US20110098676A1 - Systems and methods for delivering drugs - Google Patents

Abstract

A patch pump device generally includes at least one fluid source, a fluid communicator, and an electrochemical actuator. The fluid communicator is in fluid communication with the fluid source. The electrochemical actuator is operative to cause fluid to be delivered from the fluid source into the fluid communicator.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS
• This application claims the benefit of U.S. Provisional Application Ser. No. 60/952,217, filed Jul. 26, 2007. This application also claims the benefit of U.S. Provisional Application Ser. No. 60/989,605, filed Nov. 21, 2007. Both of these applications are incorporated herein by reference.
BACKGROUND OF THE INVENTION
• This invention is generally in the field of medical devices, and more particularly in the field of drug delivery devices.
• Drug delivery involves delivering a drug or other therapeutic compound into the body. Typically, the drug is delivered via a technology that is carefully selected based on a number of factors. These factors include but are not limited to the characteristics of the drug, such as drug dose, pharmacokinetics, complexity, cost, and absorption, the characteristics of the desired drug delivery profile (such as uniform, non-uniform, or patient-controlled), the characteristics of the administration mode (such as the ease, cost, complexity, and effectiveness of the administration mode for the patient, physician, nurse, or other caregiver), or other factors or combinations of these factors.
• Conventional drug delivery technologies present various challenges. Oral administration of a dosage form is a relatively simple delivery mode, but some drugs may not achieve the desired bioavailability and/or may cause undesirable side effects if administered orally. Further, the delay from time of administration to time of efficacy associated with oral delivery may be undesirable depending on the therapeutic need. While parenteral administration by injection may avoid some of the problems associated with oral administration, such as providing relatively quick delivery of the drug to the desired location, conventional injections may be inconvenient, difficult to self-administer, and painful or unpleasant for the patient. Furthermore, injection may not be suitable for achieving certain delivery/release profiles, particularly over a sustained period of time.
• Passive transdermal technology, such as a conventional transdermal patch, may be relatively convenient for the user and may permit relatively uniform drug release over time. However, some drugs, such as highly charged or polar drugs, peptides, proteins and other large molecule active agents, may not penetrate the stratum corneum for effective delivery. Furthermore, a relatively long start-up time may be required before the drug takes effect. Thereafter, the drug release may be relatively continuous, which may be undesirable in some cases. Also, a substantial portion of the drug payload may be undeliverable and may remain in the patch once the patch is removed.
• Active transdermal systems, including iontophoresis, sonophoresis, and poration technology, may be expensive and may yield unpredictable results. Only some drug formulations, such as aqueous stable compounds, are suited for active transdermal delivery. Further, modulating or controlling the delivery of drugs using such systems may not be possible without using complex systems.
• Infusion pump systems may be large and may require tubing between the pump and the infusion set, impacting quality of life. Further, infusion pumps may be expensive and may not be disposable. From the above, it would be desirable to provide new and improved drug delivery systems and methods that overcome some or all of these and other drawbacks.
SUMMARY OF THE INVENTION
• A patch pump device generally includes at least one fluid source, a fluid communicator, and at least one electrochemical actuator. The fluid communicator is in fluid communication with the fluid source. The electrochemical actuator is operative to cause fluid to be delivered from the fluid source into the fluid communicator.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 is a schematic block diagram illustrating an embodiment of a fluid delivery system.
• FIG. 2 is a schematic view of an embodiment of an electrochemical actuator, whereinFIG. 2(a) illustrates the electrochemical actuator in a charged state andFIG. 2(b) illustrates the electrochemical actuator as it discharges.
• FIG. 3 is a schematic view of another embodiment of an electrochemical actuator, whereinFIG. 3(a) illustrates the electrochemical actuator in a charged state andFIG. 3(b) illustrates the electrochemical actuator as it discharges.
• FIG. 4 is a side cross-sectional view of an embodiment of a pump device, whereinFIG. 4(a) illustrates the pump device in an unassembled position;FIG. 4(b) illustrates the pump device in an assembled position; andFIG. 4(c) illustrates the pump device pumping fluid therefrom.
• FIG. 5 illustrates another embodiment of a pump device, whereinFIG. 5(a) is a top plan view of the pump device in an unassembled position;FIG. 5(b) is a side cross-sectional view of the pump device in the unassembled position;FIG. 5(c) is a top plan view of the pump device in an assembled position; andFIG. 5(d) is a side cross-sectional view of the pump device in the assembled position.
• FIG. 6 is a side cross-sectional view of another embodiment of a pump device, whereinFIG. 6(a) illustrates a needle insertion mechanism being attached to a base portion of the pump device;FIG. 6(b) illustrates the needle insertion mechanism inserting a needle and cannula through the base portion of the pump device;FIG. 6(c) illustrates the pump device in an unassembled position; andFIG. 6(d) illustrates the pump device in an assembled position.
• FIG. 7 is a side cross-sectional view of another embodiment of a pump device, whereinFIG. 7(a) illustrates the pump device in an unassembled position andFIG. 7(b) illustrates the pump device in an assembled position.
• FIG. 8 is a side cross-sectional view of another embodiment of a pump device, whereinFIG. 8(a) illustrates the pump device in an unassembled position andFIG. 8(b) illustrates the pump device in an assembled position.
• FIG. 9 is a schematic illustrating an embodiment of an electrical circuit that may be used in an embodiment of a pump device.
• FIG. 10 is a graph illustrating one exemplary, non-limiting embodiment of a displacement curve, indicating the displacement behavior as a function of time for an electrochemical actuator positioned in the electrical circuit ofFIG. 9.
• FIG. 11 is a graph illustrating one exemplary, non-limiting embodiment of a fluid flow curve, indicating the fluid flow behavior as a function of time for a fluid source associated with the electrical circuit ofFIG. 9.
• FIG. 12 is a schematic illustrating an embodiment of an electrical circuit that includes electrical contacts.
• FIG. 13 is a schematic illustrating an embodiment of an electrical circuit that includes a variable resistor.
• FIG. 14 is a schematic illustrating an embodiment of an electrical circuit that includes a switch.
• FIG. 15 is a graph illustrating a displacement curve, indicating the displacement behavior as a function of time for a fluid source associated with the electrical circuit ofFIG. 14.
• FIG. 16 is a schematic view of an embodiment of a device that includes an embodiment of a control system.
• FIG. 17 is a side cross-sectional view of an embodiment of a pump device that includes multiple fluid sources operated by different electrochemical actuators.
• FIG. 18 is a side cross-sectional view of an embodiment of a pump device that includes multiple fluid sources operated by the same electrochemical actuator.
DETAILED DESCRIPTION OF THE INVENTION
• Described below are embodiments of systems and methods of delivering a fluid, which may include a drug, into a patient in need thereof. The patient may be a human or other mammal for example. In embodiments, the systems and methods may embody a pump device suited for subcutaneous or intravenous delivery of a fluid, which may or may not include one or more drugs. The pump device may employ an electrochemical actuator, which may have characteristics of both a battery and a pump. Specifically, the electrochemical actuator may include an electrochemical cell that produces a pumping force as the cell discharges. Thus, the pump device may have relatively fewer parts than a conventional drug pump, such that the pump device is relatively more compact, disposable, and reliable than conventional drug pumps. These attributes of the pump device may permit reducing the cost and the discomfort associated with infusion drug therapy. Further, such a pump device may have a control means, such as a controller and/or other circuitry, operative to regulate drug or fluid flow from the pump device. Such control means may permit implementing one or more release profiles using the pump device, including release profiles that require uniform flow, non-uniform flow, continuous flow, discontinuous flow, programmed flow, scheduled flow, user-initiated flow, or feedback responsive flow, among others. Thus, the pump device may effectively deliver a wider variety of drug therapies than other pump devices.
• FIG. 1 is a schematic block diagram illustrating an embodiment of afluid delivery system100. Thefluid delivery system100 generally includes anelectrochemical actuator102 associated with afluid source104 and afluid communicator106. Thefluid source104 may contain a fluid to be delivered into atarget108 via thefluid communicator106. Theelectrochemical actuator102 may actuate or otherwise create a pumping force to deliver the fluid from thefluid source104 into thefluid communicator106. Specifically, theelectrochemical actuator102 may be any device that experiences a change in volume or position in response to an electrochemical reaction that occurs therein. For example, theelectrochemical actuator102 may include a charged electrochemical cell, and at least a portion of the electrochemical cell may actuate as the electrochemical cell discharges. Thus, theelectrochemical actuator102 may be considered a self-powered actuator or a combination battery and actuator.
• In use, thefluid communicator106 may be associated with thetarget108, and theelectrochemical actuator102 may be operated. Specifically, theelectrochemical actuator102 may discharge and actuate. The resulting mechanical work may act on thefluid source104 or may be transferred through intervening mechanics to thefluid source104, causing the fluid to be delivered through thefluid communicator106 into thetarget108.
• In embodiments, thefluid delivery system100 may be a system for delivering a drug into a human body. In such embodiments, thefluid source104 may be a reservoir, pouch, or bladder, or other known fluid source containing a drug in fluid form, and thetarget108 may be a human in need of a drug therapy or prophylaxis. Thefluid communicator106 may be a needle, catheter, cannula, infusion set, or other known delivery device that is inserted into or otherwise associated with the human body for drug delivery. When the electrochemical reaction is occurring in theelectrochemical actuator102, theelectrochemical actuator102 may cause the drug to be communicated from thefluid source104 into the human body. Such drug delivery may be subcutaneous, intravenous, intraarterial, intramuscular, intracardiac, intraosseous, intradermal, intrathecal, intraperitoneal, intratumoral, epidural, and/or peri-neural depending on, for example, the location of thefluid communicator106 and/or the entry location of the drug.
• In embodiments, thefluid delivery system100 may be used to deliver a drug formulation which comprises a drug, meaning a therapeutic or prophylactic agent including an active pharmaceutical ingredient. In other embodiments, thefluid delivery system100 may deliver a fluid that does not contain a drug. For instance, the fluid may be a saline solution or a diagnostic agent, such as a contrast agent.
