Patent Application
20090259176
The present invention relates to transdermal patch systems. More particularly, the present invention relates to patch or pump systems or apparatus which may be positioned upon a region of a patient's skin surface and their methods of use to efficiently deliver any number of drug therapies in a controlled manner,
Transdermal delivery of drugs generally allows one or more pharmaceutical agents to be introduced into a patient's system at a controlled rate through the skin. Drug delivery may be effected via a patch which contains a drug which is applied to the patient's skin. The drug may penetrate the skin surface by various passive or active mechanisms. Examples of passive mechanisms may include simple diffusion or absorption through the skin, osmosis, etc., and some examples of active mechanisms may include introduction through the skin via mechanical insertion through needles, abrasion, etc., or through electrical methods such as iontophoresis where a suspension of the drug molecules is subjected to an electric field for passage into or through the adjacent skin surface and into the patient's blood stream. Other methods, such as the use of chemical penetration enhancers, heat, or ultrasound waves, are also typically used to increase drug delivery rates through the skin barrier.
Iontophoresis-based patches use an applied electrical current or voltage to drive pharmaceutical formulations through the skin. The electrical current can be programmed to adjust and control the rate of drug delivery into the patient skin. However, with such patches it can be difficult to control the infusion rate and may or may not be effective depending upon the condition or the patient's skin surface. Moreover, typical iontophoresis-based drug delivery is limited to certain classes of ionic molecules which exclude a wide variety of medications, particularly drugs having a relatively large molecule size.
Other patches or drug delivery pumps include infusion pumps which deliver drugs via a needle or catheter inserted through the skin for conditions such as insulin therapy for diabetes treatment. Such patches or pumps deliver drug molecules via a fluid vehicle where the fluid is typically retained within a reservoir which is coupled to a delivery mechanism such as a membrane, needle, or catheter depending upon the delivery mode. However, use of a typical fluid reservoir may be problematic with respect to maintaining the reservoir under pressure to provide adequate flow through the delivery mechanism.
Moreover, fluid reservoirs may be susceptible to the formation of bubbles within the fluid as well as the angle and orientation of the reservoir relative to the patient's body. A depressurized or non-pressurized fluid reservoir may provide only intermittent or inadequate fluid delivery depending upon the orientation of the delivery mechanism and relative fluid levels. Additionally, typical fluid reservoirs may also provide for a number of failure points through which the fluid may leak thus resulting in lowered drug delivery efficiency.
Accordingly, there exists a need for a transdermal drug delivery apparatus or system which provides for consistent drug delivery without the typical problems associated with such systems and which provides additional controllability to tailor a drug therapy regimen to affect any number of treatments.
A patch or pump apparatus or system may be placed into contact upon a region of skin to transport drugs or agents transdermally via a number of different mechanisms such as maintaining simple contact of the drugs or agents upon the skin surface for absorption (either with or without chemical penetration enhancers), iontophoresis, needles, in-dwelling catheters, etc. The patch or pump may be removably adhered or placed directly upon the user's skin surface via any number of methods such as being adhered directly to the skin via a temporary adhesive layer or optionally through direct pressure utilizing a strap or band.
Regardless of the mechanism by which the patch or pump is maintained relative to the skin surface, the system may include a number of features which facilitate drug delivery to the patient. For example, the patch or pump assembly may enclose or accommodate a fluid reservoir within a housing to contain the drug or agent suspended in a fluid vehicle. The reservoir may be fluidly coupled via a microchannel lumen through which fluids or medications may be transported to a transdermal drug delivery mechanism in contact with or in proximity to the underlying skin surface. A pump may be used to drive or urge the drugs from the reservoir and through the skin via one of the drug delivery mechanisms, such as through an array of microneedles. The pump may also be used to deliver the drugs from the reservoir for placement directly upon the skin surface where it may be left in place or maintained in contact against the skin surface for absorption, e.g., by maintaining contact against the skin with a microporous membrane. In placing the drugs against the skin surface (rather than introducing or urging the drugs through the layer of skin), a number of chemical enhancing agents may be utilized to facilitate the absorption of the drugs into the skin surface. For instance, agents such as propylene glycol, ethyl alcohol, dimethyl sulfoxide, etc., may be placed upon the skin surface prior to, during, or after placement of the drugs upon the skin or such agents may be combined with the drugs in the fluid vehicle such that they are delivered along with the drugs directly upon the skin surface.
