Patent Grant
8862223
This application is related to: (1) U.S. Design patent application Ser. No. 29/261,600 that was filed on Jun. 16, 2006, and that issued on Sep. 2, 2008 as U.S. Design Pat. No. D576,282 for a design titled “Adhesive Transdermal Medicament Patch”; (2) U.S. patent application Ser. No. 11/701,749 that was filed on Feb. 2, 2007, for an invention titled “Active Iontophoresis Delivery System.” (3) U.S. patent application Ser. No. 11/811,241 that was filed on Jun. 8, 2007, and that issued on Jun. 12, 2012 as U.S. Pat. No. 8,197,844 for an invention titled “Active Electrode For Transdermal Medicament Administration”; and (4) U.S. patent application Ser. No. 11/701,749 that was filed on Feb. 2, 2007 for an invention titled “Active Iontophoresis Delivery System.”
1. Field of the Invention
The invention disclosed herein relates to the transdermal administration of medicaments to human and animal subjects. More particularly, the present invention pertains to active iontophoretic delivery systems in which electrical contacts are applied to the surface of the skin of a subject for the purpose of delivering medicament through the surface of the skin into underlying tissue.
2. Background Art
During active iontophoresis, direct electrical current is used to cause ions of a soluble medicament to move across the surface of the skin and to diffuse into underlying tissue. The surface of the skin is not broken by this administration of the medicament. When conducted within appropriate parameters, the sensations experienced by a subject during the delivery of the medicament in this manner are not unpleasant. Therefore, active iontophoresis presents an attractive alternative to hypodermic injections and to intravascular catheterization.
The direct current employed in active iontophoresis systems may be obtained from a variety of electrical power sources. These include consumable and rechargeable batteries, paired regions of contrasting galvanic materials that when coupled by a fluid medium produce minute electrical currents, and electrical equipment that ultimately receives power from a wall socket. The later in particular are of such bulk, weight, and cost as to necessitate being configured as items of equipment distinct from the electrical contacts that are applied directly to the skin in administering a medicament iontophoretically. Accordingly, such power sources limit the mobility of the patient during the time that treatment is in progress.
A flow of electrical current requires an uninterrupted, electrically-conductive pathway from the positive pole of a power source to the other, negative pole thereof. Living tissue is made up primarily of fluid and is, therefore, a conductor of electrical current. In an iontophoretic circuit, the opposite poles of a power source are electrically coupled to respective, separated contact locations on the skin of the subject. The difference in electrical potential created by the power source between those contact locations causes a movement of electrons and electrically charged molecules, or ions, through the tissue between the contact locations.
In an active iontophoretic delivery system, the polarity of the net overall electrical charge on dissolved molecules of a medicament determines the nature of the electrical interconnection that must be effected between the power source that is used to drive the system and the supply of medicament that is positioned on the skin of the patient at one of the contact locations to be used by the system. A positively charged medicament in a reservoir against the skin of a patient is coupled to the positive pole of the power source that is to be used to administer the medicament iontophoretically. Correspondingly, a reservoir on the skin of a patient containing a negatively charged medicament must be coupled to the negative pole of such a power source. Examples of common iontophoretically administrable medicaments in each category of polarity are listed in the table below.
The medicament is housed in a fluid reservoir, or medicament, which is then positioned electrically conductively engaging the skin of the subject at an anatomical location overlying the tissue to which the medicament is to be administered. The medicament matrix can take the form of a gel suspension of the medicament or of a pad of an absorbent material, such as gauze or cotton, which is saturated with fluid containing the medicament. In some instances the fluid containing the medicament is provided from the manufacturer in the absorbent pad. More commonly, the fluid is added to the absorbent pad by a medical practitioner at the time that the medicament is about to be administered to a subject.
An iontophoretic circuit for driving the medicament through the unbroken skin is established by coupling the appropriate pole of the power source through the medicament matrix to the skin of the subject at the anatomical location at which the medicament is to be administered. Simultaneously, the other pole of the power source is coupled to an anatomical location on the skin of the subject that is distanced from the medicament matrix. The coupling of each pole of the power source is effected by the electrical connection of each pole to a respective electrode. The electrode at the medicament matrix is referred to as an active electrode; the electrode at the contact location on the skin distanced from the medicament matrix is referred to as a return electrode.
The medicament matrix with an associated active electrode may be conveniently retained against the skin by a first adhesive patch, while the return electrode may be retained against the skin at some distance from the medicament matrix using a distinct second adhesive patch. Alternatively, the medicament matrix with the associated active electrode, as well as the return electrode, may be carried on a single adhesive patch at, respective, electrically isolated locations.
The use of iontophoresis to administer medicaments to a subject is advantageous in several respects.
Medications delivered by an active iontophoretic system bypass the digestive system. This reduces digestive tract irritation. In many cases, medicaments administered orally are less potent than if administered transcutaneously. In compensation, it is often necessary in achieving a target effective dosage level to administer orally larger quantities of medicament than would be administered transcutaneously.