• The drug may be in a pure form or formulated in a solution, a suspension, or an emulsion, among others, using one or more pharmaceutically acceptable excipients known in the art. For example, a pharmaceutically acceptable vehicle for the drug may be provided, which may be essentially any aqueous or non-aqueous vehicle known in the art. Examples of aqueous vehicles include physiological saline solutions, solutions of sugars such as dextrose or mannitol, and pharmaceutically acceptable buffered solutions, and examples of non-aqueous vehicles include fixed vegetable oils, glycerin, polyethylene glycols, alcohols, and ethyl oleate. The vehicle may further include antibacterial preservatives, antioxidants, tonicity agents, buffers, stabilizers, or other components.
• Representative examples of drugs that may be delivered with embodiments of the present device include, but are not limited to, opioid narcotics such as fentanyl, remifentanyl, sufentanil, morphine, hydromorphone, oxycodiene and salts thereof; NonSteroidal Antilnflamatories (NSAIDs) such as diclofenac, naproxen, ibuprofen, and celecoxib; local anesthetics such as lidocaine, tetracaine, and bupivicaine; dopamine antagonists such as apomorphine, rotigotine, and ropinerole; drugs used for the treatment and/or prevention of allergies such as antihistamines, antileukotrienes, anticholinergics, and immunotherapeutic agents; antispastics such as tizanidine and baclofin; vitamins such as niacin; Selegiline; and rasagiline. Essentially any peptide, protein, biologic, or oligonucleotide, among others, that is normally delivered by subcutaneous, intramuscular, or intravenous injection or other parenteral routes, may be delivered using embodiments of the devices described herein. In embodiments, the device may be used to administer a drug combination of two or more different drugs using a single or multiple delivery port and being able to deliver the agents at a fixed ratio or by means enabling the delivery of each agent to be independently modulated. For example, two or more drugs can be administered simultaneously or serially, or a combination (e.g. overlapping) thereof.
• Although thefluid delivery system100 and other systems and methods described herein are generally described as communicating drugs into a human body, such systems and methods may be employed to deliver any fluid of any suitable biocompatibility or viscosity into any object, living or inanimate. For example, the systems and methods may be employed to deliver other biocompatible fluids into living beings, including human beings and other animals. Further, the systems and methods may deliver drugs or other fluids into living beings other than human beings, such as animals and plant life. Also, the systems and methods may deliver any fluids into any target, living or inanimate. The systems and methods described herein are generally systems and methods of delivering fluids using an electrochemical actuator, including a self-powered actuator and/or combined battery and actuator.
• Embodiments of such electrochemical actuators are generally described in U.S. patent application Ser. No. 11/150,477 entitled “Electrochemical Methods, Devices, and Structures” by Chiang et al., U.S. patent application Ser. No. 11/881,830 entitled “Electrochemical Actuator” by Chiang et al., and U.S. patent application Ser. No. 12/035,406 entitled “Electrochemical Actuator” by Chiang et al., each of which is herein incorporated by reference. Such electrochemical actuators may include at least one component that responds to the application of a voltage or current by experiencing a change in volume or position. The change in volume or position may produce mechanical work that may act on a fluid source or may be transferred to a fluid source, such that a fluid can be delivered out of the fluid source.
• In embodiments, the electrochemical actuator may include a positive electrode and a negative electrode, at least one of which is an actuating electrode. These and other components of the electrochemical actuator may form an electrochemical cell, which may initially be charged. The electrochemical cell may begin discharging when a circuit between the electrodes is closed, causing the actuating electrode to actuate. The actuating electrode may thereby perform work upon another structure, such as the fluid source or transfer structure associated with the fluid source. The work may cause fluid to be pumped or otherwise dispensed from the fluid source into the target.
• More specifically, the actuating electrode may experience a change in volume or position when the closed circuit is formed, and this change in volume of position may perform work upon the fluid source or transferring structure. For example, the actuating electrode may expand, bend, buckle, fold, cup, elongate, contract, or otherwise experience a change in volume, size, shape, orientation, arrangement, or location, such that at least a portion of the actuating electrode experiences a change in volume or position. In embodiments, the change in volume or position may be experienced by a portion of the actuating electrode, while the actuating electrode as a whole may experience a contrary change or no change whatsoever. It is noted that the electrochemical actuator may actually include a number of electrochemical actuators arranged in series, parallel, or some combination thereof. For example, a number of such electrochemical actuators may be stacked together. As another example, concurrent or sequenced delivery of multiple agents may be achieved by including one or more electrochemical actuators acting on two or more fluid sources.
• FIG. 2 is a schematic of an embodiment of anelectrochemical actuator202. As shown, theelectrochemical actuator202 may include apositive electrode210, anegative electrode212, and anelectrolyte214. These components may form an electrochemical cell that is initially discharged and is then charged before use, or is initially charged, as shown inFIG. 2(a). Thepositive electrode210 may be configured to expand in the presence of theelectrolyte214. When a circuit between theelectrodes210,212 is closed, current may travel from thepositive electrode210 to thenegative electrode212. Thepositive electrode210 may experience a change in volume, resulting in longitudinal displacement of at least a portion of thepositive electrode210, as shown inFIG. 2(b). Thereby, thepositive electrode210 may exert a pumping force or pressure on afluid reservoir204 or associatedtransfer structure216, such as the illustrated plate. The pumping force or pressure may cause fluid to be pumped from thefluid reservoir204. Thus, theelectrochemical actuator202 may be considered a self-powered electrochemical pump. In the illustrated embodiment, the electrochemical cell has apositive electrode210 selected to have a lower chemical potential for the working ion when the cell is charged, and is thereby able to spontaneously accept working ions from thenegative electrode212 as the cell is discharged. In embodiments the working ion includes but is not limited to the proton or lithium ion. When the working ion is lithium, thepositive electrode210 may comprise one or more lithium metal oxides including LiCoO₂, LiFePO₄, LiNiO₂, LiMn₂O₄, LiMnO₂, LiMnPO₄, Li₄Ti₅O₁₂, and their modified compositions and solid solutions; oxide compound comprising one or more of titanium oxide, manganese oxide, vanadium oxide, tin oxide, antimony oxide, cobalt oxide, nickel oxide or iron oxide; metal sulfides comprising one or more of TiSi₂, MoSi₂, WSi₂, and their modified compositions and solid solutions; a metal, metal alloy, or intermetallic compound comprising one or more of aluminum, silver, gold, boron, bismuth, gallium, germanium, indium, lead, antimony, silicon, tin, or zinc; a lithium-metal alloy; or carbon comprising one or more of graphite, a carbon fiber structure, a glassy carbon structure, a highly oriented pyrolytic graphite, or a disordered carbon structure. Thenegative electrode212 may comprise lithium metal, a lithium metal alloy, or any of the preceding compounds listed as positive electrode compounds, provided that such compounds when used as a negative electrode are paired with a positive electrode that is able to spontaneously accept lithium from the negative electrode when the cell is charged. Other configurations are also possible.
• In embodiments, the electrochemical actuator may include an anode, a cathode, and a species, such as a lithium ion. At least one of the electrodes may be an actuating electrode that includes a first portion and a second portion. The portions may have at least one differing characteristic, such that in the presence of a voltage or current, the first portion responds to the species in a different manner than the second portion. For example, the portions may be formed from different materials, or the portions may differ in thickness, dimension, porosity, density, or surface structure, among others. The electrodes may be charged, and when the circuit is closed, current may travel. The species may, intercalate, de-intercalate, alloy with, oxide, reduce, or plate with the first portion to a different extent than the second portion. Due to the first portion responding differently to the species than the second portion, the actuating electrode may experience the change in volume or position.
• An example of such an embodiment is shown inFIG. 3, which is a schematic view of another embodiment of anelectrochemical actuator302. Theelectrochemical actuator302 may include apositive electrode310, anegative electrode312, and aspecies314. Thespecies314 may be an electrolyte that includes, for example, a lithium ion. Thepositive electrode310 may include a first portion and a second portion. The first portion may include a material that is dimensionally active when in the presence of species. For example, aluminum expands upon alloying with or being intercalated by lithium. The second portion may include a material that is not dimensionally active when in the presence of the species, or is relatively less dimensionally active than the material of the first portion. For example, copper does not substantially intercalate or alloy with lithium. Thus, thepositive electrode310 may be considered a bimorph structure, with one of the portions serving as a positive current collector.
• Thenegative electrode312 may serve as a negative current collector. For example, thenegative electrode312 may include a layer of lithium metal bonded to or deposited on a layer of copper. Initially, the electrodes may be charged but may not form a closed circuit, as shown inFIG. 3(a). Thepositive electrode310 may have a lower chemical potential for lithium than thenegative electrode312. When the circuit between the two electrodes is closed, as shown inFIG. 3(b), current may flow toward thenegative electrode312. The first portion of thepositive electrode310 may alloy or intercalate with the lithium, causing an expansion in volume, while the second portion may act as a mechanical constraint. Thereby, thepositive electrode310 may bend or otherwise displace. The displacement of thepositive electrode310 may be transferred to afluid reservoir304, causing thefluid reservoir304 to expel fluid.
• As mentioned above, such an electrochemical actuator may power a fluid delivery device suited delivering of a drug-containing or non-drug containing fluid into a human patient or other target. Such a fluid delivery system may be embodied in a relatively small, self-contained, and disposable device, such as a patch device that can be removably attached to the skin of the human body. The patch device may be relatively small and self-contained because the electrochemical actuator serves as both the battery and a pump. The small and self-contained nature of the device advantageously may permit concealing the device beneath clothing and may allow the patient to continue normal activity as the drug is delivered. External tubing may not be required to communicate fluid from the fluid reservoir into the body, unlike conventional drug pumps. Instead, any tubing may be contained within the device, and a needle or other fluid communicator may extend from the device into the body. The electrochemical actuator may initially be charged, and may begin discharging once the patch device is activated to pump or otherwise deliver the drug or other fluid into the body. Once the electrochemical actuator has completely discharged or the fluid reservoir is empty, the patch device may be removed and discarded. The small and inexpensive nature of the electrochemical actuator and other components of the device may permit disposing of the entire device, unlike conventional pump devices having a pump that is retained. Thus, the device may permit drug delivery, such as subcutaneous or intravenous drug delivery, over a time period that may vary from several minutes to several days. Subsequently, the device may be removed from the body and discarded.
