Patent Application
20170182242
This disclosure relates generally to injection devices for use in delivering therapeutic fluids to a patient, and more particularly to wearable automatic injection devices and methods of using wearable automatic injection devices.
Automatic injection devices offer an alternative to manually-operated syringes for delivering therapeutic agents into patients' bodies and allowing patients to self-administer injections. Automatic injection devices have been used to deliver medications under emergency conditions, for example, to administer epinephrine to counteract the effects of a severe allergic reaction. Automatic injection devices have also been described for use in administering anti-arrhythmic medications and selective thrombolytic agents during a heart attack (See, e.g., U.S. Pat. Nos. 3,910,260; 4,004,577; 4,689,042; 4,755,169; and 4,795,433). Various types of automatic injection devices are also described in, for example, U.S. Pat. Nos. 3,941,130; 4,261,358; 5,085,642; 5,092,843; 5,102,393; 5,267,963; 6,149,626; 6,270,479; 6,371,939; and 9,180,244 and International Patent Publication No. WO/2008/005315; each of which is incorporated by reference herein in its entirety.
Conventionally, an automatic injection device houses a syringe and, when operated, causes the syringe to move forwardly and a needle to project from the housing so that a therapeutic agent contained in the syringe is ejected into a patient's skin. An automatic injection device typically includes a bung disposed within the syringe that when actuated, moves within the syringe to expel the therapeutic agent from the syringe and into the patient's skin. During operation of conventional automatic injection devices, a user actuates a firing button to cause the syringe needle to penetrate the skin and move the syringe bung within the syringe to expel the therapeutic agent into the patient's skin.
Conventional automatic injection device users may experience anxiety, pain, discomfort and frustration preparing for, actuating, upon skin penetration, and during injection, resulting in unacceptably high treatment abortion rates, non-compliance and non-persistence. Wearable automatic injection devices, such as Wearable Bolus injectors (WBI) or On-Body Delivery Systems (OBDS) for subcutaneous uses are preferred by many patients over conventional automatic injection devices, because patients associate subcutaneous injection and delivery with a WBI or OBDS as less painful, simpler, easier to learn, and generally less threatening and more comfortable. However, conventional WBI and OBDS devices are expensive, require custom filling and are bulky in size.
Accordingly, there remains a need for further improvement of known automatic injection devices. For example, it may be desirable to provide a wearable automatic injection device that can be configured for use with a variety of prefilled therapeutic agent containers, such as syringes, cartridges, vial or ampules. It may also be desirable to configure such devices by forming sterile barriers in the wearable automatic injection device while being easy to manufacture and use.
The purpose and advantages of the disclosed subject matter will be set forth in and apparent from the description that follows, as well as will be learned by practice of the disclosed subject matter. Additional advantages of the disclosed subject matter will be realized and attained by the methods and systems particularly pointed out in the written description and claims hereof, as well as from the appended drawings.
To achieve these and other advantages and in accordance with the purpose of the disclosed subject matter, as embodied and broadly described, exemplary embodiments of the disclosed subject matter provide wearable automatic injection devices that may adhere to the skin or clothing of a patient and deliver a therapeutic agent into the patient's body by subcutaneous injection at slow, controlled injection rates, e.g., in a single slow bolus. Exemplary embodiments provide methods of assembling exemplary wearable automatic injection devices. Exemplary embodiments also provide methods of using wearable automatic injection devices worn by a patient for slow, controlled therapeutic agent delivery. Exemplary wearable automatic injection devices reduce or eliminate a burning sensation often felt or perceived by patients who use a conventional automatic injection device. Exemplary wearable automatic injection devices maintain the sterility of the therapeutic agent container (e.g., syringe, cartridge, vial, ampoule), are easy to use, pre-fill capable, easy to manufacture, and/or do not require aseptic assembly. The wearable automatic injection devices provided by exemplary embodiments may deliver any therapeutic agent including, but not limited to, a biologic drug, such as, for example, an antibody, insulin, etc.
