of motion limit is exceeded too many times. Feedback can take the form of a vibration or an audible signal.
[0037] The present inventors recognized that there are three components to human energy expenditure in non-exercising subjects; basal metabolic rate (BMR), thermic effect of food (TEF) and non-exercise activity thermogenesis (NEAT). BMR is the rate at which energy is expended when an individual is laying down at rest in the postabsorptive state. In sedentary individuals it accounts for approximately 60% of total daily energy expenditure (TDEE) and is highly predicted by lean body mass within and across species, as described in a paper “Avian basal metabolic rates: their association with body composition and energy expenditure in nature,” by S. Daan, D. Masman, and A. Groenewold, Am J Physiol, 1990;259(2 Pt 2):R333-40, and in a paper “Some consequences of body size,” by L. E. Ford, Am J Physiol, 1984;247(4 Pt 2):H495-507. TEF is the increase in energy expenditure associated with the digestion, absorption, and storage of food and accounts for approximately 10% of TDEE. Several investigators believe TEF to represent a fixed proportion of TDEE, as described in a paper, “Human energy expenditure in affluent societies: an analysis of 574 doubly-labeled water measurements.” by A. E. Black, W. A. Coward, A. M. Prentice, and T. J. Cole, Eur J Clin Nutr, 1996;50(2):72-92 and to be the invariant energy cost of converting food to metabolic fuels, as described in a paper, “Meal size and thermic response to food in male subjects as a function of maximum aerobic capacity,” by J. O Hill, S. B. Heymsfield, C. D. McMannus, and M. DiGirolamo, Metabolism, 1984;33(8):743-9, and in a paper, “Thermic effect of food in lean and obese men,” by D. A. Alessio, E C Kavle, M A Mozzoli, et al., J Clin Invest, 1988;81(6):1781-9 whereas others propose that TEF is actively regulated in response to changing food intake, as described in a paper, “Independent effects of obesity and insulin resistance on postprandial thermogenesis in men,” by K R Segal J Albu, A Chun, A Edano, B Legaspi, and F X Pi-Sunyer, J Clin Invest. 1992;89(3):824-33.
[0038] NEAT is the thermogenesis that accompanies physical activities other than volitional exercise, such as the activities of daily living, such as sitting, standing and walking, body movement plus fidgeting, spontaneous muscle contraction, and maintaining posture when not recumbent. It accounts for approximately 30% of TDEE.
[0039] In one study published in a paper, “Assessment of the heart-rate method for determining energy expenditure in man, using a whole-body calorimeter,” by M. J. Dauncey and W. P. James, published in Br J Nutr, 1979; 42(1): 1-13, the energy expenditure associated with lying, sitting and standing was measured in eight men confined to a room calorimeter. Total energy expenditure increased by 10% when seated compared to lying and by 36% when standing compared to lying. Furthermore, when these subjects were allowed to make voluntary movements to resemble fidgeting, energy expenditure increased further by 26±(SD) 1% in the lying position, 17±16% in the sitting position, and by 27±14% in the standing position. This experiment and others consistently demonstrate that low grade activities such as walking at ≈2 mph or cycling at 50W is associated with 2-3 fold increases in energy expenditure (7,9,10). Furthermore, the number of hours spent per day performing these activities can be added up so that the contribution of NEAT activities to total daily energy expenditure in free living, sedentary subjects can be clarified (FIG. 1). Thus, NEAT not only accounts for many hours in each day (in fact, in sedentary individuals,all hours spent awake, not resting and not eating) but the thermogenesis associated with each of these components is sufficiently great that NEAT has the potential to contribute significantly to total energy expenditure. The substantial majority of NEAT is accounted for by identifiable components such as body movement, sitting, standing and walking; fidgeting (small, non-purposeful distal limb movements) also contribute to NEAT.
[0040] A paper, “Role of nonexercise activity thermogenesis in resistance to fat gain in humans,” by J. A. Levine, N. L. Eberhardt, and M. D. Jensen, published in Science, 1999; 283(5399):212-4, concludes that increases in NEAT predict resistance to fat gain with over-feeding. However, investigations into the mechanism of this effect are hampered by the limited information regarding the components of NEAT in free-living subjects.
[0041] The present inventors recognized that there is a large potential market for “smart” wearable instruments capable of comprehensive recording of human activity, body position, and energy expenditure is available. For example, approximately 800 obese patients are treated each year by the nutrition clinic of the Mayo Clinic. In the present invention, such patients would be allowed to keep their monitors of the present invention, and an infrastructure for remote data access over the internet over a secure server would allow clinicians, therapists, and personal trainers to improve their knowledge of each patient's activity level and compliance with treatment regimen.
[0042] Previously existing wearable monitors based on dynamic acceleration have not been able measure NEAT, since their outputs drop to zero when the subject stops moving. Heart rate monitors cannot measure NEAT reliably, since they also do not reflect the body's position or posture. However, the present inventors have provided instrumentation to overcome this difficulty. The instrument developed by the present inventors provides body position and posture, and provides information regarding slow movements of the body that can be correlated with NEAT.
[0043] The present inventors designed a comprehensive instrument to measure human activity and body position and to detect the contributions of sitting, standing, walking and fidgeting thermogenesis to NEAT. The instrument distinguishes and measures bouts of exercise as well as contributions from normal sedentary life. The instrument provides feedback to the wearer. This device can thus be used to modify human activities, and therefore has the potential to affect an individual's weight and posture.
[0044] A preliminary version of the device with a single sensor unit for placement on one body segment was evaluated in a paper, “Evaluation of Biofeedback Device in Reducing Pain and Improving Function of Individuals with Low Back Pain,” by Krag, M. H., Fox, J. R., and McDonald, L. P.: published in Rehabilitation Society of N. America, Pittsburgh, Pa., 1997. The authors showed that wearing this device can result in more erect trunk postures which may result in reduced loads on the supporting muscles of the spine. Results of tests with the device were described in a paper, “Oh, My Aching Back”, by Wolkomir, R., published in Smithsonian Magazine, pages 38-48, August, 1998.
[0045] The measurement of spinal curvature may prove useful, especially in applications where prolonged static standing and/or sitting may be encountered. Various scientific studies have documented that a prolonged seated posture, especially without proper lower back support, is detrimental to those who suffer from low back pain. Devices to monitor curvature of the spine during prolonged sitting have been developed. Such a “lordosimeter” typically includes a thin, flexible, polymeric or metallic strip or strips embedded within or covered by compliant materials. It may be placed comfortably along the spine using elastic straps. The thin, flexible strip typically includes one or more strain gauges such as bonded foil types, piezo-resistive, inductive, capacitive, or fiber optic. The strain gauge converts the bending of the strip as posture changes into an electrical signal indicative of spinal curvature. An example of these fiber optic curvature sensing devices is described in U.S. Pat. No. 5,321,257, incorporated herein by reference, and the devices are available from Measurand, Inc., Fredericton, NB, Canada.
[0046] In the present invention, output data of the lordosimeter providing spinal curvature is logged continually. The unit is programmed to provide feedback to the user if the user remains in a poor posture for too long a time. The unit is also programmed to warn the user if he or she remains in any static position for too long a time. Thus, the unit encourages the user to move around frequently and to avoid poor posture. The feedback can enhance the user's awareness of his or her posture. In addition, information about trunk inclination and orientation from measurements taken over a period of time can help determine what posture or movements are related to back pain.
[0047] In addition to monitoring position and posture, with biofeedback, wearable instruments could also enhance patient compliance with prescribed rehabilitation/exercise programs after a back injury or a spine surgery or during rehabilitation of injuries to other parts of the body.
[0048] A paper, “The Biomechanics of Low Back Injury: Implications on Current Practice in Industry and the Clinic,” by S. M. McGill, published in J. Biomechanics, Vol. 30, No. 5, pp. 465-475, 1997, suggests that changing the body's position can alleviate joint pain and joint problems associated with overuse. Overuse injuries have risen in recent years, partly due to the increased time spent using computers, where the operator may infrequently change position and posture at the keyboard, as described in “OSHA—Its Role in the American Workplace” by R. Ferrante, executive producer, reported on National Public Radio by Robert Edwards, NPR's morning edition, Apr. 4, 1996.
[0049] The instrument developed by the present inventors is a wearable trainer or coach or personal tamaguchi device that reminds its owner to change position, get up, walk, stretch, or vary activities that overuse a joint. The instrument logs data concerning the user's time history of activity, position, posture, movements, and the device can test for compliance with programmed goals. A built-in display may provide cues and/or a composite health score based on the recorded data. These capabilities could not only benefit those persons who are recovering from an injury, they could also prevent overuse related injuries.
[0050] In addition, the data gathered from the device of the present invention would be valuable to researchers and to companies who employ individuals who may be at risk for overuse injuries, including package handlers, meat packers, movers, athletes, computer users, elderly persons, etc. Wearable activity, position, and posture instruments could be also be used to record patient compliance with prescribed exercise and could proactively prompt the patient to perform prescribed activities to result in improved outcomes.
[0051] MicroStrain, Inc. designed and has long been marketing wearable dataloggers for tracking trunk inclination with biofeedback through a vibrating pager enclosure, termed the Virtual Corset (Photo 1 ). These devices run for approximately six weeks using a single AA size battery. Data are recorded in an on-board non-volatile memory and can be downloaded via a connection to the serial port of a personal computer. Inclination is measured using a triaxial array of orthogonal static & dynamic response accelerometers. Preferably the inclinometer has capability to measure 360 degrees about at least one axis, as provided in a sensor available from Microstrain, Inc. called FAS-A. Even more preferably the inclinometer has capability to measure 360 degrees about two axes, which can be accomplished by providing three orthogonal accelerometers for each device attached to a body segment. For example, for measurement's of a person's torso, such a device provides measurement of flexion/extension (forward and backward bending) and lateral bending (sideways bending).
[0052] To also measure rotation of the body about an axis along the gravity vector one can also include three orthogonal magnetometers along with the three orthogonal accelerometers, as described in a paper, “A Miniature, Sourceless, Networked, Solid State Orientation Module”, by Townsend, C. P., Guzik, D. C., Arms, S. W., published in the 9 th International Conference on Adaptive Structures & Tech. (ICAST), Cambridge, Mass., October 1998, (“the ICAST paper”), and in a patent application 1024-045. This device is is available from Microstrain, Inc. and is called 3DM.
[0053] In order to detect and distinguish body position, such as standing, sitting, and lying down, the present inventors found that a second sensor unit was needed. The present invention networks a pair of angular position sensors, one on each side of the hip joint, to distinguish the three positions. It uses a networked array of angular position sensors termed 3DM's, as described in commonly assigned U.S. patent application Ser. No. 09/457,493, incorporated herein by reference. The idea of networking sensors is also mentioned in the above mentioned ICAST paper by Towsend.
[0054] To also measure angular rotation about an axis, including angular rotation of a body and twist of a joint about the axis, the present inventors found that a second sensor unit was needed, one on each side of the joint. The sensor unit preferably provides 3 accelerometers and three magnetometers, such as the 3DM device of Microstrain, Inc., as described in the ICAST paper by Townsend. The joint can be the ankle, the knee, the hip, spine, neck, shoulder, elbow, or wrist. For example, for measuring axial rotation or twisting of the spine in a standing posture, one 3DM is mounted to the lower spine around the pelvis and the other is mounted to the upper body around the chest.
[0055] It is worth noting that for a subject in a lying down posture axial rotation of the spine can be measured with gravity referenced devices alone, without magnetometers, but gravity referenced devices cannot be used for such measurements when in a standing posture.
[0056] The present invention links a triad of dynamic and static response accelerometers and a triad of magnetometers attached to a thigh and similar triads attached to torso. The magnetometers provide absolute rotational position about an axis coincident with Earth's gravity vector (compass heading, or yaw). Network capability is provided by an RS-485 connection between the sensors. The apparatus of the invention was tested on subjects who were standing, sitting, and lying, and the results show that accelerometer outputs from sensors on thigh and torso were easily able to distinguish the three positions, as shown in Table 1.
TABLE 1 Voltage outputs from inclinometers applied to the thigh and torso to detect standing, sitting and lying in three adults. Data are the mean of ten repetitions ± SD. Subject 1 1 2 2 3 3 Thigh Torso Thigh Torso Thigh Torso Standing 0.78 ± 0.88 ± 0.84 ± 0.91 ± 0.80 ± 0.98 ± 0.01 0.03 0.01 0.04 0.01 0.03 Sitting 4.00 ± 0.93 ± 3.94 ± 0.78 ± 3.87 ± 0.78 ± 0.04 0.05 0.03 0.02 0.04 0.05 Lying 3.91 ± 3.92 ± 4.1 ± 3.87 ± 3.77 ± 4.12 ± 0.03 0.02 0.04 0.03 0.04 0.03
[0057] The data shows a large difference in the output on thigh and torso for a sitting subject and no significant difference between thigh and torso sensors for both standing and lying subjects. However, standing and lying are distinguished by the large difference in magnitude of the output for these positions. Thus, all three positions are distinguished by providing linked sensors, one on the torso and a second on the thigh.
[0058] The data shows that body position can be measured reliably using only accelerometers to perform the sagittal plane body position measurement; no magnetometers were needed to distinguish standing, sitting, and lying. This simplification allows elimination of orthogonal magnetometers, reducing system complexity, power demands, and potential errors associated associated with local variations in Earth's geomagnetic field. The magnetometers are only needed for measuring rotation or twist about an axis coincident with the gravity vector. They can be omitted to reduce cost complexity and power when measurement along such axis is not needed, as for the device to merely distinguish standing, sitting, and lying.
[0059] Preferably the accelerometers have a DC response, enabling measurement of steady state accelerations such as the gravity vector and inclination respect to the gravity vector. The same accelerometers can also be used to determine linear velocity by integrating measured acceleration over time. A block diagram of sensor system unit 20 a , shown in FIG. 1, includes inclinometer 22 . Two or three orthogonal DC response accelerometers can be used to form the sensing portion of inclinometer 22 . Accelerometers 23 a , 23 b , and 23 c , shown in FIG. 2 a , such as the ADXL202 (Analog Devices, Norwood, Mass.) have a DC response, offer very small package size and use extremely low power. The output of each accelerometer 23 a, 23 b, 23 c is fed separately to low pass filter 24 . The cutoff frequency of low pass filter 24 is typically set to ½ the sampling frequency for antialiasing. The output of low pass filter 24 is sent to the analog input of flash based microprocessor 26 (16F877 or 16C877 from Microchip Technology, Chandler, Ariz.) which includes analog to digital (A/D) converter 28 . A flash based microprocessor has on board flash memory for storing a program that will be run on the microprocessor. This on board flash memory plus additional non-volatile flash memory chip 30 are advantageous in that they allow for field reprogramming of the firmware without requiring replacement of the microprocessor chip. A crystal oscillator (not shown) is included with microprocessor 26 to control the timing of the microprocessor. Time is then determined in microprocessor 26 .
[0060] In the embodiment of FIG. 1, all the requisite electronics, power, and packaging are contained in one sensor system 20 a . Sensor system 20 a also includes signal conditioning electronics 32 , biofeedback mechanism 33 for providing feedback to the user, communications circuit 34 a , internet interface 34 b , power supply 35 , and input button 36 . Sensor system 20 a can also include magnetometers or other sensors 38 .
[0061] Microprocessor 26 samples the three accelerometers 23 a, 23 b, 23 c (FIG. 2 a ) within inclinometer 22 at a sampling rate, such as 100 Hz. The data that was low pass filtered in hardware filter 24 will also be filtered in software run on microprocessor 26 using an Infinite Impulse Response (IIR) low pass digital filter that is formed in software to run on microprocessor 26 . The IIR software filter allows very low cutoff frequencies to be achieved without using large components that would be required in hardware filters; and the filter can be made programmable by the user. Using both hardware and software filters provides additional noise reduction. Hardware low pass filter 24 also serves as an antialiasing filter, which is a filter that limits the frequency content of the sensor signal to a maximum frequency that is half the sample rate (100 Hz).
[0062] The device of the present invention employs at least one accelerometer based inclinometer 22 to measure the orientation of the wearer's body segments relative to earth's gravitational vector. In the preferred embodiment, accelerometers with a DC response are used to calculate angle so that information about the user in a quiescent state can be obtained and stored. If a triad of accelerometers 23 a, 23 b, 23 c are used than an angle from +/−180 degrees can be measured on one axis relative to the gravity vector, and an angle range of +/−70 degrees can be measured on the other axis orthogonal to the first axis relative to the gravity vector, as shown in FIG. 3. The device uses microprocessor 26 that samples data from accelerometers 23 a, 23 b, 23 c and calculates the angles θ x and θ y from equations 41 - 45 in FIG. 4 a . Offset and gain calibration coefficients a xgain , a ygain , a zgain used in equations 41 - 43 are stored in nonvolatile memory chip 30 on system 20 a . Angles θ x and θ y so calculated are also stored in nonvolatile memory 30 . Sampling is typically done at a frequency of 100 Hz but other sample frequencies can be programmed. The advantage of higher sampling frequency is that information about faster motions can be captured. The advantage of lower sampling frequency is that less data storage is needed.
[0063] a x , a y and a z are calculated from the measured accelerometer sensor values along each axis, x, y, z, using equations 41 , 42 , 43 , as shown in FIG. 4 b . In the equation to calculate the acceleration along the x axis, ax, a xraw is the raw voltage reading from the x axis accelerometer. a xoffset is the offset coeficient to adjust the accelerometer for initial offset errors. a xgain is a coefficient to convert a xraw to a true acceleration reading. A xgain has units of g's per volt. Similar equations provide the y axis acceleration, a y , and the z axis acceleration, a z .
[0064] Rotations about the x and y axes are calculated in equations 44 and 45 by combining the accelerations calculated in equations 41 , 42 , and 43 . Solid state accelerometers are well known in the art.
[0065] To measure rotations about the Z axis, magnetometers are required. The three orthogonal components of earth's magnetic field m x , m y and m z are calculated from the measured values from magnetometers 38 a, 38 b, and 38 c using using equations 71 , 72 , 73 , as shown in FIG. 4 b ′. In the equation to calculate the magnetic field along the x axis, mx, m xraw is the raw voltage reading from the x axis magnetometer. m xoffset is the offset coeficient to adjust the magnetometer for initial offset errors. m xgain has units of Gauss per volt. Similar equations provide the my and mz values. From m x , m y , and m z , θ z can be calculated from equations 74 , 75 , 76 , and 77 shown in FIG. 4 c.
[0066] Accelerometers 23 a, 23 b, 23 c are also used to calculate linear velocity. To determine the linear velocity the output of the hardware low pass filter is sampled at a rate of 100 Hz. To measure linear velocity, the portion of acceleration due to the gravity vector is eliminated using a high pass digital filter, which eliminates accelerations that remain constant. The high pass digital filtering is performed by microprocessor 26 using software stored on nonvolatile memory 30 . The gravity vector is fixed at g, and therefore has a frequency of zero, so a high pass filter eliminates the gravity portion of the acceleration signal. As described herein above, the accelerometer data is scaled for offsets and gains and the magnitude of the resultant acceleration vector components a x , a y and a z are computed, as described in equations 41 , 42 , and 43 . While a uniform velocity cannot be measured with accelerometers, the time integral of the acceleration is computed using a digital numerical integration step to obtain the change in linear velocity vector resulting from acceleration.
[0067] The results of the inclination and velocity calculations are stored in non-volatile flash memory 30 for each point in time as shown in the flow chart of FIG. 5 at box 110 . This non-volatile memory chip 30 has the capability to store up to 4 megabytes of data on a single integrated circuit. The format of data storage in non-volatile flash memory 30 is programmable.
[0068] As an alternative to storing inclination and velocity at each point in time, the format of data storage can be programmed so the average of the inclination and velocity data over a programmable time period is stored at each interval of time, as shown in the flow chart of FIG. 5 a at box 111 . As another alternative, inclination angles and velocities can be segmented into bins and data accumulated in each bin as data is obtained at each point in time, as also shown at box 111 . This provides histograms of the frequency of velocity and inclination angles over each time period. In this case, however, the sequential aspect of the information is removed.
[0069] Sensor system 20 a can be located on one body segment, such as the lower trunk or the upper trunk, as shown in FIG. 6. A pair of sensor module units 20 a, 20 b can also be provided, one on each side of a joint, such as the hip joint. The difference between measurements of pair of sensor systems, 20 a, 20 b can be provided to detect angular position of the hip joint. Pairs of sensor systems 20 a, 20 b may be connected by wired 46 and connectors 48 a, 48 b or may use wireless communications, such as RF link 34 a and antenna 49 . The difference between the measurements of sensor systems 20 a and 20 b can be used to distinguish standing from sitting positions.
[0070] Pair of sensor systems, 20 a , 20 b ′ can be provided to detect angular position of other joints in addition to or instead of the hip joint or to measure how that joint angle varies with time by taking the difference in the outputs of two sensor systems 20 a , 20 b ′ one on each side of the joint, as shown in FIG. 6 for a knee joint.
[0071] Where two or more sensor systems 20 a , 20 b or 20 b ′ are provided, sensor systems 20 b , 20 b ′ need not have all the components of sensor system 20 a , as shown in FIG. 1. Input button 36 to biofeedback mechanism 33 and internet interace 34 b can be eliminated from slave sensor systems 20 b , 20 b ′ since those functions can be provided by components in master sensor system 20 a.
[0072] Inclinometers based on DC response accelerometers such as the ADXL202 (Analog Devices, Norwood Mass.) have been described in commonly assigned U.S. patent application Ser. No. 08/990,912, docket number 1024-040, herein by reference, and may be purchased commercially as FAS-A from MicroStrain, Inc., Burlington, Vt.
[0073] Sensors 20 a preferably include accelerometer based inclinometers 22 . They can also include magnetometers 38 to provide orientation around the gravity vector and to provide a complete orientation sensor. Orientation measurement devices that include magnetometers, such as the 3DM device of MicroStrain Inc., typically use both magnetometers and inclinometers to compute rotations coincident with the gravity vector. Such devices have been described in commonly assigned copending patent application Ser. No. 09/457,493, docket number 1024-045.
[0074] Power may be supplied with battery power supply 35 that can be a battery, such as a miniature camera battery, and this battery can be rechargeable.
[0075] Biofeedback mechanism 33 can include a visual display capable of providing text or images or it can include a device that provides an audible signal, such as a piezoelectric buzzer, visual display, or a vibrator such as an electromagnetic shaker.
[0076] While biofeedback mechanism 33 can be included within sensor system 20 a , as shown in FIG. 1, biofeedback mechanism 33 can also be provided on a separate remote processing unit 39 that is used along with sensor systems 20 a , 20 b , as shown in FIG. 6. This separate remote processing unit 39 may be strapped to the user's waist, as shown in FIG. 6 and 7 , or it can mounted to another part of the user's body, such as the user's wrist, similar to a wristwatch, as shown in FIG. 9.
[0077] Feedback mechanism 33 and remote processing unit 39 can also provide for communication from a clinician treating patient as well as feedback based on the data collected by sensor system 20 a as determined by the software program stored on nonvolatile memory 30 and run on microprocessor 26 . Feedback mechanism 33 may also be combined with input unit 36 , such as a single button or a keyboard, for the user to provide additional communication back to the clinician, as shown in FIG. 1 and in FIG. 2 b . Thus, in addition to collecting data about the user's movement and posture for use by the internal program and for transmitting to the clinician, and for providing feedback, instructions, encouragement, or other display to the user, feedback mechanism 33 and remote processing unit 39 can also allow the user to let the clinician know when the user experiences pain or to communicate other information.
[0078] Data transmission between simplified sensor system 20 b and remote processing unit can be accomplished by hard wiring the two, as shown in FIG. 6. Preferably communication between simplified sensor system 20 b ′ and remote processing unit 39 ′ would be wireless, as shown in FIGS. 7 and 8 a - 8 c . In either the wired or wireless embodiments, each sensor system 20 b ′ can be simplified somewhat to eliminate biofeedback mechanism 33 , nonvolatile memory 30 , input unit 36 , and internet interface 34 b since these can be provided in remote processing unit 39 ′. Simplified sensor system 20 b ′ would now include measurement sensors, such as inclinometer 22 , signal conditioners 32 , filters 24 , a/d converter 28 , microprocessor 26 , power supply 35 and communication mechanism 34 a . Microprocessor 26 is provided with each sensor system 20 a ′ so data is reduced to inclination or joint angle as a function of time and so the time dependent inclination or angle data is transmitted in digital form.
[0079] The wireless version of communication mechanism 34 a of FIG. 1 that is shown in FIG. 8 a includes RF transmitter 50 (available from MicroStrain, Inc. Burlington, Vt.) for transmitting data from sensor system 20 b ′ to remote processing unit 39 shown in FIG. 8 b through RF transceiver 52 for remote data processing there in microprocessor 54 . Remote processing unit 39 also includes data logging in non-volatile memory 56 , biofeedback through biofeedback mechanism 58 , and display 60 , enabling the user to receive information, while power is provided to each of these components by power supply 62 . Power supply 62 can be a small watch battery. Further transmission from remote processing unit 39 ′ to host PC 64 is provided through RF transceiver 66 , as shown in FIG. 8 c.
[0080] Alternatively, RF transmitter 50 and transceivers 52 and 66 can be an infrared digital access (IRDA) link. In cases where line of sight is not practical then RF links would be employed. While wrist borne is convenient, remote processing unit 39 ′ need not be wrist-borne; it can also be attached to the waist or to another convenient part of the body. It can also be held in a pocket, or strapped to another body part or it can also be hand held.
[0081] Wireless communication facilitates free range of motion, permits greater ease of use, enhances patient acceptance, has less potential for breakage due to lead wire fatigue, and is easier to integrate into garments such as bras or other unobtrusive strap-like apparel. Miniature wireless devices are available which contain the requisite electronics for digital transmission of data using narrow band surface acoustic wave (SAW) or crystal oscillators, such as StrainLink™ modules available from MicroStrain, Inc.
[0082] Inclination data can be transmitted along with error checking from two separate sensors without RF collisions by using correctly configured Strainlink™ modules operating at different frequency transmission bands (such as 916 MHz and 303.825 MHz). Thus, data from a single pair of sensor systems 20 a ′, 20 b ′, formed of dual or triaxial accelerometers and mounted on adjacent limb segments can be used as shown in FIGS. 1 and 7. Alternatively, a plurality of sensor systems 20 b ′ can be simultaneously transmitted to remote processing unit 39 , remotely processed there, and further transmitted to provide range of motion data to the clinician, as shown in FIG. 9.
[0083] Software capable of allowing remote re-programming of pre-set parameters is provided in non-volatile memory 56 of remote processing unit 39 for processing in microprocessor 54 in this unit. This is the same software described herein above that would otherwise be provided for each individual sensor system 20 a , or 20 a ′ for each pair of sensor systems, 20 a , 20 b or 20 a ′, 20 b ′ provided across a joint.
[0084] Sensor module system 20 a , or 20 a ′ or host system 64 could also incorporate a wired or wireless transmission system to allow for data transmission back to the clinicians′ office without requiring the wearer to return to the office. In one embodiment the data is transmitted to receiver 66 and associated PC host 64 that is located in the patients′ house. When all the data for the day has been acquired, host 64 would dial into the clinician's office and send the information over a modem or internet connection, as shown in FIG. 8C. This would all be transparent to the user. This would reduce the costs of administering the service significantly, by reducing the amount of time the clinician would have to see the patient. This would also allow for the clinician to view more data than would be possible if requiring the patient to come to the office could only retrieve data.
[0085] It is advantageous to implement the capability for the device to transfer data over the internet. With this capability it is possible for the patient to transfer data to the clinician's office without requiring the physical presence of the patient. It also would allow for the device to be updated and change parameter's, such as allowable range of motion before a warning is triggered.
[0086] Remote processing unit 39 ′ includes display 56 that may provide simple text commands. Display 56 could also provide graphical representations of people doing various movements to communicate the desired information or instruction to the user. The graphical display allows for the display of a score, helps teach good posture, and helps the user through exercises. Remote processing unit 39 ′ can also be used to perform mathematical computation of joint angles. It can be the unit that uses the data to conclude that a preset limit to range of motion had been exceeded too many times, that the subject has been too sedentary. Once the data from sensor system 20 a , 20 a ′, 20 b , 20 b ′ has been received and interpreted by wrist-borne remote processing unit 39 this unit could also provide feedback to the user using a vibrational, audible, or visual signal.
[0087] When preset or remotely programmed conditions are detected, such as movement extending beyond a preset range of motion, the user is provided feedback as shown in box 113 of the flow chart in FIG. 5 a . Feedback can be negative feedback seeking to halt or reverse that motion. When the user performs a requested task well or indicates improvement in compliance with program requests, the user may be provided positive feedback, such as a higher “health” score. These conditions, programs, displays, and interactions can all be programmed by the clinician (at the office or remotely) depending on the user's behavior or the clinician's expert assessment of the user's progress.
[0088] In addition to providing a biofeedback signal, it is advantageous to continually save information about the user's range of motion, which may be changing with time. This allows the clinician to evaluate rehabilitation progress. In addition, stored information provides a valuable research tool to study how movement or lack of movement may correlate with low back pain, cardiac ailments, dietary modifications, pharmacological treatments, and postural control.
[0089] Data can be saved as inclination angle at each time. It can be saved more compactly in histograms; each histogram's sum represents the total count of trunk inclination angles measured at the programmed sample rate (binning frequency). While more data can be stored in histogram format, the association with time of each individual data point and the time sequence is lost. Binned data are very useful in reducing the datalogger's requisite memory; once collected, these histogram data are easily downloaded over the serial port of microprocessor 26 on sensor system 20 a or microprocessor 54 within remote processing unit 39 ′ for analysis. The device logs inclination in 1 degree increments (factory set, but may be programmed) over ±180 in the flexion extension axis and ±70 degrees on the lateral bending axis. The sample rate for data collection is termed the binning frequency; as data is collected, the unit builds a histogram of inclination over specified time intervals (bin save interval) and then saves this histogram to memory. The process is repeated until the device is turned off or the memory capacity is reached. The data and programming parameters are saved in non-volatile memory, and will not be lost in the event of power down or low battery capacity.
[0090] The bin save interval can be programmed for any amount of time, but longer intervals provide lower resolution of the wearer's activity. For example, if the bin save interval were set at one hour, at the end of the day there would be 24 histograms showing the wearer's trunk inclination angle at the period of the binning frequency. This would show a histogram of inclination for each hour over the course of a day. If the bin save interval were set at 12 hours, at the end of a day there would be only 2 histograms of inclination. Longer bin save intervals use less memory than shorter bin save intervals, but longer bin save intervals provide less information about daily activities. The advantage of binning over saving data sequentially over time is that binning uses less memory.
[0091] Binned data has been collected and presented in a paper, “Evaluation of Biofeedback Device in Reducing Pain and Improving Function of Individuals with Low Back Pain,” by M. H. Krag, J. R. Fox, and L. P. McDonald, Rehabilitation Society of N. America, Pittsburgh, Pa., 1997.
[0092] Binning of data saves memory but the sequential recording of events is lost with binning. This is a limitatioon when repetitive motions of activities need to be recorded or when continuous exposure to a single posture or position or vibration occurs. In these cases the product of position and time is a measure of a person's exposure to that position. The repeated pattern of movement may also be important to asess exposure in a workplace environment. This analysis requires that postural and motion measurements be recorded sequentially and along with the time of the measurement. FIG. 5 a provides a flow chart detailing this sequential recording of data.
[0093] The user can record events (such as the presence of pain) with input button 36 which can be included either in sensor system 20 a or on remote processing unit 39 . Button 36 can also be on wrist-borne remote processing unit 39 ′ to conveniently allow the wearer to provide this input when experiencing pain. When button 36 is pressed, the time may be logged and stored in the system, along with other data, such as time of day, inclination, orientation, heart rate, blood pressure, etc. This system of measurements and data communications will allow the clinician to gain insight into the pain the user has experienced along with a chronological history of the ranges of motion and activities the patient experiences leading up to the onset of pain. If a correlation can be determined, the clinician can program the biofeedback to try to discourage the wearer from performing events that led to pain. This feature may be especially important for back pain sufferers, since they often experience pain well after the physical activities that may have caused the pain.
[0094] Accelerometers 23 a, 23 b, 23 c used to sense inclination angle can also be used to sense the vibration that the user is experiencing. For example, for a worker using a jack hammer or a chain saw, the device of the present invention will measure the vibration, log the vibration exposure dose received by the worker over time, and then give feedback if this worker receives more vibration dose than a preset vibration exposure dose. The frequency and magnitude of the vibrations is determined by calculating fast fourier transforms (FFT) of the acceleration data coming from the accelerometers or logged in memory. This FFT data is logged, and feedback can be provided based on the magnitude, frequency, and time history of the calculated vibrations. It is well known how to do a FFT, and the algorithm to transform a time domain signal to a frequency domain signal is also well known.
[0095] Variables can be initialized and initial readings can also be tared out as shown in box 102 of FIG. 5 a . The sensor is initialized to a known angle, such as zero, before the first measurement is taken. This is especially useful for postural control applications, since the user may tare the device at a desired position, regardless of slight variations that may result from various mountings to the wearers′ body.
[0096] The wearer places a miniature sensor module package 20 a , 20 a ′ in a small pouch located in their bra, or bra-like device on the chest or on the wrist. This miniature sensor module package 20 a , 20 a ′ contains inclinometer 22 with vibratory biofeedback capability. The user then stands in front of a mirror to better view his or her own posture. Once a desirable physical appearance or a comfortable posture, or both, is achieved, the user initializes or “tares” the unit. When the user exceeds a pre-programmed inclination angle (in this case, say 2 degrees), the user experiences vibratory or other feedback from the feedback mechanism 33 as shown in the flow chart in box 113 of FIG. 5 a . If the subject is undergoing vigorous physical range of motions (such as sit-ups or other flexion type exercise), the unit interprets these patterns and does not provide feedback so as not to annoy the wearer during exercise.
[0097] In addition to magnetometers, the present invention also provides for data to be collected and monitored from other sensors 38 such as force measurement sensors, temperature, electrocardiogram (ECG/EKG), electromyograph (EMG), and lumbar curvature, as shown in FIG. 1.