Active iontophoretic systems do not require intensive skin site sanitation to avoid infections. Patches and the other equipment used in active iontophoresis do not interact with bodily fluids and, accordingly, need not be disposed as hazardous biological materials following use. Being a noninvasive procedure, the administration of medicament using an active iontophoretic system does not cause tissue injury of the types observed with hypodermic injections and with intravenous catheterizations. Repeated needle punctures in a single anatomical region, or long term catheter residence, can adversely affect the health of surrounding tissue. Needle punctures and catheter implantations inherently involve the experience of some degree of pain. These unintended consequences of invasive transcutaneous medicament administration are particularly undesirable in an area of the body that, being already injured, is to be treated directly for that injury with a medicament. Such might be the case, for example, in the treatment of a strained muscle or tendon.
With some exceptions, no pharmacologically significant portion of a medicament delivered iontophoretically becomes systemically distributed. Rather, a medicament delivered iontophoretically remains localized in the tissue at the site of administration. This minimizes unwanted systemic side effects, reduces required dosages, and lightens the burdens imposed on the liver and kidneys in metabolizing the medicament.
The dosage of a medicament delivered iontophoretically is conveniently and accurately measured by monitoring the amount and the duration of the current flowing during the administration. With current being measured in amperes and time being measured in minutes, the dosage of medicament given transcutaneously is given in units of ampere-minutes. Due to the minute quantities of medicament required in active iontophoresis, medicament dosage in active iontophoresis is generally prescribed in milliamp-minutes. Dosage measured in this manner is more precise than is dosage measured as a fluid volume or as a numbers of tablets.
Finally, the successful operation of an active iontophoretic system is not reliant in any significant respect on the medical skills of nurses or doctors. Foregoing the involvement of such medical personnel in the administration of medicaments, whenever appropriate, favors the convenience of patients and reduces the costs associated with the delivery of such types of therapy.
The present invention promotes the wide use of active iontophoretic systems by providing improved components and combinations of components for active iontophoretic systems. The present invention thus improves the safety of patients and reduces the technical difficulty of related tasks that must by performed by medical personnel.
The teachings of the present invention enhance the reliability and the user friendliness of active iontophoretic systems and lead to reductions in the costs associated with the manufacture of such systems, as well as with the use of such systems to deliver medication.
While selected aspects of the present invention have applicability in all types of active iontophoretic systems, including those that employ plural disposable adhesive patches in combination with reusable power sources and controls, the teachings of the present invention are most optimally applicable to such system as involve a single fully-integrated, active transdermal medicament patch.
Thus, in one aspect of the present invention, a fully-integrated, independently accurately performing adhesive active transdermal medicament patch is provided.
The present invention contemplates related methods of design and manufacture, as well as methods pertaining to the treatment of patient health problems.
Additional objects and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by the practice of the invention. The objects and advantages of the invention may be realized and obtained by means of the instruments and combinations particularly pointed out in the appended claims.
The manner in which the above-recited and other advantages and objects of the invention are obtained will be understood by a more particular description of the invention rendered by reference to specific embodiments thereof that are illustrated in the appended drawings. These figures are intended to be illustrative, not limiting. Although the invention is generally described in the context of these embodiments, it should be understood that by so doing, no intention exists to limit the scope of the invention to those particular embodiments.
Understanding that these drawings depict only typical embodiments of the invention and are not therefore to be considered limiting of scope, the invention will be described and explained with additional specificity and detail through the use of the accompanying drawings in which:
In the following description, for purpose of explanation, specific details are set forth in order to provide an understanding of the invention. Nonetheless, the present invention may be practiced without some or all of these details. The embodiments of the present invention, some of which are described below, may be incorporated into a number of elements of medical systems additional to the medical systems in which those embodiments are by way of necessity illustrated herein. Structures and devices shown in the figures illustrate merely exemplary embodiments of the present invention, thereby to facilitate discussion of teachings of the present invention. Thus, the details of the structures and devices shown in the figures are not supplied herein in order to serve detractors as instruments with which to mount colorable denials of the existence of broad teachings of present invention that are manifest from this specification taken as a whole.
Connections between components illustrated in the figures are not limited to direct connections between those components. Rather, connections between such components may be modified, reformatted, or otherwise changed to include intermediary components without departing from the teachings of the present invention.
References in the specification to “one embodiment” or to “an embodiment” mean that a particular feature, structure, characteristic, or function described in connection with the embodiment being discussed is included in at least one embodiment of the present invention. Furthermore, the use of the phrase “in one embodiment” in various places throughout the specification is not necessarily a reference in each instance of use to any single embodiment of the present invention.