• For the purposes of this disclosure, the term “disposable” generally means a single use device, or a component thereof, that is intended to be discarded. Because the electrochemical actuator may serve as a battery, the electrochemical actuator may discharge with use, and thereafter may be discarded. Because the electrochemical actuator also serves as the pumping mechanism, however, discarding the electrochemical actuator also discards the pumping mechanism. Such a configuration differs from a conventional infusion pump, which includes a pumping mechanism that is retained for subsequent reuse. Unlike a conventional infusion pump, a patch pump device comprising the electrochemical actuator may be completely disposable.
• Such a device may generally include a drug or fluid delivery system associated with a housing. As generally described above, the drug delivery system may include an electrochemical actuator suited to drive a drug from a fluid reservoir through a needle or other fluid communicator. The housing may at least partially contain the fluid delivery system and may be suit for removably associating the fluid delivery system with human skin.
• So that the device can be worn on the skin, a releasable adhesive may at least partially coat an underside of the housing. The adhesive may be non-toxic, biocompatible, and releasable from human skin. To protect the adhesive until the device is ready for use, a removable protective covering may cover the adhesive, in which case the covering may be removed before the device is applied to the skin. Alternatively, the adhesive may be heat or pressure sensitive, in which case the adhesive may be activated once the device is applied to the skin. Example adhesives include but are not limited to acrylate based medical adhesives of the type commonly used to affix medical devices such as bandages to skin. However, the adhesive is not necessary and may be omitted, in which case the housing may be associated with the skin, or generally with the body, in any other manner.
• The size, shape, and weight of the device may be selected so that the device may be comfortably worn on the skin after the device is applied via the adhesive. For example, the device may have a size in the range of about one inch by about one inch by about 0.1 inches to about five inches by about five inches by about one inch, and in some embodiments in a range of about two inches by about two inches by about 0.25 inches to about four inches by about four inches by about 0.67 inches. The weight of the device may be in the range of about five grams to about two hundred grams, and in some embodiments in a range of about fifteen grams to about one hundred grams. The device may be able to dispense a volume in the range of about 0.1 milliliters to about one thousand milliliters, and in some cases in the range of about 0.3 milliliters to about one hundred milliliters, such as between about 0.5 milliliters and about five milliliters. The shape of the device may be selected so that the device may be relatively imperceptible under clothing. For example, the housing may be relatively smooth and free from sharp edges. However, any size, shape, or weight is possible.
• The housing may be formed from a material that is relatively lightweight and flexible, yet sturdy. The housing also be may formed from a combination of materials such as to provide specific portions that are rigid and specific portions that are flexible. The material may also be relatively low-cost, so that the device may be disposable. Example materials include plastic and rubber materials, such as polystyrene, polybutene, carbonate, urethane rubbers, butene rubbers, silicone, and other comparable materials and mixtures thereof, although a combination of these materials or any other material may be used.
• In embodiments, the housing may include two portions: a base portion and a movable portion. The base portion may be suited for attaching to the skin. For example, the base portion may be relatively flexible. An adhesive may be deposited on an underside of the base portion, which may be relatively flat or shaped to mate with a particular body area. The movable portion may be sized and shaped for association with the base portion. In embodiments, the two portions may be designed to lock together, such as via a locking mechanism. In some cases, the two portions may releasably lock together, such as via a releasable locking mechanism, so that the movable portion may be removably associated with the base portion. To assemble the device, the movable portion may be movable with reference to the base portion between an unassembled position and an assembled position. In the assembled position, the two portions may form a device having an outer shape suited for concealing the device under clothing. Embodiments of such a device are generally described below with reference toFIGS. 4-10, although a range of configurations are possible.
• FIG. 4 is a side cross-sectional view of an embodiment of apatch device400. Thedevice400 generally includes a fluid delivery system associated with ahousing418, which may include abase portion422 and amovable portion424. An adhesive420 may be positioned on an underside of thebase portion422. Themovable portion424 may house one or more components of the fluid delivery system, such as anelectrochemical actuator402, afluid reservoir404, andfluid communicator406. Themovable portion424 may be sized and shaped for insertion into thebase portion422. More specifically, themovable portion424 may be movable with reference to thebase portion422 between an unassembled position shown inFIG. 4(a), and an assembled position shown inFIGS. 4(b-c). In the assembled position, the twoportions422,424 may mate and lock together. When assembled, the outer surface of thedevice400 may be relatively smooth and easy to conceal under clothing.
• In the embodiment illustrated inFIG. 4, a releasable locking mechanism is formed bydetents426 located on an exterior surface of themovable portion424 and agrooved flange428 located on an interior surface of thebase portion422. In the unassembled position, thedetents426 rest in thegrooved flange428 to support themovable portion424 above thebase portion422. To assemble thedevice400, a force F is applied to themovable portion424 to push it downward. The force F causes thegrooved flange428 to flex outward and thedetent426 to travel past thegrooved flange428. Thus, themovable portion424 travels further into thebase portion422 and becomes firmly seated therein. Thegrooved flange428 returns to prevent thedetent426 from moving upward, releasably locking thedevice400 together. When so assembled, thedevice400 takes on a bulbous shape that is relatively free from sharp edges. It is noted that, in some embodiments, the locking mechanism may not be releasable.
• In the embodiment shown inFIG. 5, thedevice500 generally includes a housing formed from abase portion522 and amovable portion524. Like thedevice400, thebase portion522 may have an adhesive on an underside for associating thedevice500 with the skin (not shown for clarity). A fluid delivery system may generally be contained in the movable portion524 (not shown for clarity).
• More specifically, thebase portion522 may have a relatively oval exterior and an interior that is sized and shaped to receive themovable portion524. For example, themovable portion524 may have abody530 and aprojection532, and thebase portion522 may have aninterior slot534 and anopening536. Theinterior slot534 may be sized and shaped for receiving theprojection532, and theopening536 may be sized and shaped for receiving thebody530. To assemble thedevice500, theprojection532 may be inserted through theopening536 along theslot534, as shown inFIG. 5(b). Thebody530 may be pressed into theopening536 so that themovable portion524 becomes firmly seated in thebase portion522, as shown inFIG. 5(d). When so assembled, the shape of themovable portion524 may naturally limit its upward and rearward movement, releasably locking the twoportions522,524 together. The assembleddevice500 may take on a smooth oval shape that is relatively free from sharp edges and has a relatively low profile, so that thedevice500 may be concealed under clothing.
• In the embodiment shown inFIG. 6, specificallyFIG. 6(c) andFIG. 6(d), thedevice600 may include amovable portion624 that snaps onto an exterior of abase portion622 instead of being inserted therein. Specifically, thebase portion622 may include abase638 and aguide640 that projects upward from thebase638. The base638 may be a layer of adhesive, such as a flexible, double-sided layer of adhesive. Alternatively, thebase638 may comprise a plate having an adhesive on an underside. Themovable portion624 may have a cavity that houses components of the fluid delivery system, such as anelectrochemical actuator602, afluid source604, and associated electronics672 (embodiments of which are described below with reference toFIG. 10). Arecess642 may be formed in themovable portion624 for receiving theguide640. To assemble thebase portion622 and themovable portion624, themovable portion624 may be positioned over thebase portion622 as shown inFIG. 6(e). Theguide640 may locate therecess642, so that theportions622,624 are properly aligned. A force may be applied to press themovable portion624 onto thebase portion622, as shown inFIG. 6(d). Theguide640 and therecess642 may form a snap fitting, such that thedevice600 becomes releasably locked together. Alternatively, themovable portion624 may adhere to thebase portion622, such as in embodiments in which thebase638 is a double-side layer of adhesive. When assembled, thedevice600 has a relatively smooth and low profile exterior that may permit concealing the device beneath clothing.
• It should be noted that different embodiments of the device may be assembled using different hand motions. For example, thedevice400 shown inFIG. 4 may be assembled by exerting a force on themovable portion424 in a direction generally perpendicular to the surface of the skin, as shown inFIG. 4(b), while thedevice500 shown inFIG. 5 may be assembled by exerting a force on themovable portion524 in a direction that forms an angle with the surface of the skin, as shown inFIG. 5(b). Thus, different embodiments of the device may be better suited for assembly on different parts of the body or with fluid communicators inserted at different angles, as further described below. It also should be noted that some embodiments of the device, such as thedevice400, thedevice500, and thedevice600 may be assembled using one hand. Assembling the device with one hand may facilitate attaching the device to a portion of the body that cannot be accessed easily. For example, some drugs or other fluids may be infused through the backside of the body, which may be difficult to access with both hands. Assembling the device on the backside of the body, for example, may be relatively easy with embodiments of the device that can be assembled using one hand.
• In embodiments, the device may be designed such that assembling the device simultaneously inserts the fluid communicator into the body. Specifically, the fluid communicator may initially be retracted inside the housing and may be transferred from the housing into the body during assembly of the device. More specifically, the force that causes the housing to move from the unassembled position to the assembled position may also be effective to cause the needle to enter the body.
• In the embodiment of thedevice400 shown inFIG. 4, for example, thefluid communicator406 may be a needle extending downward from themovable portion424. When thedevice400 is in the unassembled position, as shown inFIG. 4(a), the needle may be protected inside thebase portion422. Aseptum444 or other penetrable member may be positioned in thebase portion422 adjacent to the needle, enclosing thebase portion422 so that the needle is not exposed to contaminants. When the force F is applied to move themovable portion424 to the assembled position, as shown inFIG. 4(b), the needle penetrates theseptum444 and enters the skin. Because the force F is applied relatively perpendicular to the surface of the skin, the needle may enter the body at an angle that is relatively perpendicular to the surface of the skin. Such a configuration may be suited for patients that prefer inserting the needle in a perpendicular orientation, or for drugs or other fluids that are suited for being delivered via a needle in a perpendicular orientation. However, in other embodiments, other configurations are possible.