In accordance with an exemplary embodiment, a wearable automatic injection device is provided for providing an injection of a therapeutic agent into a patient. The device includes a housing comprising a contact portion securable to the patient, and an injection assembly moveably disposed in the housing holding an injection needle for insertion into the patient. The injection assembly is movable between a retracted position in which the injection needle does not protrude outside the housing and an extended position in which the injection needle protrudes outside the housing. The device includes a prefilled container assembly disposed in the housing for holding the therapeutic agent, the prefilled container assembly may include a barrel with a sealed distal end, the barrel may have a first stopper, a second stopper spaced from and movable relative to the first stopper, and a dispensing member coupled to a distal portion of the second stopper and configured to engage the first stopper. The dispensing member may be in fluid communication with the injection needle.
In some examples, the wearable automatic injection device may include all or a combination of the following features: a fluid line coupled to and extending between the patient injection needle and the penetrating member, the fluid line may be movable with the injection assembly, a fluid drive mechanism may be configured to urge the second stopper in a distal direction toward the first stopper, the fluid drive mechanism may be selected from the group consisting of a: hydraulic mechanism, pneumatic mechanism, spring motor or clock spring mechanism, cam actuator, and compression spring, the housing may include a top surface comprising a viewing window radially aligned with the contents of the barrel, the housing may have a bottom surface comprising an adhesive surface defining the contact portion, and the bottom surface may have an aperture therethrough, the patient injection needle extending through the aperture when the injection assembly is in the extended position.
In accordance with another exemplary embodiment, a prefilled container assembly is provided having a container including a barrel having a sealed distal end and a proximal end, a first stopper and a second stopper spaced from the first stopper toward the proximal end and movable relative to the first stopper; a dispensing member coupled to a distal portion of the second stopper and configured to engage the first stopper; and a fluid tube in fluid communication with the dispensing member and an injection needle.
In some examples, the container may include a syringe or a cartridge.
In accordance with another exemplary embodiment, a method is provided for injecting a therapeutic agent into a patient. The method includes providing a container prefilled with the therapeutic agent and a first stopper, urging a second stopper having a dispensing needle extending therefrom into engagement with the first stopper, and delivering the therapeutic agent to the patient via an injection needle in fluid communication with the second stopper.
In accordance with another exemplary embodiment, a method is provided for assembling a prefilled container and injection assembly including sealing a distal end of a container; inserting a fluid through a proximal end of the container; inserting a first stopper through the proximal end of the container to seal the fluid therein; inserting a second stopper through the proximal end of the container, the second stopper having a dispensing member extending therefrom toward the first stopper; joining the second stopper to a first end of a tubing member extending through the proximal end of the container; and joining an opposing end of the tubing member to an injection needle.
In accordance with another exemplary embodiment, a wearable automatic injection device is provided for injection of a therapeutic agent into a patient, the wearable automatic injection device comprises a housing comprising a contact portion configured to secure to the patient; an injection assembly moveably disposed in the housing, the injection assembly including an injection needle to be inserted into the patient, the injection assembly movable between a retracted position in which the injection needle does not protrude outside the housing and an extended position in which the injection needle protrudes outside the housing; a prefilled container assembly provided in the housing, the prefilled container assembly comprising a container with a sealed distal end, a first stopper spaced from the distal end and defining a fluid reservoir therebetween to hold a mixing fluid, a second stopper spaced from the first stopper toward the proximal end and movable relative to the first stopper, and a dispensing member extending from the second stopper toward the first stopper and configured to engage the first stopper, the dispensing member in fluid communication with the injection needle via a fluid line; and a mixing chamber containing the therapeutic agent, the mixing chamber disposed between and in fluid communication with the prefilled container assembly and the injection needle via the fluid line.
In accordance with another exemplary embodiment, a prefilled container assembly is provided, the prefilled container assembly comprises a barrel having a sealed distal end and a proximal end; a first stopper spaced from the distal end and defining a fluid reservoir therebetween; a second stopper spaced from the first stopper toward the proximal end; a dispensing member joined to the second stopper and configured to engage the first stopper; and a fluid tube in fluid communication with the dispensing member and an injection needle.
In some examples, the prefilled container assembly may include all or a combination of the following features: the prefilled container may include a fluid therapeutic agent in the fluid reservoir. the dispensing member may be configured to engage the first stopper and define a channel therethrough to allow the fluid therapeutic agent to move from the fluid reservoir to the fluid tube through first and second stoppers, the distal end of the barrel may have a diameter less than a diameter of the proximal end of barrel, the second stopper may be configured to urge the first stopper toward the distal end of the barrel, the injection needle may be configured to penetrate the skin of a patient and deliver the fluid therapeutic agent from the fluid reservoir to patient, the fluid therapeutic agent may include a biological agent.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the disclosure and together with the description, serve to explain the principles of the invention.