Formed generally centrally through release liner 22 is a medicament matrix aperture 28. As shown in
The side of medicament matrix 30 visible in
By way of example, the embodiment of medicament matrix 30 shown in
Accessible from therapeutic face 20 through first electrode aperture 40 is a planar first electrode, a return electrode 42 of medicament patch 16. Return electrode 42 has a periphery 44 and, interior thereof on the side of return electrode 42 visible in
Return electrode 42 is separated from medicament matrix 30, and thus electrically isolated therefrom. Skin contact surface 46 of return electrode 42 electrically conductively engages the skin of patient 10, when therapeutic face 20 of substrate 16 is disposed against and removable adhered thereto. Accordingly, when medicament patch 16 is adhered to the skin of patient 10 as shown in
Accessible from therapeutic face 20 through electrode aperture 44 is a planar second electrode, active electrode 50 of medicament patch 16. Active electrode 50 includes an electrically-conductive planar backing layer 52 and a smaller electrically-conductive planar pH-control layer 54 disposed centrally thereupon. While possible to do so, active electrode 50 is not secured directly to therapeutic face 20 of substrate 18 in the manner of medicament matrix 30. Instead, by the attachment of active electrode 50 to other structural elements of medicament patch 16, active electrode 50 is maintained in a fixed relationship to other features of medicament patch 16 with the plane of each of backing layer 52 and pH-control layer 54 parallel to and closely coincident with the plane of therapeutic face 20. Consequently, a second electrode, such as active electrode 50, will routinely be characterized herein as being carried or positioned on therapeutic face 20, and thereby being located on the same side of substrate 18 as, for example, return electrode 42 and medicament matrix 30.
In the assembled condition of medicament patch 16 shown in
Also included in dashed lines in
Electronic circuitry 60, power source 62, and switch 64 are not mounted directly to substrate 18, although any or all of these components of medicament patch 16 may be secured directly to substrate 18, or recessed in whole or in part into substrate 18. Instead, electronic circuitry 60, power source 62, and switch 64 are maintained in a fixed relationship to each other by being commonly secured to a circuit board 68. Circuit board 68 directly engages substrate 18 beneath cover 56, indirectly fixing each of electronic circuitry 60, power source 62, and switch 64 relative to each other and to other features of medicament patch 16.
Circuit board 68 will be explored in greater detail in
Sandwiched between cover 56 and upper face 70 of substrate 18 is circuit board 68. On the side of circuit board 68 visible in
Power source 62 is, by way of example, a miniature battery of about 3 volts potential. The current supplied by power source 34 to electronic circuitry 60 is thus non-alternating. Power source 62 may be a battery of higher or lower output potential, or power source 62 may be a plurality of series-connected batteries of equal or unequal output potential. Accordingly, for most medical applications, the output voltage produced by power source 62 ranges from about 1.00 volt to about 15.00 volts. Alternatively, the output voltage produced by power source 62 ranges from about 2.00 volts to about 9.00 volts, or from about 3.00 volts to about 6.00 volts.
In general, the greater the output voltage produced by a mobile power source, such as power source 62 associated with an active transdermal medicament patch, the larger will be the skin current IS produced by that medicament patch, and the shorter will be the therapy period required to enable that medicament patch to administer any predetermined total dosage DT of medicament. While such a result is salutary relative to minimizing the time during which a patient is required to be encumbered by wearing the medicament patch, the larger the skin current IS produced by a medicament patch, the greater the likelihood that a wearer of the medicament patch will experience uncomfortable sensations, or even pain, during therapy. Accordingly, an unavoidable tradeoff exists between the desirable ends of comfort and of speedy therapy. Lower levels of power source output, such as those endorsed by teachings of the present invention, are calculated to increase patient comfort and to improve the likelihood that a patient will be willing to successfully complete a prescribed course of therapy, once that course of therapy has been undertaken.
Support face 76 of circuit board 68 has a complex periphery 80 that assumes an irregular, asymmetrical barbell-shape. Alternative configurations in circuit board 68 would not depart from the teachings of the present invention. At a first end 82 of circuit board 68 located in proximity to first electrode aperture 40, periphery 80 of support face 76 is similar in shape, but smaller in extent than first electrode aperture 40. At a second end 84 of circuit board 68 located in proximity to second electrode aperture 44, periphery 80 of support face 76 is similar in shape, but smaller in extent than second electrode aperture 48. Interconnecting first end 82 and second end 84 of circuit board 68 is an intermediate portion 86 of circuit board 68 in which periphery 80 of support face 76 is made up of linear segments.
Electronic circuitry 60 is mounted on support face 76 at first end 82 of circuit board 68. Power source 62 and switch 64 are mounted on support face 74 of intermediate portion 86 of circuit board 68. Support face 76 at first end 82 of circuit board 68 is shown as being free of electrical circuit elements, other than printed circuit 78. The positions of such electrical circuit elements of medicament patch 16 may be altered without departing from the teachings of the present invention.