• For example, in the embodiment of thedevice500 shown inFIG. 5, thefluid communicator506 may be a needle positioned at an end of theprojection532. Theslot534 may extend downward through thebase portion522, forming an angle with an underside of thebase portion522. Theslot534 may terminate in anaperture546 formed through the underside of thebase portion522. Theprojection532 may be sized such when theprojection532 is positioned in theslot534, the needle passes through theaperture546 into the skin. To assemble thedevice500, theprojection532 is inserted through theslot534. The force F is applied at an angle with reference to the surface of the skin to push theprojection532 along theslot534, such that continued application of the force F inserts the needle into the body at an angle with reference to the surface of the skin. Inserting the needle at an angle may be preferred by some users and/or for some types of drug or fluid delivery.
• In the embodiments described above with reference toFIG. 4 andFIG. 5, the force that causes the device to move into the assembled position is the same force that acts on the needle to insert the needle into the body. In such embodiments, the needle travels into the body in the same direction that the movable portion travels into the base portion. In other embodiments, the device may include mechanics that alter the direction of the force before the force acts on the needle. In such embodiments, the force may act on the movable portion in one direction and may act on the needle in another direction. For example, the mechanics may alter the direction of a perpendicular force before the force acts on the needle, so that the force can insert the needle into the body at an angle. Example mechanics may include a spring and a latch, wherein associating the movable portion with the base portion releases the latch to cause the spring to insert the needle into the body. In such embodiments, the mechanics may permit selecting the insertion angle of the needle, such as by rotating a dial or sliding a slider, so that the user can adjust the insertion angle based on his personal preference. A person of skill may be able to design such mechanics based on the disclosure above.
• In still other embodiments, the force that causes the needle to enter the body may be applied completely separately from the force that places the device in the assembled position. For example, the needle may be manually inserted into the body before the device is associated with the needle. As another example, the electrochemical actuator may apply a force to the needle to insert the needle into the body. Further, a separate insertion mechanism may be provided for inserting the needle into the body.
• Such an embodiment is shown inFIG. 6, specifically with reference toFIG. 6(a) andFIG. 6(b). Specifically, thedevice600 may be suited for use with a separateneedle insertion mechanism648. Theneedle insertion mechanism648 may be adapted for inserting afluid communicator606, such as a needle or cannula, through thebase portion622 of thedevice600 and into the body. For example, thebase portion622 may include anopening650 for receiving thefluid communicator606, theopening650 being formed through theguide640 and thebase plate638. To permit aligning theneedle insertion mechanism648 with thebase portion622, and more specifically, to permit aligning thefluid communicator606 with theopening650, theneedle insertion mechanism648 may include arecess652 sized and shaped to mate with theguide640.
• To insert thefluid communicator606, theneedle insertion mechanism648 may be placed on thebase portion622, as shown inFIG. 6(b). Aspring654, which is generally retained within theneedle insertion mechanism648 in a compressed state, may be released via a releasable latch656. Thespring654 may be in communication with thefluid communicator606 and may expel thefluid communicator606 out of theneedle insertion mechanism648 when the latch656 is released. Thefluid communicator606 may travel through theopening650, as shown inFIG. 6(b), and into the body, as shown inFIG. 6(c). Thereafter, theneedle insertion mechanism648 may be removed from thebase portion622, as shown inFIG. 6(c), so that themovable portion624 may be positioned thereon as shown inFIG. 6(d). Theneedle insertion mechanism648 may subsequently be discarded, or may be saved for re-use depending on the embodiment.
• In embodiments, thefluid communicator606 may be asoft cannula658. Aneedle660 may be fixedly associated with thespring654 to initially pierce the skin and assist in inserting thesoft cannula658 into the body, as shown inFIG. 6(b). Theneedle660 may subsequently be retracted or removed from the body, leaving thesoft cannula658 in place, as shown inFIG. 6(c). An aligningguide662 may further guide thesoft cannula658 into the body, although the aligningguide662 is not necessary and may be omitted.
• In embodiments, the needle insertion mechanism may be designed for one handed operation to facilitate inserting the catheter in hard to reach places. Further, the needle insertion mechanism may be designed to insert the needle at a variety of different angles, including a user-selected angle. Fluid communicators other than needles or soft cannulas may be inserted by the needle insertion mechanism, depending on the embodiment. The needle inserting force may be supplied by the spring or in other manners, such as by the user, manually, in which case the spring may be omitted. Although the illustrated needle insertion mechanism is separate from the device, which permits reducing the size and/or weight of the device, the needle insertion mechanism may be an integral part of the device that is retained within the device after the needle is inserted. It also should be noted that the configuration described above, in which a piercing needle that assists with inserting a soft cannula is subsequently removed from the body, may be employed with reference to other embodiments.
• By way of example, the fluid communicator is described above as being a needle or a cannula. In embodiments, the needle or a soft cannula may be relatively small for comfort. In other embodiments, the fluid communicator can be any catheter or other device for delivering fluids into the body, or combinations thereof. In embodiments, the fluid communicator may be relatively sterile. Further, the device may be used in association with a conventional infusion set, in which case the fluid communicator may be one or more parts of the infusion set, such as a standard Luer lock or other connector that is adapted to connect the device to the infusion set, or the fluid communicator may be omitted completely. In another embodiment, the pump patch is not limited to subcutaneous delivery. For example, the device may be connected to an indwelling infusion port, such as a central venous access port known in the art, in which case the fluid communicator may be a suitable adaptor for associating the device with the port. In still another embodiment, the fluid communicator may comprise a microneedle array suitable for transdermal delivery of fluid drugs, as known in the art.
• Although embodiments of the device are described above as comprising two separate portions that can be assembled together, or two separate portions and a needle insertion mechanism, in other embodiments the device may be a single portion or the device may have more than two separate portions.
• Further, in the embodiments described above, the fluid delivery system is generally housed in one portion of the device, namely, the movable portion. In other embodiments, the fluid delivery system may be housed in other portions of the device, such as the base portion, or in a combination of a number of portions of the device, such as a combination of the base portion and the movable portion. Examples are shown inFIGS. 7 and 8.FIG. 7, for example, illustrates an embodiment of adevice700 that is generally similar to thedevice500. However, the fluid delivery system of thedevice700 may be split between a base portion722 and amovable portion724. In an unassembled position, shown inFIG. 7(a), the base portion722 may house anelectrochemical actuator702 while themovable portion724 may house afluid source704 and afluid communicator706. In an assembled position, shown inFIG. 7(b), theelectrochemical actuator702 may be brought into direct or indirect communication with thefluid source704.
• FIG. 8 illustrates an embodiment of adevice800 that is generally similar to thedevice600. However, the fluid delivery system of thedevice800 may be split among abase portion822 and amovable portion824. In an unassembled position, shown inFIG. 8(a), thebase portion822 may house anelectrochemical actuator802 and acontrol system872. Thefluid communicator806 may also be positioned in thebase portion822, after having been inserted via a needle insertion mechanism. Themovable portion824 may house afluid source804. In an assembled position, shown inFIG. 8(b), theelectrochemical actuator802 may be brought into direct or indirect communication with thefluid source804.
• Depending on the embodiment, the components of the fluid delivery system, including the electrochemical actuator, the fluid source, and the fluid communicator, may be positioned among various portions of the device, such as the base portion, the movable portion, and the needle insertion mechanism (if present). The components may be separated until the device is assembled to achieve selected design criteria, such as increased safety, decreased cost, or improved quality of life. For example, the wet and sterile components, such as the fluid source and fluid communicator, may be separated from the dry and non-sterile components, such as the electrochemical actuator and any associated electronics, for safety purposes. Examples of such embodiments include thedevice700 and thedevice800.
• Some components may be separated to permit reusing one or more components while discarding one or more other components. Such embodiments may permit disposing of certain spent or damaged portions while reusing other fresh and functioning portions. For example, a fluid source that contains a relatively expensive drug may be separated from the electrochemical actuator and/or associated electronics to permit reusing the fluid source if the electrochemical actuator or electronics are defective. Alternatively, a fluid source that contains a drug delivered in relatively high volumes may be separated from the electrochemical actuator and associated electronics to permit reusing the electrochemical actuator and electronics with multiple fluid sources. As another example, electronics may be separated from the fluid source and/or electrochemical actuator to permit reusing the electronics even after the fluid source is empty and/or the electrochemical actuator has completely discharged. Further, the fluid communicator may be separated from one or more other components to permit reusing the other components in the event that needle insertion fails or the needle needs to be changed. An example of such an embodiment is thedevice600, which includes the associated needle insertion mechanism. Further, some components may be separated to permit un-assembling and reassembling the device without reinserting the fluid communicator. Such an embodiment may permit certain activities, such as shopping and bathing. An example of such an embodiment is thedevice600. Based on the above disclosure, a range of other configurations are possible. For example, the device may include a fluid communicator portion, an electrochemical actuator portion, a fluid source portion, and an electronics portions. These portions may be assembled to form a device of the type described herein, yet may be unassembled and reassembled to substitute and discard portions as necessary.
• After the device is assembled, the electrochemical actuator may be activated so that the electrochemical actuator begins discharging, as further described below. The electrochemical actuator may actuate as it discharges, directly or indirectly acting on the fluid source to drive the fluid into the body. For example, the electrochemical actuator may be positioned in direct contact with the fluid source, such that actuation of the electrochemical actuator directly acts on the fluid source to deliver fluid out of the fluid source. Alternatively, a transferring structure or other appropriate mechanics may be positioned between the electrochemical actuator and the fluid source, such that actuation of the electrochemical actuator is transferred through the transferring structure to the fluid source. In embodiments, the transfer structure may amplify the change in volume or displacement experienced by the electrochemical actuator, such that a relatively small change in volume or displacement may produce the desired effect upon the fluid source.