To control the pumping of the drugs as well as different treatment regiments, electronic control circuitry may also be positioned upon the housing and in electrical communication with the pump. A battery (that may be rechargeable or replaceable) may also be positioned along the housing for providing power to the pump, control circuitry, and any other features as necessary.
The electronic control circuitry may provide a variety of functionality and determines when the pump should be active. By controlling when the pump is active or inactive, the electronic circuitry may be used to control when fluid from the reservoir is pumped to the skin. The control circuitry may also include diagnostic algorithms and indicators, such as monitoring battery power, pump operation, circuit integrity, etc. Yet another element that may be included in control circuitry is the inclusion of an on-chip clock that tracks the time and date to facilitate regulation of the fluid delivery schedule controlled by the microprocessor, particularly for chronotherapeutic drug formulations where delivery of medication is on a timed schedule corresponding to the date and/or time of day. Additionally or optionally, a flow rate monitor may also be included in the control circuitry to monitor the amount of fluid which has been delivered upon or through the skin.
Aside from the control circuitry, the microchannels fluidly coupling the various features, such as the reservoir, pump, and microporous membrane may be formed directly within or along the housing and sized to have cross-sectional dimensions ranging anywhere from 1 micron to 5000 microns and lengths varying anywhere from 1 millimeter to 1 meter or longer. Because of their size, the microchannels may facilitate the passage of fluids, such as through capillary action, such that fluid delivery through the channels is consistent regardless of the orientation or angle of the assembly. Moreover, the microchannels may also help to inhibit or prevent the formation of bubbles within the channels such that drug delivery may be metered consistently to the patient.
In yet another variation of the programmable patch or pump assembly, an elongate microchannel may be utilized as the fluid reservoir rather than a single box-like chamber. The microchannel reservoir may be configured into an elongate channel having a cross-sectional dimension ranging anywhere from 1 micron to 1000 microns and a length varying anywhere from 1 millimeter to 1 meter or longer which is looped into an alternating (or “back-and-forth”) pattern which extends over the width and/or length of patch or pump housing. Because of its micrometer scale, the microchannel reservoir reduces the degrees of freedom for liquid movement and constrains the liquid contained within. As a result, altering the orientation of microchannel reservoir in space (three dimensions), such as by rotation or vibration is much less likely to result in the formation of bubbles, gaps, or voids within the contained liquid that may interfere with pumping.
Aside from a single elongate microchannel reservoir which winds in an alternating pattern, the reservoir may be configured into various other patterns as well such as a spiral or any other configuration which allows for fluid storage in or along the housing. For example, the microchannel reservoir may be formed to have one or more separate channels which are aligned parallel to one another. Each of these separate parallel channels may converge into a single microchannel which is fluidly coupled to the pump or other mechanism. The number of channels and the lengths of the individual channels may be uniform or individually varied. Moreover, one or more of the microchannels may contain different drug formulations or varied dosages depending upon the resulting desired dosage and drug combination to be infused into the patient. Yet another variation of a microchannel reservoir may include, e.g., a first microchannel reservoir and a second microchannel reservoir which is separate and distinct from the first microchannel reservoir. Additionally, other variations may include one or more microchannel reservoirs which are aligned along multiple geometric planes within the housing. For instance, a first reservoir may be situated in a first plane along the housing while a second reservoir may be situated in a second plane below or above the first reservoir. In this manner, multiple reservoirs may be “stacked” atop or below one another in several adjacent planes which may be separate from one another or which may be fluidly interconnected between two or more reservoirs between their respective planes. The microchannel reservoirs may each contain the same or different drug formulations or dosages and may each be coupled to one or more valves which may be electronically controlled to meter or control the volume of one or both reservoirs to be pumped.