Reference will now be made in detail to the present embodiments (exemplary embodiments) of the disclosure, examples of which are illustrated in the accompanying drawings. The structure and corresponding method of operation of the disclosed subject matter will be described in conjunction with the detailed description of the system. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.
The apparatus and methods presented herein can be used for injecting any of a variety of suitable therapeutic agents or substances, such as a drug, into a patient. As used herein, an “automatic injection device” or “autoinjector” (used interchangeably herein) is intended to refer generally to a device that enables an individual (also referred to herein as a user or a patient) to self-administer a dosage of a liquid substance, such as a therapeutic agent, including a formulation in liquid form, wherein the device differs from a standard prefilled therapeutic agent container by the inclusion of a mechanism for automatically delivering the medication to the individual by injection when the mechanism is activated.
Subcutaneous injection is a typical mode of therapeutic agent delivery and involves administering a bolus of a therapeutic agent into a patient. Subcutaneous injections are highly effective in administering various therapeutic agents including insulin, vaccines, and drugs. Automatic injection devices offer an alternative to a manual injection device, such as a syringe, for delivering a therapeutic agent and allow patients to self-administer subcutaneous injections of therapeutic agents. Conventional automatic injection devices include hand held automatic injection devices and patch pumps, which are self-adhesive, patient-mounted autoinjectors. In use, a patch pump containing a therapeutic agent is mounted onto the skin or clothing of a patient and triggered to inject the therapeutic agent into the patient. Conventional patch pumps are typically filled by a patient prior to use. In addition, certain conventional patch pumps have an exposed needle inside the pump, and thus require secondary sterile packaging to maintain sterility.
There can be a correlation between the injection rate of certain therapeutic agents and the pain perceived by a patient upon injection of the therapeutic agents or agents. Some therapeutic agents can cause pain, e.g., a burning or stinging sensation, when injected rapidly into the patient. The pain sensation may be the result of a physiological response of the patient's skin to the subcutaneous injection of a therapeutic agent. Large volumes of any therapeutic agent, greater than one milliliter, may also cause pain when injected into the skin. Antibodies, and portions thereof, are exemplary therapeutic agents that are least painful when delivered at slow injection rates. Commercially available prefilled patch pumps can fail to effectively address the discomfort associated with fast injection rates of hand held automatic injection devices that are prefilled, or configured for delivery of a therapeutic agent in seconds or a few minutes.
Exemplary embodiments are described below with reference to certain illustrative embodiments. While exemplary embodiments are described with respect to using a wearable automatic injection device to provide an injection of a dose of a liquid medication, one of ordinary skill in the art will recognize that exemplary embodiments are not limited to the illustrative embodiments and that exemplary automatic injection devices may be used to inject any suitable substance into a patient. In addition, components of exemplary automatic injection devices and methods of making and using exemplary automatic injection devices are not limited to the illustrative embodiments described below.
The 1 mL prefilled glass standard syringe with pre-staked injection needle and needle cover has become a standard delivery system format for subcutaneously injected biotechnology drug products. The availability of a prefilled 1 mL syringe that ships to the user (patient, caregiver, or health care professional—HCP), allows for a relatively straightforward administration of the drug solution by users outside the HCP environment. Establishing a prefilled 1 mL glass syringe as primary package material as product presentation for an FDA and/or EMA approved drug can involve significant financial, regulatory and development time investments, which typically amounts to years of validation and qualification of drug product stability and fill-finish processes.
Additionally, certain prefilled syringes and disposable autoinjectors can cause patients to experience anxiety, pain, discomfort and frustration during injection, which can result in increased treatment abortion rates, non-compliance and non-persistence. Wearable automatic injection devices, such as Wearable Bolus Injectors (WBI) or On-Body Delivery Systems (OBDS) can be preferred by many patients over prefilled syringes, because patients associate the subcutaneous injection and delivery with a WBI or OBDS as less painful, simpler, easier to learn, and generally less threatening and more comfortable. The present subject matter thus provides the dosing experience patients perceive and experience with a wearable automatic injection device using a prefilled syringe as primary package material.