• For example, in the embodiment shown inFIG. 4, theelectrochemical actuator402 may directly act on thefluid source404. As shown inFIG. 4(a), thefluid source404 may be a deformable bladder or pouch positioned in direct contact with theelectrochemical actuator402. When theelectrochemical actuator402 actuates, a force or pressure may be applied to thefluid source404, causing thefluid source404 to deform, as shown inFIG. 4(b). The pressure within thefluid source404 may increase, driving the fluid through thefluid communicator406, as shown inFIG. 4(c).
• In the embodiment shown inFIG. 6, theelectrochemical actuator602 may indirectly act on thefluid source604 via, for example, atransfer structure668. As shown inFIG. 6(c), thefluid source604 may be a chamber, and thetransfer structure668 may be a piston in communication with the chamber. When theelectrochemical actuator602 actuates, a force may be applied to thetransfer structure668. In turn, thetransfer structure668 may apply a force to thefluid source604 to drive fluid through thefluid communicator606.
• The transfer structure is described as a piston by way of example, although the transfer structure may have any other configuration envisioned by a person of ordinary skill based on the present disclosure. Such a transfer structure may comprise one or more known mechanical or electrical components arranged in any combination and/or location in the device that permits transferring work from the electrochemical actuator to the fluid source. Including a transfer structure may permit the device to have a range of different shapes, sizes and dimensions, as the electrochemical actuator need not be in direct physical contact with the fluid source.
• By way of example, the fluid source is described above as being a bladder, reservoir, pouch, chamber or barrel. In other embodiments, the fluid source may be any component capable of retaining a fluid or drug in fluid form. In the illustrated embodiments, the fluid source may not be refillable, permitting disposal of the device. In other embodiments, the fluid source may be refilled, which may permit reusing at least a portion of the device and/or varying the drug or fluid delivered by the device.
• In embodiments, the fluid source may be sized to correlate with the electrochemical potential of the electrochemical actuator. For example, the size and/or volume of the fluid source may be selected so that the fluid source becomes about substantially empty at about the same time that the electrochemical actuator becomes about substantially discharged. Such a configuration may permit reducing the size and/or cost of the device, as the fluid source may not be too large or contain too much drug in relation to the driving potential of the electrochemical actuator, and similarly, the electrochemical may not be too large or contain too much power in relation to the amount of drug in the fluid source. In other embodiments, the electrochemical actuator may be oversized with reference to the fluid source. Such a configuration may be used with relatively expensive drugs to ensure the fluid source is about substantially empty before the electrochemical actuator completely discharges, so that waste of the drug is reduced.
• Further, the device may include more than one fluid source in some embodiments. Such a configuration may permit using a single device to deliver two or more drugs or fluids. The two or more drugs or fluids may be delivered discretely, simultaneously, alternating, according to a program or schedule, or in any other manner as further described below. In such embodiments, the fluid sources may be associated with the same or different electrochemical actuators, the same or different fluid communicators, the same or different operational electronics, or the same or different portions of the housing.
• One example embodiment is shown inFIG. 17, which is a side cross-sectional view of an embodiment of apump device1700 that includes multiplefluid sources1704aand1704b.Thefluid sources1704aand1704bare operated by differentelectrochemical actuators1702aand1702b,respectively. Thedevice1700 may be suited for delivering two or more drugs or fluids in any configuration. For example, thedevice1700 may be used in embodiments in which a drug is to be delivered at infrequent intervals over an extended period, such as a period of several days. In such an embodiment, onefluid source1704amay comprise the drug and theother fluid source1704bmay comprise a fluid such as saline. The saline may be periodically administered between doses of the drug to impede clogs from forming in thefluid communicator1706.
• Another example embodiment is shown inFIG. 18, which is a side cross-sectional view of an embodiment of apump device1800 that includes multiplefluid sources1802aand1804boperated by the sameelectrochemical actuator1802. Thedevice1800 may be suited for delivering two or more drugs or fluids in a range of configurations. For example, thedevice1800 may be used in embodiments in which the drug or fluid has constituent components that are segregated prior to delivery into the body. For example, the drug may be stored in a dry powder form (e.g., lyophilized) in one compartment and then shortly or immediately prior to administration, it may be reconstituted into a solution or suspension with a suitable fluid vehicle known in the art, e.g., saline solution, for delivery. This may be particularly advantageous for certain drugs, such as biologics or protein drugs, that may preferably be in a lyophilized or other dry powder form in order to provide drug stability during storage, i.e., shelf stability. In these and in other embodiments, thefluid source1802 may comprise a drug storage reservoir suited to store a drug or other non-fluid that can be reconstituted. In embodiments, intervening mechanics may transfer and/or amplify the displacement of theelectrochemical actuator1802 to each of thefluid sources1804aand1804bin different manners, permitting different fluid flow rates from thefluid sources1804band1804b.Although devices having two fluid sources are illustrated, one of skill would understand that more than two fluid sources may be provided in other embodiments.
• Devices having two or more fluid sources may have a number of different configurations within the scope and spirit of the present disclosure. For example, the fluid sources may be separated into different portions of the housing, which may permit replacing one of the fluid sources at a relatively higher frequency than the other fluid source. Further, the electrochemical actuator may be substituted with any other pump device, in which case one or more separate batteries may also be provided. The fluid sources may also have different sizes, shapes, and configurations depending on the use of the device.
• It should be noted that the electrochemical actuator may be relatively small. For example, the electrochemical cell may have a volume in the range of about five cubic millimeters to about ten cubic centimeters, and more specifically in a range of about 0.1 cubic centimeters to about one cubic centimeter. The small size of the electrochemical actuator may permit reducing the size of the device. Further, the electrochemical actuator may include relatively few parts, reducing the size and cost of the device and increasing its reliability. The electrochemical actuator may power other components of the device. For example, the electrochemical actuator may power a display, a needle insertion mechanism, or other components of the device. Also, the electrochemical actuator may be relatively scalable, in a manner analogous to conventional batteries. For example, two or more electrochemical actuators may be provided, and in embodiments, the electrochemical actuator may be rechargeable. By way of example, the electrochemical actuator is described as driving, pumping, or expelling fluid from the fluid source. However, a person of skill would understand that the present disclosure encompasses other manners of delivering fluid from the fluid source. For example, the electrochemical actuator may pull fluid from the fluid source, such as by creating a vacuum within the fluid source, among other potential configurations. Further, the electrochemical actuator may be substituted with any known pump or other device suited to cause fluid flow from the fluid source, in which case a separate power source may also be provided.
• The electrochemical actuator may be positioned in an electrical circuit within the device. The electrochemical actuator may comprise an electrochemical cell that is initially charged and actuates as it discharges. When the electrical circuit is open, the electrochemical actuator may be prevented from discharging, which may simultaneously prevent the electrochemical actuator from actuating. Thereby, fluid may be prevented from flowing out of the fluid source. When the electrical circuit is closed, the electrochemical actuator may begin discharging, simultaneously causing the electrochemical actuator to actuate. Thereby, fluid may be permitted to flow out of the fluid source. Thus, fluid may be expelled from the fluid source when the electrical circuit is closed but not otherwise.
• In embodiments, the electrochemical actuator may discharge and actuate at rates that are dependent upon properties of the electrical circuit. When a property of the electrical circuit is varied, the discharge rate of the electrochemical actuator may be varied, which may simultaneously vary the actuation of the electrochemical actuator. Thereby, the fluid flow rate out of the fluid source may be varied. In embodiments, the device may include means for controlling or regulating fluid flow from the device. The flow control means may be operative to vary properties associated with the electrical circuit, such as to start fluid flow from the device, stop fluid flow from the device, and/or vary a rate of fluid flow from the device. Embodiments of flow control means are described in detail below and can be implemented in any combination to permit delivering drugs according to one or more releases profiles. Release profiles that may be implemented may include release profiles having linear flow, non-linear flow, user-initiated flow, feedback responsive flow, or combinations of these flows, among others. For purposes of this disclosure, the term linear flow generally means flow that has a relatively constant flow rate. The term non-linear flow generally means flow that does not necessarily have a relatively constant flow rate, including modulated flow, pulsatile flow, discontinuous flow, and/or flow that correlates to a program or schedule that may not necessarily require a relatively constant flow rate. The term user-initiated flow generally means flow that is initiated in response to an input into the device. The term feedback-responsive flow generally means flow that adjusts in response to one or more sensed conditions, described below. Thus, the pump device may be effective to deliver a wider variety of drug therapies than other pump devices.
• FIG. 9 is a schematic illustrating an embodiment of anelectrical circuit900 that may be used to power embodiments of a pump device. As shown, theelectrical circuit900 may include anelectrochemical actuator902 positioned in electrical communication with aresistor980. Theelectrochemical actuator902 may comprise an electrochemical cell that is initially charged at a relatively constant voltage, and displaces as it discharges. Theresistor980 may have a relatively constant electrical resistance. When theelectrical circuit900 is closed, as shown, a current982 may be induced in theelectrical circuit900. Theelectrochemical actuator902 may begin discharging across theresistor980, simultaneously causing theelectrochemical actuator902 to actuate. Thereby, fluid may be permitted to flow out of the fluid source.