Superimposed by way of reference in phantom on upper face 70 of substrate 18 is periphery 80 of intermediate portion 86 of circuit board 68. In the assembled condition of medicament patch 16 shown in
Circuit board 68 is manufactured from an electrically-nonconductive material. Depending on the absolute size of circuit board 68 and the relative size of circuit board 68 to the size of substrate 18, the material from which circuit board 68 is fabricated can be rigid or minimally flexible. In the assembled condition of medicament patch 16, however, rigidity in circuit board 68 preferably does not prevent medicament patch 16 from being able to conform to curving skin surfaces at locations on the person of patient at which iontophoretic therapy is to be provided. The embodiment of circuit board 68 shown in
Intermediate portion 86 of circuit board 68 includes a single layer of circuit board material. By contrast, as revealed in the enlarged portion of periphery 80 of support face 76 of first end 82 of circuit board 68 included in
The partial disassembly of circuit board 68 depicted in
Either or both of first electrode hinge 100 and second electrode hinge 102 may be structures distinct from the portions of circuit board 68 interconnected thereby. In such an embodiment of a circuit board incorporating teachings of the present invention, one or both of secondary layer 94 and secondary layer 98 would be manufactured as distinct articles and then interconnected during further manufacturing activities by a corresponding one or both of first electrode hinge 100 and second electrode hinge 102. This could be a desirable arrangement, where the material of circuit board 68 is rigid or only partially flexible. Then, secondary layer 94, secondary layer 98, and the central portion of circuit board 68 between first axis A1 and second axis A2 could be manufactured from such a rigid or only partially flexible material and subsequently interconnected by flexible or mechanically bendable hinges, such as first electrode hinge 100 and second electrode hinge 102.
In the embodiment of circuit board 68 illustrated, however, first electrode hinge 100 and second electrode hinge 102 are coplanar extension of the portions of circuit board 68 interconnected thereby. The required capacity for bending in first electrode hinge 100 and second electrode hinge 102 arises from the flexibility of the material of which circuit board 68 is manufactured. Were that material rigid or only partially flexible, the degree of bendability required in first electrode hinge 100 and second electrode hinge 102 can be achieved without departing from teachings of the present invention by thinning or scoring the side of each of first electrode hinge 100 and second electrode hinge 102 that is not visible in
Thus, support face 76 of circuit board 68 extends in a continuous manner across first electrode hinge 100 to secondary layer 94 of first end 82 and across second electrode hinge 102 to secondary layer 98 of second end 84. Active electrode 50 can be appreciated from
Correspondingly, the side of circuit board 68 opposite from support face 76 thereof is a continuous surface that may, if convenient, remain entirely free of electrical circuit elements. A portion of such a continuous attachment face 104 of circuit board 68 is visible on the side of secondary layer 94 of first end 82 of circuit board 68 presented in
In view of the sequence of views of circuit board 68 presented in
Pursuant to such teachings, it is possible in an active transdermal medicament patch to benefit from the use of a circuit board that is in effect electrically two-sided, but that carries only on a single side thereof the electrical circuit components of the medicament patch. This leaves the other side of the circuit board free of electrical circuit components. The freedom to maintain one side of the circuit board free of electrical circuit components is an optional benefit of an electrode flexion means incorporating teachings of the present invention.
As shown by way of example in
As shown by way of example in
In
Active electrode 50 is depicted in
As suggested by arrow S in
In electrical circuits, the flow of electrical current is conventionally indicated as a flow through the circuit from the positive to the negative pole of the power source employed therewith. Therefore, in
While living tissue is a conductor of electric current, living tissue does nonetheless resist the flow of electrical current therethrough. It is the function of power source 62 to apply a sufficient electromotive force differential through skin 112 between medicament matrix 30 and return electrode 42 as to overcome this resistance. The presence of electrical resistance in skin 112 is indicated schematically in
In
To infuse a negative medicament M−, the electrical components of a medicament patch incorporating teachings of the present invention must be altered from those described above relative to
The flow of electrical current in an electrical circuit is conventionally indicated as a flow through the circuit from the positive to the negative pole of the power source employed therewith. In
For convenience and consistency in discussing various embodiments of the invention, the convention will be uniformly observed hereinafter that a negative medicament is to be administered. Nonetheless, this is not an indication that the teachings of the present invention have relevance exclusively to the administration of negative medicaments, as the present invention has applicability with equal efficacy to the administration of positive medicaments.
According to another aspect of the present invention, an active transdermal medicament patch, such as medicament patch 16 in
The inclusion in a an active transdermal medicament patch, such as medicament patch 16 in
The absolute accuracy of this manner of measuring the actual dosage of a medicament delivered by the apparatus and methods of the present invention is necessarily qualified to some degree.
At the commencement of the passage of a skin current through the skin of a patient, the resistance of the skin to the passage of electrical current is far higher than is skin resistance RS once a flow of skin current has been established. Shortly upon establishing a skin current IS, skin resistance RS of most subjects undergoes gradual transient changes before stabilizing. Accordingly, for a few initial minutes of a predetermined therapy period, the amount of skin current that will flow through the skin will vary somewhat from the stable level of current subsequently observed during the balance of the therapy period. Nonetheless, over a therapy period of a few hours, this initial variation in the amount of skin current caused by transients in skin resistance RS has been determined to have a negligible effect on the overall dose of medicament ultimately administered.