Use of a microchannel as the drug formulation reservoir may also allow for different types of pump configurations. Rather than using a pump to extract liquid from the microchannel reservoir and pumping it out to ultimately reach a user's skin, an air or gas pump can instead be used to push the liquid down the length of the microchannel reservoir to be ultimately deposited on the user's skin. In a conventional transdermal patch with a single reservoir, use of an air pump is difficult because changing an orientation of the patch or pump may result in pushing air rather than the drug formulation towards the user's skin. This may be avoided because the microchannel reservoir inhibits or prevents bubbles of air from sliding past fluid already contained within the microchannel. Rather, the contained fluid is pushed distally through the microchannel as more air is pumped behind it.
In yet another variation, the microchannel reservoir may be completely removable from the patch or pump. The microchannel reservoir can reside in a removable package or cartridge which may be inserted securely within an interface or receiving channel defined within the housing. Once the reservoir has been depleted, it may be refilled or the cartridge may be removed entirely from the housing and replaced with another cartridge without having to remove the housing from the patient's skin.
In this or any of the variations described herein, the programmable electronic circuitry of the patch or pump assembly may be equipped with a transmitter and/or receiver that allows it to communicate, wirelessly or otherwise, with an external controller such as a computer or hand-held device. The external controller can be used by a physician or the patient to program parameters such as drug delivery time-profiles for a particular patient, customizing the delivery rate profile to a particular patient's needs for a particular medication, etc. Another aspect of the transdermal patch or pump assembly may provide the capability for patient-determined “on-demand” controlled delivery of medication. User-initiated responses may be used as signals to the programmable electronic circuitry to indicate the appropriate dosage profile to be used from that point forward or until a new user-initiated signal is received. These signals may also be used, for example, to initiate an “on-demand” bolus for drug delivery when the user of the patch or pump so desires The amount and rate of drug delivery when the “on-demand” button is pushed may be pre-determined by the circuitry. When a patient desires a small dose of the medication to be administered (such as may the case for an analgesic to relieve pain or a stimulant to help maintain awareness and remain alert), the patient may actuate a control such as pushing a button on the transdermal patch or pump to release a preset bolus of the medication. The control may be part of the electronic control itself.
In delivering drugs or agents into a patient body over any extended period of time, a patch or pump apparatus or system may be placed into contact upon a region of the user's skin surface and used to transport the drugs or agents transdermally via a number of mechanisms such as maintaining simple contact of the drugs or agents upon the skin surface for absorption (either with or without chemically enhanced absorption), iontophoresis where an applied electrical current or voltage drives the drugs or agents through the skin, membranes, needles, in-dwelling catheters, etc. The patch or pump may be removably adhered or placed via any number of methods directly upon the user's skin surface, e.g., along the arms, legs, hips, abdomen, etc. For example, a portion of the patch or pump or the entire apparatus may be adhered directly to the skin via a temporary adhesive layer or optionally through direct pressure utilizing a strap or band. Alternatively, the patch or pump may be held or adhered to the patient's clothing in proximity to the user's skin in which case a catheter or microneedle array may be used to deliver the drug or agent to the patient through the skin.
Regardless of the mechanism by which the patch or pump is maintained relative to the skin surface, the system may include a number of features which facilitate drug delivery to the patient. An example is shown in the partial cross-sectional side and top views of
For illustrative purposes, housing 105 is shown in a rectangular configuration. In this example, housing 105 may be, e.g., 7 cm in length, 2.5 cm in width, and 1 cm in height. These dimensional values are given merely as examples and housing 105 is not intended to be constrained by dimensional limitations. Accordingly, housing 105 may be dimensioned according to any practicable variation and is intended to be included within this disclosure. Likewise, housing 105 may be configured into various shapes aside from that shown. For instance, housing 105 may alternatively be configured into other shapes, e.g., hemispherical, oblong, etc., so long as housing 105 may be positioned comfortably upon or in proximity to the user's skin surface. In either case, patch assembly 100 may enclose or accommodate fluid reservoir 101 within housing 105 to contain the drug or agent suspended in a fluid vehicle. Reservoir 101 may be fluidly coupled via a lumen such as microchannel 106 to reservoir input port 109 through which fluids or medications may be introduced to fill or refill reservoir 101. Pump 102, such as a peristaltic-type pump, may be fluidly coupled also via a lumen such as microchannel 106 to fluid reservoir 101 to transport or urge the drug or agent through microchannel 106 to a transdermal drug delivery mechanism in contact with or proximity to the underlying skin surface.