• More specifically, the discharge of theelectrochemical actuator902 may be relatively proportional to the current982 traveling through theelectrical circuit900, or stated alternatively, the electrical resistance of theresistor980. Because the electrical resistance of theresistor980 may be relatively constant, theelectrochemical actuator902 may discharge at a relatively constant rate. Thus, the discharge of theelectrochemical actuator902 may be relatively linear with the passage of time, meaning the displacement of theelectrochemical actuator902 may be relatively linear with the passage of time.
• FIG. 10 is a graph illustrating an embodiment of adisplacement curve1000, indicating the displacement behavior as a function of time for theelectrochemical actuator902 positioned in theelectrical circuit900 ofFIG. 9. As shown, the displacement of theelectrochemical actuator902 is relatively linear with the passage of time under the conditions described above. In embodiments, theelectrochemical actuator902 may linearly displace for a time period that ranges from several minutes to several days. For example, theelectrochemical actuator902 may linearly displace for a time period in the range of about five minutes to about five weeks, and more specifically in a range of about five hours to about five days. Thereafter, the linear displacement may taper off and become non-linear, as the electrochemical cell reaches a completely discharged state and theelectrochemical actuator902 stops actuating.
• FIG. 11 is a graph illustrating an embodiment of a fluid flow curve1100, indicating the fluid flow behavior as a function of time for a fluid source associated with theelectrical circuit900 ofFIG. 9. Because the displacement rate of theelectrochemical actuator902 is relatively constant as shown inFIG. 10, the fluid flow rate from the device also may be relatively constant, as shown inFIG. 11. Thus, a device comprising theelectrical circuit900 may deliver fluid according to a relatively continuous release profile, meaning the fluid may flow at a relatively constant rate until the fluid source becomes empty or the electrochemical actuator becomes completely discharged.
• In embodiments, the device may experience a brief priming period at start-up during which the fluid flow rate may not be relatively constant. For example, thedisplacement curve1000 demonstrates that theelectrochemical actuator902 may experience a brief priming period when theelectrochemical actuator902 is first discharged. During the priming period, reaction products may not have accumulated on theelectrochemical actuator902, preventing theelectrochemical actuator902 from displacing linearly. To compensate for such a priming period, theelectrochemical actuator902 may be briefly discharged prior to use, so that when the device is in use, theelectrochemical actuator902 may experience relatively linear displacement almost immediately. Further, the fluid flow curve1100 indicates the fluid source may experience a brief priming period when theelectrochemical actuator902 first displaces. During the priming period, the fluid source may be pressurized and fluid may begin traveling toward the fluid communicator. To compensate for such a priming period, the fluid source may initially be pressurized, and a check valve may be provided adjacent to the fluid communicator, such that fluid begins flowing through the fluid communicator almost immediately after the electrochemical actuator begins displacing. For example, thefluid source604 is not pressurized in thedevice600 shown inFIG. 6(d), and therefore fluid may not initially flow from thedevice600 at a relatively constant rate, but such issue may be addressed by pressurizing thefluid source604 and providing the check valve adjacent to thefluid communicator606.
• Because the displacement of the electrochemical actuator may be relatively proportional to the current passing through the electrical circuit, the electrochemical actuator may be relatively easy to control. For example, the displacement of the electrochemical actuator may be varied by one or more flow control means positioned in the electrical circuit. Examples of such flow control means include one or more electrical contacts, switches, controllers, circuitry components, or combinations thereof, as further described below. The flow control means may be operative to control the electrical circuit. For example, the flow control means may be operative to open or close the electrical circuit. When the flow control means open the electrical circuit, the electrochemical actuator may stop discharging and actuating, such that the fluid is not expelled from the fluid source. When the flow control means closes the electrical circuit, the electrochemical actuator may begin discharging and actuating, such that fluid is expelled from the fluid source. The flow control means also may be operative to vary the current through the electrical circuit, such as by varying the resistance of the electrical circuit. When the flow control means varies the current or the resistance, the electrochemical actuator may discharge at a varied rate, such that the electrochemical actuator displaces at a varied rate to expel from the fluid source at a varied flow rate.
• FIG. 12 is a schematic illustrating an embodiment of anelectrical circuit1200 that includeselectrical contacts1264. Theelectrical contacts1264 may permit theelectrochemical actuator1202 to displace when theelectrical contacts1264 are in electrical communication with each other, but not otherwise. As shown, theelectrical contacts1264 are not in electrical communication with each other. Therefore, theelectrical circuit1200 is broken. Theelectrochemical actuator1202 is not discharging or displacing, and therefore fluid is not flowing. In embodiments, suchelectrical contacts1264 may preserve theelectrochemical actuator1202 in the charged state until the device is assembled, so that the electrochemical cell may not lose charge until the device is to be used. Suchelectrical contacts1264 may also prevent fluid flow until the device is assembled.
• Such an embodiment is shown and described with reference back toFIG. 4. Specifically,electrical contacts464 may be positioned in thebase portion422 and themovable portion424. Theelectrical contacts464 are shown as (+) and (−) for illustrative purposes, although the configuration may be reversed in other embodiments. When thedevice400 is in the unassembled position shown inFIG. 4(a), theelectrical contacts464 may not contact each other, breaking the electrical circuit to prevent theelectrochemical actuator402 from discharging and actuating. When thedevice400 is moved into the assembled position shown inFIG. 4(b), theelectrical contacts464 may contact each other to close the electrical circuit, permitting theelectrochemical actuator402 to begin discharging and actuating, provided the electrical circuit is not broken in some other place. Subsequently, theelectrochemical actuator402 may act on thefluid reservoir404 to deliver fluid out of thefluid communicator406, as shown inFIG. 4(c). It should be noted that assembling thedevice400 may not cause theelectrical contacts464 to directly contact each other, but instead may place theelectrical contacts464 in electrical communication with each other so that the electrical circuit can be closed. Alternatively, the electrical contacts may be omitted completely, in which case the electrochemical actuator may or may not be prevented from discharging when the device is unassembled.
• With reference back toFIG. 12, when theelectrical contacts1264 are positioned in theelectrical circuit1200 with anelectrochemical actuator1202 having a relatively constant voltage and aresistor1280 having a relatively constant electrical resistance, fluid may not be delivered until the device is assembled, and thereafter fluid may be delivered according to a relatively continuous release profile. Specifically, fluid may begin flowing once the device is assembled and may continue flowing at a relatively constant rate until the electrochemical actuator becomes completely discharged or the fluid source becomes empty. Alternatively, the release profile may be varied by implementing one or more additional flow control means as further described below.
• FIG. 13 is a schematic illustrating an embodiment of anelectrical circuit1300 that includes avariable resistor1380. Thevariable resistor1380 may be any electrical component having an electrical resistance that may be altered or controlled. More specifically, varying thevariable resistor1380 may vary the current1382 induced in thecircuit1300, which in turn may vary the discharge rate of theelectrochemical actuator1302. Similarly, varying the discharge rate of theelectrochemical actuator1302 may vary the displacement rate of theelectrochemical actuator1302, which in turn may vary the fluid flow rate from the fluid source. Thus, the electrical resistance of thevariable resistor1380 may be adjusted to control the fluid flow from the fluid source. The adjustment in the fluid flow may be proportional to the adjustment in the electrical resistance, due to the principles described above.
• FIG. 14 is a schematic illustrating an embodiment of anelectrical circuit1400 that includes aswitch1484. Theswitch1484 may be operative to open or close theelectrical circuit1400. When theswitch1484 is closed, theelectrochemical actuator1402 may discharge. For example, theelectrochemical actuator1402 may discharge at a relatively constant rate in embodiments in which theresistor1480 has a relatively constant electrical resistance. When theswitch1484 is opened, theelectrochemical actuator1402 may be prevented from discharging, which prevents theelectrochemical actuator1402 from displacing. Thus, theswitch1484 may be adjusted to control the fluid flow from the fluid source.
• FIG. 15 is a graph illustrating adisplacement curve1500, indicating the displacement behavior as a function of time for a fluid source associated with theelectrical circuit1400 ofFIG. 14. Theswitch1484 may be intermittently opened and closed to vary the duty cycle of theelectrochemical actuator1402, thereby varying the displacement of theelectrochemical actuator1402. For example, during a full on cycle, theswitch1484 may be closed so that theelectrochemical actuator1402 may displace at a relatively constant rate. During a duty cycle, theswitch1484 may be intermittently opened and closed so that the effective displacement rate of theelectrochemical actuator1402 is relatively lower than the displacement rate during the full on cycle. Specifically, the effective displacement rate may depend upon the amount of time theswitch1484 spends in the opened and closed positions. Thedisplacement curve1500 illustrates the displacement for theelectrochemical actuator1402 when theswitch1484 is closed during the duty cycle for 16% of the time, 33% of the time, and 66% of the time, respectively, although any configuration is possible. As shown, closing theswitch1484 for 66% of the time results in a relatively higher effective displacement rate, and therefore a relatively higher fluid flow rate, than closing theswitch1484 for 33% of the time or 16% of the time.
• FIG. 16 is a schematic view of an embodiment of adevice1600 that includes an embodiment of acontrol system1672. Thecontrol system1672 may be adapted to control anelectrochemical actuator1602. Specifically, thecontrol system1672 may vary the displacement of theelectrochemical actuator1602 to vary the fluid flow rate from afluid source1604, through afluid communicator1606, and into auser1608. For example, thecontrol system1672 may vary the displacement of theelectrochemical actuator1602 by opening the circuit, closing the circuit, or varying the current or resistance of the circuit. Thereby, thecontrol system1672 may permit administering a selected release profile or altering a release profile. For example, thecontrol system1672 may administer a constant fluid flow rate, a varied fluid flow rate, a continuous fluid flow, a discontinuous fluid flow, a modulated fluid flow, a pulsed fluid flow, a programmed fluid flow , a scheduled fluid flow, a feedback responsive fluid flow, a user-controlled fluid flow, or a fluid flow that is varied at a rate responsive to a biological or mechanical measure. Therefore, thecontrol system1672 may permit safe delivery of the drug therapy in a manner that benefits theuser1608.