Certain embodiments described herein use a prefilled syringe or syringe barrel/cartridge as primary package material while at the same time providing a wearable automatic injection device to the user by forming sterile barriers in wearable bolus injector form factors by design and assembly of prefilled syringe primary packaging, fluid path, and needle insertion assembly and stopper penetration mechanisms. While the present disclosed subject matter is described with respect to a wearable automatic injection device to provide a subcutaneous injection of a dose from a prefilled syringe, one skilled in the art will recognize that the disclosed subject matter is not limited to the illustrative embodiment, and that the injection device can be used to inject a substance from any suitable container, including but not limited to prefilled syringes, cartridges, vials or ampules.
A syringe assembly of exemplary wearable automatic injection devices, such as WBI or OBDS devices, may contain a dose of any suitable therapeutic agent, for example, an antibody, a cytokine, a vaccine, a fusion protein or a growth factor. In a preferred embodiment, therapeutic agent is a TNFα inhibitor (e.g., an anti-TNF antibody or an antigen-binding portion thereof, a TNF fusion protein, or a recombinant TNF binding protein), such as adalimumab (HUMIRA®). Another particularly preferred therapeutic agent for use in the wearable automatic injection device is an isolated human antibody that dissociates from human TNFα with a Kd of 1×10−8 M or less and a Koff rate constant of 1×10−3 s−1 or less, both determined by surface plasmon resonance, and neutralizes human TNFα cytotoxicity in a standard in vitro L929 assay with an IC50 of 1×10−7M or less. In one example, the wearable automatic injection device, including uses and compositions thereof, comprises a dose of a TNFα inhibitor. In one example, the anti-TNFα antibody, or antigen-binding portion thereof, is a chimeric antibody, a humanized antibody, a human antibody, and a multivalent antibody. In one example, the anti-TNFα antibody is an isolated human antibody, or antigen-binding portion thereof and dissociates from human TNFα with a Koff rate constant of 1×10−3 s−1 or less, as determined by surface plasmon resonance.
In an exemplary embodiment, the human TNFα antibody or antigen-binding portion thereof may be adalimumab or golimumab. In another example, the human TNFα antibody or antigen-binding may be ABT-122 dual variable domain immunoglobulin. In another exemplary embodiment, the therapeutic agent may include a monoclonal antibody targeting interleukin 23A (IL-23A).
Exemplary embodiments provide wearable automatic injection devices that may adhere to the skin or clothing of the patient and deliver a therapeutic agent into patient by subcutaneous injection at slow, controlled injection rates, e.g., in a single slow bolus. The controlled injection rates achieved by exemplary devices in combination with the dosing experience of a wearable bolus injector may minimize the pain sensation associated with a volume of a therapeutic agent entering into the patent's tissue. Exemplary time durations for slow delivery achieved by exemplary devices may range from about 10 seconds to about 10 minutes and may depend on the injection volume, but are not limited to this exemplary range. Exemplary volumes of therapeutic agent deliverable by exemplary devices may range from about 0.4 milliliters to about 2.25 milliliter, but are not limited to this exemplary range. In addition, exemplary devices may advantageously minimize inflections in the delivery profile against time of the therapeutic agent. Exemplary viscosities of therapeutic agent deliverable by exemplary devices may range from about 1 cPs to about 50 cPs, but are not limited to this exemplary range. In addition, exemplary devices may advantageously minimize inflections in the delivery profile against time of the therapeutic agent.
Exemplary embodiments reduce or minimize the size envelope of exemplary wearable automatic injection devices, and provide scalable solutions with configurable delivery times and delivery profiles that may be used for a range of therapeutic agent viscosities.
Exemplary embodiments may use prefilled containers, such as syringes, cartridges, vials or ampules, with industry standard configurations of 1 mL, 1.5 mL and 2.25 mL. Scalable solutions with configurable delivery times and delivery maybe achieved by using 10 mL and 20 mL prefilled syringes.
Exemplary embodiments of the wearable automatic injection device may use prefilled syringes with staked needles covered by rubber needle shields, or rubber and rigid needle shield combinations as sterile barriers.