[0098] While several embodiments of the invention, together with modifications thereof, have been described in detail herein and illustrated in the accompanying drawings, it will be evident that various further modifications are possible without departing from the scope of the invention. Nothing in the above specification is intended to limit the invention more narrowly than the appended claims. The examples given are intended only to be illustrative rather than exclusive. | 1a
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FIELD OF THE INVENTION
This invention relates to an ultrasound imaging system, a three-dimensional ultrasonographic-image acquisition device as specified in the independent patent claim and a procedure for the acquisition of three-dimensional ultrasound images.
BACKGROUND OF THE INVENTION
A system for determining the position of a sensor within a given object and for the display of previously recorded images of the object corresponding to the sensor position has been described earlier by BUCHHOLZ in U.S. Pat. No. 5,383,454. With that system it is also possible to guide the tip of a sensor to a particular location within an object, while the position of the sensor can be observed on a monitor screen which also displays a previously recorded image of that particular region within the object. In that earlier concept, the position of the sensor is determined using a commercially available, three-dimensional sound digitizer.
Another example of an earlier method and appropriate system for the acquisition of diagnostically useful, three-dimensional ultrasound image data has been described by POLZ in the European patent EP 0 736 284 A2. That system incorporates a device by means of which it is possible, by freely and manually guiding the ultrasound scanning head, to assemble from a set of three-dimensional data tomographic images of an entire three-dimensional volume object or space to be examined. The position and orientation of the ultrasound scanning head are registered by an additional, electromagnetic sensor system. The ultrasound scanning head, freely guided by hand by the diagnostician, is preferably provided with a holder which also accommodates the receiver of the said electromagnetic sensor system. The sensor system whose receiver coils pick up magnetic fields emitted by a transmitter, produces sensor output data (both positional and rotational data) which precisely define the spatial position and orientation of the ultrasound scanning head. These are translational X, Y and Z axis data as well as rotational data around these axes.
A prerequisite for sufficiently precise positional and orientational determinations using magnetic field measurements is very detailed information on such extraneous parameters as:
interference fields generated for instance by display monitors, computers or electric motors;
interference patterns produced by highly permeable materials in the magnetic field, for instance metal objects moving within the measuring region; or
electromagnetic interference fields emanating from the AC power supply.
SUMMARY OF THE INVENTION
Quantifying these effects and/or minimizing them by appropriate hardware or procedures, be it shielding or continuous calibration, is a complex matter. The drawback of the earlier concept referred to thus lies in the fact that it is difficult to obtain positional and orientational determinations with the necessary degree of accuracy.
It is the objective of this invention to solve the problem. Its purpose is to provide a means for acquiring three-dimensional ultrasonographic images using a freely movable, manually guided ultrasound scanning head, an ultrasound acquisition device and a positional-determination i.e. locating device, which locating device permits the determination of the position and orientation of the ultrasound scanning head and thus of the spatial position and orientation of the tomographic ultrasound images.
The advantages offered by this invention consist essentially in the fact that the conceptual design of the device here disclosed simplifies the manipulation conditions in the following manner:
in terms of precise resolution, the system is not affected by external parameters;
the system is easy to handle; even if the positional determination were to be disrupted for instance by an object that strayed in between the acquisition device and the ultrasound scanning head, measurements can continue as soon as a clear view is restored; and
the tracking accuracy is not negatively affected by extraneous electromagnetic fields produced by display monitors and/or electrical equipment.
The present invention relates to an ultrasound imaging system for creating a three-dimensional image of a patient body. The system includes an ultrasound scanning head for acquiring a plurality of ultrasound images, a fixed control plane for determining position and orientation of the ultrasound scanning head relative to a spatial base by linear measurement, transmitters for emitting electromagnetic waves associated with either base points on the spatial base or control points on the control plane, receivers for receiving the electromagnetic waves located on the other of the base points or the control points, and an image processor for processing the ultrasound images to create the three-dimensional image of the body. The electromagnetic waves are used to determine the position and orientation of the ultrasound scanning head to thereby position and orient the plurality of ultrasound images.
In another aspect of the present invention, the ultrasound imaging system includes a freely movable, manually guided ultrasound scanning head for acquiring a plurality of ultrasound images, an ultrasound acquisition device for storing and displaying the plurality of ultrasound images, an image processor for processing the plurality of ultrasound images to create the three-dimensional image of the body, and a positional locating device for determining position and orientation of the ultrasound scanning head to thereby position and orient the plurality of ultrasound images. The locating device has a plurality of electromagnetic wave emitting devices located on the ultrasound scanning head, a plurality of electromagnetic wave sensor arrays for detecting the electromagnetic waves of the emitting devices, and an evaluation unit for computing the position and orientation of the ultrasound scanning head relative to a spatial base by linear measurements based on the electromagnetic waves.
The present invention relates to an ultrasound imaging system for creating a three-dimensional image of a patient body. The system includes an ultrasound scanning head for acquiring a plurality of ultrasound images, a fixed control plane for determining position and orientation of the ultrasound scanning head relative to a spatial base by linear measurement, transmitters for emitting electromagnetic waves associated with either base points on the spatial base or control points on the control plane, receivers for receiving the electromagnetic waves located on the other of the base points or the control points, and an image processor for processing the ultrasound images to create the three-dimensional image of the body. The eletromagnetic waves are used to determine the position and orientation of the ultrasound scanning head to thereby position and orient the plurality of ultrasound images.
In another aspect of the present invention, the ultrasound imaging system includes a freely movable, manually guided ultrasound scanning head for acquiring a plurality of ultrasound images, an ultrasound acquisition device for storing displaying the plurality of ultrasound images, an image processor for processing the plurality of ultrasound images to create the three-dimensional image of the body, and a positional locating device for determining position and orientation of the ultrasound scanning head to thereby position and orient the plurality of ultrasound images. The locating device has a plurality of electromagnetic wave emitting devices located on the ultrasound scanning head, a plurality of electromagnetic wave sensor arrays for detecting the electromagnetic waves of the emitting devices, and an evaluation unit for computing the position and orientation of the ultrasound scanning head relative to a spatial base by linear measurements based on the eletromagnetic waves.
In one implementation of the concept of this invention, the means provided on the ultrasound scanning head to emit electromagnetic waves for positional and orientational determinations are in the form of optical light sources.
In another implementation of the concept of this invention, the means provided on the ultrasound scanning head to emit electromagnetic waves for positional and orientational determinations are in the form of infrared light emitting diodes (IRLEDs).
In a different implementation of the concept of this invention, the means provided on the ultrasound scanning head to emit electromagnetic waves for positional and orientational determinations are in the form of reflectors or electrofluorescent reflectors.
In another implementation of the concept of this invention, the means provided on the ultrasound scanning head to emit electromagnetic waves for positional and orientational determinations are in the form of fiber optics connected to a light source.
In yet another implementation of the concept of this invention, the sensor systems serving to detect the electromagnetic waves within the measuring region are in the form of spatially fixed, unidimensional (linear-array) cameras, allowing an evaluation unit to determine the position and orientation of the ultrasound scanning head and thus the spatial position and orientation of the tomographic ultrasound images.
In another implementation of the concept of this invention, the sensor systems serving to detect the electromagnetic waves within the measuring region are cameras which are not spatially fixed, the position of the cameras being detectable by the acquisition and evaluation of a spatially fixed control-point reference field which in turn allows the evaluation unit to determine the spatial position and orientation of the tomographic ultrasound images. The acquisition and evaluation of the spatially fixed control-point reference field thus permits real-time measurements even under unstable environmental conditions. Every time the cameras acquire an image, the control-point reference field is used to recalculate the current camera positions, fully compensating for any positional changes of the cameras.
In another implementation of the concept of this invention, the sensor systems serving to detect the electromagnetic waves within the measuring region are spatially fixed, permitting the positional and orientational determination of a spatially variable control-point reference field for instance on a patient.
In yet another implementation of the concept of this invention, at least two of the sensors serving to detect the electromagnetic waves within the measuring region are spatially fixed cameras, allowing an evaluation unit to videogrammetrically determine the position and orientation of the ultrasound scanning head and thus the spatial position and orientation of the tomographic ultrasound images.
In a different implementation of the concept of this invention, the said minimum of two sensors serving to detect the electromagnetic waves within the measuring region are cameras which are not spatially fixed, the position of the cameras being determined by the acquisition and evaluation of a spatially fixed control-point reference field, allowing the evaluation unit to videogrammetrically determine the position and orientation of the ultrasound scanning head and thus the spatial position and orientation of the tomographic ultrasound images. The acquisition and evaluation of the spatially fixed control-point reference field thus permits real-time measurements even under unstable environmental conditions. Every time the cameras acquire an image, the control-point reference field is used to recalculate the current camera positions, fully compensating for any positional changes of the cameras.
In yet another implementation of the concept of this invention, the freely movable, manually guided ultrasound scanning head, the ultrasound acquisition device, the image processing unit and the positional locating device are connected to a computer-assisted surgery system (CAS).
One application of the procedure according to this invention is based on the design implementation in which the means provided on the ultrasound scanning head to emit electromagnetic waves for positional and orientational determinations are in the form of optical light sources.
Another application of the procedure according to this invention is based on the design implementation in which the means provided on the ultrasound scanning head to emit electromagnetic waves for positional and orientational determinations are in the form of infrared light emitting diodes (IRLEDs).
Another application of the procedure according to this invention is based on the design implementation in which the means provided on the ultrasound scanning head to emit electromagnetic waves for positional and orientational determinations are in the form of reflectors or electrofluorescent reflectors.
Another application of the procedure according to this invention is based on the design implementation in which the devices provided on the ultrasound scanning head to emit electromagnetic waves for positional and orientational determinations are in the form of fiber optics connected to a light source.
Yet another application of the procedure according to this invention is based on the design implementation in which the sensor systems serving to detect the electromagnetic waves within the measuring region are in the form of spatially fixed, unidimensional cameras, allowing an evaluation unit to determine the position and orientation of the ultrasound scanning head and thus the spatial position and orientation of the tomographic ultrasound images.
Another application of the procedure according to this invention is based on the design implementation in which the sensor systems serving to detect the electromagnetic waves within the measuring region are cameras which are not spatially fixed, the position of the cameras being detectable by the acquisition and evaluation of a spatially fixed control-point reference field which in turn allows the evaluation unit to determine the spatial position and orientation of the tomographic ultrasound images. The acquisition and evaluation of the spatially fixed control-point reference field thus permit real-time measurements even under unstable environmental conditions. Every time the cameras acquire an image, the control-point reference field is used to recalculate the current camera positions, fully compensating for any positional changes of the cameras.
Another application of the procedure according to this invention is based on the design implementation in which the sensor systems serving to detect the electromagnetic waves within the measuring region are spatially fixed, permitting the positional and orientational determination of a spatially variable control-point reference field for instance on a patient.
Yet another application of the procedure according to this invention is based on the design implementation in which at least two sensors serving to detect the electromagnetic waves within the measuring region are spatially fixed cameras, allowing an evaluation unit to videogrammetrically determine the position and orientation of the ultrasound scanning head and thus the spatial position and orientation of the tomographic ultrasound images.
Another application of the procedure according to this invention is based on the design implementation in which the said minimum of two sensors serving, to detect the electromagnetic waves within the measuring region are cameras which are not spatially fixed, the position of the cameras being determined by the acquisition and evaluation of a spatially fixed control-point reference field, allowing the evaluation unit to videogrammetrically determine the position and orientation of the ultrasound scanning, head and thus the spatial position and orientation of the tomographic ultrasound images. The acquisition and evaluation of the spatially fixed control-point reference field thus permits real-time measurements even under unstable environmental conditions. Every time the cameras acquire an image, the control-point reference field is used to recalculate the current camera positions, fully compensating for any positional changes of the cameras.
A different application of the procedure according, to this invention is based on the design implementation in which the freely movable, manually guided ultrasound scanning, head, the ultrasound acquisition device, the image processing unit and the positional locating device are connected to a computer-assisted surgery system (CAS).
The principles of optical and photogrammetric positional determination employed in this invention are described, inter alia, in the following textbook:
Jordan/Eggert/Kneissl
Handbuch der Vermessungskunde (manual of geodetic surveying)
10th edition, completely revised
Vol. IIIa/3
Photogrammetry
J. B. Metzlersche Verlagsbuchhandlung, Stuttgart, 1972
(see in particular paragraphs 144, 145, 146, 147).
As used herein, the terms ‘interference measurements’ and ‘linear measurements’ refer not only to the kind of interference measurements employed for instance in laser ranging but also, and especially, to the interference effects by virtue of which optical systems can produce images (for instance central perspectives) along an image plane or line.
Moreover, the term linear measurements is intended to express longitudinal measurements along an image plane (or line) (for instance on a CCD chip), such as the linear measurement of the distance z 1 , z 2 , in FIG. 4 (par. 146.2, FIG. 5 in the geodetic surveying manual), as well as absolute measurements of the length of the object of interest, as employed for instance in run-length measuring methodology (for example in a GPS system).
In lieu of the method shown in FIG. 4, employing two projection planes, it is also possible to use a measuring method which is likewise based on the array principle but employs at least 3 non-colinear, unidimensional CCD chips. One such product is commercially available, by the name of Optotrak™.
BRIEF DESCRIPTION OF THE DRAWINGS
The following will describe this invention and its conceptual enhancements in more detail, with the aid of partly schematic illustrations of several design examples in which:
FIG. 1 is a schematic representation of one design version of the system according to this invention;
FIG. 2 is a schematic representation of another design version of the system according to this invention;
FIG. 3 is a schematic representation of yet another design version of the system according to this invention; and
FIG. 4 is a schematic illustration serving to explain the photogrammetric procedure.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The design version of the system according to this invention as shown in FIG. 1 includes a freely movable, manually operated ultrasound scanning head 2 , an ultrasound recording i.e. acquisition device 9 , an image processing unit 8 and a positional locating device 10 , serving to acquire three-dimensional ultrasound images of the body 1 . The locating device 10 permits positional and orientational determination of the ultrasound scanning head 2 and thus the determination of the spatial position and orientation of the tomographic ultrasound images. Mounted on the ultrasound head 2 are transmitters 4 which emit electromagnetic waves. Spatially fixed cameras 6 , for example digital cameras, are provided and serve to capture the said electromagnetic waves emitted by the transmitters 4 . The transmitters 4 are imaged on the ultrasound scanning head 2 . The evaluation unit 7 then computes from these images the position and orientation of the ultrasound scanning head 2 . With the aid of a handle 5 , the operator can freely move the ultrasound scanning head 2 and is thus able to assemble a complete three-dimensional tomographic image of the body 1 as derived from the three-dimensional data record defined in the image processing unit.
FIG. 2 shows a design version of the system according to this invention, which includes a freely movable, manually guided ultrasound scanning head 2 , an ultrasound acquisition device 9 , an image processing unit 8 , a positional locating device 10 and a control-point reference field 12 consisting of light-emitting diodes (LEDs), serving to acquire three-dimensional ultrasonographic images of the body 1 . The locating device 10 permits positional and orientational determination of the ultrasound scanning head 2 and thus the determination of the spatial position and orientation of the tomographic ultrasound images. Attached to the ultrasound scanning head 2 are transmitters 4 which emit electromagnetic waves. Cameras 6 , for example digital cameras, serve to capture the said electromagnetic waves emitted by the transmitters 4 . In this implementation of the invention, the cameras 6 are not spatially fixed, their position 11 being determined by the acquisition and evaluation of the images produced by a spatially fixed control-point reference field 12 . As the two cameras 6 capture the electromagnetic waves emitted by the transmitters 4 , these transmitters 4 are imaged on individual image planes. The evaluation unit 7 then computes from the distorted perspectives of the two images the position and orientation of the ultrasound scanning head 2 . With the aid of a handle 5 , the operator can freely move the ultrasound scanning head 2 and is thus able to assemble a complete three-dimensional tomographic image of the body 1 as derived from the three-dimensional data record defined in the image processing unit.
FIG. 3 shows a design version of the system according to this invention, which includes a freely movable, manually guided ultrasound scanning head b, an ultrasound acquisition device 9 , an image processing unit 8 and a positional locating device 10 for the acquisition of ultrasound images a. The positional locating device 10 permits positional and orientational determination of the ultrasound scanning head b and thus the determination of the spatial position and orientation of the tomographic ultrasound images a. Connected to the ultrasound scanning head b are fixed transmitters f;g;h which emit electromagnetic waves. Spatially fixed cameras 6 , for instance digital cameras, are provided for recording the electromagnetic waves emitted by the transmitters f;g;h. The cameras 6 capture these electromagnetic waves emitted by the transmitters f;g;h and from the images thus acquired the evaluation unit 7 then calculates the position and orientation of the ultrasound scanning head b. With the aid of a handle 5 , the operator can freely move the ultrasound scanning head b and is thus able to assemble a complete three-dimensional tomographic image of the body as derived from the three-dimensional data record defined in the image processing unit.
FIG. 4 is intended to explain the photogrammetric method employed using the specific example titled “reconstruction (of the coordinates) from two perspective views with known positions of the image planes relative to each other and with known internal orientation”, as per Jordan/Eggert/Kneissl, manual of geodetic surveying, 1972, page 2271:
146.2 Reconstruction from two perspective views with known positions of the image planes relative to each other and with known internal orientation:
Given the respective internal orientation, one knows the visual rays [O 1 ], [O 2 ] and their position relative to the image planes. Knowing the mutual position of the image planes thus means knowing the mutual position of the visual ray bundles. The known spatial position of Π 1 , Π 2 , O 1 , O 2 yields the core axis o, the straight line s=(Π 1 Π 2 ), the epipoles K 1 , K 2 and the perspective allocation of the epipolar ray bundles relative to s. For any image pair P 1 , P 2 tied to corresponding epipolar rays, this will ensure that the visual rays s 1 =[O 1 P 1 ] and s 2 =[O 2 P 2 ] will intersect at a spatial point P. One thus knows the position of P in the system of visual ray bundles. To determine the position of P in a given spatial reference system S one must know the position of 1 , 2 within S. If the latter is not readily available, it must be determined per par. 145.3. As an example of an empirical, nonautomatic reconstruction, the following will address the so-called plane-table photogrammetry.
a) In plane-table photogrammetry (FIG. 4) <(a), in its simplest representation, with CCD chips to be assigned to the image planes 1 , 2 >
Γ is assumed to be a horizontal plane (planimetric plane). The image planes Π 1 , Π 2 are assumed to be vertical, i.e. the main visual rays [O 1 , H 1 ], [O 2 , H 2 ] to be horizontal. h 1 , h 2 constitute the image horizontal in Π 1 , Π 2 . x 1 , z 1 and x 2 , z 2 , respectively, are the image coordinates in 1 and 2 , respectively. The point of origin of each image coordinate system is the main point, the x-axis points extend in the horizontal direction. 1 , 2 are assumed to represent the height of the central points O 1 , O 2 above Γ.
It is also possible from the coordinates x 1 , x 2 of any given image points P 1 , P 2 to enter into the known planimetric planes Π′ 1 , Π′ 2 the planimetric planes P 1′ , P 2, , identifying the planimetric plane P′ of the spatial point P to be reconstructed as a cross section of the planimetric visual-ray planes s′ 1 =[O′ 1 P′ 1 ] and s′ 1 =[O′ 2 P′ 2 ] (forward section. While the base line O′ 1 O′ 2 is applied at the map scale, the image widths and x-coordinates will be multiplied by a suitable factor in a manner which will allow s′ 1 , s′ 2 to be traced with sufficient accuracy.
From the similar triangles O 2 PQ and O 2 P 2 Q 2 one can derive the height ζ 2 of P above the plane [O 2 h 2 ] via ζ 2 = Z 2 O 2 ′ P ′ O 2 ′ P 2 ′
This yields the height ζ of P above Γ by way of ζ= 2 +ζ 2 . By means of an analogous calculation of ζ= 1 +ζ 1 one can compensate for any errors.
As is shown in FIG. 4, the planimetric planes K′ 1 , K′ 2 of the epipoles K 1 , K 2 are determined as intersections i.e. crossover points of the baseline o′=[O′ 1 O′ 2 ] with Π′ 1 , Π′ 2 , their respective height above Γ, meaning their position in Π 1 , Π 2 , is found by inverting the trapezoid O′ 1 O′ 2 O 2 O 1 , dragging along the vertical carrier line for K 1 and K 2 . The epipolar rays are needed for identifying appropriate epipoles in the images of object characteristics.
If the image planes Π 1 *, Π 2 * were to be in some general spatial position, one could easily revert to the case, just discussed, of vertical image planes Π 1 , Π 2 . One would only have to reproject π 1 * from O 1 to Π 1 and π 2 * from O 2 to Π 2 . Without such reprojection, the total of the points P′ per FIG. 4 would make up the normal plane of the imaged object on a plane perpendicular to Π 1 * and Π 2 * and ζ would be the distance between point P and this plane. | 1a
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This is a continuation in part of application Ser. No. 08,478,952, filed Jun. 7, 1995, abandoned.
I. FIELD OF THE INVENTION
The present invention is directed to wireless communication for a central vacuum cleaner comprising a central machinery and a pipe system connecting the central machinery to remote working points. More particularly, the present invention is directed to low-frequency acoustic communication between the central machinery and the remote working points using the pipe system as the transmission channel, with such communication being used to control and monitor the operation of the central machinery from the working point.
II. DESCRIPTION OF THE RELATED ART
Central vacuum cleaners are popular in a variety of buildings, notably family homes. A typical central vacuum cleaner consists of a central machinery and a pipe system that connects the machinery to remote work points in the home. The machinery is usually centrally located in the garage or basement of the home and is typically comprised of a vacuum pump driven by an electric motor, control circuitry, and a plenum for collecting debris. The pipe system typically includes fixed rigid tubing, inlet valves, flexible tubing (hose), moveable rigid tubing (wands), and a cleaning nozzle. Usually, there is a handle held by the operator that connects the hose to the wands. The actual working point, where debris is vacuumed up, may be at the inlet valve or at the end of the hose, wands, or nozzle.
Because the working point can be and usually is remote from the central machinery, central vacuum cleaners involve a communication difficulty not experienced by portable vacuum cleaners; namely, the difficulty of enabling the operator at the working point to control and to monitor the central machinery. Prior art attempts to solve this communication problem have been essentially limited to the vital control function of turning the central machinery on and off; proposals have been made for controlling the speed of the motor, but none have become commercially available.
Prior art attempts to remotely turn the central machinery on and off can be divided into three categories: 1) electrical current relay using dedicated low-voltage wiring; 2) radio-frequency radiation using free space or house wiring as the primary transmission channel; and 3) pneumatic changes in pressure or airflow using a pipe system as the transmission channel.
The current relay is the oldest attempt and the one used in nearly all central vacuum cleaners. This system involves mounting an electrical switch in a wall inlet valve or in the handle of the hose. If the switch is mounted in the handle then it is connected to the inlet valve by winding two wires along the hose to contact points on the end of the hose; when the hose is inserted into the inlet valve, the contact points on the hose touch matching contact points in the inlet valve. The contact points or switch in the inlet valve are connected to a wire pair that runs along the fixed tubing to an electrical relay which switches the electrical motor on and off.
This attempt suffers from three serious disadvantages: First, it is inordinately expensive to install a wire pair running the length of the hose and tubing, particularly where electrical codes require that the wires be placed inside a separate conduit. Second, these wires are prone to breakage, creating an electrical open or a short circuit that is difficult to locate and expensive to repair. Third, the contact points frequently wear out or break, preventing the operator from activating the central machinery. In addition, safety experts have speculated that this method might not be fail-safe in the event of a fire in the home: the fire could melt the pipe and wires causing a short circuit that falsely activates the cleaner, thereby drawing air into the pipe system and possibly spreading the fire, particularly if the central machinery has a plastic housing.
Attempts employing radio frequencies have proven to be far less reliable and much more expensive than the current relay. These systems require licensing approval and are restricted to such low power that the vacuum motor is erroneously turned off and blockage and interference frequently occur. Of particular concern is the delicate electronic circuitry including a battery, which is mounted in the handle and thereby subjected to constant vibration and strong shocks when the handle is dropped. In addition, these attempts are not fail-safe since a momentary signal must be transmitted and received in order to stop the central machinery; inability to stop the machinery may be dangerous and disturbing to the remotely located operator.
Attempts employing pneumatics, such as that disclosed in U.S. Pat. No. 4,225,272, issued to Palmovist in September of 1980, also have proven to be more expensive than the current relay and far less convenient for the operator. In order to be as reliable as the current relay, pneumatic control systems must move enough air to create a sizeable change in air pressure, otherwise the system may be deceived by leaks, by natural fluctuations in atmospheric pressure or by the chimney effect in tall buildings. Pneumatic control systems also lose sensitivity over time and malfunction. Such a necessary sizeable change in air pressure can take several seconds, which combined with a motor response time of several seconds can be aggravating to the operator, in contrast to the lesser time delay of the current relay. Also compared to the current relay, considerably more effort by the operator is required to create a pneumatic pressure differential, such as by opening the inlet value, removing the hose, operating a pipe blocking mechanism or operating a manual pump. In addition, continually powering an electrical secondary pump or using a manual pump for starting to create a pressure differential is uneconomical or inconvenient. Pneumatic control systems are also subject to air leaks, which cause them to malfunction.
An alternative approach using pneumatics for stopping only is disclosed in our commonly used U.S. Pat. No. 4,829,626, issued to Harkonen et al. on May 16, 1989. This method uses acoustics for starting the vacuum motor by providing an acoustic-signal generator in the wand handle. When activated, the generator transmits a sound signal through the pipe system to a sensor in the control circuitry of the central machinery, which in response starts the motor of the vacuum cleaner. A single-frequency sound signal is generated only momentarily to start the motor. If the motor has started as intended, it keeps running until pneumatically signaled to stop by blocking airflow. Airflow is blocked by a flap usually located in the handle, which is manually swung into position by the operator. Then an airflow sensor detects the stoppage of airflow, and, in response, sends a signal to stop the motor.
The use of acoustics for starting is preferred to pneumatics because only about one-millionth the energy is required for signaling enabling the equipment to be smaller with a lesser effort required by the operator. The acoustic transmission rate is about 100 times faster and the operator should not notice any significant delay. However, Harkonen teaches that acoustics cannot be used when the vacuum cleaner is being operated because of noise and transmission problems. Consequently, Harkonen employs pneumatic signaling for stopping.
Perhaps the greatest difficulty with the pneumatic methods lies in the means for stopping the vacuum cleaner. In the normal course of using a vacuum cleaner, many possibly events could block the flow of air through the hose. For example, merely pressing the cleaning nozzle hard against a surface can block the flow of air sufficiently to cause the motor to stop. This is particularly the case when a small nozzle is used on non-porous materials or in crevices. Furthermore, objects too large to pass rapidly through the tubing may be picked up and may cause the motor to be turned off by mistake, resulting in a problematic blockage that otherwise would not have occurred. Most importantly, using the stoppage of airflow as a stop signal is not a fail-safe technique. If there is an air leak in the pipe system, if the blocking mechanism is obstructed by debris from closing completely, or if the pneumatic sensor is not kept properly calibrated or lubricated in the dusty environment, then the machinery could fail to stop. Also, the blocking mechanism can be cumbersome to operate, particularly if dirt accumulates inside, and it cannot match the "fingertip" convenience of the electrical switch of the current relay.
Additionally, Harkonen mentions that a second acoustic signal of a different frequency could be used in place of the normal start signal in order to command the use of a different motor speed. However this technique of speed control would be unsatisfactory in practice because if a change of speed is desired while vacuuming, the operator must first signal the central machinery to stop by using the flap to block airflow, then wait for the motor to stop and wait an additional lock-out period during which the control circuitry will prevent restart, and then restart the machinery by transmitting the second signal.
Regarding other uses for communication in central vacuum cleaners, prior art of portable vacuum cleaners suggest that monitoring functions are desirable. Such functions include alerting the operator that the dirt filter or bag is full or ruptured, that the cleaner is not operating properly or needs a service check, and that the cleaner is picking up a preset level of debris. These functions should be more important for central vacuum cleaners because of the remote location of the operator.
Consequently, there is a need for wireless communication to control and monitor the central machinery from the working point, with such communication being fail-safe, avoiding the blockage of airflow, and functioning even when the central machinery is activated and air is flowing in the pipe system of the central vacuum cleaner.
III. OBJECTS AND SUMMARY OF THE INVENTION
Accordingly, it is the primary object of the present invention to provide a new method of control for a central vacuum cleaner which enables a remotely-located operator to start and stop the cleaner in a fail-safe manner; another object is to provide such a method which is more economical than previous methods yet is at least as convenient for the operator and without problematic batteries, airflow blockers, or special wiring networks.
A more general object of the present invention is to provide a reliable communication method by which the operator can both control and monitor the central vacuum cleaner even when air is flowing through the pipe system. Besides starting and stopping, control functions include power boost, speed control, monitor control, and automatic vacuum regulation. Monitor functions include alerting the operator that the dirt filter or receptacle is full or ruptured, that excessive moisture or water is being picked up, that the central machinery requires a maintenance check, and that the amount of dirt being picked up is above or below a preset level.
To these ends, the invention provides a totally acoustic bidirectional method of communication using the air in the pipe system of the cleaner as the transmission channel and using as an acoustic source at the working point an air-powered reed controlled by a convenient slide switch. Such communication is made possible by use of a resonant physical structure, a continuous multifrequency signal and an adaptive signal detector.
The resonant physical structure, called a detection tube, is a special side branch added to the pipe system near the central machinery. The acoustic transducer is placed at the end of this detection tube, which is at least several pipe diameters long and is a dead end with no airflow. Consequently, the transducer is largely protected from pseudosound, which consists of non-acoustic pressure variations including vortices produced by turbulent airflow.
In the present invention, the detection tube is also designed to be a quarter-wavelength standpipe resonator which functions as a mechanical band-pass filter for the acoustic control signal with little extra cost. By substantially reducing the noise reaching the transducer, the detection tube makes it more likely that a commonly available and economical microphone can be used as the transducer. Also, the transducer can be largely protected from debris by mounting the tube vertically with the transducer end up. The tube itself can be assembled very economically out of parts already used in building the pipe system. For longer wavelengths that would require an inconveniently long tube, a Helmholtz resonator could be used, or baffles could be placed inside the tube to effectively lengthen the tube by folding or spiraling the pathway that the signal must traverse. In order to increase the filtering selectivity of the tube, sections with larger and/or smaller diameters than the tube itself could also be installed in the tube.
Alternatively, the pseudosound can be discriminated against on the basis of propagation speed by using two transducers placed a distance, D, apart on the main branch of the pipe system, where D is perhaps one meter and at least several pipe diameters to ensure sampling independence. The signal from the transducer further away from the central machinery is electrically delayed by a time, T, which is equal to the time required for an acoustic signal to travel the distance, D, between the two transducers; so T=C/D, where C is the speed of sound, neglecting the speed of air flowing in the pipe. Then the delayed signal is electrically added to the current signal from the second transducer; therefore, that portion of the signal that is due to sound propagating towards the central machinery will be doubled, but the rest of the signal will add randomly, including the non-periodic pseudosound, and should be reduced when averaged over time. The signal delay and adding can also be accomplished physically and with a single transducer by using a parallel pathway in place of the first transducer, with the pathway designed to have comparatively little airflow and to conduct the signal to the remaining transducer where the signal will combine in the air with the signal received directly from the pipe system.
Additional combining of the two transducer signals can be used to further discriminate in favor of the signal of interest, and more transducers could be employed for greater selectivity. In particular, if D is chosen to be equal to one-quarter of the wavelength of the signal interest, then acoustic noise of the same wavelength propagating from the central machinery, which can be quite noisy, will be canceled out when the signals from the two transducers are added. Furthermore, this arrangement can be used to estimate the speed of airflow in the pipe system, typically less than 20 meters per second, without the need for a special pneumatic airflow or pressure sensor than can have reliability problems. By separately adding the two signals with various time delays corresponding to speeds of under 20 meters per second, the delay that results in the best correlation can be selected, which should correspond to the speed of propagation of the vortices and thus indicate the airflow speed; if a threshold speed is of interest, then the time delay corresponding to that speed can be used and the magnitude of the sum of the signals used to indicate when the threshold speed is attained. The speed of airflow can be used to aid reliable detection of an acoustic control signal by adapting the criteria for declaring detection based on airflow and noise level.
That portion of acoustic noise that is due to rubbish moving through the pipe system is much more intense above 600 hertz, so the preferred embodiment avoids this problem by using a signal frequency below 600 hertz. However, there are other substantial sources of low frequency noise, namely noise from outside the pipe system and noise generated by the pipe system itself. This pipe system noise is generated by resonating structures such as side branches and especially the hose and also by movement of the hose and wands during the cleaning process. Still, it is possible to generate an acoustic control signal that is substantially greater than the background noise of the same frequency, particularly if the frequency of the control system is chosen to avoid probable frequencies for pipe system noise.
The present invention satisfies the objective of being fail-safe by using a new control logic requiring a continuous run signal for activation of the cleaner, rather than momentary start and stop signals. Therefore, if anything inhibits the signal, the cleaner will stop, failing safely. Also, if there is a false signal that starts the cleaner, it will stop almost immediately because the continuous signal will not be present.
The use of a continuous control signal comprised of a periodically repeated waveform is also advantageous for detection, especially when a substantial amount of noise is present. Because the signal is continuously repeated, its phase and exact waveform, as modified during transmission through the pipe system, can be determined during the start up of the cleaner and during other low noise times. This information can be used to more easily detect the signal during periods of high noise by making it possible to reject most of the noise that has the same frequency as the control signal but that differs in phase. The signal can be more reliably detected during periods of high noise by using a waveform that contains two or more major frequency components; then if the noise is too great at one frequency, the other frequencies can be checked, provided that they are sufficiently different from the first frequency so that their noise changes independently of the noise of the first frequency.
The waveform of the acoustic control signal should be selected to avoid the high-noise regions of the acoustic spectrum. The primary frequency should be below 300 hertz for good transmission in the pipe system and to avoid most rubbish noise, and it should be above 20 hertz to avoid airflow noise due to turbulence and in particular to avoid the infrasound produced by the hose. For example, a waveform could be selected with frequency components of 50, 100, and 200 hertz.