Similarly, certain electrical components of the types called for in the exemplary embodiment of an inventive circuit disclosed herein as being suitable to performing the functions of an inventive voltage means are occasionally susceptible, due to heating or otherwise, of mildly transient start-up performances. These also stabilize after a relatively short fraction of any normal therapy period and produce no more than a negligible effect on the overall dose of medicament ultimately administered during that entire therapy period.
As a result, it is contemplated that any such biological or electrical transients as might be observable in commencing the administration of medicament using apparatus and methods of the present invention do not derogate from what is medically accepted to be a substantially constant flow of skin current through the medicament matrix of an associated medicament patch and the skin of a wearer of the medicament patch during the entire course of some predetermined therapy period.
By way of example and not limitation, shown in
The negative pole P− of power source 62 is coupled through switch 64 and active electrode 50 to medicament matrix 30, which engages skin 112 of a patient at a location that is remote from return electrode 42. According to the convention set forth above, medicament matrix 30 is filled with molecules of a negative medicament M−. As a result of the electrical potential correspondingly imposed on skin 112 between return electrode 42 and medicament matrix 30, a flow of molecules of negative medicament M− is induced from medicament matrix 30, through skin 112, and toward return electrode 42 in a direction that is opposite to that of skin current IS.
Voltage regulator 120 includes a programmable microprocessor 122 having contact pins P1-P8. Microprocessor 122 is a semiconductor chip that includes a read-only memory that retains data when power to microprocessor 122 is terminated, but that can be electronically erased and reprogrammed without being removed from the circuit board upon which microprocessor 122 is mounted with other electrical circuit components. Advantageously, microprocessor 122 exhibits low power consumption requirements, which are in harmony with the use of a small, non-rechargeable mobile power source, such as power source 62.
Software installed in microprocessor 122 enables various of contact pins P1-P8 to performing multiple functions. The physical size of microprocessor 122 is accordingly small as compared with a microprocessor carrying only single-use contact pins, and the physical coupling of microprocessor 122 with other electrical circuit elements of electronic circuitry 60 necessitates fewer lead attachment soldering operations than would be the case using single-use contact pins. This reduces manufacturing costs and failures, as well as contributes to a desirably small footprint in microprocessor 122.
In voltage regulator 120 contact pin P6 and contact pin P7 of microprocessor 122 are not used. Positive pole P+ of power source 62 is coupled directly to contact pin P1, which therefore functions as an input contact for microprocessor 122. Contact pin P8 is grounded. The voltage output from voltage regulator 120 appears at contact pin P5 of microprocessor 122. Therefore, contact pin P5 functions as an output contact for microprocessor 12, and contact pin P5 is coupled directly to return electrode 42. To insure that the voltage appearing at contact pin P5 is a substantially invariant voltage output, a sensing resistor 124 is electrically coupled between contact pin P5 and contact pin P2, which therefore functions as a current monitoring contact for microprocessor 122.
According to yet another aspect of the present invention, an active transdermal medicament patch, such as medicament patch 16 in
Microprocessor 122 necessarily includes a driver that operates light-emitting diode 67 in any selected manner preferred by medical personal and suited to the sensory capacities of the patient with whom medicament patch 16 is to be used for therapy. For example, such a driver in microprocessor 122 might be programmed to operate light-emitting diode 67 only on an intermittent basis during any therapy period in order to conserve the capacity of power source 62 for use by other electrical elements of electronic circuitry 60.
The operation of light-emitting diode 67 by microprocessor 122 affords a visual indication that voltage regulator 120 is functioning. In the alternative, indicator circuit 130 could employ in place of light-emitting diode 67 an auditory indicator or a tactile indicator that engages skin 112 of the patient or that can be encountered at will by attending medical personnel in the manner of taking a pulse. Such a tactile indicator could, for example, be a vibrating element or a heating element. Auditory or tactile indicators may consume the output capacity of power source 62 more rapidly than a light-emitting diode, and particularly more rapidly than an intermittently-operated light-emitting diode.
The migration of medicament through skin 112 is reflected as a flow of skin current IS from contact pin P5 of microprocessor 122 to return electrode 42. The flow of skin current IS is detected at contact pin P2 of microprocessor 122, whereby microprocessor 122 is able, by integrating the flow of skin current IS over time, to monitor the running cumulative total of the amount of medicament administered. When the output of that integration function reaches some predetermined total dosage DT of medicament, microprocessor 122 is programmed to function as a circuit breaker and disable power source 62, thereby terminating skin current IS and the migration of medicament through skin 112.
Voltage regulator 120 is so configured as to cause the voltage applied through skin 112 between return electrode 42 and medicament matrix 30 to be substantially invariant for the full duration of a predetermined therapy period TM that ranges in duration from about 1 hour to about 6 hours, or more narrowly from about 2 hours to about 4 hours. Any such substantially invariant voltage applied through skin 112 between return electrode 42 and medicament matrix 30 will cause iontophoretic medicament migration to occur through skin 112 from medicament matrix 30 to return electrode 42 at a substantially constant rate.