• Thecontrol system1672 may comprise one or more flow control means, such as one or more of the electrical contacts, resistor, variable resistor, and switch described above, or other known circuitry components or combinations thereof. In embodiments, thecontrol system1672 may also comprise a controller and a memory, such as a microcontroller or a state machine. The memory may include a program of operation comprising a set of instructions executable by the controller. The controller may execute the program of operation to vary the current or resistance of the electrical circuit according to the set of instructions. For example, the controller may be operative to control the one or more flow control means to open the circuit, close the circuit, or vary the current or resistance of the circuit. Thereby, the controller may be operative to vary the fluid flow from the device to achieve a selected release profile. For example, the release profile may be a programmed release profile, a scheduled release profile, or a release profile that is response to one more inputs received from, for example, afeedback system1676 or auser interface1678. In embodiments, thecontrol system1672 may be powered by anexternal power source1674. Thepower source1674 may be another electrochemical actuator of suitable voltage, although thepower source1674 may have any other configuration or may be omitted.
• In other embodiments, the flow control means may be arranged within the electrical circuit to control the circuit in a particular manner as a function of time, in whichcase control system1672 may not include the controller and in which case a pre-defined release profile may be “hard-coded” into the electrical circuit.
• In embodiments, thecontrol system1672 may control the electrical circuit according to the time of day. For example, a schedule may be set by the user. Such an embodiment may permitting controlling the flow according to the circadian rhythm of the body.
• In embodiments, thecontrol system1672 may permit controlling the electrical circuit in response to inputs received from one or both of thefeedback system1676 and theuser interface1678. For example, thecontrol system1672 may open the circuit, close the circuit, or vary the current or resistance of the circuit in response to the inputs.
• Thefeedback system1676 may be adapted to measure or otherwise sense one or more conditions associated with the device and/or the user. For example, thefeedback system1676 may sense an actual current through the electrical circuit, an actual voltage across the electrical circuit, an actual discharge of theelectrochemical actuator1602, an actual displacement of theelectrochemical actuator1602, an actual fluid flow out of thefluid source1604, an actual fluid flow through thefluid communicator1606, an actual current rate through the electrical circuit, an actual voltage rate across the electrical circuit, an actual discharge rate of theelectrochemical actuator1602, an actual displacement rate of theelectrochemical actuator1602, an actual fluid flow rate out of thefluid source1604, an actual fluid flow rate through thefluid communicator1606, proxies for these conditions, other conditions, or combinations thereof. For example, thefeedback system1676 may comprise one or more sensors known in the art and appropriately positioned within thedevice1600, such as a strain gauge, a capacitive sensor, a variable resistance sensor, a flow sensor, or a vision sensor, among others. Thefeedback system1676 may provide the sensed conditions to thecontrol system1676, which may be operative to change the discharge rate of theelectrochemical actuator1602 in response to the sensed conditions, such as by opening the circuit, closing the circuit, or varying the current or resistance of the circuit. Thereby, thecontrol system1676 may maintain the desired release profile.
• In embodiments, thefeedback system1676 may be in communication with the user and may sense one or more conditions associated with the user. For example, thefeedback system1676 may remove a bodily fluid from theuser1608, and in response thecontrol system1672 may adjust the release profile. Thefeedback system1676 may also be in communication with a power source, such as thepower source1674, which may be another electrochemical actuator. In another variation, thefeedback system1676 may include a biosensor, e.g., to assess the concentration of one or more analytes in a physiological fluid of the patient.
• As mentioned above, thecontrol system1672 may be in communication with auser interface1608. Theuser interface1678 may accept one or more inputs from the user, and thecontrol system1672 may adjust the release profile in response to the input. The user inputs may comprise one or more of the following: a request to initiate fluid flow, a request to discontinue fluid flow, a request to cause temporarily fluid flow, and a request to vary the fluid flow rate. For example, the device may include one or more user-responsive controls such as a switch, a button, or a slider. The switch may permit the user to turn the fluid flow on or off, such as by opening or closing the circuit. The button may permit the user to initiate a temporary fluid flow, such as by temporarily closing the circuit. The slider may permit the user to vary the flow rate of the fluid flow, such as by varying the current through the electrical circuit. Theuser interface1608 may also include a display, which may display information delivered by thecontrol system1672, such as the number of doses dispensed and/or a number of doses remaining. Such information may be provided to thecontrol system1672 by, for example, thefeedback system1676.
• Thus, thecontrol system1672 may permit delivering drugs continuously, on-demand, or in a modulated manner. The device may be used, for example, for continuous delivery of normally injected compounds, for the delivery of compounds requiring titration and precise control, or for on-demand patient controlled analgesia.
• Thedevice1600 is shown and described by way of example, and other configurations are included within the scope of the present disclosure. For example, the displacement of theelectrochemical actuator1602 may be transferred to thefluid source1604 through atransfer mechanism1668 as shown, although thetransfer mechanism1668 may be omitted. Further, thefeedback system1676 and/or theuser interface1678 may be omitted, in which case thecontrol system1676 may not be responsive to feedback or inputs received from theuser1608, respectively.
• By way of example, the flow control means are described above as controlling the fluid flow from the device by controlling the discharge of the electrochemical actuator. Such embodiments may preserve the potential of the electrochemical actuator, such that discharge of the electrochemical actuator results in correlated fluid flow. In other embodiments, the electrochemical actuator may actuate as it charges, in which case charging the electrochemical actuator results in correlated fluid flow. In still other embodiments, the flow control means may control the fluid flow by controlling the transfer structure or other intervening mechanics between the electrochemical actuator and the fluid source. In such embodiments, the electrochemical actuator may continuously discharge, but transfer of the correlated displacement may be interrupted or reduced in amplification by the transfer mechanism. A person of skill may be able to implement such a configuration based on the above disclosure.
• Upon reading the present disclosure, a person of skill would appreciate that the described embodiments of the device are merely illustrative examples that convey the scope and breadth of the present disclosure. Other embodiments of the device that combine portions of the embodiments described above are included within the scope of the present disclosure.
• Embodiments of the present device may be used to deliver a variety of drugs according to one or more release profiles. For example, the drug may be delivered according to a relatively uniform flow rate, a varied flow rate, a preprogrammed flow rate, a modulated flow rate, in response to conditions sensed by the device, in response to a request or other input from a user or other external source, or combinations thereof. Thus, embodiments of the present device may be used to deliver drugs having a short half-life, drugs having a narrow therapeutic window, drugs delivered via on-demand dosing, normally-injected compounds for which other delivery modes such as continuous delivery are desired, drugs requiring titration and precise control, and drugs whose therapeutic effectiveness is improved through modulation delivery or delivery at a non-uniform flow rate. These drugs may already have appropriate existing injectable formulations.
• For example, the present devices may be useful in a wide variety of therapies. Representative examples include, but are not limited to, insulin delivery forType 1 or Type 2 diabetes; leutenizing hormone releasing hormone (LHRH) or follicle stimulating hormone (FSH) for infertility; immunoglobulin for autoimmune diseases; apomorphine for Parkinson's disease; interferon A for chronic hepatitis B, chronic hepatitis C, solid or hematologic malignancies; antibodies for the treatment of cancer; octreotide for acromegaly; ketamine for pain, refractory depression, or neuropathic pain; heparin for post-surgical blood thinning; corticosteroid (e.g., prednisone, hydrocortisone, dexamethasone) for treatment of MS; morphine, hydromorphone, fentanyl or other opioids or non-opioids for post-operative pain or for chronic and breakthrough pain; and tizanidine for spasticity (e.g., MS, SCI, etc.).
• In a particular embodiment, the device may be used to administer ketamine for the treatment of refractory depression or other mood disorders. In embodiments, ketamine may include either the racemate, single enantiomer (R/S), or the metabolite (wherein S-norketamine may be active).
• In another particular embodiment, an embodiment of the device herein may be used for administration of Interferon A for the treatment of hepatitis C. In one embodiment, a several hour infusion patch is worn during the day or overnight three times per week, or a continuous delivery system is worn 24 hours per day. Such a device may advantageously may replace bolus injection with a slow infusion, reducing side effects and allowing the patient to tolerate higher doses. In other Interferon A therapies, the device may also be used in the treatment of malignant melanoma, renal cell carcinoma, hairy cell leukemia, chronic hepatitis B, condylomata acuminata, follicular (non-Hodgkin's lymphoma, and AIDS-related Kaposi's sarcoma.
• In still another particular embodiment, an embodiment of the device described herein may be used for administration of apomorphine or other dopamine agonists in the treatment of Parkinson's Disease (“PD”). Currently, a bolus subcutaneous injection of apomorphine may be used to quickly jolt a PD patient out of an “off” state. However, apomorphine has a relatively short half-life and relatively severe side effects, limiting its use. The device described herein may provide continuous delivery and may dramatically reduce side effects associated with both apomorphine and dopamine fluctuation. In one particular embodiment, the device provides continuous delivery of apomorphine or other dopamine agonist, with, optionally, an adjustable baseline and/or a bolus button for treating an “off” state in the patient. Advantageously, this method of treatment may provide improved dopaminergic levels in the body, such as fewer dyskinetic events, fewer “off” states, less total time in “off” states, less cycling between “on” and “off” states, and reduced need for levodopa; quick recovery from “off” state if it occurs; and reduced or eliminated nausea/vomiting side effect of apomorphine, resulting from slow steady infusion rather than bolus dosing.
• In yet another embodiment, an embodiment of the device may be used for administration of an analgesic, such as morphine, hydromorphone, fentanyl or other opioids, in the treatment of pain. Advantageously, the device may provide improved comfort in a less cumbersome and/or less invasive technique, such as for post-operative pain management. Particularly, the device may be configured for patient-controlled analgesia.
• Publications cited herein and the materials for which they are cited are specifically incorporated by reference. Modifications and variations of the methods and devices described herein will be obvious to those skilled in the art from the foregoing detailed description. Such modifications and variations are intended to come within the scope of the appended claims.