The use of very low frequencies enables the acoustic signal to pass through a blockage in the pipe system, in effect, so that the cleaner can still be controlled, as long as the blockage is not rigid and airtight or longer than the wavelength of the signal. For example, the hose can be stepped on and kinked, shutting off nearly all the airflow and yet the control signal will still pass through. In the event of a blockage, it is important that the cleaner not be shut off because the blockage may be slowly moving or disintegrating and will clear by itself if the cleaner continues to run. However, even very low frequency signals can have a problem with certain components of central vacuum cleaners, including gate valves and intercepter canisters. The present invention proposes to bypass these components with tubing that contains a flexible diaphragm which blocks airflow but transmits very low frequency sound; the diaphragm can also be built directly into the component.
The most powerful algorithm for detection of a multi-frequency control signal is to convolve a predicted control signal with the output of the transducer. The control-signal prediction is made on the basis of the known phase and waveform as received at earlier times. This signal is multiplied by the output signal and the resulting product is integrated over a fixed time period; for better discrimination against noise, the time period should be longer, but it should be smaller than the response time desired by the operator, say two seconds.
If no control signal is present in the output signal, then the integral will contain only the product of the predicted signal and random noise, which will average out to zero over time. If the control signal is present, then the integral additionally will contain the square of the control signal, approximately, which will always be non-negative and will average out to a positive value over time. Subsequently, the value of the convolution integral can be compared to a detection criterion level, with detection being declared and thus the machinery remaining activated if the level is exceeded.
The convolution requires an accurate prediction of the phase of the control signal. However, the phase will change slowly over time due to changes in airflow or in the vibrating reed. For example, airflow can cause a typical phase shift of 180 degrees at a frequency of 200 hertz. Therefore, the present invention uses an adaptive prediction scheme that can track the phase of the control signal as it shifts over time. One such scheme is to narrowly filter the output signal of the transducer at the primary frequency of the control signal, then shift the phase of the predicted control signal to match shifts in the phase of the output signal of the filter.
Convolution may be the best choice for detection mathematically but it may be unnecessarily expensive to implement electrically, particularly for single-frequency control signals. For single frequencies, simple phase-locked loop circuitry will suffice and will automatically adjust for shifts in phase.
The detection processes may be made adaptive by lowering the detection criterion level during periods of high noise and airflow, thereby lowering the possibility of a false stopping of the machinery. The noise and airflow can be conveniently and economically estimated without the need for a separate and problematic airflow sensor by examination of the output signal of the detector transducer. The amount of broad-band noise can be estimated from the amplitude of the output signal, and the signal can be filtered for frequencies characteristic of pseudosound, with the filtered amplitude indicating the airflow. Electrically, this can be realized with common circuitry used for automatic gain control.
The problem with using a continuous signal as the control signal is to provide power for its generation at the work point; batteries may work for a momentary signal, but they are unsuitable for a continuous signal. The solution adopted by the present invention is to use air power from the central vacuum cleaner itself. Very little of the airflow is required.
There are many possibilities for air-driven acoustic generators, including whistles, sirens, and even an electrical speaker powered by an air-driven generator. However, the present invention embraces one type of generator as particularly advantageous in regards to frequency stability, efficiency at low frequencies, reliability, and cost. The best choice for an acoustic generator is a freely vibrating reed, as used in harmonicas, accordions, and reed organs. The reed can be manually plucked as well as powered by airflow, although when powered by unidirectional airflow the signal is in effect rectified so that the primary frequency component of the airflow signal will be twice that of the plucked signal even though the reed itself is vibrating at the same rate. The reed can be manufactured easily, and the frequency components of the generated signal can be changed easily by twisting or bending the tip of the reed, as is done when organ reeds are voiced.
Certain features of the waveform generated by the reed can be easily changed during operation. Such waveform changes can be used for signaling other control functions, such as motor speed control. Changes can be made to the waveform by varying the pressure drop or airflow across the reed, by adjusting a feeler wire that exerts pressure on the throat of the reed, or by altering the airflow pattern around the tip of the reed. This pattern can be altered, for example, by altering the base plate of the reed or by opening another pathway for air to reach the tip of the reed.
In particular, the waveform change associated with a change in air pressure across the reed can be exploited to signal the pressure directly as part of a system to automatically control the pressure at the working point, so no special pressure sensor is needed. The major change in the waveform that occurs with increasing pressure is that air flows through the reed for a longer portion of each cycle of the vibrating reed. Using the reed, a pressure change can typically be signaled to the central machinery within one-tenth of a second, in contrast to the several seconds required for the pressure change itself to reach the central machinery. The faster signaling time is critical if the central machinery is to be used in the regulation of pressure at the working point.
The generator for the acoustic control would most naturally be located in the handle held by the operator, however, it could be placed elsewhere. For example, a reed could be built into each inlet valve so that the inlet could be used as a working point without the hose or wands. Also, the reed could be put inside the end of the hose that is inserted into the inlet valve, yet it could still be controlled from the handle by means of a mechanical linkage or a small-diameter air tube running the length of the hose. With the reed located in this position, the signal generated by the reed would not have to travel through the acoustically muffling hose and could therefore contain higher frequencies or less power.
The housing of the reed must include an air cavity on the supply side of the reed. The cavity acts as an air reservoir or capacitor for the reed so that it can vibrate freely and not be constrained by a pressure drop during each vibration cycle. The reed should be connected to the pipe system by a duct that is horn-shaped for good acoustic coupling and for the protection of the reed from debris.
Optionally, a resonator can be placed in communication with the reed to enhance or absorb particular frequencies. A resonator can stabilize the phase and frequency of the reed. Also, a resonator can restore the fundamental vibration frequency of a reed whose acoustic signal has been rectified by airflow, as is done by the action of the sounding board in a reed organ. Also, a resonator can extend the time that the reed vibrates after being plucked manually. Unfortunately, the handle is too small to conveniently accommodate a quarter-wavelength standpipe resonator suitable for very low frequencies. However, a Helmholtz resonator may be constructed easily by using the normally hollow interior of the handle as the resonator volume, which can be connected to the reed by means of a small-diameter tube whose length and diameter have been chosen to tune the resonator. The resonator can also be filled with foam or equipped with discs in order to lower the resonant frequency.
For less harmonic distortion, the reed should be made as wide as possible with weight concentrated at the tip. The other end of the reed can be narrowed to lower the fundamental frequency. Also, a larger reed should be more durable and easier to pluck. The handle should have enough space for a reed as large as two centimeters wide by ten centimeters long.
The reed can be conveniently controlled by the operator by means of a slide switch on the handle. This switch should be as convenient for the operator to use as the current relay switch. The acoustic switch has the additional advantage that it cannot unintentionally activate the cleaner when the hose is inserted into the inlet valve, as is the case if the current relay switch is left in the ON position. Also, the acoustic control slide switch can easily incorporate the bleed-air control slide, which is not the case with the current relay switch.
The slide switch should have three positions: OFF, ON, and START, with the START position being spring-loaded to return to the ON position. When the switch is moved to the START position, the reed is manually plucked by a finger attached to the switch; when released, the switch slides to the ON position, but the finger is diverted on the return stroke from hitting the reed again. Optionally, the reed can be plucked by the rotation of a star wheel that is pushed when the switch slides to the START position. In either the START or ON position, the switch exposes an orifice that admits air to the air cavity of the reed, so that the reed will continue vibrating after the central machinery has started. When the switch is moved to the OFF position, the orifice is closed, thus removing power from the reed. Although the reed continues to vibrate for a time, its output is no longer rectified so that the fundamental frequency returns immediately and continues until the reed stops vibrating. The shift from rectified to fundamental frequency is more easily detected than is just the cessation of the rectified frequency even if the reed were stopped instantly.
The pathway that connects the orifice at the slide switch to the air cavity of the reed can be designed to regulate the pressure across the reed, which can increase the frequency stability and life of the reed. Pressure can be partially regulated by putting many twists and turns into the pathway or by providing a second air pathway that bypasses the reed.
More than one reed can be controlled by the slide switch. There could be separate start and run reeds, for example, or reeds for other control functions. However, a single reed should be able to handle all control functions together more economically.
Although vibrating reeds can be designed to be quite powerful at very low frequencies, as evidenced by reed organs, there still may be some larger applications where more power is desirable. For such applications, the reed can be replaced with a valvular reed, also called a diaphone, in which a disc or small cylinder is attached to the tip of the reed and is used to open and close an air pathway. A valvular reed can generate much greater acoustic power and yet has the same frequency stability as the vibrating reed.
Also because of the greater power, the valvular reed may be chosen as the acoustic generator for the alert signals issued from near the central machinery by the monitor system. Greater power would be needed by the monitor system, for example, if the alert signal were to be issued during periods of high airflow and if the alert were to be indicated to the operator by the alert signal causing the hose to vibrate.
In the present invention, acoustic signals can also enable the operator to monitor the central machinery. Monitor alerts can be communicated to the operator by transmitting acoustic signals backwards through the pipe system from near the central machinery to the working point. Such monitor alerts could include the need to check an alert panel on the central machinery, to check the dirt filter, or to have the cleaner serviced. In most cases the alert does not have to be issued immediately; it could be postponed for several minutes during periods of high noise or even held until the operator is through vacuuming or until the cleaner is started up again. Before the cleaner is started, the alerting acoustic signal could be a simple tone or a voice message, perhaps synthesized from bass frequencies for better transmission; such an alert could be heard when the operator opens the inlet valve to insert the hose. After start up, the alert signal could be designed to cause vibrational contractions noticeable by the operator in the hose or in a membrane in the handle, for example, or an electrical detector and indicator could be installed in the handle. Alternatively, the alert could be given while slowing or stopping the central machinery for a brief period. Much of the control detector electronics and the detector transducer could be shared to produce the monitor alert signals.
A detector transducer that is also used to generate monitor alert signals must be a bidirectional transducer; it should not be a velocity-type microphone, for example. The present invention embraces one type of transducer as particularly well suited to doing both jobs at low cost. That transducer is a two-centimeter square piezo-electric crystal attached to a metal foil diaphragm and housed in a metal case with a diameter of 5 centimeters. The large size of the transducer allows it to better handle very low frequencies as compared to other widely-available microphones. Also, it will fit in the end of the detector tube without additional provisions, other than a cushioning foam to isolate it from tube-wall vibrations. The metal construction is preferred for the harsh operating environment of the pipe system.
In summary, the invention provides a reliable communication method by which the remotely located operator can control and monitor a central vacuum cleaner. The method is totally acoustic, fail-safe, and bidirectional, and it uses the air in the pipe system of the cleaner as the transmission channel. With the method, reliable communication is possible even during periods of high airflow and noise in the pipe system.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side elevation schematic drawing of a central vacuum system according to the present invention.
FIG. 2 is a block diagram of the electrical circuitry used for controlling the on and off switching of the central vacuum cleaner.
FIG. 3 is a side elevation of the handle shown in FIG. 4.
FIG. 4 is a cross sectional side elevation of the handle assembly.
FIG. 5 is a side elevation of the detection tube for receiving the start and run sound signals.
FIG. 6 is a longitudinal sectional view of a bypass tube arrangement.
FIG. 7 is a schematic diagram of a second monitoring circuit used in the present invention.
FIG. 8 is a graph of energy distribution functions for pseudosound.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
As required by the statutes and case law, a detailed embodiment of the present invention is disclosed herein. It is, however, to be understood that the disclosed embodiment is merely exemplary of the invention, which may be embodied in various forms. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present invention in virtually any appropriately detailed structure.
Referring to FIG. 1, there is shown a central vacuum cleaner 10 having a housing 12 resting on the floor 14 of a basement. The housing 12 includes a vacuum pump and electric motor assembly 16, an air inlet 18, and an exhaust duct 20. A network of ducts or tubing 22 is connected to the air inlet 18. The tubing 22 is fixed to the inlet valve 24 in the wall 26 of a room where the vacuuming is to be done. The inlet valve 24 includes a flap valve 28 for covering and sealing the vacuum opening 30 when the inlet valve 24 is not in use. A wand set 32 includes a nozzle 34 connected to the wand tube 36, and a handle 38. A hose or flexible tube 40 is connected to the handle 38 and is removably connected to the inlet valve 24 by the coupling 42.
The handle 38 is adapted to transmit sound signals through the hose 40 and the network of tubing 22, and, as will be described in detail below, to the detection tube 44. A shielded wire or lead 46 connects an acoustic transducer 48 (FIG. 2) seated within the detection tube 44 to the electronic circuitry shown in block form in FIG. 2.
When the vacuum pump and electric motor assembly 16 are turned on, air is drawn through the entire system from the nozzle 34 until it is exhausted through the exhaust duct 20, carrying debris picked up from the floor 50 and depositing it in a receptacle, such as a bag (not shown) located inside the housing 12.
Referring to FIG. 3, there is shown the handle 38 having a handhold portion 52 including an elongated aperture 54 that the operator can grasp, if desired. The handle 38 includes a moveable switch 56, which is a slide switch.
Referring to FIG. 4 the handle 38 is shown in cross section illustrating the duct 58 that the air is drawn through when the central vacuum cleaner 10 is operating. The handle 38 includes an internal air cavity 60, which houses a start-signal reed 62. The start reed oscillates at a frequency of 240 hz when struck or plucked.
The start reed 62 is plucked by a pick 66 that is an integral portion of the moveable slide switch 56 when the slide switch 56 is moved to the start position, that is, downward as shown in FIG. 4. The sound developed or generated by the start reed 62 in conjunction with the air cavity 60 is transmitted through the horn-shaped duct 64 and all associated tubing of the central vacuum cleaner 10 to the detection tube 44, whose design and function are described below.
The pick 66 is preferably made of a flexible material, such as soft plastic or rubber, so that it will bend when it contacts the reed. The tip of the pick 66 is pointed and is bent in the direction of the tip of the start reed 62. When the slide switch 56 is moved to the start position, the pick 66 will wipe against the start reed 62 and thereby be bent backwards slightly. Consequently, the start reed 62 will be pushed downward further until the pick 66 has been moved forward enough to release the reed. The shape and flexibility of the pick 66 are such that the tip of the pick will spring forward at the movement of release and be out of the path of the start reed 62, thereby giving the required quick release for plucking even though the slide switch 56 may be moving relatively slowly. The tip of the start reed 62 is rounded slightly and bent down; this configuration helps the tip of the pick 66 to bend by riding up and over the reed or by diverting to the side of the reed when the slide switch is returned to the off position. In this embodiment of the invention, the run position of the slide switch is the same as the start position; however, a spring could be added to the front edge of the slide switch to move the switch backwards to a separate on position that would still leave uncovered an orifice 74 of the run cavity 68. The particular material and dimensions of the pick 66 and start reed 62 are selected so as to provide the target frequency of 240 hz when struck or plucked.
Both the start reed 62 and the run reed 70 can be described as a freely vibrating beam clamped at one end and having a rectangular cross-section. Such a beam is known to vibrate at a frequency, f, which is related to the beam length, L, the beam thickness, A, and the speed of sound in the beam material, C, as described by the following formula: A=6.2 * f * L 2 /C, where the units are consistent. For example, a reed with a frequency of 240 hz could be made from copper having a value of C of 350000 cm/sec and would then be 0.064 cm thick with a length of 4 cm. This reed could be shortened while keeping the same frequency if sufficient weight were added to the tip or if the area near the clamped end (the throat of the reed) were sufficiently thinned, grooved, or drilled. Since the frequency of vibration is not dependent on the width of the reed, the reed can be made as wide as possible, 2 cm for example, to maximize the output power of the reed.
Other frequencies can be added to the waveform of the reed by twisting, rounding, or splitting the tip, as is done in the voicing of reeds in reed organs. The exact frequency of vibration of the reed depends on the size and shape of the cavity in which the reed is mounted. The cavity should be resonant at the desired frequency of vibration for the reed. The run reed is additionally influenced by the base plate 72, which surrounds the reed, and particularly by the width of the gap between the plate and the reed. For maximum power, the gap should be as small as possible without distorting the frequency of vibration of the reed.
A reed frequency as high as 240 hz is preferred primarily because of size limitations of currently available hose handles, although this frequency is somewhat easier to detect and process than lower frequencies if standard electronic components are used. However, a lower frequency would be preferred if custom components are used or if more space is available for a bigger reed, or if space is economized by using a single reed for both the start reed 62 and the run reed 70. Frequencies in the neighborhood of 16 hz are preferred because of lower attenuation in the hose and piping system and because of lower background noise at these frequencies, including noise from rubbish; however, mechanical filters, such as that shown in FIG. 5, are harder to construct for these frequencies because of their longer wavelengths.
The second or run cavity 68 is formed within the handle 38. A run reed 70 mounted on a base plate 72 is seated and fixed within the run cavity 68. An orifice 74 is covered by the flap end 76 of the moveable slide switch 56 when the switch 56 is in the off position. When the slide switch 56 is in the start position or the run position, the orifice 74 is uncovered. When the motor 16 is turned on, therefore, air is drawn through the orifice 74, where it causes the run reed 70 to oscillate. The sound waves thus generated are transmitted through the horn-shaped duct 78 into the duct 58 and throughout the tubing 22 and duct work of the system to the detection tube. The run reed vibrates at the rate of 132 hertz, but the air passing through the run cavity 68 rectifies this rate to produce a run signal having a frequency of 263 hz +/-10 hz. The frequency difference between the start signal, about 240 hz, and the run signal, about 263 hz, allows these two signals to be received by the same microphone and analog amplifiers but to be further processed by different electrical circuitry that is only responsive to signals within a narrow range.
In operation, the slide switch 56 is moved downward along the handle 38 to the start position, which causes the pick 66 to pluck the start reed 62, thereby generating a signal of 240 hz. This start sound signal is transmitted through the hose 40 and the network of tubing 22 to the detector tube 44, where an electrical circuit responsive to this signal turns on the vacuum cleaner. The moveable slide switch 56 has been moved to the run position in the process of plucking the start reed 62, thereby uncovering and exposing the orifice 74. When the electric motor 16 comes on, air is drawn through the orifice 74 and the run cavity 68, where it causes the run reed 70 to generate a continuous tone of about 263 hz, which is conducted through the horn-shaped run port 78 into the duct 58 and through the network tubing 22 to the detection tube 44, where the run sound signal is converted to electrical signals that are transmitted to electrical circuitry responsive to the run sound signal thus generated, which maintains the vacuum pump and electric motor assembly 16 in the on state.
The transducer or microphone 48 located within the detection tube 44 transduces the sound signals into electrical signals for further processing by the electrical circuitry shown in FIG. 2. When the moveable slide switch 56 is moved upward to the off position, the end flap 76 of the moveable slide switch 56 covers the orifice 74, preventing the run reed 70 from oscillating by blocking the air flow across it. Electrical circuitry responsive to the absence of the sound signal from the run reed turns off the central vacuum cleaner 10.
Naturally, once the central vacuum cleaner 10 is turned on, the tubing network 22 is filled with noise generated by striking objects with the nozzle 34, the air rushing through the tubing 22, noises generated by the vacuum pump and electric motor assembly 16, and so forth. This makes it difficult to detect reliably the sound signals generated by the run reed 70. Much of the detection apparatus of the central vacuum cleaner 10 is directed to selecting or detecting the desired start and run signals from among all the other sounds or noise generated by the central vacuum cleaner 10.
Referring to FIG. 5, the first stage in the detection process occurs in the detection tube 44. The detection tube 44 comprises a standpipe 80 having a diameter of approximately 2 inches (5.08 cm) and a length between 23 and 27 inches (58-69 cm), preferably about 251/2 inches (65 cm), and 3 inch segment for fastening into the tubing 22 so that the standpipe is in fluid communication with the duct work and tubing 22. The standpipe 80 is basically a quarter-wave standpipe, although it is not open to the atmosphere at both ends. The optimal dimensions of the standpipe 80 must be empirically determined for each specific application due to the effect of noise, air pressure changes, and so forth that are unique in different applications. A resonate chamber 82 near the top of the standpipe 80 houses the crystal microphone 48, which is a circular microphone approximately 2 inches (5 cm) in diameter having a frequency response range of 50 hz to 8 Khz, a 26 ohm impedance and a -50 dB response within that frequency range. A plug 84 seals the top end of the standpipe 80. Two foam cushions 86 approximately 1 inch thick (2.54 cm) are located within the standpipe 80 adjacent to the microphone 48, with one foam cushion 86 above the microphone 48 and one foam cushion 86 below it. The microphone shielded wire or lead 46 passes between the plug 84 and the standpipe 80 to carry the electrical signals generated by the microphone in response to the appropriate sound signals to the electrical circuitry illustrated in FIG. 2.
The detection tube 44 further comprises a filtering disk 88 sealed within the standpipe approximately 3 inches (7.62 cm) from the bottom end 90 and including a centrally located aperture 3/4 inch (1.9 cm) in diameter. As described, the detection tube 44 mechanically filters the noise that is conducted throughout the central vacuum cleaner 10, screening out many of the unwanted frequencies and at the same time mechanically amplifying the desired frequencies, centered on about 263 hz. It has been found that triggering or signaling frequencies below 600 hz are best because less of the noise generated by the central vacuum system 10 during operation falls below 600 hz than above it. Both the start signal from the start reed 62 and the run signal from the run reed 70 are received by the microphone 48 within the detection tube 44 and are conducted to the electrical circuitry shown in FIG. 2 by the shielded cable 46. They are, however, processed differently by the electronic circuits, which will be discussed next.
Referring to FIG. 2, the signal of about 240 hz +/-10 hz from the start reed 62 is converted to an analog electrical signal by the microphone 48 and conducted to the high gain band-pass amplifier 92. The amplifier 92 amplifies the start signal by a factor of approximately 9,000. Then the signal is sent to a band-pass filter within the module 92. The filter has a low Q of approximately 15 and a gain of 10. The filter clock is set at 23.5 Khz, for maximum run reed 70 signal gain at a frequency of 263 hz. The filter is primarily responsible for cleaning up the start signal and integrating it over time so that the start signal lasts approximately 325 ms. The signal is transmitted on lead 93 to the start-signal tone detector 94, which includes a microprocessor and associated circuitry. The center frequency of the tone detector 94 is set at 240 hz, the signal of the start reed 62. The output of the start-signal tone detector 94 is either high (1) or low (0). When a valid start signal is detected, the output of the start-signal tone detector 94 goes low for the 325 ms duration of the integrated start signal.
The output signal of the start-signal tone detector 94 on the lead 98 drives the timer window 96. The timer window circuit 96 develops three time windows, the early window consisting of 275 ms from the time a signal is received on lead 98, a late window of 375 ms that begins at the end of the early window, and an enable window, which is a 100 ms overlap of the early window and late window. If the output to the timer window 96 on the lead 98 goes high or stays high during the early window, thereby indicating no valid start signal, the timer window 96 is set in the "noise detected" state and the start timer and the start enable functions are reset and locked out. The window timer circuit 96 provides a discrimination function that prevents the vacuum cleaner motor from starting until a proper start signal is received. For example, if an extraneous signal is received and happens to be of the correct frequency, but is too short in duration, it is received in the early window, and if too long, in the late window. In either case the vacuum motor will not start. Thus, the timer window prevents the motor 16 from starting until the tone detector receives a start signal of the proper duration and frequency.
The tone detector 94 output on the lead 98 goes low for the 325 ms duration of the signal from the start reed 62 when it recognizes a valid start signal, and the start function of the timer window 96 is enabled for the entire duration of the enable window. When the start signal from the start reed 62 ends, the tone-detection signal on the lead 98 goes from low to high and the motor 16 is started in response thereto. If the signal on the tone-detection lead 98 remains low, indicating the presence of a valid start tone signal during the entire early window, the start function is enabled for the duration of the 100 ms enable window. If the tone detection lead 98 goes from low to high during the enable window, i.e., 275 to 375 ms after the tone detection lead 98 first goes low in response to receiving a valid start signal, then the central vacuum cleaner 10 is started. The output relay 101 is locked on, starting the vacuum pump and electric motor assembly 16. The timer window 96 keeps the motor runing for approximately 3 seconds. If no further signals are received, the motor stops running.
The run reed 70 must generate a run sound signal in order to keep the motor 16 running. When the start-signal tone detector 94 output on the lead 98 goes from low to high after the enable window ends, the timer window 96 is reset in preparation for the next start tone signal. The run-signal circuitry is now enabled.
With the vacuum pump and electric motor assembly 16 now turned on and running, the central vacuum cleaner 10 begins pulling air through the nozzle 34, the wand 32, the hose 40 and the rigid tubing 22. The orifice 74 in the handle 38 is already uncovered because the moveable slide switch 56 has been moved to the run position. The orifice 74 allows air to enter the run reed 70, generating a 263 hz signal, which is carried along with the airborne particulate materials down the tubing 22 to the housing 12.
The signal and noise arrive at the detection tube 44 where all frequencies that are not near 263 hz are attenuated by 12 dB or more by the mechanical filtering of the standpipe resonator 80, as described above. The microphone 48 picks up the resulting signals and sends them via the shielded cable 46 to the high gain band-pass amplifier 92. This signal is sent through a band-pass filter set to 263 hz, which removes all other frequencies. The band-pass filter is a MF10 band-pass filter, which superimposes a step function on the signal, resulting in a 263 hz signal wave which is sent to a buffer/driver and then into the run-signal phase-shift detector 100. The phase shift detector consists of a microprocessor, such as Motorola MC 1496 (not shown) and associated hardware consisting of resistors, capacitors, and a few solid state logic devices.
The frequency and phase of the output of the run reed 70 may drift over time as the operating conditions change. For example, changes in airflow may change the frequency output from the run reed 70 while it is oscillating. The frequency output from the run reed 70 may change from perhaps about 253 hz to 273 hz slowly and probably through a slight phase shift in each additional cycle as the pitch changes from one frequency to another. The run signal phase shift detector 100 tracks this low rate of frequency shift and locks onto that signal when the frequency shift is occurring at a rate of a fraction of a cycle per second. This capability allows the phase-shift detector 100 to operate through a very narrow window of positive or negative portions of a cycle for each phase shift, but will still be able to track the signal even though it may drift anywhere within +/-5 hz to 10 hz window allowed. Thus, the run signal phase shift detector 100 will detect and tract, thereby reporting as valid, a run signal from the run reed 70 that moves within a range of about 250 hz to about 275 hz.
The analog signal from the amplifier 92 to phase-shift detector 100 along the lead 102 is converted to a digital signal by the microprocessor, which does the sampling to detect any phase shift that may occur. After the microprocessor has locked onto the signal and processed it, it produces a synthetic analog signal based on the analog signal that entered the phase-shift detector 100 on the lead 102. The digital circuitry on the phase-shift detector 100 is clocked by the crystal clock 104, whose output signal is conducted on leads 93, 94 and 95.
The microprocessor, phase detector, modulator, and demodulator, of the phase shift detector 100 samples the amplitude of the incoming signal at a rate of 283 or 244 hz. This sample rate must be stable and is controlled by the crystal clock 104. The output of the phase-shift detector 100 on the lead 106 is a synthesized analog signal comprising a combination of the input signal and the clock signal. This output on lead 106 contains the phase data in analog form. It is then filtered by a low-pass filter and its output is approximately 20 hz.
The signal on lead 106 is transmitted to the auto track/integrator 108. There, the signal is input to a low QMF10 band-pass and a high 10 band-pass. The low Q 10 band-pass drives a frequency multiplier that multiples the frequency by 100 times and locks on and tracks the phase-shift signal. The low Q band-pass filter controls the high Q band-pass filter so that the high Q filter is locked onto the run signal. If the run reed 70 changes frequency, the efficiency of the system is maintained by selecting a clock speed to drive the high Q MF10 filter for maximum band-pass amplitude. The auto tract/integrator 108 will lock onto and track a signal in the range of about +/-5 hz from the center frequency of 263 hz. The output of the high Q 20 hz band-pass filter in the auto track/integrator 108 is the phase shift data integrated over a long time, that is, in blocks of approximately 2 seconds each. The amplitude of the analog output signal from the auto track/integrator 108 on the lead 110 is directly proportional to the degree of phase difference of the signal entering the auto track/integrator 108 on the lead 106 and the reference signal, which is generated by the crystal clock 104. This phase-shift signal is compared to a minimum level of 1.8 volts and if the phase-shift signal average is less than 1.8 volts, it indicates that the sound signal expected from the run reed 70 is absent or weak, and the vacuum motor 16 is turned off. So long as the signal maintains an average amplitude greater than about 1.8 volts, the vacuum motor 16 remains in the on state.
This signal comparison is undertaken in the signal level comparator 112, whose output is transmitted on the lead 114 to the output relay 100. The output from the output relay 100 is conducted on the lead set 116 to the electric motor 16.
An automatic gain control feedback loop partially controls the gain of amplifier 92 based on the output signal level on lead 110, which is fed back to the amplifier on lead 120. In effect, this feedback adapts the amplifier to changing noise and signal levels based on their immediate prior histories.
As described, the circuit illustrated in FIG. 2 comprises an adaptive circuit. The circuit can adapt for run reed 70 signal frequency and phase changes, signal level changes or noise amplitude changes, and adjust by adapting circuit parameters for maximum signal processing efficiency. This is equivalent to changing criteria for detection. As the central vacuum cleaner comes up to full speed, the run reed 70 signal is very much louder than the background noise, by up to about 60 percent. This characteristic helps the system lock onto the run signal and start the motor 16. Because of the relatively long period of signal integration in the auto track/integrator 108, however, the motor 16 will continue running even if the orifice 74 is blocked for a few seconds after the motor 118 has started. When the blockage is removed, the circuit shown in FIG. 2 will still lock onto and track the run signal from the run reed 70 without interrupting the operation of the central vacuum cleaner 10.
Another adaptive correction can be made for background noise. Noise caused by pseudosound, which is not acoustic but is generated by the pressure variations of turbulent airflow, can be predicted if the speed of the airflow is known. The level of noise predicted for the frequency band of the run signal can then be used as a basis for modifying either the detection level criteria used by the signal level comparator 112 or the gain of the input amplifier 92. This adaptive correction is particularly useful because it is based on current conditions rather than prior signal histories. However, regular air speed sensors tend to be too expensive and too easily damaged by dust for use in central vacuum tubing; consequently, a method has been developed using microphones to estimate the speed of the air flow.
The speed of the airflow can be estimated by using two microphones and correlating their outputs as previously described, assuming that the airflow is 20 meters per second or less. Once the airflow speed, v, is known, the probability distribution function (PDF) or the cumulative distribution function (CDF) given in FIG. 8 can be used to predict the noise energy at frequency f, the frequency of the run signal. In FIG. 8, F is the frequency of maximum noise energy, which is related to the average air speed in regular vacuum tubing by the following formula: F=0.5 v/d, where d is the diameter of the tubing in consistent units.
Alternatively, the speed of airflow can be estimated by using only one microphone together with a simple spectrum analyzer; this can be more economical because most of the required equipment, including the microphone and microprocessor which can be used to analyze the spectrum, is already available in the circuitry represented in FIG. 2. With one microphone, the received frequency spectrum is analyzed to identify the most energetic frequency, F. The air speed can be determined from the above formula, but this is not necessary for the present purpose because the noise energy at the run signal frequency can be predicted directly using FIG. 8. Predicting the energy is better than assuming that the energy will remain the same as just received by the microphone because of the random nature of the noise and because the feedback loop requires a relatively steady feedback signal in order to maintain stability.
In the preferred embodiment disclosed herein, two sound signals are employed for controlling the on and off switching of the central vacuum cleaner 10. The start reed 62 is plucked by the pick 66 to transmit the initial start signal to turn the unit on. A separate run reed 70 in a separate cavity 68 is employed to keep the unit running once it has been started. The two sound signals have slightly different frequencies, which allows them to be converted to electrical signals by a single microphone or other transducer and amplified in one initial amplifier 92, but to be processed by different electrical circuits thereafter to produce two different results--ie., (1) starting the motor; and (2) keeping it running.
In an alternative embodiment, a single reed may be employed both to provide a start sound signal and a continuous run signal by using a reed that can be plucked and can also be stimulated by air flowing over it from an orifice leading to the resonate cavity in which the reed is seated. In such an alternative embodiment, the circuitry for the start signal tone detector is integrated with the run signal circuitry, which is responsive to a start signal and a run signal.
The teachings disclosed herein may also be used to control functions in addition to the on-and-off switching of the central vacuum cleaner 10. For example, acoustic signals developed by reeds can be used to run the motor 16 at different speeds, such as a low speed and high speed, to make the central vacuum cleaner 10 more responsive to the demands of different types of cleaning. For example, the moveable switch 56 can be equipped with picks adapted to pluck the start reed 62 once to start with the central vacuum system 10, as described above, and a second time, while the motor 16 is running, to change the speed of the motor 16. Moving the slide switch 56 from a low speed to a high speed position would accomplish this result and moving the moveable slide switch 56 from high to low would again pluck the start reed 62, causing the motor 16 to slow down to the low speed. The functions of turning the motor 16 on, keeping it running and turning it off would remain as disclosed herein. When the single reed 62 is used for the function of changing the motor speed, the electrical circuit is adapted to process signals from the start reed 62 differently, depending upon whether the motor 16 is running when the signal is received. Alternatively, a third reed may be employed at a different frequency than the start reed 62 or the run reed 70 to provide a distinctive sound or acoustic signal for changing the motor speed, while may be processed by additional electrical circuitry.
Even very low frequency signals can be blocked by certain components of central vacuum cleaners, including gate valves and interceptor canisters. The present invention proposes to bypass these components with tubing, FIG. 6, that contains a flexible diaphragm 122 which blocks air flow, but transmits very low frequency. The diaphragm 122 can also be built directly into the component.
In review and summary, for starting and stopping the central machinery of the cleaner 10, the operator moves a slide switch 56 that plucks a vibrating reed 62 and opens a pathway for air to be drawn through the reed 62. The acoustic signal generated by the plucked reed is transmitted through the pipe system or duct 58 of the cleaner 10 to a detector tube 44 located near the central machinery. Upon detection of the signal, the central machinery is activated; consequently, air is drawn through the reed 70, which thereby generates a continuous signal. To stop the machinery, the operator slides the switch 56 backwards, which closes the air pathway so that the reed 70 stops generating the acoustic signal. When the signal is no longer detected, the central machinery is stopped.
To signal other control functions, such as motor speed control, the operator can move the slide switch 56 to another position, which will change the waveform of the acoustic control signal. Alternatively, motor speed can be regulated automatically to maintain a constant pressure at the working point; for this purpose, a special pressure sensor is not necessary because the waveform of acoustic control signal will directly reflect pressure changes.