When medicament migration occurs at a substantially constant rate, skin current IS is substantially constant, and the integration function to be performed by microprocessor 122 in monitoring the administration of total dosage DT of medicament reduces to one of using a clock in microprocessor 122 to time the duration of the period during which the substantially constant skin current IS has been produced. When the output of that timer reaches the ratio of total dosage DT Of medicament divided by the substantially constant skin current IS, microprocessor 122 is programmed to function as a circuit breaker and disable power source 62, thereby terminating skin current IS and the migration of additional medicament through skin 112.
For a skin resistance RS=10 kilo-ohms, the following electrical circuit component values and identities in voltage regulator 120 and in indicator circuit 130 produced a substantially invariant voltage V=2.75 volts and a corresponding substantially constant skin current IS=0.275 milliamperes during the course of a therapy period TM=280 minutes:
At time T=0 minutes, power source 62 is activated by a user through the operation of switch 64. Immediately, but only momentarily, voltage V=3.18 volts, greater even than the nominal 3.00 volt rating of power source 62 when configured as a battery B of the type specified in the above list of electrical circuit component in
The initial behavior of voltage V depicted in
The initial transient behavior of voltage V is closely reflected in skin current IS.
At time T=0 minutes, skin current IS=0.318 milliamperes. From time T=0 minutes, skin current IS declines steeply in a seemingly linear manner. By time T=5 minutes, skin current IS=0.300 milliamperes. Then, skin current IS commences a relatively sharp decline in slope, decaying asymptotically toward the horizontal. At about time T=20 minutes, skin current IS arrives at a substantially constant skin current IS=0.275±0.02 milliamperes, which is then sustained throughout the balance of therapy subsession S1 and all of therapy subsessions S2, S3, and S4 remaining in therapy period TM. In the context of the totality of therapy period TM, that initial transient behavior of skin current IS has a negligible effect on the total dosage DT of medicament administered.
The area below the performance curve of skin current IS in
During the administration of a medication using an active medicament patch, such as medicament patch 16, it may become necessary or it may occur accidentally that therapy is interrupted before the end of a full predetermined therapy period TM during which a corresponding predetermined total dosage DT of medicament was intended to be administered. This might occur, for example, due to the removal of medicament patch 16 from the skin of the patient. Once the interruption of therapy is detected, and the cause of the interruption remedied, therapy can and should be resumed toward the completion of the administration of total dosage DT of medicament. Under such circumstances, uncertainty will exist relative to how much medicament was actually administered before the interruption. Correspondingly uncertain will be the amount of additional medicament that needs to be administered once therapy is resumed in order to cumulatively administer total dosage DT of medicament.
Accordingly, in one aspect of the present invention, an active medicament patch, such as medicament patch 16, is provided with dosage control means carried non-removably on the substrate of the medicament patch for limiting to a predetermined medicament quantity the total medicament migrated iontophoretically from the medicament matrix into the skin of the patient during, what under the circumstances becomes, a plurality of temporally non-contiguous therapy subsessions. The portion of therapy period TM preceding any interruption thereof and the balance of therapy period TM that must of necessity be undertaken following such an interruption are examples of a pair of such temporally non-contiguous therapy subsessions.
Yet, it is contemplated that a dosage control means incorporating teachings of the present invention be able to accommodate for any number of interruptions in therapy during any single intended therapy period TM. Such a situation might arise, for example, were it desirable under circumstances like those depicted in the performance curves of
Accordingly, as shown by way of example in
In combination with such a medicament migration detector, a dosage control means incorporating teachings of the present invention includes a dosage integrator that operates on the output of the medicament migration detector to produce as an output a running cumulative total of the amount of medicament delivered by iontophoretic migration. Such a dosage control means may, for example, be effected in the software in microprocessor 122, or in the alternative may be embodied in software or hardware located elsewhere than within microprocessor 122. A circuit breaker disables power source 62, when the output of the dosage integrator equals the predetermined total dosage DT associated with the full predetermined therapy period TM. Such a circuit breaker may, for example, be effected in the software in microprocessor 122, or in the alternative may be embodied in software or hardware located elsewhere than within microprocessor 122. In this manner, following any interruption in the administration of medication, the dosage control means resumes monitoring the amount of medication administered where that administration was at the time of the interruption.