Pump 102 is illustrated in this example as fluidly coupled to a microporous membrane 107 which may be placed into contact directly against a skin surface to maintain contact between the drugs pumped from reservoir 101 and the skin. The drugs may simply be left in place or maintained in contact for absorption, e.g., by maintaining contact against the skin with microporous membrane 107. In placing the drugs against the skin surface (rather than introducing or urging the drugs through the layer of skin), a number of chemical enhancing agents may be utilized to facilitate the absorption of the drugs into the skin surface. For instance, agents such as propylene glycol, ethyl alcohol, dimethyl sulfoxide, etc., may be placed upon the skin surface prior to, during, or after placement of the drugs upon the skin or such agents may be combined with the drugs in the fluid vehicle such that they are delivered along with the drugs directly upon the skin surface. Microporous membranes 107 may include membranes having pores in the micrometer range and having a height which extends beyond housing 105 for contacting the underlying skin surface while being attached to housing 105.
In yet other examples, microporous membrane 107 may be omitted entirely from housing 105 and the drugs pumped from reservoir 101 may be deposited directly upon the skin surface. In this case, the drugs may be simply left upon the skin to be absorbed eventually or with any of the chemical enhancing agents mentioned above to facilitate the absorption into the skin.
As mentioned above, assembly 100 may be maintained against the user's skin surface via a strap or band or via an adhesive layer 108 placed directly along housing 105 for contact against the skin surface. Adhesive layer 108 may be comprised of a layer of double-sided adhesive which is attached to the undersurface of housing 105. To control the pumping of the drugs as well as different treatment regiments, an electronic control circuitry 103 may also be positioned upon housing 105 and in electrical communication with pump 102. A battery 104 (rechargeable or replaceable) may also be positioned along housing 105 for providing power to pump 102, control circuitry 103, and any other features as necessary.
Electronic control circuitry 103 may be directly accessible to the user or certain functions may be accessible to the user. Alternatively, circuitry 103 may be completely disabled to the user such that only a physician or other appropriate medical personnel may access the functions or programming features of circuitry 103. In either case, control circuitry 103 may include a processor and/or memory components to control various features of assembly 100. The electronic control circuitry 103 may comprise a printed circuit board with a programmable microcontroller, voltage converter, diagnostic systems, indicators (e.g., light emitting diodes), control switches, actuators, etc. The design and fabrication used to create the electronic control circuitry 103 is standard to those skilled in the art of circuit design.
The electronic control circuitry 103 provides a variety of functionality and determines when the pump 102 should be active. By controlling when pump 102 is active or inactive, electronic circuitry 103 may be used to control when fluid from reservoir 101 is pumped to the skin. Varying the pumping rate adjusts the effective delivery rate of a drug formulation. For example, control circuitry 103 may be programmed to deliver a particular dosage where drug delivery is to be delivered over a specified period of time which may be either preset or determined by the prescribing physician or other appropriate medical personnel. The dosage function may be selected from several preset dosage profiles programmed in a microcontroller within control circuitry 103 or the dosage profile may be customized and entered into control circuitry 103 via a user interface. The control circuitry 103 may also contain input pins to program the microprocessor with customized or tailored drug delivery profiles.
The control circuitry 103 may also include diagnostic algorithms and indicators, such as monitoring battery power, pump operation, circuit integrity, monitoring fluid flow, etc. Yet another element that may be included in control circuitry 103 is the inclusion of an on-chip clock that tracks the time and date to facilitate regulation of the fluid delivery schedule controlled by the microprocessor, particularly for chronotherapeutic drug formulations where delivery of medication is on a timed schedule corresponding to the date and/or time of day. An on-chip clock may also be utilized to regulate drug delivery rates based upon an input of a user's circadian rhythms. If multiple patches or pumps are worn sequentially, e.g., a new patch each day, the clock may be used to provide a changing drug delivery profile that depends on the particular date or the particular number of days that has passed since the first patch or pump was used or according to a customized dosage delivery profile.