For monitoring, the economically preferred embodiment, FIG. 7, of the invention provides only a single alert signal for the operator. The operator than goes to the central machinery and checks a monitoring panel 130 that indicates the exact condition of the central machinery that needs attention. The alert signal is heard directly by the operator when the operator holds the inlet valve open while connecting or disconnecting the hose; the signal is not transmitted while the control machinery is running, specifically while the control signal on either lead 99 or lead 114 is high.
Also, the alert signal is transmitted only if no possible start signal has been detected, specifically, only during the period that the signal on lead 99 is held high for at least 100 ms, indicating that the start-signal tone detector 94 is not receiving any signal that could possibly be the start signal. The alert signal consists of a 100-millisecond beep repeated once every second with a frequency of 600 hertz. Several components of the control circuitry are shared to produce the alert signal. The output of the crystal clock 104 is input to a counter 135 to produce a square wave of desired frequency, which is input to an output amplifier 138 used to drive the bidirectional detection transducer 48. After each beep, the transducer is switched back by switch 139 to the start detection circuitry so that a start signal can be detected.
The invention achieves acoustic communication even during periods of high airflow in the pipe system by using the following:
1) A continuous periodic signal is used which permits detection by convolution and also permits the use of a fail-safe detection logic.
2) The resonant structure, termed a detector tube 44, is used to isolate the acoustic transducer 48 from turbulence in the pipe system and to physically filter out some of the noise before it reaches the transducer.
3) An adaptive circuit is used that tracks phase and that is able to change detection criteria based on changes in airflow and noise.
Also, the invention uses a high-power vibrating reed 62 as a signal source controlled by a convenient slide switch 56 located on the handle 38 of the cleaner 10.
While certain forms of this invention have been illustrated and described herein, the invention is not limited thereto, except and insofar as such limitations are included in the following claims. | 1a
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RELATED APPLICATIONS
[0001] This application claims priority to application Ser. No. 61/347,512 filed May 24, 2010 and incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
[0002] a. Field of Invention
[0003] This application pertains to a method and apparatus for performing injections, and more particularly to an apparatus that applies a vibration as a skin stimulation selected to reduce pain during the injection.
[0004] b. Description of the Prior Art
[0005] Injections are one of the most common ways used by doctors and other health care providers to introduce drugs into a patient. Traditionally, injections are typically performed using a syringe with a needle attached to a barrel filled with the appropriate drug. The needle is first inserted through the skin (either on the arm, or other parts of the body), and then a piston is advanced manually forcing the drug to be expressed through the needle into the patient's tissues. Alternatively, the drug is fed to the needle through a long tube attached either to an IV tube directly or through a pumping mechanism.
[0006] Regardless of which system is used, one problem with all injections have been that they require the piercing of the skin and the subcutaneous tissues lying immediately under the skin. Since the skin and the subcutaneous tissues are laced with numerous nerves, during the piercing step, the patient feels discomfort and pain. Depending on the individual, the injection site, the size of the needle and other factors, the discomfort and pain could be mild or could be very severe. Children and infants are particularly susceptible and, hence, they very often fear injections and administrating an injection in such cases could be a tough experience for both the doctor and the parent.
[0007] Attempts have been made to resolve these problems but they have not been successful. For example, it has been suggested that the syringe be vibrated during injection. Of course, this solution is unacceptable because a vibrating syringe can be difficult to hold. Moreover, a vibrating needle tears the tissues during injection, causing much more harm than good. Other attempts made use of devices with vibrating needles. These attempts are also unacceptable from a mechanical view since it is difficult and expensive to make such a device and from a medical view as discussed above.
SUMMARY OF THE INVENTION
[0008] The present inventor has found that the discomfort and pain suffered at the beginning of an injection can be eliminated or significantly reduced if just prior to and/or during an injection, vibration or other similar mechanical excitation is applied to the skin and the subcutaneous tissues at the injection site. It is believed that this action can either confuse or mask-the nerve endings and their pathways so that the nerves will not transmit impulses to the brain resulting in discomfort or pain.
[0009] Briefly, a device constructed in accordance with this invention includes:
[0010] a housing having an aperture sized and shaped to accept a syringe with a needle and a front section with a tip, said tip having an opening through which the needle is selectively extended from the housing for administering of an injection; and
[0011] a vibrating mechanism disposed within said housing and adapted to selectively vibrate said front section during said injection.
[0012] Preferably the housing includes a first chamber for accepting a portion of the syringe during the injection, said chamber being in communication with said aperture and said opening and holding said syringe during said injection. The housing may also include a second chamber, said vibrating mechanism being disposed in said second chamber. In one advantageous embodiment, the vibrating mechanism includes a motor having a rotating shaft with a weight having an off-axis center of gravity, and a switch selectively activating said motor.
[0013] The housing includes a third chamber holding a battery for providing current to the motor.
[0014] A syringe holder may be provided that extends into the aperture and configured to hold the syringe, the syringe holder being selectively movable between a first position in which the syringe needle is disposed inside the housing and a second position in which needle extends outwardly of said housing.
[0015] When the vibrating mechanism is activated, it causes at least a front part of the housing to vibrate. A care provider loads a syringe having a barrel with a drug into the housing, activates the vibrating mechanism and positions the housing so that it is contact with a patient's skin at a desired injection site. At least the front portion of the housing vibrates thereby making the nerve endings in the skin at the injection somewhat insensitive to pain. The needle is then advanced so that it extends from the housing penetrating the skin until it reaches the desired injection zone. The drug is then expelled from the syringe in a normal manner.
BRIEF DESCRIPTION OF THE FIGURES
[0016] FIG. 1 shows a side view of an injection apparatus constructed in accordance with this invention;
[0017] FIG. 2 shows a bottom view of the apparatus of FIG. 1 ;
[0018] FIG. 3 shows a side sectional view with the injection apparatus being introduced into the housing;
[0019] FIG. 4 shows an exploded view of the apparatus of FIGS. 1-3 ; and
[0020] FIG. 5 shows a side view with the needle fully extended through the housing.
DETAILED DESCRIPTION OF THE INVENTION
[0021] As shown in the drawings, an apparatus 100 constructed in accordance with this invention includes a housing 102 with a wall 104 . The housing 102 can be made in a single piece by molding or can be made from two segments 102 A, 102 B joined together by a screw 106 . The housing can be made of a transparent material or a bottom portion 108 of the housing is transparent window 106 .
[0022] Housing 102 is formed with a front portion 110 including a conical extension 110 having an opening 112 . The opening 112 is preferably circular and has a diameter D.
[0023] Housing 102 further includes a rear wall 120 that is generally flat with a large opening 122 . Opening 122 is aligned with opening 112 .
[0024] The interior of the housing 102 is partitioned into three chambers 124 , 126 and 128 . A top portion 130 of the housing is removable to give access to chamber 124 . Chamber 124 is used to house a removable standard battery (typically an AAA battery) 132 . Also contained within the chamber 124 are a spring terminal 136 and a flat terminal 138 that contact the positive and negative terminals of the battery 132 in the normal manner.
[0025] Chamber 126 houses an electric motor 140 having a shaft 142 with a weight 144 . Chamber 126 further includes a switch 148 operated by a switch cover 146 slidably mounted on wall 106 . Moving the switch cover 146 in one direction closes the switch 148 which in turn provides power to the motor 140 from battery 132 . Moving the switch cover 146 in the opposite direction turns the motor off. The weight 144 is not rotationally symmetrical but instead it is configured so that its center of gravity is offset from the axis of the shaft of the motor 140 . As a result, when the motor 140 is turned on, it causes the weight to rotate and this action causes the front section of the housing 102 , including conical extension 110 to vibrate laterally. Preferably, the apparatus is configured so that the motor 140 rotates at about 15000 RPM and causes the conical section to vibrate gently at a small amplitude of less than 1/16″.
[0026] Chamber 128 houses a portion of a syringe holder 150 . As best seen in FIG. 4 , this syringe holder 150 has an elongated portion 152 having an outer surface 154 . A semi-cylindrical longitudinal channel 156 extends through the holder 150 . The syringe holder 150 further includes an enlarged head 158 attached to one end of portion 152 . A window 160 is formed in the portion 152 adjacent to the head 158 . Opposite head 158 , the portion 152 is formed with a tab 162 . The portion 152 is sized and shaped to fit through opening 122 . The tab 162 is provided to trap the portion 152 to insure that the syringe holder 150 does not fall out and get lost. The syringe holder 150 is configured so that its portion 152 can be moved back and forth axially through the chamber 128 .
[0027] Preferably, the channel 156 is sized and shaped to form an interference fit with the barrel of a typical syringe, such as a conventional 1 cc syringe 170 available from Becton Dickinson. As shown in FIG. 2 , such a conventional syringe 170 includes a barrel 172 terminating with a replaceable needle 174 . The barrel 172 has gradations 176 to indicate the progress of an injection and the amount of fluid that has been expelled from the barrel 172 . Disposed inside the barrel is a piston 178 (see FIG. 3 ) that is attached to a shaft 180 . The shaft 180 is terminated with a thumb pad 182 .
[0028] The apparatus 100 is operated as follows. First the syringe 170 is loaded with an appropriate drug (or any other substance that a health care provider desires to inject into a patient). The loaded syringe is then inserted into syringe holder 150 so that its barrel 172 is held tightly and securely by the channel 156 . In this configuration, the needle 174 is completely contained within the apparatus 100 , and the health care provider, as well as the patient and others around the patient are protected from injury. In addition, the needle is hidden from view of a potentially anxious patient at all times. The barrel 172 and its gradations 176 are visible through the transparent wall 106 .
[0029] Next, the motor 140 is turned on by switch 148 causing the front end and conical section 110 to vibrate transversally with respect to the longitudinal axis of the syringe 170 . The tip of the conical section 110 is placed in contact with the skin of the patient at the site of injection. The vibration of the conical section is transferred to the skin of the patient and the tissues underlying the skin.
[0030] The health care provider holds the apparatus 100 in this position with two fingers and then pushes the enlarged head 158 with his thumb axially toward the front of the apparatus 100 thereby causing the syringe to move forward with the needle 174 extending outwardly of the conical section 110 . Since the conical section is touching the skin at the site of the injection, as the needle is advanced, it penetrates the vibrated skin and the tissues to the predetermined depth. Next, the health care provider shifts his thumb from the enlarged head 158 to the thumb pad 182 and starts pushing it inward to inject the contents of the barrel. During this time, the conical section 110 keeps on vibrating thereby confusing the nerve pathways of the skin and tissues and reducing or eliminating pain to the patient. Preferably the diameter D of opening 112 is sized so that is large enough to insure that as the conical section 110 vibrates, it does not touch needle 174 and therefore the vibration is not transmitted to the needle itself. The motor can be kept on until the injection is completed and the needle is withdrawn, or can be turned off any time before or after, thereafter stopping the vibration.
[0031] It should be appreciated that the whole process can be performed with one hand holding the apparatus 100 while the skin can be held and manipulated with the other hand as needed. If multiple sites are injected sequentially, the needle can be retracted first, the conical section 112 can be moved to a new site, and the needle can then be extended again. Once the process is completed, the syringe is removed from the holder 150 and at least its tip can be disposed. The conical section 102 is wiped with alcohol or other disinfectant and the apparatus 100 is ready to be used again.
[0032] The apparatus can be sized and shaped to so that it can be used with several syringes of similar sizes, e.g. 1, 3 or 5 cc, needles from 18 to 25 gauges and injection depth of up to ½ in or more. An apparatus with somewhat larger housing is needed for syringes of 3, 5, 10, 20 or 60 ccs.
[0033] As illustrated in the Figures, the apparatus can be made with only five parts having special shapes and sizes, the rest of the parts being of standard shapes and sizes.
[0034] The apparatus can be used for many different procedures including pediatric treatments, anesthesia, cosmetic treatments, drawing blood and blood donations, treatments for diabetes, veterinarian treatments, vaccines, etc.
[0035] Obviously numerous modifications may be made to the claims without departing from its scope as defined in the appended claims. For example the housing can be easily adapted to work with automated injection devices. | 1a
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PRIORITY CLAIM
[0001] This application is a continuation of U.S. patent application Ser. No. 11/617,543, filed Dec. 28, 2006, entitled “Method And Apparatus For Monitoring And Controlling Peritoneal Dialysis Therapy,” which is a continuation of U.S. patent application Ser. No. 10/446,068, filed May 27, 2003, having the same title as above, issued as U.S. Pat. No. 7,507,220, which is a divisional of U.S. patent application Ser. No. 10/078,568, filed Feb. 14, 2002, having the same title as above, issued as U.S. Pat. No. 6,592,542, which is a continuation of U.S. patent application Ser. No. 09/501,778, filed Feb. 10, 2000, having the same title as above, issued as U.S. Pat. No. 6,497,676. Each of these disclosures is hereby incorporated by reference herein.
BACKGROUND
[0002] The present invention relates generally to the treatment of end stage renal disease. More specifically, the present invention relates to methods and apparatuses for monitoring the performance of peritoneal dialysis.
[0003] Using dialysis to support a patient whose renal function has decreased to the point where the kidneys no longer sufficiently function is known. Two principal dialysis methods are utilized: hemodialysis; and peritoneal dialysis.
[0004] In hemodialysis, the patient's blood is passed through an artificial kidney dialysis machine. A membrane in the machine acts as an artificial kidney for cleansing the blood. Because it is an extracorporeal treatment that requires special machinery, certain inherent disadvantages exist with hemodialysis.
[0005] To overcome the disadvantages associated with hemodialysis, peritoneal dialysis was developed. Peritoneal dialysis utilizes the patient's own peritoneum as a semi-permeable membrane. The peritoneum is a membranous lining of the abdominal body cavity. Due to good perfusion; the peritoneum is capable of acting as a natural semi-permeable membrane.
[0006] Peritoneal dialysis periodically infuses sterile aqueous solution into the peritoneal cavity. This solution is called peritoneal dialysis solution, or dialysate. Diffusion and osmosis exchanges take place between the solution and the blood stream across the natural body membranes. These exchanges remove the waste products that the kidneys normally excrete. The waste products typically consist of solutes like urea and creatinine. The kidneys also maintain the levels of other substances such as sodium and water which need to be regulated by dialysis. The diffusion of water and solutes across the peritoneal membrane during dialysis is called ultrafiltration.
[0007] In continuous ambulatory peritoneal dialysis, a dialysis solution is introduced into the peritoneal cavity utilizing a catheter. An exchange of solutes between the dialysate and the blood is achieved by diffusion. Further removal is achieved by providing a suitable osmotic gradient from the blood to the dialysate to permit water outflow from the blood. This allows a proper acid-base, electrolyte and fluid balance to be achieved in the body. The dialysis solution is simply drained from the body cavity through the catheter.
[0008] Peritoneal dialysis raises a number of concerns including: the danger of peritonitis; a lower efficiency and therefore increased duration of dialysis hours compared to hemodialysis; and costs incurred when automated equipment is utilized.
[0009] A number of variations on peritoneal dialysis have been explored. One such variation is automated peritoneal dialysis (“APD”). APD uses a machine, called a cycler, to automatically infuse, dwell, and drain peritoneal dialysis solution to and from the patient's peritoneal cavity. APD is particularly attractive to a peritoneal dialysis patient, because it can be performed at night while the patient is asleep. This frees the patient from the day-to-day demands of continuous ambulatory peritoneal dialysis during his/her waking and working hours.
[0010] The APD sequence typically lasts for several hours. It often begins with an initial drain cycle to empty the peritoneal cavity of spent dialysate. The APD sequence then proceeds through a succession of fill, dwell, and drain phases that follow one after the other. Each fill/dwell/drain sequence is called a cycle. APD can be and is practiced in a number of different ways.
[0011] Current APD systems do not monitor the patient intraperitoneal pressure during a therapy session. Current systems simply limit the external pressure (or suction) that a pump can apply to the line or lumen that is attached to the patient catheter. If the patient is located below the system, sometimes referred to as a cycler, a gravity head will add to the positive fill pressure that the cycler can apply to the patient catheter. Conversely, if the patient is located above the cycler, the gravity head will decrease from the positive fill pressure that the cycler can apply to the patient catheter.
[0012] The monitoring of intraperitoneal pressure would be useful because cyclers will sometimes not fully drain a patient between cycles. Specifically, currently-available cyclers are unable to determine whether a patient absorbed some fluid or whether some fluid is simply not able to be drained out because of the position of the patient or the catheter.
[0013] As a result, some currently-available systems utilize a minimum drain threshold to determine the amount of fluid that should be delivered to the patient during the next fill. For example, if 85% of the fill volume has been drained when the cycler determines that the patient is “empty”, the next fill volume will be 100%. If only 80% were drained, the next fill volume would be limited to 95%.
[0014] A negative ultrafiltrate (uF) alarm will sound when the patient has retained more than a predetermined percentage of the fill volume. The predetermined percentage can typically be either 50% or 100% of the fill volume. However, the patient can override this alarm if he/she does not feel overfull. The number of times the patients can override the uF alarm during a single therapy may be limited by the software of the cycler. However, the uF alarm typically does not consider the actual ultrafiltrate that may also accumulate in the peritoneal cavity along with the dialysate.
[0015] Currently-available cyclers fill the patient to a specific, preprogrammed volume during each cycle. The doctor prescribes this fill volume based upon the patient's size, weight and other factors. However, because currently-available cyclers cannot monitor intraperitoneal pressure, the doctor cannot take this factor into account when formulating the prescription. It is also known that intraperitoneal pressure (IPP) has an effect on ultrafiltration (UF).
[0016] FIGS. 1-3 provide schematic illustrations of current APD cyclers. None of them attempt to monitor intraperitoneal pressure.
[0017] Referring to FIG. 1 , a cycler 10 a is illustrated which includes a dialysate container 11 , a patient 12 and a drain container 13 . The infusion of dialysate from the container 11 into the patient 12 is caused by the gravitational head indicated at 14 while the draining of used dialysate from the patient 12 to the drain container 13 is caused by the drain head indicated at 15 . The cycler 10 a includes no sensors for monitoring the pressure inside the peritoneum of the patient 12 . A single lumen 16 connects both the dialysate container 11 and drain container 13 to the patient 12 . Valves 17 , 18 operated by the cycler 10 a control the flow of either dialysate from the container 11 to the patient 12 or waste material from the patient 12 to the drain container 13 .
[0018] Turning to FIG. 2 , in the cycler 10 b , the drain container 13 and dialysate container 11 are contained within a pressurized chamber 19 . The chamber 19 can be pressurized or evacuated to either fill or drain the patient. Again, the selective operation of valves 17 , 18 control whether dialysate is being transferred to or from the patient 12 . Again, no sensors are provided for detecting or monitoring intraperitoneal pressure of the patient 12 .
[0019] Turning to FIG. 3 , in the system 10 c , a dialysate container 11 is connected to a pump 21 which, in turn, connects the dialysate container 11 to a common lumen or catheter 16 which is connected to the patient. A fluid flow control valve is provided at 23 and is controlled by the cycler 10 c . The drain container 13 is also connected to a pump 24 which, in turn, connects the drain container 13 to the lumen 16 . A control valve is again provided at 25 .
[0020] The drain and fill rates of the cyclers 10 a - 10 c illustrated in FIGS. 1-3 are determined by the gravitational head (see FIG. 1 ) or the suction or pressure (see FIGS. 2 and 3 ) applied to the patient line 16 . Typically, the cyclers 10 a - 10 c fail to optimize either the fill rate or the drain rate because the pressure is either fixed by the gravitational head or the pressure or suction applied by the chamber 10 b of FIG. 2 which occurs at the opposing end of the patient line 16 . Thus, without measuring the intraperitoneal pressure or having a way to estimate the same, it is difficult to optimize either the drain or fill rate. In the case of the cycler 10 c in FIG. 3 , optimizing the drain or fill rate is guesswork due to the lack of any pressure reading at all.
[0021] Accordingly, there is a need for an improved cycler that measures patient intraperitoneal pressure during a therapy session, including both during the drain and the fill as well as the dwell. Further, there is a need for an improved cycler that measures intraperitoneal pressure and which would use that data to more completely drain a patient between cycles. Further, there is a need for an improved cycler which would accurately measure intraperitoneal pressure to avoid overfilling a patient. Finally, there is a need for an improved cycler which would monitor intraperitoneal pressure during both the fill and drain cycles to optimize the speed at which the patient is filled and drained and to therefore increase the dwell portion of a therapy session.
SUMMARY
[0022] The present invention satisfies the aforenoted needs by providing a system for providing peritoneal dialysis to a patient which comprises a dialysate container connected to the patient with a first pressure sensor connected in-line herebetween, and a drain container connected to the patient with a second pressure sensor connected in-line therebetween.
[0023] In an embodiment, the system further comprises a first pump disposed in-line between the dialysate container and the first pressure sensor.
[0024] In an embodiment, the dialysate flows from the dialysate container into the patient under a hydrostatic head.
[0025] In an embodiment, a second pump is disposed in-line between the drain container and the second pressure sensor.
[0026] In an embodiment, the dialysate flows from the patient to the drain container under a hydrostatic head.
[0027] In an embodiment, the second pressure sensor measures an intraperitoneal pressure of the patient while dialysate flows from the dialysate container to the patient.
[0028] In an embodiment, the first pressure sensor measures an intraperitoneal pressure of the patient while dialysate flows from the patient to the drain container.
[0029] In an embodiment, the system further comprises a first lumen connecting the dialysate container to the first sensor and the first sensor to a catheter, and a second lumen connecting the drain container to the second sensor and the second sensor to the catheter, the catheter being connected to the patient, a flow of dialysate from the patient to the drain container evacuating dialysate from the first lumen and causing said dialysate from the first lumen to flow through the second lumen and to the drain container.
[0030] In an embodiment, the catheter is a dual lumen catheter.
[0031] In an embodiment, the first and second sensors are redundant in-line pressure/vacuum sensors.
[0032] In an embodiment, the present invention provides a method for dialyzing a patient comprising the steps of: placing a catheter in a peritoneum of the patient; providing at least one dialysate container; connecting the dialysate container to the catheter with a first lumen that includes a first pressure sensor disposed in-line and between the catheter and the dialysate container; providing at least one drain container; connecting the drain container to the catheter with a second lumen that includes a second pressure sensor disposed in-line and between the catheter and the drain container; transferring dialysate from the dialysate container to the peritoneum of the patient and monitoring an intraperitoneal pressure of the patient with the second pressure sensor; and transferring dialysate from the peritoneum of the patient to the drain container and monitoring the intraperitoneal pressure of the patient with the first pressure sensor.
[0033] In an embodiment, the step of transferring dialysate from the dialysate container to the peritoneum of the patient further comprises pumping dialysate from the dialysate container to the patient with a first pump disposed in-line between the dialysate container and the first pressure sensor.
[0034] In an embodiment, the step of transferring dialysate from the peritoneum of the patient to the drain container further comprises pumping dialysate from the peritoneum of the patient to the drain container with a second pump disposed in-line between the drain container and the second pressure sensor.
[0035] In an embodiment, the dialysate container is disposed vertically above the peritoneum of the patient and the step of transferring dialysate from the dialysate container to the peritoneum of the patient further comprises flowing dialysate from the dialysate container to the patient under a hydrostatic head.
[0036] In an embodiment, the drain container is disposed vertically below the peritoneum of the patient and the step of transferring dialysate from the peritoneum of the patient to the drain container further comprises flowing dialysate from the peritoneum of the patient to the drain container under a hydrostatic head.
[0037] Other objects and advantages of the invention will become apparent upon reading the following detailed description and appended claims, and upon reference to the accompanying drawings.
BRIEF DESCRIPTION OF THE FIGURES
[0038] FIG. 1 illustrates, schematically, a prior art automated peritoneal dialysis system;
[0039] FIG. 2 illustrates, schematically, a prior art automated peritoneal dialysis system;
[0040] FIG. 3 illustrates, schematically, a prior art automated peritoneal dialysis system;
[0041] FIG. 4 illustrates, schematically, an automated peritoneal dialysis system made in accordance with the present invention;
[0042] FIG. 5 illustrates, schematically, a second embodiment of an automated peritoneal dialysis system made in accordance with the present invention;
[0043] FIG. 6 illustrates, schematically, a third embodiment of an automated peritoneal dialysis system made in accordance with the present invention;
[0044] FIG. 7 illustrates, schematically, a fourth embodiment of an automated peritoneal dialysis system made in accordance with the present invention;
[0045] FIG. 8 illustrates a pressure sensor made in accordance with the present invention;
[0046] FIG. 9 illustrates a fifth embodiment incorporating dual pumping chambers and pressure sensors made in accordance with the present invention;
[0047] FIG. 10 illustrates, schematically, a dual lumen catheter that can be utilized with the present invention;
[0048] FIG. 11 is a sectional view taken substantially along line 11 - 11 of FIG. 10 ;
[0049] FIG. 12 illustrates, graphically, the urea concentration in blood and the urea concentration in a dialysate during a multiple dwell dialysis session;
[0050] FIG. 13 illustrates, graphically, the concentration of urea in a patient's bloodstream versus the concentration of urea in a dialysate solution for an automated peritoneal dialysis solution practiced in accordance with the prior art; and
[0051] FIG. 14 illustrates, graphically, the concentration of urea in a patient's bloodstream versus the concentration of urea in a dialysate for an automated peritoneal dialysis therapy session carried out in accordance with the present invention.
[0052] It should be understood that the drawings are not necessarily to scale and that the embodiments are sometimes illustrated by graphic symbols, phantom lines, diagrammatic representations and fragmentary views. In certain instances, details which are not necessary for an understanding of the present invention or which render other details difficult to perceive may have been omitted. It should be understood, of course, that the invention is not necessarily limited to the particular embodiments illustrated herein.
DETAILED DESCRIPTION
[0053] Turning to FIG. 4 , a cycler 30 includes a dialysate container 11 connected to a pump 31 . The pump 31 is connected to a pressure sensor 32 . The pump 31 and pressure sensor 32 are disposed in-line in a lumen 33 that connects the dialysate container 11 to a catheter 34 . Control valves are provided at 35 , 36 . A drain container 13 is also connected to a pump 36 which is connected to a sensor 37 . The pump 36 and sensor 37 are also connected in-line to a lumen 38 which connects the drain container 13 to the catheter 34 . Control valves are again provided at 41 , 42 . During the fill, the pump 31 pumps dialysate from the container 11 through the lumen 33 and catheter 34 into the peritoneum (not shown) of the patient 12 . During this time, the sensor 37 monitors and measures the intraperitoneal pressure. A signal is sent to the controller of the cycler 30 shown schematically at 43 . A control panel is indicated generally at 44 .
[0054] During the drain, the sensor 31 can accurately monitor and measure the intraperitoneal pressure of the patient 12 . In the embodiment illustrated in FIG. 4 , no pumps or control valves are disposed between the sensor 32 and the patient 12 .
[0055] Turning to FIG. 5 , a cycler 50 is illustrated which includes reversible pumping chambers 51 , 52 with sensors 53 , 54 disposed between the reversible pumping chambers 51 , 52 and the patient 12 respectively. Control valves 55 and 56 are disposed on another side of the reversible pumping chamber 51 and the sensor 53 and control valves 57 , 58 are provided on either side of the reversible pumping chamber 52 and sensor 54 . The sensors 53 , 54 actually measure the pressure on the diaphragms of the reversible pumping chambers 51 , 52 .
[0056] Turning to FIG. 6 , a cycler 60 is illustrated with a chamber 61 for accommodating the drain container 13 and a chamber 62 for accommodating the dialysate container 11 . Each chamber 61 , 62 is equipped with an integrated valve assembly and pressure sensor shown at 63 , 64 . In the embodiment 60 shown in FIG. 6 , the chamber 61 must be capable of being evacuated. Dialysate may flow from the dialysate container 11 by way of gravity or pressure fill. Again, the sensors of the valve assembly/sensor combinations 63 , 64 monitor the intraperitoneal pressure of the patient 12 as discussed above.
[0057] In the embodiment 70 illustrated in FIG. 7 , the dialysate container 11 and drain container 13 are both connected to integrated control valves and pressure sensors 71 , 72 . Each of the integrated control valves and pressure sensors 71 , 72 are connected to lumens 73 , 74 respectively which are connected to the catheter 75 a by way of a Y-connection. The details of all the Y-connections and clamps are not shown but are known to those skilled in the art. Flow from the dialysate container 11 to the patient is carried out under the gravitational head shown at 75 while flow from the patient to the drain container 13 is carried out under the gravitational head shown at 76 .
[0058] FIG. 8 illustrates one in-line pressure sensor 80 that is suitable for use with the present invention. Redundant load cells 81 , 82 are connected to the flexible pressure sensing membrane 83 by a vacuum connected by the line 84 , 85 . A lumen connecting the cycler to the patient is shown at 86 .
[0059] FIG. 9 illustrates a dual-pumping chamber cassette 87 which includes an output line 88 which connects the cassette 87 to the patient and an input line 89 connecting the patient to the cassette 87 . The line 90 connects the cassette 87 to the dialysate container (not shown). Each pumping chamber 91 , 92 is in communication with all three lines 88 , 89 and 90 . Thus, every line can be connected to either pumping chamber 91 , 92 . The pumping chambers 91 , 92 are bound on one side by a common diaphragm shown at 93 . Flow is controlled by the use of diaphragm valves shown at 94 , 95 , 96 and 97 . Pressure sensors are shown at 120 , 121 , 122 , 123 , 124 and 125 . However, pressure sensors 123 and 120 are the sensors used to measure intraperitoneal pressure in accordance with the present invention. The remaining sensors 121 , 122 , 124 , 125 are used to monitor the operation of the pumps 126 , 127 .
[0060] When the left diaphragm pump 126 is pushing dialysate to the patient, the sensor 123 can measure the intraperitoneal pressure through the line 89 . When the left diaphragm pump 126 is draining fluid from the patient through the line 89 , the sensor 120 can measure intraperitoneal pressure through the line 88 and while the right pump 127 is pumping fluid to the drain container (not shown) through the drain line shown schematically at 128 . When the right diaphragm pump 127 is being used to drain fluid from the patient, the sensor 120 can measure intraperitoneal pressure while the left diaphragm pump 126 is pumping fluid to the drain container (not shown) through the drain line shown schematically at 129 .
[0061] FIGS. 10 and 11 illustrate a dual-lumen catheter 100 which includes separate passageways 101 , 102 . The employment of a dual lumen catheter 100 as compared to a dual lumen patient line can move the point at which the pressure is measured to within the peritoneum itself by way of communication through the separate flowpaths 101 , 102 . The dual lumen catheter 100 installs like a single lumen catheter, yet will function either as a flow through or a standard catheter. Both fluid pathways 101 , 102 are used to withdraw and deliver fluid during the drain and fill. While one pathway delivers fluid, the other pathway drains. The end section, shown generally at 103 , is perforated.
[0062] A comparison of an APD therapy for a prior art APD cyclers and one manufactured in accordance with the present invention are summarized as follows:
[0000]
Therapy Parameter
Current APD Cycler
Cycler Using Invention
Total Therapy Volume
15 liters
15 liters
Fill Volume
2.2 liters
2.5 liters max
Fill Pressure Limit
not applicable
14 mm Hg max
Total Therapy Time
8 hours
8 hours
Last (Day) Fill Volume
1,500 ml
1,500 ml
Last Fill Dextrose
Same
Same
Initial Drain Alarm
1,200 ml
1,200 ml
Drain X of N Alarm
80%
80%
[0000]
TABLE 1
Comparison of Therapies for Current Cyders versus Cycler using Invention Method
Therapy Phase
Therapy Parameter
Prior Art Cycler I
Prior Art Cycler 2
Invention Cycler 3
Initial Drain
Drain Volume
1,200 ml
1,200 ml
1,200 ml
Patient Volume
300 ml
300 ml
300 ml
Fill I of 5
Fill Volume
2,200 ml
2,200 ml
2,500 ml
Patient Volume
2,500
2,500
2,800
Fill Pressure
not applicable
not applicable
12 mm Hg
Drain 1 of 5
Drain Volume
1,800 ml
2,200 ml
2,200 ml
Patient Volume
700 ml
300 ml
600 ml
Fill 2 of 5
Fill Volume
2,200 ml
2,200 ml
2,400 ml
Patient Volume
2,900 ml
2,500 ml
3,000 ml
Patient Pressure
not applicable
not applicable
14 mm Hg
Drain 2 of 5
Drain Volume
1,800 ml
2,200 ml
2,200 ml
Patient Volume
1,100 ml
300 ml
800 ml
Fill 3 of 5
Fill Volume
2,200 ml
2,200 ml
2,200 ml
Patient Volume
3,300 ml
2,500 ml
3,000 ml
Patient Pressure
not applicable
not applicable
14 mm Hg
Drain 3 of 5
Drain Volume
1,801 ml
2,200 ml
2,200 ml
Patient Volume
1,499 ml
300 ml
800 ml
Fill 4 of 5
Fill Volume
2,200 ml
2,200 ml
2,200 ml
Patient Volume
3,699 ml
2,500
3.000 ml
Patient Pressure
not applicable
not applicable
3,000 ml
Drain 4 of 5
I Drain Volume
1,800 ml
2,200 ml .
2,200 ml
Patient Volume
1,899 ml
300 ml
800 ml
Fill 5 of 5
Fill Volume
uF Alarm Bypass
2,200 ml
2,200 ml
2,200 ml
Patient Volume
4,099 ml
2,500 ml
3,00 ml
Patient Pressure
Patient Wakes
not
14 mm Hg
Overfull,
applicable
Manually Drains
1,500 ml
Drain 5 of 5
Drain Volume
1,800 ml
2,200 ml
2,200 ml
Patient Volume
799 ml
300 ml
800 ml
Final Fill
Fill Volume
1,500 ml
1,500 ml
1,500 ml
[0063] Inspection of Table 1 shows that cycler 1 woke the patient at around 4:30 in the morning with a negative uF alarm at the beginning of Fill 5. The patient bypassed the alarm because he did not feel overfull and immediately fell back asleep. He woke up about minutes later when he had difficulty breathing and felt extremely overfull. He manually drained about 1500 ml but was unable to go back to sleep. He filed a formal product complaint with the manufacturer.
[0064] The data of Table I shows that cycler 2 ran a completely normal therapy but the total therapy clearance (calculated based upon the sum of the night patient volumes) was only 84.5% of that obtained by cycler 3, which was using the cycler that used the method of the current invention.