Exemplary embodiments of the wearable automatic injection device may use prefilled syringes where the step of needle staking and needle covering with needle shields to provide a sterile barrier has been skipped and omitted during the manufacturing process of the syringe.
Other exemplary embodiments of the wearable automatic injection device may use prefilled syringes where the manufacturing steps of needle staking and needle covering with needle shields and forming the cone or conical portion at the tip of the needle have been skipped and omitted.
Exemplary embodiments provide wearable automatic injection devices that deliver a therapeutic agent into a patient by subcutaneous injection at slow, controlled injection rates, e.g., in a single slow bolus. Exemplary embodiments may also provide methods of using the wearable automatic injection devices for slow, controlled therapeutic agent delivery. The wearable automatic injection devices provided by exemplary embodiments are pre-fillable prior to delivery to the patient; maintain sterility of the therapeutic agent and all subcutaneous contact surfaces (i.e., an injection needle) to avoid the need for aseptic assembly and address the perceived patient discomfort due to injection by conventional hand held automatic injection devices. Exemplary wearable automatic injection devices are disposable, easy to use, pre-fill capable, and may substantially or completely eliminate injection discomfort and/or injection anxiety often experienced by a patient that uses a prefilled syringe or a wearable automatic injection device that a patient needs to fill and self-assemble before injection of the drug occurs. The wearable automatic injection devices provided by exemplary embodiments can be used to deliver any therapeutic agent that may be delivered subcutaneously including, but not limited to, an antibody or insulin, etc.
The wearable automatic injection device of the exemplary embodiments may include a “therapeutically effective amount” or a “prophylactically effective amount” of a therapeutic composition such as an antibody or antibody portion. A “therapeutically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic result. A therapeutically effective amount of an antibody, antibody portion, or other TNFα inhibitor may vary according to factors such as the disease state, age, sex, and weight of the patient, and the ability of the antibody, antibody portion, or other TNFα inhibitor to elicit a desired response in the patient. A therapeutically effective amount can also be one in which any toxic or detrimental effects of the antibody, antibody portion, or other TNFα inhibitor are outweighed by the therapeutically beneficial effects. A “prophylactically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically, since a prophylactic dose is used in patients prior to or at an earlier stage of disease, the prophylactically effective amount will be less than the therapeutically effective amount.
The terms “substance” and “therapeutic agent” refer to any type of drug, biologically active agent, biological substance, chemical substance or biochemical substance that is capable of being administered in a therapeutically effective amount to a patient employing exemplary automatic injection devices. Exemplary substances include, but are not limited to, agents in a liquid state. Such agents may include, but are not limited to, adalimumab (HUMIRA®), ABT-122 (a dual variable domain immunoglobulin targeting TNFα. IL-23A and IL-17, and proteins that are in a liquid solution, e.g., fusion proteins and enzymes.
In an exemplary wearable automatic injection device including a prefilled container assembly, a dispensing needle may be coupled directly to the barrel portion of the syringe and may be in fluid communication with the barrel portion. The term “pre-injection state” refers to a state of a wearable automatic injection device prior to the start of delivery of a therapeutic agent contained in the device. The term “injection state” refers to one or more states of a wearable automatic injection device during the delivery of a therapeutic agent contained in the device. The term “post-injection state” refers to completion of delivery of a therapeutically effective dose of a therapeutic agent contained in the device and also to removal of the device from the patient prior to completion of delivery of a therapeutically effective dose of the therapeutic agent.
The term “slow” refers to a delivery rate of a volume of a therapeutic agent. In an exemplary embodiment, a volume of about 0.1 milliliters to about 1 milliliter or more may be delivered in a delivery time period of about ten seconds to about 60 seconds. In a preferred embodiment, the delivery time period may range from about 8 seconds to about 20 seconds for up to 1 milliliter volume of therapeutic agent, from about 20 seconds to about 60 seconds for up to 1.5 mL, from about 60 seconds to about 140 seconds for up to 2.25 mL. For every 0.4 mL delivery volume added to the delivery volume of 2.25 mL delivered in about 60 seconds to 140 seconds, an additional delivery time of about 50-70 seconds may be added to the overall delivery time.