A related implementation of control circuitry 103 may include a user-activated interface control such as a button which may be programmed to start or activate a treatment regiment for a specified period of time, e.g., a sleep button. These user-initiated responses may be used as signals to the microprocessor to indicate the appropriate dosage profile to be used from that point forward or until a new user-initiated signal is received. These signals may also be used, for example, to indicate the start or ending of a part of the user's circadian rhythm cycle. Alternatively, such a control may be used to initiate an “on-demand” bolus for drug delivery when the user of the patch or pump so desires. The amount and rate of drug delivery when the “on-demand” button is pushed may be pre-determined by the microcontroller. The fluid amount delivered may be programmed to provide a gradually reduced amount with subsequent “on-demand” requests as well have a minimum time between “on-demand” responses. These examples are intended to be illustrative of some of the possible programmable treatment regimens and are not intended to be limiting.
In addition to controlling the various features described above, assembly 100 may further incorporate an optional radio-frequency identification (RFID) antenna and chip assembly 110 either integrated with control circuitry 103 or separately within housing 105 to allow for further wireless control and monitoring of various parameters. For example, information such as the date, time, and dosage of administered medications, drug formulations, or other prescription-related information, etc., may be stored on RFID assembly 110 for wireless transmission to and/or access by the user or physician. With RFID assembly 110 in electrical communication with control circuitry 103, the user and/or physician may also actively and wirelessly alter parameters such as the patient's dosage depending upon the patient conditions. Examples of such RFID chip assemblies 110 may be commercially available such as the ISIS PATCH as manufactured by Isis Biopolymer, Inc. (Warwick, R.I.).
Aside from control circuitry 103, the microchannels 106 fluidly coupling the various features, such as reservoir 101, pump 102, and microporous membrane 107 may be formed directly within or along housing 105 and sized to have cross-sectional dimensions ranging anywhere from 1 micron to 1000 microns and lengths varying anywhere from 1 millimeter to 1 meter or longer. Microchannels 106 may be configured to have a cross-sectional height and width or it may be configured into circular shapes as well. In other alternatives, separate tubes or lumens having such dimensions may be utilized to transport the fluids accordingly. The use of microchannels 106 to transport fluids within assembly 100 may provide for efficient fluid transport. Because of their size, microchannels 106 may facilitate the passage of fluids, such as through capillary action, such that fluid delivery through the channels is consistent regardless of the orientation or angle of assembly 100. Moreover, microchannels 106 may also help to inhibit or prevent the formation of bubbles within the channels such that drug delivery may be metered consistently to the patient.
In assembling the patch or pump, housing 105 may be fabricated into a continuous and integral unit by mechanically forming the housing, e.g., by drilling, machining, injection molding, etc., or by other methods such as stereolithography. In other methods, the housing may be fabricated from two or more separate sections which may be attached or coupled to one another to form a single unit. For example,
In either case, first housing assembly 200 may have materials removed or cut from the starting block or it may be formed to create appropriately sized channels such as channels 201, 202, 204, 207 to form locations for the reservoir 101, pump 102, battery 104, and reservoir input port 109, respectively. To form microchannels 206 extending from their respective channels 201, 202 of the resulting housing 205, stereolithography may be utilized to maintain smooth microchannel surfaces. Other methods for forming the housing assemblies and/or channels may also include a number of other manufacturing processes, such as injection molding, stamping, micromachining, etc. Similarly, second housing assembly 210 may be processed to create microchannels 211 as well as channel 212 for microporous membrane 107. The resulting housing 213 may be joined, coupled, or otherwise attached (e.g., thermally annealed, mechanically coupled, adhered via adhesives, etc.) to housing 205 to create a single patch assembly. The microchannels 206, 211 may also be optionally coated or chemically altered prior to being sealed to make the channel walls more hydrophilic or hydrophobic as desired to make them react in a particular manner with a particular fluid formulation. Alternatively, various other coatings may be applied to enhance other characteristics of microchannels 206, 211.
With the two sections of housing, 205, 213 attached to one another, the remaining components may be included. For instance, pump 102 may be aligned within channel 202 so that its inlet port connects to the microchannel 206 leading from the reservoir 101 and its outlet port connects to the microchannel 206 leading to the microporous membrane 107 within channel 212. Depending upon the particular type of pump utilized, gaskets such as rubber O-rings may be used to seal openings leading to or from pump 102. Alternatively, if the pump's inlet and outlet ports extend perpendicularly relative to pump 102, the sidewalls of the ends of the microchannels 206 and the ports of pump 102 may form a natural seal.