[0065] The data of Table 1 shows that cycler 3 ran a completely normal therapy and that the fill volume was limited on one occasion by the maximum fill volume but on four occasions by the patient's intraperitoneal pressure. This patient never felt any discomfort and had no alarms during the night. The limit on the IPP prevented him from being overfilled even though he had successive drains that were not complete. The volume of fluid in his peritoneum never exceeded 3 liters.
[0066] The patient on cycler 1 had an intraperitoneal pressure in excess of 14 mm Hg during dwells 3 and 4. His breathing may have been impaired and his heart may have had to work harder but the discomfort was not enough to wake him up from a sound sleep until it peaked at 4,099 ml during dwell 5.
[0067] In conclusion, the method of the present invention provides for optimum fills and therefore more clearance while preventing overfills that bring discomfort and inhibit the function of vital body organs. A negative uF alarm would seldom occur because overfills of the required magnitude would be prevented by the IPP sensors.
Calculation of Intraperitoneal Pressure (IPP)
[0068] In order to calculate the IPP, one may first calculate the patient head height correction using conservation of energy:
[0000] Δ(½ ρV 2 +P−pa g h )+Frictional Losses=0
[0069] The velocity V of fluid through the patient line is the same at both ends of the line as is the fluid density, so this equation can be written as
[0000] ( P 2 −P 1 )− pa g ( h 2 h )+Frictional Losses=0
[0070] which can be rearranged as
[0000]
Δ
h
=
(
P
1
-
P
2
)
-
Frictional
Losses
ρ
a
g
Example 1
[0071] P1=1.25 psig=85060 (gram/cm)/(cm 2 -sec 2 )
[0072] P2=0.9 psig=61240 (gram/cm)/(cm 2 -sec 2 )
[0073] Frictional Losses=39130 (gram/cm)/(cm 2 -sec 2 ) with flow of 197 cm/min in a 4 mm ID line at a velocity of approximately 172 cm/sec, wherein
[0000]
a
g
=
981
cm
/
sec
2
ρ
=
1
gram
/
cm
3
Δ
h
=
(
(
85060
-
61240
)
-
39130
)
(
gram
/
cm
)
/
(
cm
2
-
sec
2
)
1
gram
/
cm
*
981
cm
/
sec
2
[0074] Δh=−15.6 cm (The patient is 15.6 cm below the membrane)
Example 2
[0075] PI=1.25 psig=85060 (gram/cm)/(cm 2 -sec 2 ) P2=0.45 psig=30620 (gram/cm)/(cm 2 -sec 2 )
[0076] Frictional Losses=39130 (gram/cm)/(cm 2 -sec 2 ) with flow of 197 cmn/min in a 4 mm ID line at a velocity of approximately 172 cm/sec, wherein
[0000]
a
g
=
981
cm
/
sec
2
ρ
=
1
gram
/
cm
3
Δ
h
=
(
(
85060
-
30620
)
-
390130
)
(
gram
/
cm
)
/
(
cm
2
-
sec
2
)
1
gram
/
cm
3
*
981
cm
/
sec
2
[0077] Δh=+15.6 cm (The patient is 15.6 cm above the membrane)
[0078] The patient head height can be established at the beginning of each fill. Any changes in the head height that occur during the fill can be attributed to an increase in intraperitoneal pressure (IPP) since the patient is asleep.
[0079] Turning to FIG. 12 , the concentration gradient between the urea concentration 110 in the patient's blood and the urea concentration 111 in the dialysate for typical APD cyclers is illustrated graphically. Comparing the results illustrated in FIGS. 13 and 14 , it is evident that APD cyclers equipped with the sensors of the present invention provide superior results. Specifically, the data illustrated graphically in FIG. 13 was obtained using a prior art APD cycler. The data obtained in FIG. 14 was obtained using an APD cycler utilizing two sensors for monitoring intraperitoneal pressure. Note that the urea concentration 110 in the bloodstream is lower in FIG. 14 than in FIG. 13 . Further note, the dialysate volume or fill volume is lower for the therapy illustrated in FIG. 14 than the therapy illustrated in FIG. 13 . Thus, the present invention provides improved urea clearance with lower fill volumes.
[0080] It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the spirit and scope of the present invention and without diminishing its attendant advantages. It is, therefore, intended that such changes and modifications be covered by the appended claims. | 1a
|
This application claims priority under 35 U.S.C. §119(e) to U.S. provisional patent application Ser. No. 60/419,231, filed Oct. 17, 2002. The entire contents of this provisional application is incorporated by reference.
FIELD OF THE INVENTION
The present invention relates to the oral administration of 5-fluorouracil (5-FU) prodrugs to treat inflammatory skin conditions. In a preferred embodiment, the invention relates to the oral administration of 5-FU prodrugs to treat psoriasis. In an especially preferred embodiment, the invention provides a treatment for psoriasis by oral administration of capecitabine.
BACKGROUND OF THE INVENTION
Psoriasis
Inflammatory skin conditions include psoriasis, keloid (hypertrophic scar), atopic dermatitis, lichen simplex chronicus, prurigo nodularis, Reiter syndrome, pityriasis rubra pilaris, pityriasis rosea, stasis dermatitis, rosacea, acne, lichen planus, scleroderma, seborrheic dermatitis, granuloma annulare, rheumatoid arthritis, dermatomyositis, alopecia areata, lichen planopilaris, vitiligo, and discoid lupus erythematosis. Psoriasis is a common skin condition with a prevalence of 1–2% in the general population. The disease is of undetermined etiology and affects patients of all ages with no gender preference. The most common presentation is plaque psoriasis, which is characterized by well-demarcated, erythematous plaques with scale on the extensor surfaces of the extremities, especially the elbows and knees, and the scalp. The plaques are highly vascularized and frequently bleed with mechanical removal of the scale (Auspitz sign). Histologically, the plaques have a characteristic epidermal hyperplasia with rete ridges hyper-extending in a regular fashion into the dermis and the intervening epidermis. The abnormal hyperplasia of the epidermis results in the characteristic scale due to incomplete terminal differentiation of keratinocytes. Neutrophils may also be typically found within the scale layers and may occasionally contribute to a pustular presentation. A lymphocyte predominant inflammatory infiltrate is present which is usually limited to the superficial plexus of blood vessels in the skin. (Dosik J, Shupack J Current Dermatologic Diagnosis and Treatment , edited by I M Reedberg and M R Sanchez. Philadelphia: Current Medicine Inc. 2001. pp.178–179).
Subcategories of psoriasis include pustular psoriasis, inverse psoriasis, guttate psoriasis, nail psoriasis, psoriatic arthritis, and exfoliative erythrodermic (Von Zumbusch) psoriasis. Pustular psoriasis is characterized by neutrophil predominance, pustule formation and sometimes systemic symptoms. Inverse psoriasis presents in intertriginous areas. Guttate psoriasis characteristics include a widespread presentation on the body, truncal lesions, small teardrop lesions, and eruptive lesions. Psoriatic arthritis is usually an asymmetric oligoarthritis. Exfoliative, or Von Zumbusch, psoriasis is a life threatening form. (see Dosik et al. supra).
The existing treatments for psoriasis are targeted at the major histopathologic components of the disease. Broad immunosuppression or T-lymphocyte specific immunosuppression is achieved by treatment with UVB, cyclosporine, methotrexate, topical steroids, and other immunosuppressive modalities. Keratinocyte terminal differentiation is targeted by calcipotriene and salicyclic acid. Retinoids target both immunosuppression and keratinocyte terminal differentiation. A drawback to many of the agents currently employed to treat psoriasis is that they must be administered by injection or in the hospital. Orally administered treatments have a better rate of patient compliance and are therefore preferable as compared to treatments that are administered via the intravenous route.
Oral treatments for inflammatory skin conditions are also preferable to topical treatments. Topical treatments are often ineffective because of washing or rubbing away from the affected area. Patients are inconvenienced by staining of clothes and furniture by topical treatments, and by the need to cover the affected area with occlusive or bulky dressings. Oral treatments have a better rate of patient compliance than topical treatments because they are more convenient. Orally administered treatments provide more reliable drug delivery because the problem of washing or rubbing away of topical treatments is avoided.
Poor efficacy and high recurrence rates are also common problems of existing treatments for psoriasis. Few treatments are rapid acting or cause the disease to become less severe for a time without absolutely ceasing. No existing treatment for psoriasis is both rapidly acting and causes the disease to become less severe for a time without absolutely ceasing. Existing treatments for other inflammatory skin conditions suffer from similar shortcomings.
5-fluorouracil
5-fluorouracil (5-FU) is a cytotoxic antimetabolite that is widely used against solid tumors including gastrointestinal, breast, and head and neck cancers. The efficacy of 5-FU in treating solid tumors is enhanced when 5-FU is used in combination with leucovorin, the calcium salt of folinic acid. (Malet-Martino M et al. Clinical Studies of Three Oral Prodrugs of 5-Fluorouracil (Capecitabine, UFT, S-1): A Review. Oncologist 2002;7(4)288–323).
5-FU is a known treatment for psoriasis. Administration is generally by intravenous catheter. The use of 5-FU is limited by its toxicity and its unpredictable bioavailability. The enzyme dihydropyrimidine dehydrogenase (DPD) deactivates more than 85% of the injected dose of 5-FU. The bioavailability of 5-FU is unpredictable, especially after oral administration. In some patients, where DPD has strong activity, little 5-FU is available. If DPD has weak activity then 5-FU levels are elevated, which may lead to toxicity from overdose. (Malet-Martino et al., supra).
Toxicities of 5-FU include myelosuppression, oral mucositis, diarrhea, nausea, vomiting, cardiotoxicity, and neurotoxicity. Continuous intravenous (IV) infusion of 5-FU may result in the hand-foot syndrome. (Malet-Martino et al., supra) Because of the possibility of severe toxic reactions, it is recommended that patients be hospitalized for, at least, their initial course of therapy with IV 5-FU. ( Physician's Desk Reference , 56 edition 2002) The administration of 5-FU by protracted IV infusion is costly and is often associated with infectious and thrombotic complications related to the intravenous catheter. (de Bono J S, Twelves C J. The oral fluorinated pyrimidines. Invest New Drugs 2001; 19(1):41–59).
Because of the low effectiveness, side effects and toxicity of the existing treatments for inflammatory skin conditions, particularly psoriasis, there is a need in the art for an easily administered, efficacious and safe treatment for the disease.
Prodrugs
A prodrug is a pharmacologically inactive compound that is converted into a pharmacologically active agent by a metabolic transformation. In vivo, a prodrug is acted on by naturally occurring enzyme(s) resulting in liberation of the pharmacologically active agent. Prodrugs of 5-FU include capecitabine (N 4 -pentyloxycarbonyl-5′-deoxy-5-fuorocytidine), 5-fluoro-pyrimidinone (5FP), TS-1 (S-1, ftorafur), FdUMP, 1-(2′-oxopropyl)-5FU, and alkyl-carbonyl-5-FU. Each 5-FU prodrug is enzymatically converted to 5-FU in the body.
Capecitabine
Capecitabine is a preferred 5-FU prodrug of the present invention. Capecitabine is known for use in the treatment of breast and colorectal cancer. Capecitabine has been studied for use in the treatment of advanced gastric cancer, non-small cell lung cancer and pancreatic cancer.
Capecitabine is customarily administered via the oral route, crosses the gastrointestinal barrier intact, and is rapidly and almost completely absorbed by humans. (Malet-Martino et al., supra) Capecitabine is converted into 5-FU in a three-stage process involving several enzymes. In the first step, capecitabine is metabolized to 5′-deoxy-5-fluorocytidine (5′-dFCR) by hepatic carboxylesterase. 5′-dFCR is deaminated to 5′d5-FUrd by cytidine deaminase. 5′d5-FUrd is transformed into 5-FU by thymidine phosphorylase (TP). TP has higher activity in tumor than in normal tissues. (Malet-Martino et al., supra) Capecitabine is preferentially converted to 5-FU at highly angiogenic sites in the body including psoriatic plaques. (Creamer D et al., Overexpression of the angiogenic factor platelet-derived endothelial growth factor/thymidine phosphorylase in psoriatic epidermis. Br J Dermatol December 1997) Capecitabine has an improved therapeutic index over 5-FU because capecitabine increases the concentration of the active principle at the tumor site with a resulting greater activity and decreases the concentration of drug in healthy tissues with a consequent reduction in systemic toxicity.
The most common toxicities of capecitabine are hand-foot syndrome and diarrhea. Other reported toxicities include mucositis, nausea, stomatitis, vomiting, alopecia, fatigue, leopard-like vitiligo, onychomadesis, and onycholysis.
Hand-foot syndrome is an adverse event that occurs more frequently with capecitabine than with 5-FU/leucovorin. Hand-foot syndrome occurred in 53% of patients treated with capecitabine versus 6% of patients treated with 5-FU/leucovorin. In the capecitabine group 17% of patients had the most severe form (grade 3) of hand-foot syndrome versus 1% of patients in the 5-FU/leucovorin group. (Malet-Martino et al., supra) TS-1 also induces hand-foot syndrome. (Elasmar SA et al. Case report: hand-foot syndrome induced by the oral fluorpyrimidine S-1 . Jpn J Clin Oncol 2001 April; 31(4):172–4.).
Also known as palmar-plantar erythrodyesthesia, hand-foot syndrome results in painful reddening of the skin of the hands and feet in its mildest form, and in severe pain and loss of skin in its most severe form. The syndrome is graded on a scale between 1 and 3. Patients with Grade 1 disease experience numbness, dysesthesia, tingling, swelling, and erythema. Patients with Grade 2 disease experience painful erythema and swelling that affects activities of daily living. In Grade 3 disease, patients experience moist desquamation, ulceration, blistering, and severe pain that may result in inability to work or perform activities of daily living. (Blum J L et al. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol 1999; 17:485–493) Hand-foot syndrome initially starts with dysesthesia (an abnormal feeling of discomfort with weight bearing or touch) in the hands and feet, followed by edema and erythema, and ultimately, fissuring and ulceration involving the fingers, toes, palms and plantar aspects of the feet. As the syndrome progresses, the patient may experience extreme pain when grasping objects or walking. Hand-foot syndrome may also affect areas of the body other than the hands and feet, for example areas of the skin to which pressure is applied, such as at the belt or bra line. (Dorr et al. U.S. Pat. No. 6,060,083).
All references cited and discussed in this specification are incorporated herein by reference in their entirety.
SUMMARY OF THE INVENTION
The present invention provides a method for treating inflammatory skin conditions by orally administering an effective amount of a prodrug of 5-FU. The present invention additionally provides a method of treating psoriasis by orally administering an effective amount of an oral prodrug of 5-FU. In a preferred embodiment, the invention provides a method for treating psoriasis by oral administration of capecitabine. According to the invention an effective amount of capecitabine is orally administered to treat psoriasis.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a method of treating inflammatory skin conditions, particularly psoriasis, by orally administering a prodrug of 5-FU. In a preferred embodiment, the present invention employs oral administration of capecitabine for treating psoriasis.
It has now been unexpectedly discovered that oral administration of 5-FU prodrugs can be used to treat psoriasis in humans. In a preferred embodiment, capecitabine (a 5-FU prodrug) is orally administered to treat psoriasis in humans. The 5-FU prodrugs that have been found to be useful for treatment of psoriasis in humans are capecitabine (N 4 -pentyloxycarbonyl-5′-deoxy-5-fuorocytidine), 5-fluoro-pyrimidinone (5FP), TS-1 (S-1, ftorafur), FdUMP, 1-(2′-oxopropyl)-5FU, and alkyl-carbonyl-5-FU.
The preferred 5-FU prodrug for use in the present invention is capecitabine. Capecitabine is a prodrug of the antimetabolite 5-FU, crosses the gastrointestinal barrier intact, and is rapidly and almost completely absorbed. Surprisingly, this drug, which is responsible for the skin disease known as hand-foot syndrome, is effective as a treatment for another skin disease, psoriasis. The effectiveness of capecitabine for the treatment of psoriasis is especially surprising because hand and foot syndrome (which involves erythema, pain and ulceration) and psoriasis may occur in the same area of the body. As an example, inverse psoriasis occurs in intertriginous areas, which are areas between folds or juxtaposed surfaces of skin. (Stedman's Medical Dictionary, 26 th edition) Intertriginous areas include the skin beneath pendulous breasts and abdominal skin folds. Hand-foot syndrome is known to occur at the intertriginous areas of the bra-line and belt-line. Moreover, pustular psoriasis is known to localize to the palms and soles. (Merck Manual of Diagnosis and Therapy, 17 th edition, section 10 ch. 117).
The use of capecitabine to treat psoriasis is a significant advance because it avoids the serious side effects of 5-FU. Furthermore, capecitabine can be reliably and effectively administered via the oral route. Most adverse events associated with capecitabine administration are reversible and do not require discontinuation of the drug. (Physician's Desk Reference, supra) A benefit of oral prodrugs of 5-FU, and capacitabine particularly, is that patients are more likely to initiate treatment if the active agent can be taken orally rather than undergo the additional pain, expense and inconvenience of IV treatment. Treatment with oral capecitabine does not require hospitalization as does initial IV therapy with 5-FU. (Malet-Martino et al., supra) In addition to the 5-FU specific toxicities, any intravenous catheterization carries the risk of local infection and/or thrombophlebitis. (de Bono J S, Twelves C J, supra).
The 5-FU prodrugs capecitabine (N 4 -pentyloxycarbonyl-5′-deoxy-5-fuorocytidine), 5-fluoro-pyrimidinone (5FP), TS-1 (S-1, ftorafur), FdUMP, 1-(2′-oxopropyl)-5FU, and alkyl-carbonyl-5-FU can be orally administered to treat psoriasis and other inflammatory skin conditions (e.g., keloid (hypertrophic scar), atopic dermatitis, lichen simplex chronicus, prurigo nodularis, Reiter syndrome, pityriasis rubra pilaris, pityriasis rosea, stasis dermatitis, rosacea, acne, lichen planus, scleroderma, seborrheic dermatitis, granuloma annulare, rheumatoid arthritis, dermatomyositis, alopecia greata, lichen planopilaris, vitiligo, and discoid lupus erythematosis) in humans. Therapeutically effective oral doses of 5-FU prodrugs for treating psoriasis and other inflammatory skin conditions in humans in a non-pulse dosing regimen are between 5 and 2500 milligrams per square meter of body surface area per day, a preferred effective amount is between 100 and 1500 milligrams per square meter of body surface area per day and an especially preferred dose is 1250 milligrams per square meter of body surface area per day.
The preferred prodrug, capecitabine, is therapeutically effective for treating psoriasis and other inflammatory skin conditions in humans at doses below 2500 milligrams per square meter of body surface area per day, and capecitabine does not produce a 5-FU like adverse effect profile until dose levels exceed 2500 milligrams per square meter of body surface area per day. Adverse effects experienced at levels in excess of 2500 milligrams per square meter of body surface per day include nausea, vomiting and skin rashes. A therapeutically effective amount is that amount of capecitabine which will relieve or improve to some extent one or more of the symptoms or signs of psoriasis or other inflammatory skin condition.
An effective amount of capecitabine for treating psoriasis or other inflammatory skin condition in a non-pulse dosing regimen is between 100 and 2500 milligrams per square meter of body surface area per day, a preferred effective amount is between 750 and 1500 milligrams per square meter of body surface area per day and an especially preferred dose is 1250 milligrams per square meter of body surface area per day.
Capecitabine (offered under the brand name Xeloda® by Roche Labs, Nutley, N.J. 07110) is commercially available in 150 mg and 500 mg tablets. Xeloda® is indicated for the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracyline-containing chemotherapy regimen, or resistant to paclitaxel and for whom further anthracycline therapy is not indicated. (Physician's Desk Reference 2002) Peak plasma concentrations for capecitabine and its two main metabolites occur about 0.5 to 1.5 hours after administration. Plasma concentrations decline exponentially with a half-life of about 0.5 to 1 hour.
An additional dosing regimen is pulse-dosing. In pulse-dosing, an effective amount of a biologically active agent is administered to the patient and then sufficient time is allowed to permit the active agent to clear from the patient's body (i.e. to be metabolized or discharged) prior to the administration of additional doses. The quantity of drug administered to the patient in pulse-dosing may be greater than the dosage administered in a non-pulse-dosing regimen. The quantity, length of administration and interval between doses in pulse-dosing vary according to an individual patient's response to the pulse-dosing regimen.
An effective amount of oral 5-FU prodrug for treating psoriasis or other inflammatory skin condition by pulse dosing is between 5 and 5000 milligrams per square meter of body surface area, a preferred effective amount is between 100 and 3000 milligrams per square meter of body surface area and an especially preferred dose is 1250 milligrams per square meter of body surface area. A preferred pulse-dosing regimen is administration of the effective amount of the 5-FU prodrug daily for one week, an interval of two weeks without administration, repeat the schedule.
A preferred pulse-dosing regimen for treating psoriasis or other inflammatory skin condition is administering oral capecitabine in an effective amount between 100 and 5000 milligrams per square meter of body surface area, a preferred effective amount of between 750 and 3000 milligrams per square meter of body surface area and an especially preferred dose of 1250 milligrams per square meter of body surface area. In the pulse-dose regimen, the effective amount of capecitabine is administered orally each day for one week followed by an interval of one week without administration; the weekly cycle is repeated. Pulse-dose quantity, the period of time during which the effective amount is administered, and interval without dosing are adjusted for patient response and occurrence of adverse effects.
A 5-FU prodrug of the present invention is preferably administered as a pharmaceutical composition in hard shell dosage form such as a pill, tablet, capsule, or caplet. The pharmaceutical composition may be formulated as unit dosage forms, such as tablets, pills, capsules, boluses, powders, granules, elixirs, tinctures, metered aerosol or liquid sprays, drops, ampoules, autoinjector devices or suppositories. Unit dosage forms may be used for oral, intranasal, sublingual or rectal administration, or for administration by inhalation or insufflation, transdermal patches, and a lyophilized composition. Preferably the unit dosage form is an oral dosage form, most preferably a solid oral dosage, therefore the preferred dosage forms are tablets, pills, and capsules.
The pharmaceutical composition may contain capecitabine or an enantiomer, diastereomer, N-oxide, crystalline form, hydrate, solvate, active metabolite or pharmaceutically acceptable salt of the compound. The pharmaceutical composition may also include optional additives, such as a pharmaceutically acceptable carrier or diluent, a flavouring, a sweetener, a preservative, a dye, a binder, a suspending agent, a dispersing agent, a colorant, a disintegrator, an excipient, a diluent, a lubricant, an absorption enhancer, a bactericide and the like, a stabiliser, a plasticizer, an edible oil, or any combination of two or more of said additives.
Suitable pharmaceutically acceptable carriers or diluents include, but are not limited to, ethanol, water, glycerol, aloe vera gel, allantoin, glycerine, vitamin-A and E oils, mineral oil, phosphate buffered saline, PPG2 myristyl propionate, magnesium carbonate, potassium phosphate, vegetable oil, animal oil and solketal.
Suitable binders include, but are not limited to, starch, gelatine, natural sugars such as glucose, sucrose and lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth, vegetable gum, sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes and the like.
Suitable disintegrators include, but are not limited to, starch such as corn starch, methyl cellulose, agar, bentonite, xanthan gum and the like.
Suitable lubricants include, but are not limited to, sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like.
Suitable suspending agents include, but are not limited to, bentonite.
Suitable dispersing and suspending agents include, but are not limited to, synthetic and natural gums such as vegetable gum, tragacanth, acacia, alginate, dextran, sodium carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone and gelatine.
Suitable edible oils include, but are not limited to, cottonseed oil, sesame oil, coconut oil and peanut oil.
Examples of additional additives include, but are not limited to, sorbitol, talc, stearic acid and dicalcium phosphate.
Solid unit dosage forms may be prepared by mixing the active agents of the present invention with a pharmaceutically acceptable carrier and any other desired additives as described above. The mixture is typically mixed until a homogeneous mixture of the active agents of the present invention is obtained and the carrier and any other desired additives are formed, i.e. the active agents are dispersed evenly throughout the composition.
Tablets or pills can be coated or otherwise prepared so as to form a unit dosage form that has delayed and/or sustained action, such as controlled release and delayed release unit dosage forms. For example, the tablet or pill can comprise an inner dosage and an outer dosage component, the latter being in the form of a layer or envelope over the former. The two components can be separated by an enteric layer which serves to resist disintegration in the stomach and permits the inner component to pass intact into the duodenum or to be delayed in release.
Biodegradable polymers for controlling the release of the active agents include, but are not limited to, polylactic acid, polyepsilon caprolactone, polyhydroxybutyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates and crosslinked or amphipathic block copolymers of hydrogels.
For liquid dosage forms, the active substances or their physiologically acceptable salts are dissolved, suspended or emulsified, optionally with the usually employed substances such as solubilizers, emulsifiers or other auxiliaries. Solvents for the active combinations and the corresponding physiologically acceptable salts can include water, physiological salt solutions or alcohols, e.g. ethanol, propanediol or glycerol. Additionally, sugar solutions such as glucose or mannitol solutions may be used. A mixture of the various solvents mentioned may be used in the present invention too.
The active agents of the present invention may also be coupled with soluble polymers such as targetable drug carriers. Such polymers include, but are not limited to, polyvinylpyrrolidone, pyran copolymers, polyhydroxypropylmethacrylamidophenol, polyhydroxyethylaspartamidophenol, and polyethylenoxypolylysine substituted with palmitoyl residues.
A transdermal dosage form also is contemplated by the present invention. Transdermal forms may be a diffusion-driven transdermal system (transdermal patch) using either a fluid reservoir or a drug-in-adhesive matrix system. Other transdermal dosage forms include, but are not limited to, topical gels, lotions, ointments, transmucosal systems and devices, and iontohoretic (electrical diffusion) delivery system. Transdermal dosage forms may be used for timed release and sustained release of the active agents of the present invention.
The total daily dose should be taken as two divided doses approximately 12 hours apart, within 30 minutes of eating. The tablets should be taken with water. (Xeloda™ Patient Package Insert).
The number of daily tablets of a 5-FU prodrug to be taken by a patient for treatment of psoriasis or other inflammatory skin condition is shown in the following dosing table.
TABLE 1 Dosing table for 1250 milligrams per square of body surface area per day Dose level 1250 (mg/m 2 /day) Number of tablets to be Body surface area Total daily dose taken at each dose (m 2 ) (mg) 150 mg tablet 500 mg tablet ≦1.41 1600 2 1 1.41–1.56 1900 3 1 1.57–1.72 2000 0 2 1.73–1.95 2300 1 2 >1.95 2600 2 2
The Body Surface Area (BSA) is calculated using a BSA nomogram well known to those skilled in the art and the patient's height and mass. (Mosteller RD. Simplified calculation of body-surface area. NEJM 1987;317:1098). For any given BSA in the first column of Table 1, the total daily dose is disclosed in the second column of the table. The third and fourth columns of Table 1 show, respectively, the number of 150 milligram tablets and the number of 500 milligram tablets to be taken at each administration (morning and evening).
Duration of individual patient treatment will depend on individual response and tolerance. However, treatment with an effective amount of a 5-FU prodrug for 2 to 12 weeks should provide relief from psoriasis and other inflammatory skin conditions in most patients. The dosing regimen may be modified in the event of adverse events. An adverse event includes any adverse change from the patient's pre-treatment condition.
EXAMPLES
The following example is intended to illustrate more specifically the operation of the invention. The example is intended to illustrate and not to limit the scope of the invention. Other aspects, advantages and modifications within the scope of the invention will be apparent to those skilled in the art to which the invention pertains.
Example 1
Initiation of Treatment for Psoriasis with Capecitabine
Treatment of an adult with active psoriasis involving 10–75% body surface area (BSA) is carried out as follows. The physician obtains a complete medical history from the patient and conducts a physical examination. A Psoriasis Area and Severity Index (Fredriksson T, Petersson U, Severe psoriasis—oral therapy with a new retinoid. Dermatologica 1978;157:238–244), is obtained. A hematology profile (complete blood count and platelet count), chemistry profile (BUN, creatinine, SGOT, SGPT, total protein, and albumin), HIV screen, and urinalysis are also obtained. Women of child-bearing potential must have a negative serum pregnancy test within 7 days of the first dose of capecitabine.
The BSA is calculated using a BSA nomogram based on the patient's height and mass. A patient with a normal history, physical exam, blood and urine profiles is started on a course of capecitabine at 1250 milligrams per square meter of BSA per day according to Table 1. For example, a patient with a BSA of 1.50 square meters would receive a total daily dose of 1900 mg of capecitabine.
The patient is to take three 150 mg tablets and one 500 mg tablet with a glass of water within 30 minutes after eating breakfast. The same dose is repeated in the evening, approximately 12 hours later, with a glass of water within 30 minutes after dinner. The patient takes the daily dose for two days of the week and repeats this dosing schedule on the same days of the week on subsequent weeks.
From the foregoing disclosure it is evident that the present invention provides an advance in the treatment for psoriasis and inflammatory skin conditions. The present invention is preferably administered orally, which improves patient compliance with treatment and does not require hospitalization. Oral administration avoids the complications associated with intravenous catheterization. 5-FU prodrugs, preferably capecitabine, are effective for the treatment of psoriasis and other inflammatory skin conditions, and are safer than other drugs used for the treatment of psoriasis and other inflammatory skin conditions. | 1a
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BACKGROUND OF THE INVENTION
The present invention relates to improvements in toasters, particularly those toasters with one or more upwardly open slots to receive a product such as a slice of bread, a crumpet, a muffin or the like to be toasted. The invention is particularly aimed at toasters of the aforementioned kind having a single slot.
Although not very common, fires can occur when toasters are utilized. The causes of such fires include (1) a build-up of crumb material in the toaster base; and (2) a food product being toasted for a period of time that exceeds the normal level for that product due to operator misuse or a malfunction in the toaster itself.
The principal objective of the present invention is to provide a toaster which will prevent the effects of an escape of fire from a toaster in the unfortunate event of the occurrence of a fire. Toasters are generally required to be produced from materials that will not burn. Thus, even the plastic materials commonly used for many toaster bodies are made from resins which will not ignite. Thus, the effects of a toaster fire result from the flame escaping through the access opening to the toasting chamber.
SUMMARY OF THE INVENTION
Accordingly the present invention provides a toasting device including at least one toasting compartment with an access opening permitting a product to be toasted to be introduced into said toasting compartment, said device including flame proof member means capable of movement from a first position permitting access through said access opening to a second position closing said access opening, said flame proof member means, when in said second position, closing said access opening in a manner preventing escape of a flame from said toasting compartment. The flame proof member means may comprise one or a number of cover members. Conveniently the toaster includes means to define a toasting cycle and to discontinue power to toasting element means of the toaster upon completion of the toasting cycle, and a manually releasable latch mechanism preventing automatic movement of said flame proof member means to said first position upon completion of said toasting cycle.
In a particularly preferred arrangement, it is desired to provide a toasting device as aforesaid which ensures that the flame containment mechanism is necessarily used each time the device is used and more particularly that an operator is at the device when the toasted product is removed. That is to say, that the flame containment mechanism is always maintained in active operation until the toasted product is removed from the toasting compartment. In accordance with this aspect, the present invention provides a toasting device including at least one toasting compartment with an access opening for said toasting compartment, said device including flame proof member means capable of movement from a first position permitting access through said access opening to a second position closing said access opening, said flame proof member means, when in said second position, closing said access opening in a manner preventing escape of a flame from said toasting compartment, first control means being provided to automatically move said flame proof member means to said second position prior to completion of a toasting cycle, and second control means preventing said flame proof member means moving from said second position to said first position without manual intervention.
Conveniently the toasting device may include a product supporting carriage within said toasting chamber movable to a lowered position for a toasting cycle, actuation means being provided to enable movement of said carriage to said lowered position for toasting and said first control means being operably located so as to move said flame proof member means in response to movement of the product supporting carriage to said lowered position. Advantageously the flame proof member means comprises a single cover member adapted to, in use, overly said access opening. Preferably said second control means comprises a manually releasable latch means to maintain said flame proof cover means in said second position upon completion of a said toasting cycle until manually released.
In accordance with a still further aspect, the present invention aims at providing a closure for an open slot toaster, the closure at all times being retained within the confines of the toaster body.
According to this aspect, the present invention provides a toasting device including at least one toasting compartment with an access opening permitting a product to be toasted to be introduced into said toasting compartment, said device including flameproof member means capable of movement from a first position permitting access through said access opening to a second position closing said access opening, said flameproof member means when in said second position, closing said access opening in a manner preventing escape of a flame from said toasting compartment, and when said flameproof member means is in said second position, said flameproof member means is located within the confines of an outer housing of said toasting device.
In accordance with another aspect, the present invention provides a toasting device comprising a toasting compartment with an access opening permitting a product to be toasted to be introduced into said toasting compartment, said device including flameproof member means capable of movement from a first position permitting access through said access opening to a second position closing said access opening, said flameproof member means comprising at least two cover flap members which in said second position overly said access opening in a manner preventing escape of flame from said toasting compartment. Conveniently each said cover flap member comprises depending skirt members arranged in use in said second position to depend downwardly and outwardly of at least one wall of said toasting compartment.
Conveniently, the toasting cycle comprises an inner enclosure defining the toasting compartment and said outer housing surrounds said inner enclosure with at least one said access opening passing through both the outer housing and said inner enclosure, said flameproof member means being located at least partially between said inner enclosure and said outer casing when in said second position. Preferably said flameproof member means is formed by two cover members each of which is moved in opposite directions relative to one another when moving to said second position so as to be located substantially between said inner enclosure and said outer housing.
Conveniently operating means is provided connected to said cover members to move said cover members between said first and second positions. Preferably, said operating means moves said cover members in response to movement of a product support carriage in said toasting compartment, said operating means acting to move said cover members to the second (or closed) position when said product support carriage has moved through at least 70% and preferably between 85 and 95% of its permitted travel from its upper limit. Advantageously the operating means moves said cover members to said first (or open) position within 0 to 15% of the permitted travel of the product support carriage from the bottom toasting position of the support carriage. Conveniently, the cover members commence moving to their first (or open) position immediately the product support carriage starts to move upwardly.