Claims (21)

1-53. (canceled)

54. A device for delivering a therapeutic to a patient comprising:

an electrochemical actuator including a negative electrode, a positive electrode, and a species formulated to intercalate, de-intercalate, alloy with, oxidize, reduce, or plate with a first portion of the electrochemical actuator to an extent different than with a second portion of the electrochemical actuator, thereby imparting a differential strain between the first and second portions and causing a displacement of at least a portion of the electrochemical actuator; and

an electrical circuit electrically coupled to the electrochemical actuator so as to allow the electrochemical actuator to discharge therethrough, the electrical circuit including only fixed resistive elements, the electrical circuit configured to allow the electrochemical actuator to discharge such that the therapeutic is delivered to the patient with linear flow.

55. The device ofclaim 54, further comprising:

a housing being movable between an unassembled configuration in which the electrochemical actuator is in a deactivated state, and an assembled configuration in which the electrochemical actuator is in an activated state such that the electrical circuit is closed causing the electrochemical actuator to discharge, thereby delivering the therapeutic to the patient.

56. The device ofclaim 55, wherein the housing includes a first portion and a second portion, the first portion and the second portion configured to form a cooperative fit when the housing is in the assembled position to activate the electrochemical actuator.

57. The device ofclaim 56, wherein when the housing is in the assembled position, the first portion of the housing and the second portion of the housing releasably lock together.

58. The device ofclaim 56, wherein the first portion of the housing includes a first electrical contact and the second portion of the housing includes a second electrical contact, the first and second electrical contacts are positioned to contact each other when the housing is in the assembled position but not when the housing is in the unassembled position.

59. The device ofclaim 54, wherein one of the negative electrode and the positive electrode is a bimorph electrode.

60. The device ofclaim 54, wherein the first portion of the electrochemical actuator and the second portion of the electrochemical actuator are formed of different materials.

61. The device ofclaim 54, wherein one of the first portion of the electrochemical actuator and the second portion of the electrochemical actuator comprises a dimensionally-active material.

62. The device ofclaim 54, wherein the first portion of the electrochemical actuator is configured to allow intercalation of a species to a different extent than to the second portion of the electrochemical actuator, thereby imparting differential strain between the first portion and the second portion to cause deflection of the electrode.

63. The device ofclaim 54, wherein the displacement of the electrochemical actuator is approximately proportional to a current though the electrical circuit, and the therapeutic is delivered to the patient at a rate approximately proportional to the displacement rate of the electrochemical actuator.

64. A device for delivering a flowable material a patient comprising:

a delivery system including a source, a cannula, and an electrochemical actuator including an electrode configured to deflect as the electrochemical actuator undergoes a change in electrical potential, the deflection of the electrode being operative to cause the flowable material to be delivered from the source; and

a housing configured for removably associating the delivery system with the body of the patient, the housing being movable between an unassembled configuration in which the delivery system is in a deactivated state, and an assembled configuration in which a first portion forms a cooperative fit with a second portion and activates the electrochemical actuator, thereby delivering the flowable material from the source through the cannula.

65. The device ofclaim 64, wherein the cannula is in fluidically isolated from the source in the unassembled configuration.

66. The device ofclaim 64, wherein the cannula is movable from a retracted position in which the cannula is disposed inside the housing when the housing is in the unassembled configuration and a deployed position in which the cannula protrudes outside the housing when the housing is in the assembled configuration.

67. The device ofclaim 64, further comprising:

an insertion mechanism, the insertion mechanism configured to insert the cannula into the body of the patient when the housing is moved between an unassembled configuration and the assembled configuration.

68. The device ofclaim 64, further comprising:

an insertion mechanism, the insertion mechanism including a needle slidably disposed within the cannula, the insertion mechanism configured to insert the cannula into the body of the patient when the housing is moved between an unassembled configuration and the assembled configuration.

69. The device ofclaim 68, wherein the insertion mechanism includes a spring coupled to the needle to urge the needle in a direction to insert the cannula into the body of the patient, and a latch configured to restrain the spring in a compressed state.

70. The device ofclaim 64, wherein the first portion of the housing includes a first electrical contact and the second portion of the housing includes a second electrical contact, the first and second electrical contacts positioned to contact each other when the housing is in the assembled position to activate the electrochemical actuator thereby delivering the flowable material from the source through the cannula.

71. A method for administering a drug to a patient, the method comprising:

securing a disposable infusion pump to the patient's skin, wherein the disposable infusion pump comprises (i) a reservoir storing a fluid which includes at least one drug; (ii) an electrochemical actuator including an electrode configured to deflect as the electrochemical actuator discharges; and (iii) at least one fluid communicator positionable to penetrate the patient's skin; and

activating the electrochemical actuator causing the electrode to deflect, thereby delivering fluid from the reservoir, through the fluid communicator, and into the patient.

72. The method ofclaim 71, further comprising:

discharging the electrochemical actuator through an electrical circuit having only fixed resistive elements, the discharging of the electrochemical actuator causing the electrochemical actuator to deflect at a rate approximately proportional to a current though the electrical circuit, thereby delivering fluid from the reservoir, through the fluid communicator, and into the patient at a substantially linear flow rate.

73. The method ofclaim 71, wherein the drug includes at least one of an opioid narcotic, a NonSteroidal AntiInflamatory, a local anesthetic, a dopamine antagonist, an antihistamine, an antileukotriene, an anticholinergic, an immunotherapeutic agent, an antispastic, a vitamin, a selegiline and a rasagiline.

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