During use of the patch or pump assembly when fluid is pumped, fluid reservoir 101 may be sealed such that it is fluid tight yet gas-permeable to allow for the introduction of a gas such as air to prevent or inhibit the formation of a vacuum within reservoir 101. One variation may include securely placing or sealing a lid assembly 300 upon fluid reservoir 101 where lid 301, which may be made from any of the suitable materials described above, may having one or more openings 303 drilled or otherwise formed through lid 301. A gas-permeable membrane 302, e.g., gas-permeable TEFLON® (E. I. DuPont De Nemours, Wilmington, Del.) may be placed upon or secured to lid 301 such that the one or more openings 303 are covered by membrane 302. Thus, assembly 300 may be secured over fluid reservoir 101 to maintain a fluid-tight seal yet allow for gas to be infused into reservoir 101 through openings 303 via membrane 302 to prevent the formation of a vacuum within the reservoir 101.
Alternatively, fluid reservoir 101 may be formed by a reconfigurable membrane which collapses upon itself as fluid is drained from the reservoir 101. In yet another variation, one of the walls of fluid reservoir 101 may be movable such that as the fluid level is decreased within reservoir 101, the wall may be urged, e.g., via a spring, to reduce the volume of reservoir 101.
In other variations of the patch or pump assembly, rather than using a microporous membrane 107, an array of microneedles may be used to transport the drug or agent transdermally through the underlying skin surface.
An example of a patch or pump assembly is illustrated having fluid reservoir 404 fluidly coupled to pump 405 and to microneedle assembly 400 via microchannels 408 through housing 409. Reservoir port 410 and battery 406 as well as control electronics 407 are also illustrated. Microchannels 408 may deliver the fluid suspension through the microneedles 402 and through the patient skin surface. The patch or pump assembly may be simply secured to the patient body via a support band or strap, as described above, and/or via an adhesive layer 411 placed along the portion of housing 409 in contact with the skin.
Adhesive sheet 403 may adhere directly to the portion of the skin through which microneedles 402 are pierced such that the region of skin immediately beneath and/or adjacent to microneedles 402 are stabilized relative to microneedles 402 to inhibit any motion which may occur if the patch or pump is moved relative to the skin surface or from any muscle movement. This localized isolation of the skin surface relative to the inserted microneedles 402 may inhibit or prevent tearing of skin or damage to the microneedles 402 themselves. Moreover, adhesive sheet 403 may localize the securement of the skin surface to stabilize microneedles 402 while allowing for a greater degree of flexibility of the remaining skin relative to housing 409. This in turn provides for greater patient movement comfort and greater comfort. Additionally, if adhesive layer 411 is utilized along the contacting surface of housing 409 along with adhesive sheet 403, a gap or space 412 may separate the two layers effectively isolating adhesive sheet 403, as shown, thus leaving the skin between adhesive sheet 403 and adhesive layer 411 relatively free to move. While adhesive sheet 403 secures the skin immediately beneath and/or adjacent to microneedles 402, gap or space 412 may provide for added flexibility of housing 409.
Other methods for applying an adhesive layer may include temporarily covering microneedles 402 and/or subsequently spraying on a biocompatible adhesive to microneedle array 401 or wicking a liquid adhesive along the base of array 401 in-between microneedles 402. In addition to adhesive sheet 403, an additional adhesive layer 411 may also be placed along the surface of housing 409 for secure placement against the skin surface. The additional adhesive layer 411 may be integrated along microneedle assembly 400 or it may be separate from the microneedle array 401 such that assembly 400 is removably replaceable.
In another variation of the patch or pump assembly, rather than utilizing a single integrated assembly, the housing may be separated into two or more discrete sections which are connect by wire or capillary tube where appropriate. For example, the reservoir 404, pump 405, battery 406, and electronic control 407 might reside in a first section while microporous membrane or microneedle assembly might resides in a separate second section. This configuration may allow for a relatively lighter and more flexible patch to be used where the drug formulation directly interacts with the skin.