BRIEF DESCRIPTION OF THE DRAWING
Preferred embodiments of the present invention will be described hereinafter with reference to the accompanying drawing in which:
FIG. 1 is a perspective view of a double slice single slot toaster according to the present invention;
FIG. 2 is a schematic illustration of one form of control mechanism usable with the toaster shown in FIG. 1;
FIG. 3 is a perspective view of the top section of a toaster similar to FIG. 1 showing a second preferred embodiment;
FIG. 4 is a traverse section through the access slot region of a toaster as shown in FIG. 3;
FIG. 5 is a partial perspective view of one end of the toasting compartment of the toaster of FIG. 3 with the outer casing and other parts removed for the sake of clarity;
FIG. 6 is an end elevation view of an upper part of the mechanism shown in FIG. 5;
FIG. 7 is a side elevation view of a lower part of the mechanism shown in FIG. 5; and
FIG. 8 is a view similar to FIG. 7 showing the mechanism in a different position of use.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to the drawing, a toaster 10 is shown with an outer casing body 11 defining an upper access opening 12 to a vertically arranged toasting compartment 13. The compartment 13 includes resistance heating elements 31 arranged on either side of the toasting compartment 13 in any conventional or known array. The casing body 11 illustrated is a non burnable plastic material, however, it is clearly also possible to use any other non burnable material such as sheet metal. The casing body 11, however, provides a substantially enclosed inner space accessed only through the upper access opening or slot 12. Arranged within the toasting compartment 13 is a product supporting carriage 14 movable between an upper product receiving position and a lowered position (FIG. 2) for a toasting cycle. At one end of the compartment 13, the carriage 14 is moved corresponding to movement of the lug 19. Alternatively a motorized movement mechanism could be provided to move the carriage 14 between the upper and lower positions. A conventional or known brownness selection knob 16 is provided together with any suitable and known toasting control system. Obviously the system should preferably include features adapted to minimize the likelihood of fires commencing, however, these features are not relevant to the present invention and are not further discussed hereinafter.
As shown in FIGS. 1 and 2, a flameproof member in the form of a cover flap 17 is provided hinged at 18 along one side of the access slot 12 so that it can be pivoted from an access providing position (FIG. 1) to a second position overlying the slot 12 as shown in FIG. 2. The flap member 17 may be formed from any other material that prevents a flame passing outwardly from the toasting compartment 13.
One possible form of linkage connection means is shown in FIG. 2 although it should be appreciated that other arrangements could also be employed. The mechanism is shown outwardly of the body 11 in schematic fashion although normally the mechanism would be located within the body 11 adjacent one end of the toasting compartment 13. As shown in FIG. 2, a lost motion link 60 is provided so that it slides up and down on a stationary substantially vertical guide member 20. An upper end of the link 60 is pivoted at 21 to a transversely extending part 22 of the cover 17. A carriage supporting member 23 is moved up and down on the guide member 20 by actuation of the external lug 19. The member 23 is generally urged upwardly by a spring element 66 so that the carriage 14 is normally located in its upper position. A lower end 25 of the member 23 mechanically latches with a catch member 26 when the member is moved to lower the carriage 14 to the lowered toasting position. In so doing a wake up or power actuating switch 27 is activated to enable power supply to the toasting elements for commencement of a toasting cycle. Alternatively a separate manually operable toasting cycle start up switch could be employed for reasons discussed hereinafter.
As illustrated in FIG. 2, the member 23 includes a portion 61 which is adapted to engage opposed abutment parts 62 and 63. Thus with the cover flap 17 in an open position (FIG. 1) the lug 19 and therefor the member 23 must be moved downwardly a certain distance before the portion 61 engages the abutment part 63 to thereafter automatically move the cover flap 17 from the position shown in FIG. 1 to the closed position shown in FIG. 2. Similarly there is a certain distance of travel of the lug 19 upwardly from the position shown in FIG. 2 before the portion 61 engages the part 62 to commence opening of the cover flap 17. This arrangement enables the cover flap 17 to be manually moved to the closed position (FIG. 2) without movement of the lug 19 for storage purposes. In an alternative arrangement, if the wake up switch 27 is omitted and a separate start up switch is used, then the lug 19 can be moved to its lowered position so that the end 25 catches with catch member 26 to lower the cover flap 17 for storage without the need of any lost motion mechanism as illustrated in FIG. 2. It is, however, desirable with this latter configuration that some separate means be provided to ensure that the separate start up switch does not commence a toasting cycle with the cover flap 17 in an open position.
In accordance with a preferred aspect of the present invention, the latch mechanism 32 identified illustratively in FIG. 2 by members 25,26 form an automatic mechanical latch which must be manually delatched to enable the cover flap 17 to be only operable by a person upon completion of a toasting cycle. Thus, in the unlikely event of a fire having ignited in the chamber, the cover flap 17 will not have automatically opened by the toaster mechanism (when unattended by the operator) to allow flames to escape from the compartment 13.
FIGS. 3 to 8 illustrate a second preferred embodiment of the present invention. In this embodiment, the toaster 10 also has an outer casing 11 (preferably formed from a non-burnable plastics material, metal or the like) having an upper access slot 12 adapted to receive a product to be toasted and to ultimately eject a toasted product therethrough after completion of a toasting cycle. As can be seen in FIGS. 4 and 5, an inner enclosure 64 is provided (conveniently produced from sheet metal) within the outer casing 11, the inner enclosure also has a generally rectangular upper access opening 65 substantially aligned with the access slot 12 in the outer casing. The inner enclosure 64 defines a toasting compartment 13 with heating elements of any known configuration (not shown) located adjacent the inner face of each longitudinal side wall 15,16 directing radiant and convection heat inwardly of the toasting compartment 13 when energized. Similar to FIG. 1, a lug 19 capable of being operatively gripped is provided which is directly connected to a product support carriage 14 located at least partially within the toasting compartment 13. The product support carriage 14 is mounted on a vertical slide post (not shown) so that it is capable of movement upwardly and downwardly thereon. A spring 66 is provided to normally urge the carriage 14 upwardly but against which an operator can move the carriage 14 down to a lowered toasting position by gripping the member 19 and moving same downwardly in the slot 67 in the outer casing 11. The product supporting carriage 14 has a part 23 located outwardly of the toasting chamber 13 and a part 24 located within the toasting chamber on which a slice of bread or the like is supported during a toasting cycle. The part 24 extends through a vertical slot 68 in an end wall 69 of the inner enclosure 64.
As shown in FIGS. 3 to 6, a closure means 70 is provided arranged to overly the access openings 12,14 to the toasting compartment 13. In the preferred embodiment illustrated, the closure means is conveniently located generally between the outer casing 11 and the inner enclosure 64 and comprises a pair of cover members 28,29. Each cover member 28,29 comprises an upper plate 30 covering approximately half of the access opening 65 when closed, a longitudinally extending side plate 31 adapted to extend downwardly from the access opening 65 outwardly of one of the inner enclosure side walls 15,16 and a pair of end plates 32,33 adapted to extend downwardly and outwardly of the end walls of the inner enclosure 64. One of the cover members 28,29 preferably has an inwardly (or outwardly) located laterally extending lip 34 adapted to overly the small longitudinally extending space between the cover members 28,29 when closed as illustrated in FIG. 4. Conveniently, if the cover members 28,29 are to be identically shaped (as may be desirable for manufacturing purposes) the lip 34 may extend over only half the length of the cover member 28 or 29 so that in an assembly, the overlying lip extends from each cover member over half the length of the cover member with an overlying obstruction thereby extending the full length of the access opening 65. By this means, the escape of flame is prevented from the toasting chamber 13 between the cover members 28,29.
An operating mechanism 36 for moving the cover members 28,29 from the generally closed (illustrated) position to an open position is best seen in FIGS. 5 to 8 of the annexed drawings. Each end plate 32,33 of the cover members has a downwardly depending hinge plate member 37 so as to locate a fixed hinge connection 38 to an end wall 69 of the inner enclosure 64 downwardly of the lower edge of the cover members 28,29 and outwardly spaced from the central dividing line 42 between the cover members 28,29. In addition a floating hinge connection 39 is provided acting between the two cover members 28,29. The floating hinge connection is formed by tab members 40,41 located at the lower edge of the members 28,29 adjacent the dividing line 42 between the cover members 28,29. Each tab member 40,41 has a first portion 43 extending outwardly from and at the same level as the lower edge of the cover member and a second portion 44 extending downwardly and towards or across the dividing line 42. One or both of the portions 44 includes a slot 45 and a hinge pin 46 extends through portion 44 connecting same together with a downwardly directed link member 47. Movement of the link member 47 downwardly or upwardly causes the hinge pin 46 to move downwardly or upwardly. As a result the cover members pivot about hinge pins 38 and also tend to move outwardly when opening or inwardly when closing because of the floating hinge 39 caused by the slot or slots 45. Thus the cover members 28,29 can be arranged to completely close the access opening 65 to the inner enclosure 64 (when closed), or open this access opening 65 with the cover members 28,29 moving to a position between the outer casing 11 and the inner enclosure 64.
The operating link member 47 is divided along most of its length from its lower end to form a first part 48 and a second part 49. The first part 48 has a lateral tab 50 at its lowermost end which is engaged by he carriage part 23 on its downward travel near to the end of its downward travel and in so doing the final downward movement of the carriage part 23 drags with it the link member 47 and thereby the pivot pin 46 to close the cover members 28,29. FIG. 7 shows the carriage part 23 at its uppermost position whereas FIG. 8 shows the carriage part 23 at its lowered toasting position. In the lowered toasting position, the carriage part 23 has been stopped by a physical limit ledge 51 and a manual latch member 52 has been engaged to prevent the carriage part 23 from moving upwardly from the position shown in FIG. 5 whether or not a toasting cycle has been completed. Moreover in the lowered toasting position (FIG. 8), a dowel pin 53 carried by the carriage part 23 is engaged in a recess 54 formed in the lower end of the second part 49 of the link member 47 and is locked therein by fixed cam ledge 55. Thus when the carriage part 23 is moved upwardly at the end of a toasting cycle and after delatching the member 52, the dowel pin 53 drives the second link 49 upwardly (and thereby the link member 47 and hinge pin 46) to immediately open the cover members upon the carriage 20 starting its upward eject motion. A slot 59 is formed in the part 48 of the link member 47 and the carriage part 24 extends through the slot 59 and slot 25 into the toasting chamber 13. The carriage part 24 through spring 66 keeps the link 47 in its up position in the absence of external manipulation. As will be apparent from the foregoing, the latch member 52 and latch 51 form an automatically engaged manual latch which must be manually delatched to enable the cover members 28,29 to be opened and necessarily requires the attention of a person at the toaster when this event occurs. Thus in an unlikely event of a fire having ignited in the chamber, the cover members 28,29 will not have been automatically opened by the toaster mechanism (when unattended by the operator) thereby allowing flames to escape from the toasting chamber 13. Conveniently, to assist operation of the toaster, visual and/or audible indicators 71,72 may be provided to show that a toasting cycle has commenced and separately has been completed. Although the foregoing description has been given with reference to a toaster having a carriage 23 moved manually down and a spring 66 to eject the toasted product, it should of course be appreciated that any known mechanism for driving or moving the carriage 23 might also be employed. | 1a
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to a method and system for measuring and reporting time based parameters associated with heart activity. More particularly, the present invention relates to a method and system for combining information gained from an independent signal with information gained from an impedance cardiography signal for monitoring and recording signals derived from heart valve activity.
[0003] 2. Discussion of the Related Art
[0004] Impedance cardiography (ICG) is a technique used to provide non-invasive monitoring and analysis of a patient's cardiac performance. ICG systems measure and report several time-based parameters related to cardiac performance, including the pre-ejection period (PEP) and the left ventricular ejection time (LVET). ICG systems produce ICG signals from monitoring movement and volume of blood as a result of the heart contracting. Exemplary ICG systems are shown and described in Ackmann et al., U.S. Pat. No. 5,178,154; and Reining, U.S. Pat. No. 5,505,209 both incorporated by reference herein in their entireties. The '154 and '209 patents disclose the use of electrode bands placed on a patient with high frequency, low magnitude electrical current applied to the electrode bands. Voltage changes across the bands are read, filtered and converted into thoracic impedance. The ICG system displays the thoracic impedance signal versus time to create a visual display or ICG waveform. The '154 patent further discloses that ICG systems can receive conventional electrocardiograph signals, signals from blood pressure monitors, signals from piezoelectric microphones attached to the chest of the patient and the like. These signals, in addition to thoracic impedance, can be stored and averaged via a memory storage device connected to the ICG system.
[0005] Phonocardiography (PCG) is a non-invasive technique used by healthcare professionals to monitor cardiac performance. PCG systems use a microphone that records sounds of heart valve activity, similar to electronic stethoscopes known in the art, in order to provide signals of acoustic events emanating from the heart. Analysis of signals recorded by PCG systems can be used to identify aortic valve opening (shown as S 1 on FIG. 1 ) and aortic valve closing (shown as S 2 on FIG. 1 ) of valves within a patient's heart.
[0006] Echocardiography (ECG) is another non-invasive system used to monitor heart activity. ECG uses a transducer to direct ultrasound waves into a patient's chest to produce an image of the heart muscle and heart valves. The transducer, also called a probe, is a small handheld device at the end of a flexible cable. The transducer, essentially a modified microphone, is placed against the chest and directs ultrasound waves into the chest such that some of the waves get echoed (or reflected) back to the transducer. Since different tissues and blood reflect ultrasound waves differently, these sound waves can be translated into a meaningful image of the heart that can be displayed on a monitor or recorded on paper or tape.
[0007] Still another non-invasive system used by healthcare professionals to monitor cardiac performance is a blood pressure system. A patient's blood pressure is monitored according to known techniques and converted into a blood pressure signal. The blood pressure signal is then displayed on a blood pressure waveform. Blood pressure waveforms, similar to PCG waveforms, can be used by healthcare professionals to identify heart valve closure because the dicrotic notch in blood pressure waveforms reflects closure of the aortic heart valve. Other exemplary systems using signals that have pulsatile characteristics resulting from the contraction of the heart are shown and described in Kimball et al., U.S. Pat. No. 6,763,256, herein incorporated by reference in its entirety.
[0008] The PEP is defined as the period of isovolumic ventricular contraction when the patient's heart is pumping against the closed aortic valve. In ICG systems, the PEP is measured starting with the initiation of the QRS complex (the “Q” point on FIG. 1 ) of the ECG signal and ending with the start of the mechanical systole as marked by the initial deflection of the systolic waveform (the “B” point on FIG. 1 ) of the ECG signal coincident with the opening of the aortic valve or the onset of left ventricular ejection into the aorta. The LVET begins at the end of the PEP and ends at the closure of the aortic valve (the “X” Point on FIG. 1 ) when ejections ends.
[0009] It is important that ICG systems provide accurate results for the PEP and the LVET because healthcare professionals utilize the results of these parameters when making decisions about patient diagnosis and care. Additionally, accurate determination of the PEP and the LVET time intervals is also required for accurate and reliable determination of subsequent and dependent parameters. For example, results from determination of the PEP and the LVET are used to calculate the systolic time ratio (STR), where STR=PEP/LVET. While many ICG systems use proprietary equations for determination of stroke volume (SV), it is commonly known that SV equations frequently incorporate LVET as an input parameter. Accordingly, accurate determination of time intervals between the PEP and the LVET is also necessary for accurate determination of SV, and subsequently for cardiac output (CO) based on SV and heart rate (HR), where CO=SV*HR.
[0010] Many ICG waveforms, particularly for healthy individuals, provide sufficient detail so that healthcare professionals can identify the location of the aortic valve opening and closing, or the LVET, with a high degree of confidence. For example, in the ICG waveform 10 depicted in FIG. 1 , opening, B point, of the aortic valve and closing, X point, of the aortic valve are easily identifiable. When comparing the ICG waveform 10 with the phonocardiograph (PCG) waveform 12 (both shown in FIG. 1 ), marking of the B point in the ICG waveform 10 is confirmed by the time-associated presence of the S 1 component in the PCG waveform 12 . Similarly, marking of the X point in the ICG waveform 10 is confirmed by the time associated presence of the S 2 component in the PCG waveform 12 .
[0011] Traditionally, ICG systems only analyze attributes of the impedance signal when determining the location of heart valve activity. Some ICG systems may record and display PCG signals, blood pressure signals, and/or other signals having pulsatile characteristics resulting from contraction of the heart, but these ICG systems do not integrate the signals into an automatic location of heart valve activity. ICG systems alone often lack sufficient information for healthcare professionals to accurately and reliably determine the PEP and the LVET because of confounding information related to opening and closing of the patient's aortic valve. For example, in the ICG waveform 10 depicted in FIG. 2 , closure, X point, of the aortic valve could be any of several depressions following the peak blood flow, C. The known algorithm selected the deepest depression in the ICG waveform 10 because the aortic valve closure is often thought to produce the strongest negative signal. However, when the ICG waveform 10 depicted in FIG. 2 is compared with the PCG waveform 12 depicted in FIG. 2 , the aortic valve closure, X point, should have been one of the later depressions in the ICG waveform 10 in order to correlate with the time associated presence of the S 2 component in the PCG waveform 12 . Accordingly, there is a need for a method and system for measuring and reporting time based parameters associated with heart activity that correlates impedance signals from ICG systems with independent signals derived from heart valve activity in order to provide more accurate identification of heart valve activity.
[0012] It is known that experienced healthcare professionals can recognize, or diagnose, certain disease states by analyzing hemodynamic parameters and ICG waveforms provided by some ICG systems. Experienced healthcare professionals can easily recognize the systolic and diastolic segments of ICG waveforms in addition to other attributes of the waveform, such as amplitude, shape, tone, slope and timing, in combination with hemodynamic parameters. Analysis of these attributes allows experienced healthcare professionals to ascertain an underlying disease state.
[0013] It is also known that some ICG systems provide minimal ICG waveform information. When using these types of systems, healthcare professionals must rely largely on numeric parameters to make a diagnosis because these systems do not provide other information. With ICG systems that display waveforms but provide them individually, experienced healthcare professionals may still be unable to analyze all waveform attributes and relationships to make a diagnosis. Accordingly, there exists a need for an improved method for displaying ICG waveform information in combination with information obtained from independent signals.
[0014] Based on the foregoing, there exists a need for a method and system that provides better identification of heart valve activity when measuring cardiac function within an ICG system. There also exists a need for method and system for measuring and reporting time based parameters associated with heart activity that correlates impedance signals from ICG systems with independent signals derived from heart valve activity in order to provide more accurate identification of heart valve activity. There exists yet another need for an improved method for displaying waveform information in combination with information obtained from independent signals.
SUMMARY OF THE INVENTION
[0015] It is one object of the present invention to provide an improved method and system for measuring and reporting heart valve activity by combining information obtained from independent signals with information obtained from ICG signals, such that the signals derived from heart valve activity are used as confirmation that the ICG system is accurately identifying heart valve activity. It is a second object of the present invention to provide improved accuracy in reported values such as PEP, LVET, STR, SV and CO. It is a third object of the present invention to provide improved accuracy of graphic presentation of heart activity where the graphic presentation includes identifying heart valve activity.
[0016] These and other objects and advantages of the present invention are accomplished by the improved impedance cardiography method and system in accordance with the present invention. The invention will be further described with reference to the following detailed description taken in conjunction with the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 represents ICG and PCG waveforms of a patient with easily recognizable heart valve activity;
[0018] FIG. 2 represents ICG and PCG waveforms of a patient with difficult to recognize heart valve activity;
[0019] FIG. 3 is an exemplary schematic diagram of one embodiment of the system of the present invention illustrating the principal components thereof;
[0020] FIG. 4 is a flowchart illustrating one embodiment for deriving an ensemble average;
[0021] FIG. 5 is a flowchart illustrating one embodiment for determination of likely valve activity;
[0022] FIG. 6 is a flowchart illustrating one embodiment for identifying aortic valve closing point;
[0023] FIG. 7 represents a traditional graphic representation of an ICG waveform and an ECG waveform;
[0024] FIG. 8 represents a graphic representation of a combined waveform, or single overlay graph;
[0025] FIG. 9 is a block diagram of the exemplary components of an electronic processing device used in accordance with the system of the present invention.
DETAILED DESCRIPTION
[0026] Referring to FIGS. 1 and 2 , there is shown an ICG waveform 10 and a PCG waveform 12 in accordance with the system and method of the present invention. Both figures depict heart valve activity in ICG waveform 10 . The PEP is determined by identifying the time period between the starting point of the QRS complex based on an ECG signal, labeled as the Q point, and the starting point of the mechanical systole as marked by the initial deflection of the systolic waveform based on the ICG signal coincident with the opening of the aortic valve or the onset of left ventricular ejection into the aorta, labeled as the B point. The LVET is determined by identifying the time period between the end of the PEP and the closure of the aortic valve when ejection ends, labeled as the X point. Both figures also depict heart valve activity in PCG waveform 12 , where known devices and methods are used to monitor and record sounds associated with the aortic valve opening, labeled as S 1 , and closing, labeled as S 2 . While FIGS. 1 and 2 depict PCG waveforms 12 , those skilled in the art can appreciate that waveforms generated from any independent signals derived from heart valve activity can be depicted in relation to ICG waveforms 10 .
[0027] Referring to FIG. 3 , one embodiment of the system in accordance with the present invention includes a display device 13 used to display waveforms and a processing device 14 used to receive inputs from a sensor system 15 hooked to a patient in order to generate waveforms and communicate with display device 13 . Those skilled in the art can appreciate that display device 13 may include any type of device for presenting visual information such as, for example, a computer monitor or flat-screen display. Display device 13 may be equipped with user input devices, such as buttons or touch screen capabilities for enabling user input, operation and control of the system. Those skilled in the art can also appreciate that sensor system 15 may include electrodes for measuring ICG signals and ECG signals, microphones for measuring and recording heart sounds, blood pressure monitors, signals representing central venous pressure, finger phlethysmographs and the like. Those skilled in the art will appreciate that the system in accordance with the present invention may include stationary systems used in intensive care units or emergency rooms in hospitals, or may comprise portable units for use by emergency medical technicians in ambulances, at the scene of accidents, and when responding to other emergency situations.
[0028] In another embodiment in accordance with the present invention, independent signals can be produced from one or more means that are sensitive to heart valve activity. Sources of the independent signals include but are not limited to PCG's, blood pressure waveforms, heart sounds, ECG's or user input. In one embodiment, an algorithm based on an empirical, mathematical model can be used to combine information from independent signals with information from ICG signals to determine heart valve activity and placement of the same on waveforms. The algorithm can include a set of coefficients, such as probability coefficients, applied to recent values of the differences between the ICG signals and the independent signals derived from heart valve activity in order to provide accurate weight to input signals being received by a processing device (such as a computer processor) in order to generate accurate graphic representations depicting heart valve activity. These coefficients can be multiplied by a sensitivity factor based on individual sensor errors, system errors or historic errors in correlating ICG signals with independent signals derived from heart valve activity for a particular patient. In this manner, sensor and system errors can be accounted for when modifying ICG waveforms based on independent signals derived from heart valve activity. FIGS. 4 through 6 depict embodiments in accordance with the present invention in which information generated from independent signals can be depicted in relation to ICG waveforms.
[0029] Referring to FIG. 4 , one embodiment of a method for deriving an ensemble average in accordance with the present invention includes steps for: inputting an ICG signal 16 ; inputting an ECG signal 18 ; inputting a PCG signal 20 ; identifying C-waves from the ICG signal 22 ; identifying R-waves and heart rate from the ECG signal 24 ; filtering the PCG signal through a bandpass filter 26 ; and deriving an R-wave triggered ensemble average 28 . While FIG. 4 depicts inputting signals from an ICG, an ECG and a PCG, those skilled in the art can appreciate that input signals can be derived from other sources as previously discussed, manipulated, and combined with other input signals to derive an ensemble average that can be used to determine proper placement of heart valve activity on a graphic representation, such as a waveform or a combined waveform.
[0030] Referring now to FIG. 5 , one embodiment for a method of determining preferred areas for aortic valve opening and closing in accordance with the present invention includes the steps of: inputting an R-wave triggered ensemble average PCG waveform 30 ; deriving an absolute value 32 ; calculating a window integration 34 ; inputting an S 1 , or aortic valve opening, window 36 ; inputting an S 2 , or aortic valve closure, window 38 ; determining an S 1 maximum 40 ; determining an S 2 maximum 42 ; determining an S 1 extent 44 ; determining an S 2 extent 46 ; determining a preferred area to be identified as the aortic valve opening point on a graphic representation 50 ; and determining a preferred area to be identified as the aortic valve closure point on a graphic representation 52 . In one embodiment, the S 1 and S 2 extent values can be used to find a value for PCG signal to noise 48 . The value for PCG signal to noise can be used to determine preferred areas to be identified as the aortic valve closure and opening points on the graphic representation. While FIG. 5 depicts an embodiment for determining aortic valve opening and closure points on a graphic representation starting with an R-wave triggered ensemble average PCG waveform, those skilled in the art can appreciate that the input PCG signal could be pre-processed in manners other than ensemble averaging, including but not limited to the input PCG signal being a raw unprocessed signal or a signal from an independent source other than PCG that can be used to derive aortic valve opening and closing points and/or other heart valve activity that can be depicted graphically in combination with ICG waveforms. Examples of other independent source signals are echocardiography, blood pressure, and the like.
[0031] As illustrated in the flowchart depicted in FIG. 6 , one method for determining the best overall rank for aortic valve closing point on the graphic representation includes the steps of: inputting an R-wave triggered ensemble average ICG waveform 54 ; finding the B point, which represents the opening of the aortic valve or the onset of left ventricular ejection into the aorta, 56 ; finding the O-wave, which represents the diastolic segment of the ICG waveform, 58 ; determining limits for the X-point using the B-point and the O-wave as inputs 60 ; ranking waveform amplitudes 62 ; ranking waveform slopes 66 ; utilizing a preferred time of aortic valve closure as determined from the signal of an independent source 64 ; utilizing heart rate as determined from ECG or other signal 68 ; determining a window for the LVET using the heart rate as an input 70 ; and finding the best overall ranking for the aortic valve closing 72 . In this embodiment, steps for ranking waveform amplitudes 62 , ranking waveform slopes 66 , utilizing a preferred time of aortic valve closure as determined from the signal of an independent source 64 , and utilizing heart rate as determined from ECG or other signal 68 are conducted before and utilized to find the best overall ranking for the aortic valve closing 72 . Those skilled in the art can appreciate that steps 62 , 66 , 64 and 68 can be conducted in varying orders or simultaneously. While FIG. 6 depicts a method for finding the best overall ranking for graphically representing aortic valve closure using an R-wave triggered ensemble average ICG waveform, those skilled in the art can appreciate that the input PCG signal can be pre-processed in manners other than ensemble averaging, including but not limited to using a raw unprocessed signal or a signal from an independent source other than PCG that can be used to derive aortic valve opening and closing points, and/or other heart valve activity that can be depicted graphically in combination with ICG waveforms.
[0032] Referring now to FIGS. 7 and 8 , an alternate embodiment in accordance with the present invention provides a method for displaying waveforms. According to the prior art as depicted in FIG. 7 , ECG waveforms 74 and ICG waveforms 76 are traditionally viewed separate from one another. FIG. 8 depicts a new method for displaying waveforms in according to the present invention where ICG waveforms 76 are combined with ECG waveforms 74 on a single overlay graph 78 such that users can obtain greater utility from the combined waveform than can be obtained by viewing the two waveforms individually. The increase in utility is a result of both ECG waveforms 74 and ICG waveforms 76 depicting systolic time interval characteristics. For example, the onset of PEP is typically obtained from the Q-point of the ECG signal and the end of the PEP is typically obtained form the upward portion of the ICG signal in ICG systems. Waveforms depicting a combined graphical representation of the systolic intervals, such as the PEP and the LVET, convey information to users more efficiently than separate waveforms.
[0033] Single overlay graph 78 also assists users in identifying the diastolic interval. The key points of the systolic time interval are marked by vertical lines 80 , 82 , 84 in FIGS. 6 and 7 . Line 80 marks the onset of the PEP and is determined by the Q-point of the ECG. Line 82 marks the end of the PEP and the start of the LVET and is determined by the ICG signal. Line 82 can optionally be determined via one or a combination of more than one the aforementioned independent signals, which can include the ICG signal. Line 84 marks the end of the LVET and is determined by the ICG signal. Line 84 can also optionally be determined via one or a combination of more than one of the aforementioned independent signals, which can include the ICG signal.
[0034] While the waveforms depicted in FIGS. 7 and 8 are ICG and ECG waveforms 74 , 76 , those skilled in the art can recognize that this method may be used on any type of waveform. Those skilled in the art can also recognize that this method may be used with graphic representations that correlate ICG signals with any signals measured, derived from or related to cardiac sources, and any other combination thereof.
[0035] Referring now to FIG. 9 , processing device 14 illustrates typical components of a processing device. Processing device 14 includes a local memory 86 , a secondary storage device 94 , a processor 96 , a user interface device 100 and an output device 98 . Local memory 86 may include random access memory (RAM) or similar types of memory, and it may store one or more applications 88 , including system software 90 , and a web server 92 , for execution by processor 96 . Local memory 86 is generally located in individual pieces of equipment used to monitor cardiac performance of patients. Secondary storage device 94 may include a hard disk drive, floppy disk drive, CD-ROM drive, or other types of non-volatile data storage. The local cache that includes a patient's waveform and heart valve activity data may be stored on secondary storage device 94 . Processor 96 may execute system software 90 and other applications 88 stored in local memory 86 or secondary storage 94 . Processor 96 may execute system software 90 in order to provide the functions described in this specification including measuring, reporting and displaying individual and/or combined waveforms with or without other graphic representations of heart valve activity. User interface device 100 may include any device for entering information into processing device 14 , such as a keyboard, mouse, cursor-control device, touch-screen, infrared, microphone, digital camera, video recorder, or any other instrument or device necessary to measure, report and display individual and/or combined waveforms with or without other graphic representations of heart valve activity. Output device 98 may include any type of device for presenting a hard copy of information, such as a printer, and other types of output devices include speakers or any device for providing information in audio form.
[0036] Web server 92 is used to provide access to patient data stored in memory 86 and on secondary storage devices 94 and display the data. Web server 92 allows users secure remote access to the system through which they can monitor the status of a patient's cardiovasculograms and access patient data. Web server 92 can allow access to a user running a web browser. Examples of web browsers include the Netscape Navigator program and the Microsoft Internet Explorer program. Any web browser, co-browser, or other application capable of retrieving content from a network and displaying pages or screens may be used.
[0037] Examples of processing devices 14 for interacting within the system for measuring and displaying individual or combined waveforms with or without graphic representation of other valve activity include embedded microprocessors, digital signal processors, personal computers, laptop computers, notebook computers, palm top computers, network computers, Internet appliances, or any processor-controlled device capable of storing data, system software 90 and any other type of application 88 stored in local memory 86 or accessible via secondary storage device 94 .
[0038] While the invention has been described with reference to the specific embodiments thereof, those skilled in the art will be able to make various modifications to the described embodiments of the invention without departing from the true spirit and scope of the invention. The terms and descriptions used herein are set forth by way of illustration only and are not meant as limitations. Those skilled in the art will recognize that these and other variations are possible within the spirit and scope of the invention as defined in the following claims and their equivalents. | 1a
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INTRODUCTION
The present invention relates to antibacterial peptides and their multimeric analogues, with wide range of action and low haemolytic activity. In particular, the invention relates to peptide molecules that exhibit a high antimicrobial activity against numerous bacterial species, with reduced cytotoxicity and a low haemolysis rate. The molecules of the invention are advantageously usable as therapeutic agents and coadjutants against infections caused by strains that are resistant to common antibiotics.
The peptides of the invention are in the form of synthetic and/or recombinant peptides, linear and multimerised in any chemical, physical and/or biological form which function as antibacterial agents with broad spectrum.
Antimicrobial peptides are an important component of the innate defences of many living species and they constitute the first line of defence of the immune system against infections, even before antibody and/or cell-mediated responses are fully activated.
At present, more than 800 natural antimicrobial peptides can be counted, and many others have been prepared synthetically.
Some peptides derived from natural sequences are undergoing pharmaceutical development (1).
Natural antimicrobial peptides constitute a numerous and heterogeneous group both in terms of composition and amino acid length. The most widely known natural antimicrobial peptides are cecropin, magainins, tachyplesin, protegrin, indolicidin, defensin and buforin. Their length generally ranges from 12 to 35 amino acids and they have a wide variety of secondary structures. Based on their conformational properties, peptides have been classified in five categories (2):
1. With alpha helix conformation: cecropins (3). 2. Constituted by the predominance of one or two specific residues, such as tryptophan for indolicidin (4) or arginine and proline for peptide PR39 (5). 3. Containing a disulphide bridge: bactenicin (6). 4. Containing multiple disulphide bridges which lead to the formation of relatively rigid beta sheets: defensins (7). 5. Polypeptide derivatives with greater dimensions, known for other biological functions, such as peptides derived from the GIP (gastric inhibitory peptide) (8).
Regardless of the secondary structure exhibited by the antimicrobial peptides, a characteristic they share is the amphipathic nature, due to the ability to adopt a conformation in which groups of hydrophobic amino acids and of positively charged amino acids are spatially organised in distinct regions. The cationic as well as hydrophobic nature of antimicrobial peptides enables them to selectively interact with the membrane of bacterial cells, composed mainly of negatively charged phospholipids. Although the action mechanism of antimicrobial peptides has not yet been fully explained, a model has been proposed that explains the activity of most of these compounds, known as the Shai-Matsuzaki-Huang (SMH) (9, 10, 11) model. The model proposes the interaction of the peptide with the external membrane (carpeting), followed by an alteration in the structure of the membrane itself, due to the displacement of lipidic molecules with the formation of toroidal pores that allow the passage and, in some cases, the diffusion of the peptide towards intracellular targets. A certain number of peptides have been proven to be able to bind the lipopolysaccharide (LPS) (12) with a certain affinity exercising both a destabilising effect on the outer membrane of Gram negative bacteria, and a detoxifying effect.
Therefore, most peptides with antimicrobial activity, apparently act according to a non-specific mechanism as confirmed by the fact that the D and L enantiomers of cecropin remain equally active (13, 14, 15). This fact would lead to exclude the hypothesis that there may be a stereo-specific interaction of the receptor-ligand type, and would explain the wide range of action of natural peptides against Gram negative and Gram positive bacteria, yeasts and fungi, tumour cells, and some viruses (HIV and Herpes Simplex).