The accompanying figures, where like reference numerals refer to identical or functionally similar elements throughout the separate views, serve to further illustrate various embodiments and to explain various principles and advantages all in accordance with the disclosed subject matter. For purpose of explanation and illustration, and not limitation, exemplary embodiments of the wearable automatic injection device, and exemplary techniques for making and using the wearable automatic injection device, in accordance with the disclosed subject matter are shown in
Exemplary wearable automatic injection devices may employ a prefilled container assembly, which can include a prefilled container, such as a syringe or cartridge, for holding a dose of a therapeutic agent that may be delivered into a patient's body through an injection assembly. Generally, and unless otherwise noted, the term “first end” or “distal end” refers to the portion or end of the prefilled container having a sealed end to prevent the therapeutic agent from exiting therethrough. The term “second end” or “proximal end” refers to the portion or end of the prefilled container spaced from the distal end and having a channel or opening to allow the therapeutic agent to exit therethrough. As such, the prefilled container and injection assembly is configured to deliver the therapeutic agent from a proximal end of the prefilled container via a cannula disposed proximate the proximal end of the syringe, the cannula being in fluid communication with the injection assembly, which can include a patient needle. The prefilled container assembly and the injection assembly can be joined, for example and as embodied herein, via a fluid channel.
The prefilled container and injection assembly 10 may include a first and second sealing component, such as stopper, such as a distal stopper 18 and a proximal stopper 20. The proximal stopper 20 may include a dispensing member 22 extending therefrom or therethrough, which can include a dispensing needle joined to the proximal stopper 20 by overmolding, adhesive, bonding, or via mechanical fixation. The dispensing member 22 may be configured to penetrate the distal stopper 18, as described herein. The dual stoppers (distal and proximal stoppers 18, 20) may be manufactured using the same or different materials and the dispensing member 22 extending from or disposed through the proximal stopper 20 may include a tip configured to minimize coring of the proximal stopper 20. The stoppers 18 and 20 may be configured in the syringe 12 to maintain sterile barriers for maintaining the sterility of the therapeutic agent held in the syringe 12. The prefilled container and injection assembly 10 may include tubing 24 having a first end 24a in fluid communication with the proximal stopper 20 and dispensing member 22 and a second end 24b in fluid communication with a needle hub 26. The tubing 24 may be manufactured using polypropylene, PVC, silicone, Teflon or any other suitable materials. The needle hub 26 may be in fluid communication with an injection needle 28 and disposed at a proximal end of the injection needle 28, the distal end of the injection needle 28 being configured to inject the therapeutic agent in the syringe 12 to a patient. The needle hub 26 may be manufactured using any suitable material(s) such as polyester, co-polyester, or other thermoplastics. The dispensing member 22 and injection needle 28 may be manufactured using any suitable materials such as stainless steel. The dispensing needle 22 and/or injection needle 28 may have any suitable gauge/length. In some embodiments, the length of each needle 22 and 28 may be less than the gauge/length of a hypodermic needle attached to a conventional prefilled syringe for subcutaneous delivery (e.g. via an autoinjector). As shown in
The prefilled container and injection assembly 300 may include a distal stopper 318 and a proximal stopper 320. The proximal stopper 320 may be penetrated by a dispensing needle 322 similar to dispensing member 22. The prefilled container and injection assembly 300 may include tubing 324 having a first end 24a in fluid communication with the proximal stopper 320 and disposed proximate a slot 334 formed in a portion of the proximal stopper 320 and a dispensing needle 322. Tubing 324 may include a second end 324b in fluid communication with a needle hub 326. As shown in
The wearable automatic injection device 500 may be manufactured using any suitable materials. The wearable automatic injection device 500 also may include other actuators or control features configured to control various functions of the wearable automatic injection device 500 and also may include a display (not shown) for displaying information about the wearable automatic injection device 500 and/or receiving input from the user of the wearable automatic injection device 500. As shown in
With continued reference to
In use, a user may remove a cover (not shown) disposed proximate the bottom surface of the wearable automatic injection device 500 to expose adhesive surface 516 and aperture 518 and place the wearable automatic injection device 500 with aperture 518 proximate the injection site. The user may then actuate the actuation button 510 of the wearable automatic injection device 500 when the sensor 514 detects contact with the injection site. The injection needle may then be urged into an extended position extending through the hole 518 to penetrate the injection site. In addition, if the sensor no longer detects contact with the injection site, the injection needle may be retracted and delivery of the therapeutic agent may stop. At the same time or in close temporal proximity to the injection needle being urged into an extended position, the fluid actuation mechanism may move the proximal stopper with the dispensing needle in a distal direction toward the distal stopper to penetrate the distal stopper and allow the therapeutic agent in the prefilled container to flow through the dispensing needle as the distal stopper moves distally to the distal most end of the prefilled container to force the therapeutic agent out of the syringe and into the fluid pathway via the dispensing needle. The therapeutic agent may thus flow through the dispensing needle, through the proximal stopper and into the tubing. The therapeutic agent may continue to flow through the tubing through the proximal end of the prefilled container to the injection needle to deliver the therapeutic agent to the patient. In this manner, and as described further herein, the sterile conditions of the prefilled container and injection assembly are maintained.