Yet another variation may omit a microporous membrane or microneedle assembly entirely. Typical passive drug delivery patches utilize membranes to prevent the contents of the patch from becoming absorbed at an uncontrolled rate through the skin surface without any regulation at all. It also often serves to contain the liquid in the patch itself to form part of the effective barrier of the drug formulation reservoir. However, in the present patch or pump assembly, the rate of delivery may be strictly limited by the pump 405 even when the microporous membrane or microneedle assembly is omitted entirely. As a result, a programmable transdermal patch may be designed in which the output of the pump 405 leads directly to the skin without any intervening delivery interface. The liquid is spread across the area of the skin within the surrounding boundary of the adhesive layer 108 by, e.g., gravity, diffusion, surface tension, and/or rubbing against the base of the programmable transdermal patch or pump.
In yet another variation of the programmable patch or pump assembly,
Because of its micrometer scale, microchannel reservoir 501 reduces the degrees of freedom for liquid movement and constrains the liquid contained within. As a result, altering the orientation of microchannel reservoir 501 in space (three dimensions), such as by rotation or vibration is much less likely to result in the formation of bubbles, gaps, or voids within the contained liquid that may interfere with pumping. Moreover, the walls of microchannel reservoir 501 may also be coated or modified to increase or decrease their hydrophobic or hydrophilic properties. Also illustrated are pump 502 and microporous material 507 (or any other fluid delivery mechanism) in fluid communication with microchannel reservoir 501 also via microchannels 506. Electronic control 503 and battery 504 as well as adhesive layer 508 are also shown.
Additionally, a fluid detector 510 may also be optionally included within patch or pump assembly 500 to detect the presence of fluid or air within at least one of the microchannels 506. Alternatively, fluid detector 510 may also be included along a portion of microchannel reservoir 501 to detect whether reservoir 501 is empty. In one example of how fluid detector 510 may operate, detector 510 may comprise two metallic or otherwise conductive surfaces positioned in apposition to one another, such as on opposite sides of the output microchannel 506 that connects pump 502 to microporous membrane 507. In the presence of liquid, the resistivity between the electrodes drops while in the presence of air or a bubble, the resistance rises. This resistivity measurement can be used to ensure that if bubbles, voids, or air is introduced into pump 502 and pushed downstream, the subsequent absence of liquid can be detected and pump 502 may be controlled via electronic control 503 to continue pumping until the proper dosage is achieved or an error signal is illuminated for alerting the user. Moreover, fluid detector 510 may be coupled to electronic control 503 to also monitor and track the volume of fluid which has been delivered from reservoir 501 to microporous material 507 (or other fluid delivery mechanism).
Aside from a single elongate microchannel reservoir which winds in an alternating pattern, the reservoir may be configured into various other patterns as well such as a spiral or any other configuration which allows for fluid storage in or along the housing.
Yet another variation of a microchannel reservoir is illustrated in the top view of assembly 800 which illustrates multiple reservoirs formed within housing 801, e.g., a first microchannel reservoir 804 and a second microchannel reservoir 805 which is separate and distinct from the first microchannel reservoir 804. Additionally, other variations may include one or more microchannel reservoirs which are aligned along multiple geometric planes within the housing. For instance, a first reservoir may be situated in a first plane along the housing while a second reservoir may be situated in a second plane below or above the first reservoir. In this manner, multiple reservoirs may be “stacked” atop or below one another in several adjacent planes which may be separate from one another or which may be fluidly interconnected between two or more reservoirs between their respective planes. Microchannel reservoirs 804, 805 may each contain the same or different drug formulations or dosages and may each be coupled to one or more valves 806, which may be electronically controlled to meter or control the volume of one or both reservoirs 804, 805 to be pumped via pump 802 to microporous membrane 803 (or other delivery mechanism). The microchannel reservoirs 804, 805 may be fluidly coupled to pump 802 via microchannel 807 and pump 802 may be further fluidly coupled to microporous membrane 803 (or other drug delivery mechanism) via microchannel 808. By alternating the frequency and duration of which reservoir is available to pump 802, as well as the pumping rate and duration, the medication from each of the reservoirs 804, 805 can be independently and nearly-simultaneously controlled and delivered to the patient.