Power source 62 may be so electrically coupled between return electrode 42 and medicament matrix 30 as to cause iontophoretic medicament migration from medicament matrix 30 into the skin of the patient to occur at a substantially constant rate. Such would be the case where the capability of a voltage regulator, such as voltage regulator 120, is included among associated electrical circuit components. Under such circumstances, a dosage control means incorporating teachings of the present invention includes, a medicament migration detector as described above and a timer active only when the output of the medicament migration detector exceeds a predetermined minimum rate of medicament migration associated with a closed circuit. Such a timer may, for example, be effected in the software in microprocessor 122, or in the alternative may be embodied in software or hardware located elsewhere than within microprocessor 122. A circuit breaker disables power source 62, when the duration of the activity of the timer equals the ratio of the predetermined total dose DT of medicament divided by the substantially constant rate of iontophoretic medicament migration being produced
It has been found to be helpful to apprise a user of an active medicament patch, such as medicament patch 16, as to the degree to which the administration of any total dosage DT of medicament has been completed. Accordingly, in another aspect of the present invention, an active medicament patch, such as medicament patch 16, includes therapy status advisement means that is non-removably carried on the substrate of that medicament patch, and that is driven by a power source, such as power source 62. The therapy status advisement means performs the function of communicating to a user the extent of completion of predetermined therapy period TM during which a medicament is to be iontophoretically delivered from medicament matrix 30 into the skin of a patient.
Accordingly, as shown by way of example in
Also included in a therapy status advisement means configured according to teachings of the present invention is a timer that is active only during therapy period TM and a driver for light-emitting diode 67 that causes light-emitting diode 67 to operate only when the timer is active. Typically, light-emitting diode 67 is operated intermittently to minimize power consumption. Such a timer and such a driver may, for example, be effected in the software in microprocessor 122, or in the alternative may be embodied in software or hardware located elsewhere than within microprocessor 122.
Therapy period TM may include a sequence of non-overlapping predetermined therapy subsessions, such as therapy subsessions S1, S2, S3, and S4 of therapy period TM depicted in the performance curves of
The overall operation of therapy status advisement means is thus governed by the driver of therapy status advisement means, which activates light-emitting diode 67, or any auditory or tactile indicator used in place thereof, in a discrete variety of operative modes P, each of which is reflective of a foreseeable medicament administration status condition X. Each status condition X thus includes temporal and electrical information, information relative to the time T within therapy period TM and information relative to the existence or nonexistence of skin current IS in the skin of the patient. Temporally, status condition X can denote that therapy is in a specific one of a plurality of therapy subsessions, such as therapy subsessions S1, S2, S3, and S4, or that therapy is at the end of a chosen one or of all of those therapy subsessions. Electrically, status condition X denotes whether skin current IS is flowing, or whether skin current IS is zero by being less than some predetermined minimum amount chosen to evidence an open circuit. The later would be the case, for example, were the resistance between medicament matrix 30 and return electrode 42 to be detectable as exceeding an arbitrary upper threshold, such as 500 kilo-ohms, which is beyond the range of the likely skin resistance RS in any patient.
In this light, the operative mode P of light-emitting diode 67, or any auditory or tactile indicator used in place thereof, is a function of status condition X. Presented below is a table listing typical status conditions X and an exemplary operative mode P(X) corresponding to each for a therapy period TM that is comprised of a non-overlapping sequence of therapy subsessions S1, S2, S3, and S4. An operative alarm mode is produced in light-emitting diode 67 whenever skin current IS=0. Distinct first and second operative transition modes are produced in light-emitting diode 67 half way through therapy period TM at the end of therapy subsession S2, and at the completion of therapy period TM when therapy subsession S4 ends.
Typical possible durations for the events appearing among the operative modes P(X) in the table above are as follows:
The depicted methodology commences at initiation oval 140 by turning voltage V on as required in procedure rectangle 142. This occurs when power source 62 is activated by a user through the operation of switch 64. Thereupon, if medicament patch 16 is in place on skin 112 of a patient, voltage regulator 120 should begin to apply voltage V across skin 112 between medicament matrix 30 and return electrode 42, and skin current IS should begin to flow.
These actions may not always succeed in creating a closed circuit in which a flow of skin current IS possible. Accordingly, as required by decision diamond 144, microprocessor 122 inquires toward that end. If as a result, microprocessor 122 determines that no skin current IS is flowing, then as stipulated in procedure rectangle 146, in order to alert a user that medicament patch 16 is not yet operating as intended, the driver of light-emitting diode 67 in microprocessor 122 operates light-emitting diode 67 in operative mode P(IS=0), the alarm mode. As specified in procedure rectangle 148, microprocessor 122 then idles for a predetermined period Wait1 during which to permit a user to detect and remedy the situation. After idling for predetermined period Wait1, microprocessor 122 undertakes the inquiry in decision diamond 144 to determine whether skin current IS has commenced. If not, microprocessor 122 continues repeatedly to operate in a functional loop 150 that includes decision diamond 144, procedure rectangle 146, and procedure rectangle 148.
On any circuit of functional loop 150, if microprocessor 122 detects that skin current IS has commenced through skin 112, the depicted methodology moves ahead to procedure rectangle 152. Consequently, a timer in microprocessor 122 of the duration of therapy is prepared for activity by setting time T=0, and a counter N identifying the therapy subsession SN in which therapy is occurring is set to N=1. This signifies that therapy subsession S1 will be the initial therapy subsession. As directed in procedure rectangle 154, the timer in microprocessor 122 is turned on, and time T advances continuously from time T=0 until the timer is turned off.