In general, peptides that act at membrane level according to the SMH model are effective against micro-organisms at micromolar concentrations (1). However, there are some exceptions, such as nisin, a peptide of 14 amino acids produced by the bacteria of the Lactococcus genus, which binds Lipid II, a precursor of the peptidoglycan of the bacterial membrane, with high affinity. The specificity of this interaction would justify the antimicrobic effect of nisin even at nanomolar concentrations (16).
For antimicrobial peptides to be employed in clinical use, the selectivity of the action mechanism is crucial to prevent them from being toxic for the receiving organism. Antimicrobial peptides generally have less affinity for the membrane of the cells of the host organism, which exhibit a different phospholipidic composition from bacteria and fungi. In particular, bilayers enriched in the zwitterionic phospholipids phosphatidylethanolamine, phosphatidylcholine, or sphingomyelin, commonly found in mammalian cytoplasmic membranes, are generally neutral in net charge (9, 11). Moreover, the presence of cholesterol in the target membrane in general reduces the activity of antimicrobial peptides, due either to stabilization of the lipid bilayer or to interactions between cholesterol and the peptide.
The interest of antimicrobial peptides in clinical use is also related to their mechanism of action, which is potentially able to overcome the urgent problem of resistance to antibiotics. Since the target of antimicrobial peptides is the bacterial membrane, a microbe would have to redesign its membrane, changing the composition and/or organization of its lipids, which is probably a ‘costly’ solution for most microbial species. Antimicrobial peptides, therefore, are the best candidates to become a new class of wide range antibiotic drugs.
However, some problems related to their in vivo use have yet to be solved, since some of these natural peptides (e.g. mellitin) are particularly haemolytic or exhibit a short half-life due to their low stability in blood because of the presence of protease and in particular of peptidase.
The use of combinatorial library is a modern, efficient method that allows to select new “lead compounds” with antibiotic activity, selecting them from an extremely high number of different potential peptides. The greater the complexity of the peptide library, the higher the possibility of identifying highly effective compounds. For this purpose, three different combinatorial libraries can be used, but the person skilled in the art may identify other reference sources for peptides:
1. Peptide libraries obtained by chemical synthesis on solid phase (17). 2. Peptide libraries obtained by chemical synthesis as a mixture of free compounds in solution (18). 3. Peptide libraries expressed on the surface of filament phages (19).
The combination of the approach 3 and the chemical synthesis of peptides in solid phase has allowed the discovery of the molecules of the present invention.
DESCRIPTION OF THE INVENTION
The authors of the invention have identified peptide sequences capable of interacting with the bacterial membrane and hence potentially to perform an antibiotic effect according to the mechanism proposed for natural antimicrobial peptides.
Therefore, the object of the present invention is an antibacterial peptide having one of the following amino acid sequences from the amino to the carboxylic terminal: QEKIRVRLSA [SEQ ID NO: 1], QAKIRVRLSA [SEQ ID NO: 2], QKKIRVRLSA [SEQ ID NO: 4], KIRVRLSA [SEQ ID NO: 3] or any derivative thereof, wherein one amino acid residue is replaced by an alanine residue or wherein one positively charged amino acid is replaced by another positively charged amino acid.
Preferably the peptide has one of the following amino acid sequences from the amino to
the carboxylic terminal: AKKIRVRLSA [SEQ ID NO: 5], QAKIRVRLSA [SEQ ID NO: 2], QKAIRVRLSA [SEQ ID NO: 6], QKKARVRLSA [SEQ ID NO: 7], QKKIAVRLSA [SEQ ID NO: 8], QKKIRARLSA [SEQ ID NO: 9], QKKIRVALSA [SEQ ID NO: 10], QKKIRVRASA [SEQ ID NO: 11], QKKIRVRLAA [SEQ ID NO: 12]. More preferably the peptide has the amino acid sequence QKAIRVRLSA [SEQ ID NO: 6]. Alternatively the peptide has one of the following amino acid sequence: QRKIRVRLSA [SEQ ID NO: 13], QKRIRVRLSA [SEQ ID NO: 14], QRRIRVRLSA [SEQ ID NO: 15].
In an embodiment the peptide is of linear form, preferably multimerised on a skeleton of polyacrylamide, on a skeleton of dextrane units or on a skeleton of ethylene glycol units.
In a preferred embodiment the peptide is in the form of Multiple Antigenic Peptides (MAP), having the following formula:
in which R is the peptide as claimed in claim 1 - 4 ; X is a trifunctional molecule; m=0 or 1; n=0, if m=0; n=0 or 1, if m=1.
Preferably X is an amino acid having at least two functional aminic groups, more preferably X is lysine, ornithine, nor-lysine or amino alanine.
Alternatively X is aspartic acid or glutamic acid.
Alternatively X is propylene glycol, succinic acid, diisocyanates or diamines.
The peptides of the invention are used for the preparation of a medicament with antibacterial activity. The person skilled in the art will choose the appropriate form of administration and dosage, selecting suitable dilutants, coadjutants and/or excipients. Preferred forms are eyewashes, mouthwashes, solutions for topical use.
The peptides of the invention are also used for the preparation of disinfectant and/or detergent products with antibacterial activity.
The peptides of the invention are also used as preservatives for the preparation of food products and/or of cosmetic products and/or of homeopathic products.
DESCRIPTION OF THE FIGURES
FIG. 1 . Antibacterial activity of L 1 and M1 on E. coli (TG1 strain) compared to non correlated MAP (MNC) used as negative control. The effect on bacterial growth was assessed at various concentrations (2-0.12 mg/mL). M1 and L1 inhibited significantly E. coli growth while MNC, as expected, exhibited no antibacterial activity.
FIG. 2 . Antibacterial activity of (A) monomeric linear peptides L1 (▪), L4 (▪), L5 (▪) and L6 (□) and (B) tetrabranched MAP4 form M1 (▪), M4 (▪), M5 (▪) and M6 (□). Experiments were performed incubating E. coli TG1 cells (8×10 7 CFU/ml) with the indicated amounts of peptide. The survival percentage is the number of living colonies with respect to the number of colonies in controls without peptides.
FIG. 3 . Time-kill kinetics of M6 against E. coli ATCC 25922 (A) and P. aeruginosa ATCC 27853 (B). Symbols: ♦, growth control; ▪, 2×MIC concentration (16 μg/ml) for E. coli ATCC 25922 and 8 μg/ml for P. aeruginosa ATCC 27853); ▴, 4×MIC (32 μg/ml) for E. coli ATCC 25922 and 16 μg/ml for P. aeruginosa ATCC 27853).
FIG. 4 . Cytotoxicity of M1 on J774 A.1, CHO and SPO cells. The figure shows the cytotoxicity of the MAP M1 peptide expressed in terms of percent of survival evaluated on murine macrophage cells (J774 A.1), murine myeloma (SPO) and Chinese hamster ovary epithelium cells (CHO K1) by means of a colorimetric assay (MTT). M1 was added to the various cell lines (6×10 4 cells/well) at three different concentrations and incubated for 24 hours at 37° C. Then 100 μl of MTT were added to each well and incubated for 90 min at 37° C. The absorbance values at 595 and 650 nm were measured.
FIG. 5 . Toxicity of M4 (*), M5 (▴) and M6 (●) dendrimeric peptides on (A) mouse macrophage cell line J774.A1 and (B) human HaCaT keratinocytes. Cell viability was measured by a colorimetric assay (MTT). Data points represent means of three replicates.
FIG. 6 . Stability of M1 peptide in solution. Time course of antibacterial activity of M1 on E. coli strain TG1. MAP M1 peptide was dissolved in PBS at a concentration of 0.5 mg/ml and bactericide activity was measured 1, 48 and 72 hours after re-suspension in PBS.
FIG. 7 . HPLC profiles of linear (L1) and dendrimeric (M1) peptides in serum. (A) L 1 in serum at 0 h. (B) L 1 after incubation in serum for 2 h: the peptide is no longer detectable. (C) M1 in serum at 0 h. (D) M1 after incubation in serum for 24 h: the peptide is still present. The vertical bar indicates peptide retention time (min). Experiments performed in plasma were comparable.
FIG. 8 . Stability of M4, M5 and M6 peptides in solution. Time course of antibacterial activity of M4, M5 and M6 on E. coli strain TG1. M4, M5 and M6 peptides were dissolved in PBS at a concentration of 0.5 mg/ml and bactericide activity was measured 1, 48 and 144 hours after re-suspension in PBS.
FIG. 9 . Effect of M5 and M6 on haemolysis of human erythrocytes. The figures show the haemolytic activity of MAP M5 and M6 peptides on human erythrocytes evaluated by means of erythrocyte osmotic resistance of Parpart method in NaCl. The percentage of haemolysis is calculated by means of a calibration curve obtained by incubating erythrocytes with increasing concentrations of NaCl. After 30 min of incubation, M5 and M6 (at the maximum concentration tested) displayed only a weak haemolytic activity (<5%). After 19 hours of incubation, the haemolysis induced by M6 and M5 at 125 μg/ml is 7% and 19%, respectively. The percentage of haemolysis of untreated blood after 19 hours (control) is very limited (<1).
FIG. 10 . Kinetics of membrane permeabilization of ML-35 E. coli by M4 (*), M5 (▴), M6 (●) and of untreated cells (□). Permeabilization was determined by spectrophotometric recording of hydrolysis of p-nitrophenyl-β-D-galactopyranoside, a substrate for β-galactosidase in the cytosol of bacterial cells. Bacteria were treated with 16 μg/ml of dendrimeric peptides.
FIG. 11 . Binding analysis between MAP M6 peptide and LPS in BIACORE. The figure shows the sensorgram derived from the binding of LPS on MAP M6 immobilised in the dextrane matrix of the BIACORE sensorchip. On the y-axis are shown the Units of Response derived from the binding between LPS and M6 as a function of time expressed in seconds (on the x-axis)
FIG. 12 . Gel retardation assay. Binding was assayed by the inhibitory effect of peptides on the migration of DNA. Various amounts of M6 peptide were incubated with 200 ng of E. coli plasmid vector pCEP4 at room temperature for 1 h and the reaction mixtures were applied to a 1% (w/v) agarose gel electrophoresis.
FIG. 13 . CLSM image of TG1 E. coli cells treated with rhodamine-labelled M6 after (A) 5 min and (B) 240 min of incubation.
FIG. 14 . Bacterial inner-membrane permeation induced by M6 and visualized by FITC fluorescence.
FIG. 15 . Detection of membrane-perturbed bacteria using double staining with FITC and PI fluorescent probes. (A) M6 at 5 μg/ml and (B) M6 at 40 μg/ml.
RESULTS
Selection and Modification of Peptides with Antimicrobial Activity
The authors have produced and used a phage library of peptides with random sequence at high variability (˜10 10 ), in which each peptide is formed by 10 amino acid residues. The selection of the specific ligands was made by incubating the entire library with a solution of whole cells of E. coli , strain TG1 (at the OD 600 of about 0.1) in PBS. After 1 hour of incubation, the bacteria were centrifuged and the supernatant was eliminated. Several washings with PBS-Tween followed by centrifugation and elimination of the supernatant were performed to eliminate all the phages which bind aspecifically to the bacterial surface or which expose peptides with low affinity for the bacterial membrane. A glycine solution (0.2 M, pH 2.2) was added to the test tube containing bacteria and specific phages for 10 minutes, in order to determine the detachment of the phages bound to the membrane. After further centrifugation, the supernatant containing the eluted phages was collected. The selected phages were amplified in bacterial cells and used for two more rounds of selection. At the end of the process, the presence of specific phages was verified by ELISA assay. DNA analysis revealed the predominance of a sequence with potential amphipathic properties and positive net charge: QEKIRVRLSA [SEQ ID NO: 1] (L1). The letters are the acronyms of the aminoacids in accordance with IUPAC-IUB nomenclature.
It should be noted that the isolated sequence has the typical pattern of antimicrobic peptides which is characterised by alternating hydrophobic residues and positively charged residues (K and R). The peptide in question was synthesised in linear form and in tetrabranched multimeric form MAP (Multiple Antigen Peptide) (20), in which four identical peptides are bonded to a lysine core (U.S. Pat. No. 5,229,490). It has been shown that MAP multimeric forms, due to the presence of 4 peptides in the same molecule, displayed increased antimicrobial activity. In addition, MAP multimeric form constitute peptides that are more resistant to the peptidase activity of blood, compared to their homologous linear peptides (22, 23), enabling to overcome the bottleneck of the development and in vivo use of new peptide drugs.
M1 efficacy showed a drop in activity over time ( FIG. 6 ), once resuspended in solution. Mass spectrometry analysis performed on the peptide at various time points indicated that the loss of activity was probably due to amide bond formation between the carboxylic group of the glutamic acid (E) in position two and the adjacent aminic group of lysine (K), with the elimination of an H 2 O molecule (not shown).
In order to potentially improve the characteristics of the original sequence QEKIRVRLSA [SEQ ID NO: 1], three peptides were synthesised, starting from the original sequence and replacing glutamic acid (E) with a hydrophobic residue such as alanine (A), or with a positively charged residue such as lysine (K), and lastly performing a deletion of the first two aminoacids at the amino-terminal end. The sequences of the MAP peptides thus modified are QAKIRVRLSA [SEQ ID NO: 2] (M4), QKKIRVRLSA [SEQ ID NO: 4](M6), KIRVRLSA [SEQ ID NO: 3] (M5) (Table 1).
TABLE 1
Peptide sequence of L1, L4, L5, L6
Peptide sequence
chemical form
abbreviation
QEKIRVRLSA
Linear and MAP
L1 and M1
[SEQ ID NO: 1]
QAKIRVRLSA
Linear and MAP
L4 and M4
[SEQ ID NO: 2]
KIRVRLSA
Linear and MAP
L5 and M5
[SEQ ID NO: 3]
QKKIRVRLSA
Linear and MAP
L6 and M6
[SEQ ID NO: 4]
The bactericidial activity of M4, M5 and M6 was stable over time (up to 144 hours after solubilization, FIG. 8 ).
Antimicrobial Activity
The antimicrobic activity of the peptides in linear form (L1, L4, L5, L6) and in MAP form (M1, M4, M5, M6) was assayed on the TG1 strain of E. coli . The peptides were incubated at various concentrations (2-1-0.5-0.25-0.12 mg/ml) with cells of E. coli (OD 600 =0.2) for about 1 hour at 37° C. Subsequently, the cells were plated on agar at dilution such to allow counting of individual colonies. The antimicrobic activity of the synthesised peptide L 1 and M1 is shown FIG. 1 and is compared to a non correlated MAP peptide (MNC) used as negative control. While the non correlated MAP peptide exhibits no activity on bacterial colony growth, the authors observed that the inhibitory activity of the peptide M1 in dendrimeric form is greater than the one of the linear peptide, L1. This demonstrates that the efficacy of the antibacterial peptide depends exclusively on its primary sequence.
The survival percentage (number of living colonies with respect to the number of colonies in control conditions without peptide) after treatment with the original peptide and with the modified peptides was determined ( FIG. 2 ). The authors observed that in dendrimeric MAP4 form the peptides M1, M4, M5 and M6 presented a greater activity than their linear counterparts (L1, L4, L5 and L6) ( FIGS. 2A and B). The modified peptides (M4, M5, M6) showed good antibacterial activity. Notably, M5 and M6 (which contain one and two additional positive charges, respectively) prevented TG1 E. coli colony growth at concentrations down to 6.25 μg/ml, whereas M1 and M4 appeared less effective at the same concentrations ( FIG. 2B ).
Minimum inhibitory concentrations (MIC) of M4, M5 and M6 were determined for the reference strains: S. aureus ATCC 25923, E. coli ATCC 25922, Chryseobacterium meningosepticum CCUG 4310 and P. aeruginosa ATCC 27853, as well as for a number of recent clinical isolates (including multidrug-resistant ones) of various species (Table 2).
TABLE 2
MICs of antimicrobial peptides for various Gram negative and Gram positive
bacteria.
MIC (Molarity) of:
Species and strain
Relevant Features a
M4
M5
M6
Escherichia coli ATCC 25922
Reference strain
2.6 × 10 −5
3.8 × 10 −6
1.5 × 10 −6
Escherichia coli W99FI0077
FQ R ESC R (ESBL/SHV type)
3.2 × 10 −6
3.1 × 10 −5
1.5 × 10 −6
Escherichia coli W03BG0025
FQ R AG R ESC R (ESBL/CTX-M-
ND b
ND
1.5 × 10 −6
15)
Escherichia coli W03NO0013
FQ R ESC R (ESBL/CTX-M-1)
ND
ND
1.5 × 10 −6
Pseudomonas aeruginosa
Reference strain
6.4 × 10 −6
3.8 × 10 −6
7.6 × 10 −7
ATCC27853
Pseudomonas aeruginosa 885149
FQ R AG R ESC R CP R
1.3 × 10 −5
7.6 × 10 −6
1.5 × 10 −6
(MBL/IMP-13)
Pseudomonas aeruginosa 891
FQ R AG R ESC R
1.3 × 10 −5
3.8 × 10 −6
1.5 × 10 −6
CP R (MBL/VIM-2)
Pseudomonas aeruginosa
FQ R AG R ESC R (ESBL/PER-1)
ND
ND
7.6 × 10 −7
VA463/98
Klebsiella pneumoniae W99FI0057
ESC R (ESBL/SHV type)
1.3 × 10 −5
>3.1 × 10 −5
7.6 × 10 −7
Klebsiella pneumoniae
ESC R (ESBL/CTX-M-1)
ND
ND
3.0 × 10 −6
W03NO0078
Klebsiella pneumoniae
AG R ESC R (ESBL/CTX-M-15)
ND
ND
1.5 × 10 −6
W03BG0019
Klebsiella oxytoca W99FI00049
ESC R (ESBL/SHV-12)
ND
ND
1.2 × 10 −5
Proteus mirabilis W99FI0089
FQ R
ND
ND
>4.9 × 10 −5
Proteus mirabilis W03VA1144
FQ R AG R ESC R (ESBL/PER-1)
ND
ND
1.2 × 10 −5
Enterobacter aerogenes
AG R ESC R (ESBL/SHV-5)
ND
ND
1.5 × 10 −6
W03BG0067
Enterobacter cloacae W03AN0041
ESC R (ESBL/SHV-12)
ND
ND
7.6 × 10 −7
Morganella morganii W03VA1342
FQ R ESC R (ESBL/CTX-M-1)
ND
ND
>4.9 × 10 −5
Acinetobacter baumannii AB1MG
FQ R AG R ESC R (ESBL/TEM-
ND
ND
3.0 × 10 −6
92)
Acinetobacter baumannii AB7MG
FQ R AG R ESC R
ND
ND
6.0 × 10 −6
Citrobacter freundii W99FI00007
ESC R (ESBL/SHV-12)
ND
ND
3.0 × 10 −6
Chryseobacterium meningosepticum
Reference strain
ND
ND
>4.9 × 10 −5
CCUG4310
Burkholderia cepacia SMC71
FQ R AG R ESC R
ND
ND
1.2 × 10 −5
Serratia marcescens W99FI0111
FQ R AG R ESC R (ESBL/SHV-5)
ND
ND
>4.9 × 10 −5
Stenotrophomonas maltophilia
Wild-type profile
ND
ND
>4.9 × 10 −5
PT4/99
Providencia stuartii W03FI0001
AG R ESC R (ESBL/PER-1)
ND
ND
>4.9 × 10 −5
Staphylococcus aureus ATCC
Reference strain
1.3 × 10 −5
3.1 × 10 −5
>4.9 × 10 −5
25923
Staphylococus aureus MIU-68A
MS
>2.6 × 10 −5
3.1 × 10 −5
4.9 × 10 −5
Except for reference strains, all other strains were clinical isolates. Relevant resistance phenotypes and known resistance mechanisms are indicated.
FQ R , resistance to fluoroquinolones (ciprofloxacin);
AG R , resistance to aminoglycosides (gentamicin and/or amikacin and/or tobramycin);
ESC R , resistance to extended-spectrum cephalosporins (cefotaxime and/or ceftazidime and/or cefepime);
CP R , resistance to carbapenems (imipenem and/or meropenem);
ESBL, extended-spectrum β-lactamase;
MBL, metallo β-lactamase;
MS, meticillin-susceptible.
ND, not determined.
MIC is defined as the lowest concentration, in an antibiotic dilution range, that inhibits visible bacterial growth. The importance of MIC sensitivity test is based on the principle that in vitro sensitivity provides a predictive indication of the in vivo efficacy of the antibiotic therapy. Values are expressed as molar concentration and compared to MIC values obtained with commercially available antibiotics such as amikacin, ceftriaxone and levofloxacin (Table 3).
TABLE 3
MIC of known antibiotics against reference bacterial species
AMIKACIN
CEFTRIAXONE
LEVOFLOXACIN
Strain
MIC (Molarity)
MIC (Molarity)
MIC (Molarity)
S. aureus ATCC
8.5 × 10 −7 -6.8 × 10 −6
5.4 × 10 −8 -2.1 × 10 −7
2.2 × 10 −8 -1.6 × 10 −5
25923
E. coli ATCC
1.7 × 10 −6 -6.8 × 10 −6
1.4 × 10 −5 -1.1 × 10 −4
1.3 × 10 −6 -1.1 × 10 −5
25922
P. aeruginosa ATCC
1.7 × 10 −6 -6.8 × 10 −6
1.7 × 10 −6 -1.4 × 10 −5
1.6 × 10 −7 -1.3 × 10 −6
27853
From these data, it is readily apparent that the values of MIC for M4, M5 and M6 are low (in the order of 10 −6 -10 −7 M) whereas the best antimicrobic peptides known in the literature reach MIC values of around 10 −6 M (0.25-4 μg/mL) (25).
All peptides showed relatively poor activity against S. aureus , appearing to be more active against gram-negative bacteria, with M6 being the most active against all species. M6 presented also a good inhibitory activity against E. coli, Klebsiella pneumoniae, Enterobacter spp. and P. aeruginosa , including clinical isolates showing a multiple-drug resistance phenotype. A somewhat lower activity was observed against Citrobacter freundii and Acinetobacter baumannii , and even lower activity against Proteus mirabilis, Morganella morganii, Providencia stuartii, Stenotrophomonas maltophilia, Burkholderia cepacia , and Chryseobacterium meningosepticum (Table 2). Subsequently, the minimal concentration of the M4, M5 and M6 peptides able to kill 99.9% of the original bacterial inoculum (MBC) was evaluated. The MBC was calculated on strains of E. coli ATCC 25922 and P. aeruginosa ATCC 27853 and it was found to be equal to the calculated values of MIC for the same strains. The equality of the values of MIC and MBC provides the indication that M4, M5 and M6 peptides are bactericidal and not bacteriostatic.
Time-kill experiments demonstrated that M6 exhibited rapid bactericidal activity against E. coli ATCC 25922 and P. aeruginosa ATCC 27853, reducing an inoculum larger than 10 7 CFU by >99.9% in 4 h, at a concentration of 16 μg/ml ( FIG. 3 ). Bactericidal activity appeared to be concentration-dependent, especially with P. aeruginosa.
Due to their low MIC values, the peptides could be administered at low doses, improving patient compliance, but also the cost-effect ratio of such therapy.
Cytotoxicity
The cytotoxicity of antibacterial MAP peptides was evaluated on different eukaryotic cell lines by a colorimetric assay (MTT). This assay measures the cells' ability to convert a soluble tetrazolium salt into an insoluble precipitate: formazan. The cytotoxicity of M1 was evaluated on murine macrophagic cells (J774 A.1), murine myeloma cells (SPO) and Chinese hamster ovary epithelium cells (CHO K1). As shown FIG. 4 , even at high concentrations (1 mg/ml) M1 cytotoxicity on CHO K1 cells and on SPO cells is low (percent survival is 80-90%). By contrast, murine macrophage cells, J774 A1 were found to be more sensitive to M1 (percent survival ˜50%).
The toxicity of M4, M5 and M6 towards mouse macrophage cells J774.A1 was also tested by MTT and is shown in FIG. 5A . Treatment of cells overnight with 30 μg/ml of M4, M5 or M6, did not substantially affect cell viability, whereas a drop in cell viability was evident after treatment with peptide M4 at concentrations of 250 μg/ml and over, and with peptides M5 and M6 at 125 μg/ml and over. The same dendrimeric peptides showed low toxicity for human keratinocyte HaCaT cells ( FIG. 5B ) even when used at high concentration (1 mg/ml). Moreover, the effect of M4, M5 and M6 on the Pichia pastoris yeast, strain X33, was evaluated. The number of colonies of yeast treated with the three antimicrobial peptides did not differ from the negative control suggesting an absence of toxicity of the peptides on yeast (data not shown).
Peptide Stability in Plasma and Serum
Since the use of peptides as therapeutic agents is severely limited by their in vivo half-life, the stability to human serum protease of the linear peptide L1 and of the MAP peptides M1, M4, M5 and M6 was evaluated. The peptides were incubated at the concentration of 10 mM with plasma and with human serum for 2 and 24 hours; the samples were subsequently analysed in HPLC on column C18 (see materials and methods) to evaluate the presence of linear and MAP peptide not digested by the protease. The authors observed that monomeric peptide L1 was completely degraded within 2 h in serum, whereas the dendrimeric form of the same peptide (M1) was still detected after 24 h in plasma and serum ( FIG. 7 , Table 4). Comparable results were obtained with dendrimeric peptides M4, M5 and M6 (Table 4).
TABLE 4 Resistance to serum and plasmatic protease of L1, M1, M4, M5 and M6. Plasma Serum PEPTIDES 2 h 24 h >2 h 24 h L1 + − − − M1 + + + + M4 + + + + M5 + + + + M6 + + + +
Haemolytic Activity
The haemolytic activity of M5 and M6 was also evaluated and is represented FIG. 9 . Haemolysis of fresh human erythrocytes was determined at peptide concentrations ranging from 1 to 125 μg/ml. At a concentration of 125 μg/ml all dendrimeric peptides showed very poor haemolytic activity (less than 5%) after an incubation of 30 min. By contrast, after 19 hours of incubation, the haemolysis induced by M6 and M5 at 125 μg/ml is 7% and 19%, respectively. The percentage of haemolysis of untreated blood after 19 hours (control) is very limited (<1%).
Mechanism of Action
a) Permeabilization
The ability of MAP peptides to perforate the bacterial membrane was evaluated measuring the activity of cytoplasmatic beta-galactosidase (24) in surpernatants of E. coli strain ML-35 incubated with the peptide and using p-nitrophenyl-β-D-galactopyranoside (pNPG) as a substrate. pNPG is digested by beta-galactosidase, therefore releasing p-nitro-phenolate detectable by spectrophotometric reading at 420 nm ( FIG. 10 ). The permeabilization assays showed that peptides M4, M5 and M6 permeabilize the bacterial inner membrane, unmasking cytoplasmic β-galactosidase in ML-35 E. coli permease-negative mutant. The activity of dendrimeric peptides against the inner membrane was evaluated at concentrations of 16, 32 and 64 μg/ml. All dendrimeric peptides permeabilized bacterial inner membrane at 16 μg/ml ( FIG. 9 ). Permeabilization occurred after a lag of less than 1 minute, and the rate of permeabilization depended on peptide concentration (not shown). Moreover, the ability of the M6 MAP peptide to bind the bacterial lipopolysaccharide (LPS) was assayed by Plasmon Surface Resonance in a Biacore 1000 instrument ( FIG. 11 ) using a protocol perfected by the authors (26). The sensorgram shows the rapid binding of M6 to the LPS. This experiment suggests that M6 might have a detoxifying activity.
b) DNA Binding Assay
In an attempt to clarify the molecular mechanism of action, the authors examined the binding properties on DNA exerted by M6 dendrimeric peptide and magainin 2, an antimicrobial peptide which has a pore-forming activity on the cell membrane. The DNA binding abilities of M6 and magainin 2 were examined by analyzing the electrophoretic mobility of DNA bands at the various weight ratios of peptides to DNA on a 1% (w/v) agarose gel. M6 inhibited the migration of DNA above weight ratio of 0.2 ( FIG. 12 ) while magainin 2 did not suppress the migration of DNA until the weight ratio of 5. This result indicates that M6 binds to DNA at least over 25 times tightly than magainin 2.
c) Confocal Laser-Scanning Microscopy Experiments (CLSM)
CLSM experiments showed that rhodamine-labelled M6 is able to enter the cells within 5 minutes and tends to cluster in discrete patches, often situated at the cell poles, instead of distributing evenly inside the bacteria ( FIG. 13 ). Moreover, there are no significant differences between E. coli images taken after 5 ( FIG. 13A ) or 240 min ( FIG. 13B ) of incubation with 20 μg/ml M6.
To further visualize the membrane-perturbing activity of M6, the authors used FITC, a low molecular-mass (389.4 Da) green fluorescent probe. FITC was unable to cross the cytoplasmic membrane of control intact cells. Indeed, when E. coli TG1 cells were incubated with the probe without pretreatment with the peptide, no appreciable fluorescent signal was discerned (data not shown). In contrast, FITC was readily accumulated in bacteria after their exposure to 20 μg/ml M6, suggesting that M6 increases the permeability of the bacterial membrane as assessed by CLSM analysis ( FIG. 14 ). The results obtained with the double FITC-PI staining approach are illustrated in FIG. 15 . E. coli cells were incubated respectively with 5 μg/ml ( FIG. 15A ), and 40 μg/ml of M6 (( FIG. 15B ). The authors observed that microbial cells treated with the highest peptide concentration display an increased membrane permeability to both FITC and PI ( FIG. 15B ). The lowest concentration of M6 lead to a limited alteration of bacterial membrane ( FIG. 15A ). Surprisingly, the membrane remained almost impermeable to the smaller dye (FITC, 389.4 Da) but was permeable to the larger dye (PI, 668.4 Da). This finding could be explained by electrostatic interactions of the dye with the bacterial outer membrane: FITC in solution is negatively charged while PI has two positive charges that can promote its uptake. All treated bacteria maintain a typical “stick” shape without losing their nucleic acids content, as manifested by their clear, intense red fluorescence due to propidium iodine binding to DNA.
Improvement in M6 Peptide Activity
In order to identify the critical residues responsible for the antibacterial activity of M6, the sequence of M6 was subjected to “Alanine Scanning”. “Alanine Scanning” is a procedure in which every amino acid of the peptide in question is sequentially replaced by an alanine. A mini-library in MAP form of 9 peptides was thereby synthesised (Table 5).
Peptide sequence
chemical form
abbreviation
QKKIRVRLSA
MAP
M6
[SEQ ID NO: 4]
A KKIRVRLSA
MAP
M31
[SEQ ID NO: 5]
Q A KIRVRLSA
MAP
M32 = M4
[SEQ ID NO: 2]
QK A IRVRLSA
MAP
M33
[SEQ ID NO: 6]
QKK A RVRLSA
MAP
M34
[SEQ ID NO: 7]
QKKI A VRLSA
MAP
M35
[SEQ ID NO: 8]
QKKIR A RLSA
MAP
M36
[SEQ ID NO: 9]
QKKIRV A LSA
MAP
M37
[SEQ ID NO: 10]
QKKIRVR A SA
MAP
M38
[SEQ ID NO: 11]
QKKIRVRL A A
MAP
M39
[SEQ ID NO: 12]
For each MAP peptide, MIC was then calculated on three reference strains: E. coli ATCC 25922, P. aeruginosa ATCC 27853 (Gram negative) and ATTC25923 (Gram positive)
TABLE 6
MIC values of the peptides derived from Alanine Scanning of M6
E. coli ATCC
P. aeruginosa
S. aureus ATCC
25922
ATCC 27853
25923
Peptide
MIC (Molarity)
MIC (Molarity)
MIC (Molarity)
M6
1.5 × 10 −6
7.6 × 10 −7
>4.9 × 10 −5
M31
3.0 × 10 −6
3.0 × 10 −6
>1.2 × 10 −5
M32 = M4
1.2 × 10 −5
6.4 × 10 −6
>1.2 × 10 −5
M33
1.5 × 10 −6
1.5 × 10 −6
>1.2 × 10 −5
M34
>1.2 × 10 −5
1.2 × 10 −5
>1.2 × 10 −5
M35
6.0 × 10 −6
1.5 × 10 −6
>1.2 × 10 −5
M36
>1.2 × 10 −5
>1.2 × 10 −5
>1.2 × 10 −5
M37
3.0 × 10 −6
3.0 × 10 −6
>1.2 × 10 −5
M38
>1.2 × 10 −5
>1.2 × 10 −5
>1.2 × 10 −5
M39
3.0 × 10 −6
3.0 × 10 −6
>1.2 × 10 −5
MIC values obtained for the M6 derivative peptides show that the replacement of alanine with any hydrophobic residue led to a significant increase in MIC reflecting (?) a diminished antimicrobic activity.
From the mini-library, the peptide M33 was identified as particularly active against the Gram negative bacteria, E. coli ATCC 25922, and P. aeruginosa ATCC 27853 with MIC values, expressed in molarity, of 1.5×10 −6 M for both strains.
Lastly, the effect of replacing the lysines of the M6 peptide with another positively charged aminoacid, arginine (R) was evaluated. Arginine has a more distributed positive charge than lysine, due to the presence of the guanidinium group. The primary amine of lysine and the guanidinium group of arginine appear to interact differently with the bacterial phospholipids (27). For this purpose, 3 peptides in MAP form were synthesised (Table 7).
TABLE 7
Sequence of M6 modified peptides M28, M29 and
M30
Peptide sequence
chemical form
abbreviation
Q R KIRVRLSA
MAP
M28
[SEQ ID NO: 13]
QK R IRVRLSA
MAP
M29
[SEQ ID NO: 14]
Q RR IRVRLSA
MAP
M30
[SEQ ID NO: 15]
For each peptides, MIC was calculated on three reference strains: E. coli ATCC 25922, P. aeruginosa ATCC 27853 (Gram negative) and S. aureus ATTC25923 (Gram positive). MIC values obtained from replacing M6 lysines with the arginines show that the replacement of lysine in position 2 with an arginine does not influence the antimicrobial activity of MAP (Table 8).
TABLE 8
MIC values of M6 modified peptides M28, M29 and M30
P. aeruginosa
S. aureus
E. coli ATCC 25922
ATCC 27853
ATCC 25923
Peptide
MIC (Molarity)
MIC (Molarity)
MIC (Molarity)
M6
1.5 × 10 −6
7.6 × 10 −7
>4.9 × 10 −5
M28
3.8 × 10 −7
7.6 × 10 −7
>1.2 × 10 −5
M29
6.0 × 10 −6
6.0 × 10 −6
>1.2 × 10 −5
M30
3.0 × 10 −6
1.2 × 10 −5
>1.2 × 10 −5
From this mini-library, the petide M28 was identified as particularly active against the Gram negative bacteria E. coli ATCC 25922 and P. aeruginosa ATCC 27853 with MIC values, expressed in molarity, respectively of 3.8 × 10 −7 and 7.6 × 10 −7 M.