Although a single pump 802 is illustrated for pumping both reservoirs 804, 805, each reservoir may alternatively be coupled to a separate pump for controlling the pumping rate of each reservoir individually. Moreover, two microchannel reservoirs are described for illustrative purposes and additional microchannel reservoirs may also be utilized with a common or separate pumping mechanism in other variations.
Use of a microchannel as the drug formulation reservoir may also allow for different types of pump configurations. Rather than using a pump to extract liquid from the microchannel reservoir and pumping it out to ultimately reach a user's skin, an air pump can instead be used to push the liquid down the length of the microchannel reservoir to be ultimately deposited on the user's skin. In a conventional transdermal patch with a single reservoir, use of an air pump is difficult because changing an orientation of the patch or pump may result in pushing air rather than the drug formulation towards the user's skin. This may be avoided because the microchannel reservoir inhibits or prevents bubbles of air from sliding past fluid already contained within the microchannel. Rather, the contained fluid is pushed distally through the microchannel as more air is pumped behind it.
In yet another variation,
In this or any of the variations described herein, the programmable electronic circuitry 1102 of patch or pump assembly 1101 may be equipped with a transmitter and/or receiver that allows it to communicate, wirelessly 1104 or otherwise, with an external controller 1103 such as a computer or hand-held device, as shown in the schematic illustration of system 1100 in
Another aspect of the transdermal patch or pump assembly 1200 may provide the capability for patient-determined “on-demand” controlled delivery of medication, as illustrated schematically in
Alternatively, and as illustrated schematically in the system 1300 in
Aside from the various types of pumps described above for transferring the fluids and drug formulations into or out of a reservoir, linear actuators may be used instead. Generally, such a linear actuator may act as a piston to push or urge the fluids out of the reservoir such that as the piston head is advanced distally as driven by an actuator, voids, vacuum, or air are unable to be mixed with the remaining fluid in the reservoir. Thus, the formation of voids or bubbles may be avoided in the remaining liquid as the reservoir is emptied since the reduction in the volume of the reservoir results in the same volume of liquid (drug formulation) exiting from the reservoir and being deposited onto the skin through any of the methods and devices described herein.
Linear actuator 1402 may be comprised of any number of actuators, such as a mechanical screw-drive, electromagnetically driven actuation, etc. Another example of a linear actuator which may be utilized with the assemblies described herein are actuators which incorporate a threaded shaft assembly and a threaded nut or carriage which may be subjected to vibrations, e.g., ultrasonic vibrations, which thereby cause the shaft to rotate and/or translate axially. One or more transducers (e.g., piezoelectric, electrostrictive, electrostatic, electromagnetic, etc.) within actuator 1402 may be vibrationally coupled to the nut and/or shaft to force the nut and/or shaft to vibrate at their first mode resonant frequencies. The resulting bending moments may in turn cause the shaft and/or nut to rotate to thereby translate the shaft in a first or second direction. This linear movement may be captured to urge piston head 1403 distally (or proximally) to force the liquid from reservoir 1404. Examples of such vibrationally-driven linear actuators 1402 are described in further detail in U.S. Pat. Nos. 6,940,209; 7,170,214; and 7,309,943, each of which are incorporated herein by reference its entirety.
To accurately determine the amount of fluid delivered at any given time, positioning sensor assembly 1400 may optionally include a system for determining the relative position of piston head 1403 with respect to the reservoir. Given the relative position of piston head 1403 prior to, during, and/or after actuation, the differential volume of fluid delivered from reservoir 1404 may be accurately calculated and/or metered in real-time. Any number of mechanisms may be implemented to determine positioning. One example is illustrated in the top view of
Although these examples illustrate the use of linear actuators and sensing systems with reservoirs 1404, they may also be incorporated with any of the microchannel reservoirs described above to directly urge the fluids contained therewithin or to indirectly urge the fluids by moving a piston to pump a gas which in turn drives the fluid through the microchannel reservoir, as described above.
The applications of the devices and methods discussed above are not limited to any specific treatments but may include any number of further treatment applications. Moreover, such devices and methods may be applied to various treatment sites upon the body. Modification of the above-described assemblies and methods for carrying out the invention, combinations between different variations as practicable, and variations of aspects of the invention that are obvious to those of skill in the art are intended to be within the scope of the claims.