Additionally or alternatively, a thermal liner can be disposed proximate an adhesive layer on the bottom surface of the device 1400 and can be configured to adhere to an injection site, such as a patient's skin. Such a thermal liner may be manufactured using one or more materials having insulating properties similar to the high thermal mass member 1430 and thus configured to reduce the temperature ramp rate after removal of the device 1400 from a refrigerated environment and prior to application to the patient's skin. When the adhesive layer is removed, the high thermal mass member 1430 may be exposed and can be positioned against the patient skin when the device 1400 is on the injection site. Additionally or alternatively, the device 500 may include other pain reduction components, such as a vibrating component configured to vibrate the device during needle insertion to distract needle insertion sensation.
In another example, the wearable automatic injection device, such as device 500, may include a mechanical visual indicator to provide feedback to a user of the device status. The mechanical visual indicator may provide a visual indication to the user that the wearable automatic injection device is in a “ready” configuration e.g. when the device is adequately adhered to the patient skin and the injection can be initiated. A viewing window can be disposed in the housing of the device. A mechanism actuated by a skin sensor (such as sensor 514 described herein) can toggle a visual indicator, for example and as embodied herein, indicating “no go” (or a red color or particular symbol) when the sensor does not detect contact with the injection site and indicating “go” (or a green color or other particular symbol) when the sensor detects contact with the injection site. Additionally or alternatively, an indicator can be urged into alignment with the viewing window after completion of a successful injection and/or an interrupted injection by joining the indicator mechanism to the prefilled container and injection assembly.
In another example, a wearable automatic injection device, such as device 500, may include a two-stage actuation button in combination with a viewing window to allow a user to prime the fluid pathway and/or purge air from the fluid pathway prior to delivery of the therapeutic agent. In this manner, priming the fluid pathway and/or purging air from the fluid pathway can include tilting the device about 90 degrees to a vertical orientation prior to adhering the device to the injection site in a horizontal orientation. In the vertical orientation, the user can actuate the two-stage actuation button to a first position, which opens a viewing window to visually inspect the syringe therethrough, positions an air bubble inside the prefilled syringe, and initiates movement of the proximal stopper and the dispensing needle toward the distal stopper. In this manner, the dispensing needle can penetrate the distal stopper, thereby priming the fluid pathway and/or purging air from the prefilled syringe prior to adhering the device to the skin. The user can place the primed device proximate the injection site, and actuate the two-stage actuation button to a second position, or alternatively, actuate a second actuation button, to deliver the therapeutic agent, as described herein, without air bubbles.
In use, as the therapeutic agent delivery is initiated in the device, the first stopper 1918 can be pierced by the dispensing needle 1922 joined to the second stopper 1920, and the mixing fluid 1915 in the container 1904 can be urged through the sterile fluid path 1924 to the mixing chamber 1902 to be mixed with the dried therapeutic agent to create a fluid therapeutic agent solution. The flow of the mixing fluid under pressure can mix the dried therapeutic agent with the mixing fluid. In some examples, the mixing chamber 1902 can include a separate power source configured to power a mixing mechanism (not shown) to provide additional or alternative mixing of the dried therapeutic agent. The geometry of the mixing chamber 1902 can be such that the therapeutic agent is sufficiently mixed without damage to the therapeutic agent molecules prior to being urged to the distal end of the sterile fluid path 1924 for delivery to the patient via injection needle 1928. In some examples, the mixing chamber 1902 may include separate internal chambers for holding two or more separate therapeutic agents and/or separate amounts of dried or partially dried therapeutic agents. The sterile path 1924 may deliver the mixing fluid 1915 to each of the internal chambers to allow the therapeutic agents to be mixed and reconstituted together, or alternatively, separately reconstituted and then delivered to the patient, e.g. via a bifurcated portion of the sterile path 1924. The reconstitution assembly 1900 may be contained in a wearable automatic injection device housing, such as housing 502 of device 500.