In decision diamond 156, microprocessor 122 compares the ongoing time T to a schedule of times for the intended therapy subsessions to verify that therapy is occurring in therapy subsession SN with N=1. If as a result, it is determined that that therapy is occurring in therapy subsession S1, then as specified in procedure rectangle 158, the driver of light-emitting diode 67 in microprocessor 122 operates light-emitting diode 67 in operative mode P(S1) to advise the user that medicament patch 16 is operational and that therapy is progressing in therapy subsession S1. According to the above table of operative mode P(X), during therapy subsession S1 light-emitting diode 67 is made to flash once for 0.25 seconds at regular intervals of 0.50 seconds.
In procedure rectangle 160, microprocessor 122 idles for a predetermined period Wait2 and then undertakes the inquiry in decision diamond 162 to determine whether a closed circuit continues to exist in which a flow of skin current IS is occurring. If it is determined that skin current IS continues to be flowing, activity returns to decision diamond 156 and continues repeatedly through a functional loop 164 that includes decision diamond 156, procedure rectangle 158, procedure rectangle 160, and decision diamond 162.
On any transit of functional loop 164, if it is determined in decision diamond 162 that no skin current IS is flowing, the timer in microprocessor 122 is turned off as required in procedure rectangle 166. Time T ceases to advance, until the timer is next turned on. As stipulated in procedure rectangle 168, in order to alert the user that medicament patch 16 is no longer operating as intended, the driver of light-emitting diode 67 in microprocessor 122 operates light-emitting diode 67 in operative mode P(IS=0), the alarm mode. Then, as required in procedure rectangle 170, microprocessor 122 idles for a predetermined period Wait3 to allow a user to detect and remedy the situation. After idling for predetermined period Wait3, microprocessor 122 undertakes the inquiry in decision diamond 172 to determine whether skin current IS has resumed. If not, microprocessor 122 continues repeatedly to operate in a functional loop 174 that includes decision diamond 172, procedure rectangle 168, and procedure rectangle 170.
On any transit of functional loop 174, if microprocessor 122 detects at decision diamond 172 that skin current IS has recommenced through skin 112, the depicted methodology leaves functional loop 174 and moves ahead to procedure rectangle 154. The timer in microprocessor 122 is again turned on. As a consequence thereof, time T advances continuously once again, but from the time T at which the timer was turned off in procedure rectangle 166. Activity returns to functional loop 164, until such time as in undertaking the inquiry in decision diamond 156, microprocessor 122 compares time T to the schedule of times for the intended therapy subsessions and discovers that therapy is no longer in therapy subsession SN with N=1.
Thereupon, the illustrated methodology advances to procedure rectangle 176, and microprocessor 122 increases counter N by one; so that N=2. As a consequence, therapy is understood to be starting the next successive therapy subsession SN+1, or in other words to be starting therapy subsession S2, which follows therapy subsession S1. In decision diamond 178, microprocessor 122 ascertains whether therapy period TM has yet fully transpired. If not, the administration of total dosage DT of medicament has not yet been completed, and the illustrated methodology returns to functional loop 164 by way of procedure rectangle 158, but with N=2. Procedure rectangle 176 and decision diamond 178 thus make up a functional branch 180 by which microprocessor 122 resisters that therapy has advanced into a successive therapy subsession.
On each successive circuit of functional loop 164, the driver of light-emitting diode 67 in microprocessor 122 operates light-emitting diode 67 in operative mode P(S2) to advise the user that medicament patch 16 is operational and that therapy is progressing in therapy subsession S2. According to the above table of operative mode P(X), during therapy subsession S2 light-emitting diode 67 is made to flash twice for 0.25 seconds at regular intervals of 0.50 seconds. The illustrated methodology continues in functional loop 164, until the inquiry undertaken by microprocessor 122 in decision diamond 156 reveals that therapy subsession S2 has been completed.
Then, by way of a functional branch 180 counter N is again increased by one, and activity resumes, reentering functional loop 164 through procedure rectangle 158. On each occasion that the inquiry in decision diamond 156 diverts activity out of functional loop 164 and through functional branch 180, a successive therapy subsession is commenced.
Eventually, in conducting the inquiry in decision diamond 178 it will be revealed to microprocessor 122 that therapy period TM has fully transpired, or in other words that time T=TM. As specified in procedure rectangle 182, the driver of light-emitting diode 67 in microprocessor 122 then operates light-emitting diode 67 in operative mode P(T=TM) in order to alert the user that operation of medicament patch 16 is about to cease. Finally, as called for in procedure rectangle 184, the circuit breaker in microprocessor 122 turns voltage V off by disabling power source 62, and the illustrated methodology concludes in termination oval 188.
The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, to be defined by the appended claims, rather than by the foregoing description. All variations from the literal recitations of the claims that are, nonetheless, within the range of equivalency correctly attributable to the literal recitations are, however, to be considered to be within the scope of those claims.
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| Number | Date | Country | |
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| 20090186072 A1 | Jul 2009 | US |