From this mini-library, the peptide M28 was identified as particularly active against the Gram negative bacteria E. coli ATCC 25922 and P. aeruginosa ATCC 27853 with MIC values, expressed in molarity, respectively of 3.8×10 −7 and 7.6×10 −7 M.
EXAMPLES
Example 1
In one example, the tetrabranched MAP peptides with the amino acid sequence: QAKIRVRLSA [SEQ ID NO: 2], KIRVRLSA [SEQ ID NO: 3], QKKIRVRLSA [SEQ ID NO: 4] are used individually in a bacterial colony growth inhibition test. The test is conducted by incubating different concentrations of MAP peptides with E. coli (strain TG1) and plating bacterial cells on agar at a dilution such to allow for individual colonies counting. The following day, the number of colonies grown after treatment with the three MAP peptides is compared. The MAP peptides with sequence KIRVRLSA [SEQ ID NO: 3] and QKKIRVRLSA [SEQ ID NO: 4] exhibit a bactericidal activity on TG1 cells down to a concentration of 6.25 μg/ml.
Example 2
In an additional example, the minimum inhibitory concentration (MIC) of the tetrabranched MAP peptides having the sequence: QAKIRVRLSA [SEQ ID NO: 2], KIRVRLSA [SEQ ID NO: 3], QKKIRVRLSA [SEQ ID NO: 4] was calculated on different Gram negative bacterial strains. The MIC values of KIRVRLSA [SEQ ID NO: 3] and QKKIRVRLSA [SEQ ID NO: 4], expressed in molarity, are in the order of 10 −6 -10 −7 M for the Gram negative bacteria E. coli ATCC 25922 and P. aeruginosa ATCC 27853.
Example 3
In an additional example, the minimum inhibitory concentration (MIC) of the tetrabranched MAP peptides having the sequence: QAKIRVRLSA [SEQ ID NO: 2], KIRVRLSA [SEQ ID NO: 3], QKKIRVRLSA [SEQ ID NO: 4] was calculated on different Gram positive bacterial strains, such as S. aureus ATTC25923. The values of MIC computed for the three MAP peptides are in the order of 10 −5 M.
Example 4
In another example, the minimal concentration able to kill 99.9% of the micro-organisms (MBC) of the tetrabranched MAP peptides having the sequence: QAKIRVRLSA [SEQ ID NO: 2], KIRVRLSA [SEQ ID NO: 3], QKKIRVRLSA [SEQ ID NO: 4], was evaluated. The MBCs were calculated on strains of E. coli ATCC 25922 and P. aeruginosa ATCC 27853 and were found to be equal to the corresponding MIC values for the same strains.
Example 5
In a further example, the haemolytic activity on human erythrocytes of the tetrabranched MAP having the sequence: KIRVRLSA [SEQ ID NO: 3], QKKIRVRLSA [SEQ ID NO: 4] was calculated. The percentage of haemolysis is calculated using the Parpart method by means of a calibration curve obtained incubating the erythrocytes with increasing concentrations of NaCl. At a concentration of 125 μg/ml QKKIRVRLSA [SEQ ID NO: 4] and KIRVRLSA [SEQ ID NO: 3] showed very poor haemolytic activity (less than 5%) after an incubation of 30 min. By contrast, after 19 hours of incubation, the haemolysis induced by QKKIRVRLSA [SEQ ID NO: 4] and KIRVRLSA [SEQ ID NO: 3] at 125 μg/ml is 7% and 19%, respectively.
Example 6
In another example, the tetrabranched MAP peptides having the sequence: QAKIRVRLSA [SEQ ID NO: 2], KIRVRLSA [SEQ ID NO: 3], QKKIRVRLSA [SEQ ID NO: 4] are tested in an in vitro assay, in which their cytotoxicity on murine macrophage J774 A.1 cells and on human HaCaT keratinocytes is determined by a colorimetric assay (MTT). As the concentration of MAP peptides increases, the vitality of J774 A.1 cells decreases, whilst human HaCaT keratinocytes are particularly resistant to the peptides even when administered at a concentration of 1 mg/ml.
Example 7
In a further example, the MAP peptide M6 (sequence QKKIRVRLSA [SEQ ID NO: 4]) demonstrated that it effectively binds the bacterial Lipopolysaccharide when it is passed on a sensorchip of a BIACORE instrument, previously sensitised with the same MAP peptide M6.
Example 8
In an additional example, the MAP peptides derived from “Alanine Scanning”, conducted on the sequence of M6 peptide (Table 6) are each one used to calculate their minimum inhibitory concentration (MIC) on the bacterial strains E. coli ATCC 25922, P. aeruginosa ATCC 27853 and S. aureus ATTC25923. Alanine Scanning by replacing sequentially every amino acid of M6 with an alanine, allows to identify the critical residues responsible for bactericidal activity of the peptide. From this mini-library, a peptide was identified (M33) which proved to be particularly active against the Gram negative bacteria E. coli ATCC 25922 and P. aeruginosa ATCC 27853 with MIC values of 1.5×10 −6 M for both strains (Table 6).
Example 9
In an additional example, MAP peptides obtained by replacing the lysines (K) with arginines (R) of the MAP peptide M6 (Table 7) are each used to calculate their minimum inhibitory concentration (MIC) on the bacterial strains E. coli ATCC 25922, P. aeruginosa ATCC 27853 and S. aureus ATTC25923. From this mini-library, a peptide was identified (M28) which proved to be particularly active against the Gram negative bacteria E. coli ATCC 25922 and P. aeruginosa ATCC 27853 with MIC values of 3.8×10 −7 and 7.6×10 −7 M, respectively (Table 8).
Materials and Methods
Selection of the Antibacterial Peptides from the Phage Library
The peptides able to have an antibacterial effect were selected using a phage library of random peptides of 10 mer, following standard protocols for the use of these libraries. The peptides were selected by means of three pannings. 1 ml of cells of E. coli strain TG1 at the OD 600 =0.1 (about 0.8×10 7 cells) was centrifuged at 17000×g for 3 min. The pellet was re-suspended in 1 ml of PBS and incubated under slow agitation for about 10 14 phages for 60 minutes at ambient temperature. Cells and phages were recovered after a centrifugation at 17000×g for 3 min. The supernatant was aspirated and the pellet washed 10 times with PBS-tween 0.1% to remove the phages not bound in the first selection round and washed with PBS-tween 0.5% in the subsequent rounds. The cells with the phages attached were centrifuged at 17000×g for 3 min and the pellet was re-suspended in 1 ml of elution buffer [0.2 M glycine-HCl (pH 2.2)] leaving under slow agitation for about 5 minutes at ambient temperature. The sample was centrifuged as done previously and the supernatant transferred into an Eppendorf tube and neutralised with 150 μL of 1M Tris-HCl (pH 9.1). 100 μL of eluted phage were used to infect 10 ml of E. coli TG1 in exponential growth phase for 30 min at 37° C. After the infection, the bacteria were centrifuged for 10 minutes at 3300×g, re-suspended in 1 ml of 2×TY (DESCRIVERE) and plated on agar containing ampicillin (100 μg/mL)-glucose (1%). After overnight incubation (o.n.) at 30° C., the colonies were recovered from the plate by adding 5-10 mL of 2×TY in such a way as to obtain an homogeneous suspension. 100 mL of 2×TY-ampicillin (100 μg/ml)-glucose (1%) were inoculated with 100 μl of a bacterial suspension until obtaining an OD 600 =0.4-0.5, 10 ml of culture were drawn and infected with 100 μl of the phage helper VCS.M13 (>10 11 transforming unit (tu)/ml). The infected bacteria were centrifuged at 3300×g for 10 min, the recovered pellet was then re-suspended in 100 ml of 2×TY-ampicillin (100 μl/ml)-kanamycin (25 μg/ml) and agitated over night at 30° C. The phages were purified and concentrated for precipitation with PEG/NaCl (20% polyethylene glycol 6000-2.5 M NaCl) and re-suspended in 2 ml of PBS. The eluted phages were recovered, amplified and used for two more selection cycles. At the end of the process, the presence of specific phages for the bacterial surface was verified by ELISA assay.
Synthesis of the Peptides
The solid phase synthesis of the linear peptides was conducted by means of Syro MultiSynTech (WittenBochum, D) peptide synthesiser, using a resin of p-(2,4-dimethoxyphenyl-Fmoc-aminomethyl)-phenoxyacetamidonorleucyl-(4-methylbenzydryl-amine) (Rink-MBHA) and the chemistry of fluorenylmethoxycarbonyl (Fmoc). The de-protection reaction was obtained by adding 40% of piperidine in N-methylpyrrolidone and, for the attack reaction, N-hydroxybenzotriazole esters of F-moc-aminoacids prepared in situ were used for the conjugation reaction. The peptides were detached from the resin and simultaneously de-protected using a trifluoroacetic acid/thioanisole/ethaneditiol/water mixture (93/2/3/2) for 3 hours at ambient temperature. The peptides were purified by means of reverse phase HPLC on a Vydac C18 semi-preparative column using a 30 min gradient of buffer B from 0% to 100% (buffer A: 0.1% trifluoroacetic acid/water; buffer B: 0.1% trifluoroacetic acid/methanol).
The synthesis of the multiple tetraramified antigenic peptides (MAP) was achieved by a solid phase procedure on Wang Fmoc 4 -K 2 —K-A resin, using Fmoc chemistry. The MAP peptides were separated from the support using standard techniques and purified by means of reverse phase HPLC. The peptides were checked by mass spectrometry.
Test of Antibacterial Activity on E. Coli Strain Tg1.
Antimicrobic tests were conducted incubating for 75 min at 37° C., 25 μL of E. coli at the OD 600 of 0.2 with 25 μl of MAP peptide dissolved in PBS at the various concentrations. The different incubations were further diluted 1:1000 in 2×TY medium and 100 μl were plated on solid 2×TY medium. The plates were left overnight at 30° C. and the individual grown colonies were counted and compared with a control, not treated with MAP peptide.
Minimum Inhibitory Concentration (MIC) determination
Reference strains ( Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococus aureus ATCC 25923 and Chryseobacterium meningosepticum CCUG 4310) and several recent clinical isolates (including multidrug-resistant ones) of various species (Table 2) were used for conventional susceptibility testing experiments. Minimum Inhibitory Concentration (MIC) was determined by a standard microdilution assay as recommended by the National Commitee for Clinical Laboratory Standards (NCCLS) using cation-supplemented Mueller-Hinton (MH) broth (Oxoid Ltd. Basingstoke, UK) and a bacterial inoculum of 5×10 4 CFU per well, in a final volume of 100 μl. Results were recorded by visual inspection after 24 h of incubation at 37° C. Minimum Bactericidal Concentration (MBC), defined as the concentration at which ≧99.9% of the bacterial inoculum is killed, was determined as recommended by the NCCLS after MIC testing.
Calculation of the Minimal Bactericidal Concentration (MBC)
The MBC is defined as the minimal concentration of antibiotic able to kill 99.9% of the micro-organisms of the original inoculation of the species in question. The MBC was determined as recommended by the National Committee for Clinical Laboratory Standards (NCCLS) on strains of E. coli ATCC 25922 and P. aeruginosa ATCC 27853.
Time-Kill Kinetics
Assay of bactericidal activity in time-kill experiments was carried out as follows. The peptide was added, at the desired concentration, to exponentially growing cultures of the test strain in MH broth containing a total inoculum of 5×10 7 CFU (1×10 7 CFU/ml) at 37° C. Samples were drawn at different times and suitable dilutions were plated on MH agar to score the residual number of CFU. A culture without peptide was always grown in parallel as control.
Cytotoxicity Test by MTT
For cytotoxicity tests, different cell lines were used: murine myeloma cells SPO, hamster ovary epithelium cells CHO K 1, murine macrophage cells J774 A.1 and human keratinocytes HaCaT. The cells were plated in medium in RPMI 1640 (SPO and CHO K 1) and DMEM (J774 A.1 and HaCaT) with antibiotics and bovine foetal serum at 10%, in 96-well plates at the concentration of 6×10 4 (SPO, CHO K1 and J774 A.1) and 3×10 4 (HaCaT). Peptides, previously filtered with a 0.2 μm filter disk (Whatman), were added at various concentrations to the different cell lines and left in incubation over night at 37° C. Cell viability was determined adding the MTT tetrazolium salt at the concentration of 0.5 mg/ml and incubating for 90 min. The cells were solubilised with a solution at pH 4.5 containing SDS 10% and dimethylformamide 45% and read at the dual wavelength of 595/650 nm with a plate reader.
Effect of QAKIRVRLSA (M4), KIRVRLSA (M5) and QKKIRVRLSA (M6) on the Pichia Pastoris Yeast Strain X33
To a volume of 50 μl of culture of Pichia pastoris grown 24 hour at 30° C. in YPD (Yeast Extract/Peptone/Dextrose) medium, 50 μl of MAP peptides (2 mg/ml) were added and left in incubation 150 min at 37° C. Subsequently, 50 μl of each incubation were plated on YPD solid medium and it was allowed to grow for 48 hours at 30° C. The number of colonies grown was compared with a control, where the yeast was not treated with the MAP.
Stability to Serum and Plasmatic Protease
The various peptides in MAP form and the linear peptide (L1) were dissolved in H 2 O at the concentration of 10 mM and incubated with 10 μl of plasma and human serum for 2 and 24 hours at 37° C. To each sample were added 150 μl of methanol to block the proteolytic reaction; each sample was then centrifuged at 13,000 rpm for 2 min and to the supernatant were added 0.75 ml of 0.1% trifluoroacetic acid. The samples were analysed in reverse phase HPLC on a Vydac C18 semi-preparative column using a 30 min gradient of buffer B from 20% to 95% (buffer A: 0.1% trifluoroacetic acid/water; buffer B: 0.1% trifluoroacetic acid/methanol), to evaluate the presence of linear and MAP peptide after the proteolytic treatment.
Haemolysis
The haemolytic activity of the KIRVRLSA [SEQ ID NO: 3] (M5) and QKKIRVRLSA [SEQ ID NO: 4] (M6) peptides was evaluated by the Parpart erythrocyte osmotic resistance assay in NaCl. The percentage of haemolysis was calculated by means of a calibration curve obtained incubating the erythrocytes with increasing concentrations of NaCl and measuring the absorbance increase, due to haemolysis, at 540 nm. 0.9% NaCl solutions containing the MAP peptides at different concentrations were then prepared, whereto was added human blood in the ratio of 1:100 (v/v). The samples were left at ambient temperature for 30 min and 19 hours; subsequently, a portion was drawn for each incubation, centrifuged at 1500 rpm for 5 min and the absorbance of the super was measured with the spectrophotometer at 540 nm.
Beta-Galactosidase Activity Assay
The ability of the QAKIRVRLSA [SEQ ID NO: 2] (M4), KIRVRLSA [SEQ ID NO: 3] (M5) and QKKIRVRLSA [SEQ ID NO: 4] (M6) MAP peptides to perforate the bacterial membrane was evaluated measuring the activity of cytoplasmatic beta-galactosidase using as a substrate p-nitrophenyl-β-D-galactopyranoside (pNPG), which, digested by the beta-galactosidase, frees the p-nitro-phenolate detectable by spectrophotometric reading at 420 nm. In order to do this, E. coli cells of the strain ML-35 were used: they constitutively produce beta-galactosidase and their lactose transporter is deactivated. The bacterial cells were drawn during the logarithmic growth phase (OD 600 =0.4-0.5) and re-suspended in phosphate buffer 10 mM containing NaCl 100 mM (pH 7.4) and 1.5 mM pNPG. At time zero, the peptide in MAP form was added at the final concentration of 16, 32 and 64 μg/ml and the absorbance change was measured at 420 nm.
DNA Binding Assay
Gel-retardation experiments were performed by mixing 200 ng of the E. coli plasmid vector pCEP4 (Invitrogen) with increasing amounts of M6 peptide in 20 μl of binding buffer (5% glycerol, 10 mM Tris-HCl (pH 8.0), 1 mM EDTA, 1 mM DTT, 20 mM KCl and 50 μg/ml BSA). The reaction mixtures were incubated at room temperature for 1 h. Subsequently, 4 μl of native loading buffer was added (40% saccarose, 0.25% bromophenol blue) and an aliquot of 12 μl was applied to a 1% agarose gel electrophoresis in 1 mM Tris borate-EDTA buffer.
Confocal Laser-Scanning Microscopy
TG1 E. coli cells were grown overnight in 2×TY. After dilution 1:10 in cell medium, 5×1 ml aliquots were prepared, washed two times with 10 mM sodium phosphate buffer (PBS) pH 7.4 and incubated in 200 μl of a tetramethylrhodamine (TMR) labelled peptide solution (20 μg/ml in PBS) for 5 min at 37° C. After washing with PBS, each aliquot of the cells were resuspended in 200 μl of PBS and kept in the dark at 37° C. respectively for 2, 30, 60, 120, 240 min. The cells were then mounted in a glass slide and observed with a Bio-Rad MRC600 laser scanning confocal microscope (CLSM). Fluorescent images were obtained with a 568 nm bandpass filter for excitation of TMR. Software merging of images was carried out by using a COMOS software. A double-staining method was developed to visualize, with two marker at the same time, the membrane perturbating activity induced by M6 on bacteria. The following fluorochromes were used: (i) the propidium iodide (PI), a DNA-staining fluorescent; and (ii) the green fluorescent probe fluoresceine iso-thiocyanate (FITC), which is unable to traverse the cytoplasmic membrane of cells unless permeabilized by a peptide. E. coli cells were prepared as described above and treated with 5, 10, 20, 40 μg/mL of peptide for 30 min at 37° C. The cells were then washed with PBS, and a FITC solution (6 μg/ml in PBS) was added. After 30 min at 37° C., the FITC solution was removed and the cells were washed again with PBS. A DAPI solution (6 μg/ml in PBS) was then added to the cells. Fluorescent images were obtained with a 568 nm bandpass filter for excitation of TMR and with a 488 nm bandpass filter for FITC.
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FIELD OF THE INVENTION
This invention relates to coating compositions for increasing the strength of shell eggs, and to shell eggs coated with such compositions.
BACKGROUND
The shell of a whole egg provides an effective package that protects the egg contents against contaminants from the environment and other sources. Integrity of the shell is critical for egg quality and safety. Shell cracks or imperfections permit ingress of bacteria that often grow rapidly when they migrate to the egg yolk. Growth of bacteria in egg contents leads to spoilage and increased risk of disease transmission. Egg shells are, however, inherently brittle; consequently, eggs are subject to unintentional cracking during laying, processing (including washing, rapid cooling, sanitization, and pasteurization), packing, shipping, stocking and handling by the end user. Mechanical handling during these operations further increases the potential for egg cracking. Pasteurization processes that rely on heat or heat combined with chemical treatments (e.g., heat-ozone combination) can weaken the egg shell and increase its tendency to shatter.
Upon detection (usually before packing and shipping), cracked eggs (known as “checks”) are diverted away from the retail market. However, eggs with weak shells are not detected by crack-checking devices, and may find their way onto supermarket shelves. These eggs tend to crack during routine shipping, stocking, or handling by the end purchaser. Furthermore, eggs having weak shells tend to shatter during use, often disrupting the yolk and mixing it with the albumen, or leaving shell fragments in egg contents. Shell weakness is disadvantageous, as it requires that the egg is cracked in a controlled manner so that the egg contents are preserved intact, if desired, during use. Therefore, methods and formulations which improve the strength of egg shells without adverse effect on their positive characteristics would be beneficial to the egg industry as well as consumers.
SUMMARY
The invention concerns a shell egg having improved strength. In one example embodiment, the shell egg comprises a shell having an outer surface. A coating covers at least a portion of the outer surface. The coating comprises a food grade natural resin. In a particular example, the food grade natural resin comprises shellac. The shellac may comprise dewaxed raw shellac, decolorized shellac and/or bleached shellac. The coating has a thickness sufficient to increase the energy required to crush the shell egg as compared with a similar shell egg having no coating. Additionally, the coating has a thickness sufficient to prevent the shell egg from shattering when cracked open. Both the coating thickness and its inherent strength contribute to the improvement in shell strength.
In an example embodiment, the coating extends in a band around the shell egg. In another example embodiment, the coating extends over the outer surface in its entirety. In a particular example embodiment, the coating has a uniform thickness. For example, the coating may have a thickness from about 0.04 mm to about 0.45 mm.
By way of further example, the shell egg may comprise a shell having an outer surface and a coating covering at least a portion of the outer surface wherein the coating comprises a wax, such as paraffin wax or beeswax, and particularly a combination of paraffin wax and beeswax. In an example embodiment, the coating may comprise a ratio of the paraffin wax to the beeswax from about 2:8 to about 8:2 by weight. In a particular example embodiment, the coating comprises a ratio of the paraffin wax to the beeswax in a ratio of about 1 to 1 by weight.
When coated with paraffin wax, beeswax, or paraffin wax-beeswax mixtures, the coating of the shell egg has a thickness sufficient to increase the energy required to crush the shell egg as compared with a comparable shell egg having no coating, as well as to prevent the shell egg from shattering when cracked open.
In an example embodiment, the coating may extend in a band around the shell egg, or the coating may extend over the outer surface in its entirety. In a particular example embodiment, the coating has a uniform thickness. The coating may, for example, have a thickness from about 0.05 mm to about 0.50 mm.
In another example embodiment, the shell egg comprises a shell having an outer surface and a coating covering at least a portion of the outer surface. In this example the coating comprising paraffin wax. In his example the coating has a thickness sufficient to increase the energy required to crush the shell egg as compared with a comparable shell egg having no coating. In another example embodiment, the shell egg comprises a shell having an outer surface and a coating covering at least a portion of the outer surface. The coating comprises beeswax in this example. The coating has a thickness sufficient to increase the energy required to crush the shell egg as compared with a comparable shell egg having no coating.
In another example embodiment, the shell egg comprises a shell having an outer surface and a coating covering at least a portion of the outer surface. The coating comprises a food grade polymer emulsion in this example. In a particular example embodiment, the food grade polymer emulsion comprises polyvinyl acetate. The coating has a thickness sufficient to increase the energy required to crush the shell egg as compared with a comparable shell egg having no coating. The coating may extend in a band around the shell egg. By way of further example, the coating may extend over the outer surface in its entirety. The coating may have a uniform thickness. By way of example, the coating may have a thickness from about 0.02 mm to about 0.40 mm. In a particular example embodiment, the coating has a thickness sufficient to increase the energy required to crush the shell egg as compared with a comparable shell egg having no coating. The coating also has a thickness sufficient to prevent the shell egg from shattering when cracked open.
For all of the above-described example embodiments, the coating may further comprise a food-grade colorant (including FD&C Blue No. 1, FD&C Red No. 3, Cochineal extract, Carmine, or other natural or synthetic colorants) a food-grade fungicide (including benzoic acid, sorbic acid, other organic acids, parabens, or natamycin), a food-grade anti-bacterial agent (including nitrites, nisin or other antimicrobial peptides, or antimicrobial plant extracts) as well as combinations thereof. The coating may contain solvents (including ethanol and/or acetone) which also makes the coating itself an antimicrobial agent.
The invention further encompasses a method of increasing the strength of a shell egg. The shell egg has a shell with an outer surface. In an example embodiment, the method comprises applying a food grade natural resin coating to at least a portion of the outer surface. The food grade natural resin comprises shellac in a particular example. The example method may further comprise spraying the shellac onto at least a portion of the outer surface. The shellac is in a liquid solution. The shellac is dissolved in organic solvents including ethanol, acetone or their combinations. The method further comprises drying the shellac. In one example, the liquid solution comprises shellac and ethanol. The ethanol may be about 190 proof and the shellac may comprise about 5% to about 30% of the solution by weight. In a particular example, the ethanol is about 190 proof and the shellac comprises about 20% of the solution by weight. In another example, the liquid solution comprises shellac and acetone. The shellac may comprise about 5% to about 30% of the solution by weight. In a third example, the liquid solution comprises shellac dissolved in a mixture of ethanol and acetone. The shellac may comprise about 5% to about 30% of the solution by weight. The ratio of ethanol to acetone in the solvent mixture ranges from about 90:10 to 10:90 by weight. In a particular embodiment, the ratio of ethanol to acetone in the liquid solution is about 3:1 by weight.
By way of example, drying is effected by subjecting the coating to a stream of gas at ambient temperature or heated to a temperature above ambient. The stream of heated gas may, for example, comprise air at temperature between about 20° C. and about 50° C.
The invention further includes a method of increasing the strength of a shell egg, the shell egg having a shell with an outer surface, where in the example method comprises applying a food grade polymeric emulsion coating to at least a portion of the outer surface. The food grade polymeric emulsion may comprise polyvinyl acetate in a particular example. This example method may further comprise spraying the polyvinyl acetate onto at least a portion of the outer surface and drying the polyvinyl acetate.
Another example embodiment of a method of increasing the strength of a shell egg, the shell egg having a shell with an outer surface, comprises applying a coating comprising paraffin wax and beeswax onto at least a portion of the outer surface. This method may further comprise spraying the coating onto at least a portion of the outer surface and drying the coating. The example method may further comprise polishing the coating.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a cross sectional view of an example shell egg having a coating according to the invention; and
FIGS. 2 and 3 are isometric views of example shell eggs having a coating according to the invention.
FIG. 4 is a graph showing an example of shell egg strength analysis.
FIG. 5 is a table showing the effect of different coating materials on strength of the shell of whole eggs.
FIG. 6 is a graph showing the strength of shell of whole eggs that were processed and coated with various coating materials.
DETAILED DESCRIPTION
FIG. 1 shows a shell egg 10 comprising a shell 12 surrounding an interior space 14 , the interior space containing an albumen layer 16 surrounding a yolk 18 . Shell 12 has an outer surface 20 . A coating 22 covers at least a portion of the shell outer surface 20 . For example, as shown in FIG. 2 , the coating 22 may comprise a band 24 extending around the shell egg 10 . FIG. 3 shows another embodiment, wherein the coating 22 covers the entire outer surface 20 of the egg 10 . With reference again to FIG. 1 , coating 22 may have a thickness 24 which is uniform over the entire coating, or the thickness 24 of coating 22 may vary as a function of position about the outer surface 20 . The minimum thickness of the coating 22 is such that it strengthens the shell 12 , i.e., coating 22 has a thickness 24 sufficient to increase the energy required to crush the shell egg 10 when compared with a comparable shell egg having no coating. The thickness 24 of the coating 22 should also be sufficient to prevent the shell egg 10 from shattering when cracked open.
In one example embodiment, the coating 22 comprises a food grade natural resin, for example, shellac. The shellac may be dewaxed raw shellac, decolorized shellac, bleached shellac, and/or combinations thereof. When shellac is used as the coating 22 , the thickness 24 may range from about 0.04 mm to about 0.45 mm. The shellac may be brushed or sprayed in liquid form onto the outer surface 20 of shell 12 to form the coating 22 . In one example, the liquid shellac comprises a shellac and ethanol solution. Experiments have shown that ethanol of 190 proof is an effective vehicle for the shellac. The shellac may comprise from about 5% to about 30% of the solution by weight. Experiments have also shown that a solution comprising 190 proof ethanol and about 20% shellac by weight is advantageous. After the liquid shellac-ethanol solution is applied to the shell eggs 10 the solution is dried to form the coating 22 . Drying may be effected by subjecting the shell eggs to a stream of heated gas, such as air heated to between about 20° C. and about 50° C. Multiple spraying and drying steps may be used to achieve a coating 22 having the desired thickness 24 .
In another example, the liquid shellac comprises a shellac and acetone solution. The shellac may comprise from about 5% to about 30% of the solution by weight. After the liquid shellac-acetone solution is applied to the shell eggs 10 the solution is dried to form the coating 22 . Drying may be effected by subjecting the shell eggs to a stream of heated gas, such as air heated to between about 20° C. and about 50° C. Multiple spraying and drying steps may be used to achieve a coating 22 having the desired thickness 24 .
In a further example, the liquid shellac comprises shellac, ethanol and acetone in solution. The shellac may comprise from about 5% to about 30% of the solution by weight. It is expected that the ratio of ethanol to acetone may range from about 90:10 to 10:90 by weight for practical applications. It has been found that a ratio of ethanol to acetone of about 3:1 by weight is advantageous and promotes rapid drying. After the liquid shellac-ethanol-acetone solution is applied to the shell eggs 10 the solution is dried to form the coating 22 . Drying may be effected by subjecting the shell eggs to a stream of heated gas, such as air heated to between about 20° C. and about 50° C. Multiple spraying and drying steps may be used to achieve a coating 22 having the desired thickness 24 .
In another example embodiment, the coating 22 comprises a mixture of paraffin wax and beeswax. When the mixture of paraffin wax and beeswax is used as the coating 22 , the thickness 24 may range from about 0.05 mm to about 0.5 mm. The ratio of paraffin wax to beeswax in the mixture may range from about 2:8 to about 8:2 by weight, with a ratio of paraffin wax to bees wax of about 1:1 being found advantageous in experiments. The mixture of paraffin wax and beeswax is applied to the outer surface 20 of the shell egg 10 in liquid form and may be effected by dipping the shell eggs into a molten wax bath, or by spraying or brushing the molten wax mixture onto the outer surface.
In a particular dip coating method, the paraffin and beeswax were heated in a double-walled boiler at 80° C. to 90° C. until fully liquefied. Eggs at 4° C. to 25° C. were dipped in the molten wax using a wire holder and quickly removed once fully submerged. Within seconds of removal from the wax, eggs were polished using a blotting paper (although it is expected that filter paper should be equally useful). The paper removes and spreads any excess wax that was not fully solidified.
In a particular spray coating method, a gravity-fed sprayer was used to spray-coat the eggs. The sprayer used a Venturi-type nozzle to pull the molten wax mixture from a reservoir and then used other air passages to force the spray pattern in a certain direction ranging from almost linear to circular application. In this example, air at ambient temperature was passed through the sprayer. To prevent cooling the wax and clogging the spry nozzles, the sprayer was heated up to 90° C. until it was at a temperature equal to that of the molten wax mixture. Similarly, hot air could be used to maintain wax spray in the molten state. As the hot wax contacted the eggs, it solidified. As only one side of the eggs could be coated at a time, the eggs were rotated to ensure complete coverage of the outer surface 20 . This application method may be repeated until the desired number of coats, providing a desired coating thickness, is achieved.
The dip and spray coating methods described above may also be used to apply a coating of only paraffin wax or only beeswax to achieve a coating having a thickness sufficient to increase the energy required to crush the shell egg as compared with a comparable shell egg having no coating.
In another example embodiment, the coating 22 comprises a food grade polymeric emulsion, for example, polyvinyl acetate. When polyvinyl acetate is used as the coating 22 , the thickness 24 may range from about 0.02 mm to about 0.4 mm. The polyvinyl acetate may be brushed or sprayed in liquid form onto the outer surface 20 of shell 12 to form the coating 22 . Drying may be effected by subjecting the shell eggs to a stream of heated gas, such as air heated to between about 20° C. and about 50° C. Multiple spraying and drying steps may be used to achieve a coating 22 having the desired thickness 24 .
The coatings listed above, i.e., the food grade natural resin (shellac), the wax mixture (paraffin and beeswax), single wax coatings, and food grade polymeric resins (polyvinyl acetate) may also be mixed with other agents such as food-grade colorant (including FD&C Blue No. 1, FD&C Red No. 3, Cochineal extract, Carmine, or other natural or synthetic colorants) a food-grade fungicide (including benzoic acid, sorbic acid, other organic acids, parabens, or natamycin), a food-grade anti-bacterial agent (including nitrites, nisin or other antimicrobial peptides, or antimicrobial plant extracts) as well as combinations thereof.
Result Summary of Testing of Egg Shell Strength as Affected by Processing and Coating
Eggs tested in these experiments were obtained from Hemmelgarn & Sons, Inc., Coldwater, Ohio. Each trail involved treating eggs collect on the same day from the same farm. Before coating, shell eggs were processed using a procedure known to weaken the shell. This procedure involves heating shell eggs in a water bath at 58° C. and treating heated eggs with a high concentration of gaseous ozone (more than 10%, wt/wt, of ozone in oxygen). In one of the experiments, processed eggs were coated with three coating materials; these are shellac, paraffin wax and beeswax. Different varieties of shellac were tested as coating materials. Fresh uncoated eggs were included in the experiment to represent eggs with normal shell strength. Additionally, processed uncoated eggs also were included in the study.
Eggs were tested for strength of the shell and its tendency to shatter using a material testing instrument (Instron 5542; Instron, Norwood, Mass., USA) equipped with an appropriate compression anvil (S5402A). Data from the tests indicates that two distinctive regions of strength are evident. The first region is simply a force required to initially crack the egg. Application of a coating was shown to increase the initial cracking force above that of processed eggs. The second region described the force needed to crush the eggs when the anvil proceeds for a distance of 4 mm (Graph 1 in FIG. 4 ).
When the work (energy) required to crush the eggs was calculated from the data, the trends indicated that the fresh egg required more work (30 to 40 N*mm) to crush its shell, compared to the work required to crushed an egg processed in a way to weaken its shells (15 to 20 N*mm). The data also indicated that the processed eggs coated by dipping in beeswax had the strongest shell (45 N*mm). Processed eggs coated with shellac have stronger shell (23-30 N*mm), compared to that of processed and uncoated eggs. Although coatings materials varied in ability to protect egg shell, beeswax and shellac showed significant improvement in shell strength. Examples of these data are presented in Table 1 of FIG. 5 and Graph 2 of FIG. 6 .
The following advantages are expected from coated eggs according to the invention as disclosed herein:
Coated eggs are expected to have longer shelf life in consumer's refrigerators. The coating allows for application of antifungal agents that prevent mold growth during storage. The coating is expected to improve the safety of shell eggs by preventing cross contamination and ingress of pathogenic organisms through cracks in the shell. The coatings are expected to decrease egg loss and improve consumers experience during egg preparation. It is expected that coated eggs will be easier to label with company logos. Coating material could be colored to distinguish brands and to appeal to consumers. | 1a
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