In another example, a wearable automatic injection device, such as device 500, the device may include an electronic circuit board to provide electronic features for the device. For example, and as embodied herein, the electronic circuit board can provide a power and/or data connection from the wearable automatic injection device to an external device, such as a personal computer or mobile device, via a data bus and power connector, such as USB, micro USB, Lightning, or other standard or proprietary data bus and/or power connector. In this manner, the device can obtain power for an electric motor for use instead of, or in addition to, the fluid drive mechanisms described herein. Additionally or alternatively, the data bus and power connection can also provide data collection, such as telemetry data, from the device 500 to the personal computer or mobile device. In addition, or as a further alternative, the data bus and power connection can also allow the external device to provide a user interface for control of the wearable automatic injection device and/or to provide visual or audible feedback to the user in addition to or as an alternative to the mechanical control and feedback features described herein.
Exemplary automatic injection devices may be used to administer essentially any substance or therapeutic agent that is suitable for administration by injection. Typically, the substance or therapeutic agent will be in a fluid, e.g., liquid form, although medications in other forms such as gels or semi-solids, slurries, particulate solutions, etc. also may suitable for use with the wearable automatic injection devices according to the disclosed subject matter. Preferred therapeutic agents include biological agents, such as antibodies, cytokines, vaccines, fusion proteins and growth factors.
The contents of all references, including patents and patent applications, cited throughout this application are hereby incorporated herein by reference in their entirety. The appropriate components and methods of those references may be selected for the invention and embodiments thereof. Still further, the components and methods identified in the Background section are integral to this disclosure and can be used in conjunction with or substituted for components and methods described elsewhere in the disclosure within the scope of the invention.
In describing exemplary embodiments, specific terminology is used for the sake of clarity. For purposes of description, each specific term is intended to at least include all technical and functional equivalents that operate in a similar manner to accomplish a similar purpose. Additionally, in some instances where a particular exemplary embodiment includes a plurality of system elements or method steps, those elements or steps may be replaced with a single element or step. Likewise, a single element or step may be replaced with a plurality of elements or steps that serve the same purpose. Further, where parameters for various properties are specified herein for exemplary embodiments, those parameters may be adjusted up or down by 1/20th, 1/10th, ⅕th, ⅓rd, ½, etc., or by rounded-off approximations thereof, unless otherwise specified. Moreover, while exemplary embodiments have been shown and described with references to particular embodiments thereof, those of ordinary skill in the art will understand that various substitutions and alterations in form and details may be made therein without departing from the scope of the invention. Further still, other aspects, functions and advantages are also within the scope of the invention.
Exemplary flow diagrams are provided herein for illustrative purposes and are non-limiting examples of methods. One of ordinary skill in the art will recognize that exemplary methods may include more or fewer steps than those illustrated in the exemplary flow diagrams, and that the steps in the exemplary flow diagrams may be performed in a different order than shown.
Other embodiments of the disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.
Various embodiments of wearable automatic injection devices have been described herein. These embodiments are given by way of example and are not intended to limit the scope of the present invention. It should be appreciated, moreover, that the various features of the embodiments that have been described may be combined in various ways to produce numerous additional embodiments. Moreover, while various materials, dimensions, shapes, injection locations, etc. have been described for use with disclosed embodiments, others besides those disclosed may be utilized without exceeding the scope of the invention.
The present application claims priority to U.S. Provisional Application No. 62/271,283, filed Dec. 27, 2015, and U.S. Provisional Application No. 62/352,362, filed Jun. 20, 2016, both of which are incorporated herein in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| 62271283 | Dec 2015 | US | |
| 62352362 | Jun 2016 | US |
