Devices and methods for delivering therapeutic fluids

Abstract

A therapeutic agent delivery system includes a therapeutic agent delivery assembly carried by a housing. The therapeutic agent delivery assembly includes a chamber having a first passageway, a therapeutic agent transported in the first passageway, and a needle in communication with the first passageway. The therapeutic agent delivery assembly is translatable relative to the housing from a stowed configuration to a deployed configuration. The therapeutic agent delivery assembly is also translatable relative to the housing from the deployed configuration to a retracted configuration. The system also includes a user input device actuatable to translate the therapeutic agent delivery assembly from the stowed configuration to the deployed configuration. The system also includes a retraction mechanism actuatable to translate the therapeutic agent delivery assembly from the deployed configuration to the retracted configuration.

Description

Technical Field

[0001] This disclosure relates to methods and apparatus for parenteral / non-gastrointestinal delivery of therapeutic agents. More specifically, this disclosure relates to methods and apparatus for parenteral delivery of high-viscosity therapeutic fluids (e.g., protein therapeutic agents). Background Technology

[0002] Protein therapy drugs are an emerging class of drug therapies that can provide treatment for a variety of diseases, such as autoimmune diseases, cardiovascular diseases, diabetes, and cancer. A common delivery method for some protein therapy drugs (such as monoclonal antibodies) is intravenous infusion, in which large volumes of diluted solution are delivered over time. Intravenous infusions typically require the supervision of a physician or nurse and are performed in a clinical setting. This can be inconvenient for patients, and efforts are underway to allow protein therapy drugs to be delivered at home. Ideally, protein therapy drug formulations could be administered using syringes designed for subcutaneous delivery, eliminating the need for intravenous administration. Subcutaneous injections are often performed by non-professionals, such as when a diabetic patient injects insulin.

[0003] The transition from intravenous delivery of therapeutic protein formulations to injection devices such as syringes and pens presents challenges related to delivering high concentrations of high molecular weight molecules in a simple, reliable, and minimally painful manner for patients. In this regard, while intravenous infusion bags typically have a volume of 1 liter, the standard volume range of syringes is 0.3 ml to 25 ml. Therefore, depending on the drug, the concentration may need to be increased 40 times or more to deliver the same amount of therapeutic protein. Furthermore, for patient comfort and compliance, injection therapy is evolving towards smaller needle diameters and faster delivery times.

[0004] Delivery of protein therapeutic agents is also challenging due to the high viscosity associated with such formulations and the high forces required to propel them through parenteral devices. Formulations with an absolute viscosity higher than 40–60 centipoise (cP) may be difficult to deliver using conventional spring-driven autoinjectors for several reasons. Structurally, the spring footprint used to deliver pressure is relatively large and fixed in a specific shape, reducing design flexibility for the delivery device. Secondly, autoinjectors are typically made of plastic components. However, a significant amount of energy must be stored in the spring to reliably deliver high-viscosity fluids. If poorly designed, this stored energy can lead to damage to the plastic components due to creep, which tends to cause permanent deformation under stress. Autoinjectors are typically operated by using a spring to push an internal component containing the needle against the outer edge of the injector housing. The noise associated with operating spring-based autoinjectors can cause patient anxiety, potentially reducing future compliance. The pressure-time curve generated by such spring-driven autoinjectors cannot be easily modified, preventing users from fine-tuning the pressure to meet their delivery needs.

[0005] It is desirable to provide a method and apparatus for the auto-administration of therapeutic fluids, particularly high-viscosity fluids, within a reasonable timeframe and using limited injection space. These methods and apparatus can be used to deliver high-concentration proteins, high-viscosity pharmaceutical formulations, or other therapeutic fluids. Summary of the Invention

[0006] According to one embodiment of this disclosure, a therapeutic agent delivery system includes a housing having a distal portion. The system also includes a therapeutic agent delivery assembly carried by the housing. The therapeutic agent delivery assembly includes a chamber having a first passage, a therapeutic agent delivered in the first passage, and a needle communicating with the first passage. The therapeutic agent delivery assembly is translatable relative to the housing from a storage configuration to an unfolded configuration. In the unfolded configuration, the needle extends at least partially distally from the distal portion of the housing. The therapeutic agent delivery assembly is also translatable relative to the housing from the unfolded configuration to a retracted configuration. In the retracted configuration, the needle is positioned proximally relative to the distal portion of the housing. The system also includes a user input device configured to be actuated by a user. Actuation of the user input device translates the therapeutic agent delivery assembly from the storage configuration to the unfolded configuration. The system also includes a retraction mechanism actuable to translate the therapeutic agent delivery assembly from the unfolded configuration to the retracted configuration. The retraction mechanism includes a first chamber, fluid carried in the first chamber, an expandable device including a second chamber, and a valve actuable from a closed position to an open position. In the closed position, the valve prevents fluid communication between the first and second chambers. In the open position, the valve allows fluid communication between the first and second chambers, enabling the first chamber to deliver fluid to the second chamber. The expandable device thereby expands and translates the therapeutic agent delivery assembly from an deployed configuration to a retracted configuration.

[0007] According to another embodiment of this disclosure, a therapeutic agent delivery system includes a housing having a distal portion. The system also includes a therapeutic agent delivery assembly carried by the housing. The therapeutic agent delivery assembly includes a chamber having a passage, a therapeutic agent delivered in the passage, and a needle communicating with the passage. The therapeutic agent delivery assembly includes a chamber having a first passage, a therapeutic agent delivered in the first passage, and a needle communicating with the first passage. The therapeutic agent delivery assembly is translatable relative to the housing from a storage configuration to an unfolded configuration. In the unfolded configuration, the needle extends at least partially distally from the distal portion of the housing. The therapeutic agent delivery assembly is translatable relative to the housing from the unfolded configuration to a retracted configuration. In the retracted configuration, the needle is positioned proximally relative to the distal portion of the housing. The system also includes a user input device configured to be actuated by a user. Actuation of the user input device translates the therapeutic agent delivery assembly from the storage configuration to the unfolded configuration. The system also includes a retraction mechanism actuable to translate the therapeutic agent delivery assembly from the unfolded configuration to the retracted configuration. The retraction mechanism includes a first chamber, fluid carried in the first chamber, a second chamber, an electronic component assembly configured to send a retraction signal, and a valve operatively coupled to the electronic component assembly. Upon receiving the retraction signal, the valve is actuated from a closed position to an open position. In the closed position, the valve prevents fluid communication between the first and second chambers. In the open position, the valve allows fluid communication between the first and second chambers, enabling the first chamber to deliver fluid to the second chamber. The retraction mechanism thereby translates the therapeutic agent delivery assembly from an deployed configuration to a retracted configuration. Attached Figure Description

[0008] The above and other features and advantages of the present invention, as well as the ways in which they are implemented, will become more apparent and better understood by referring to the following description of embodiments of the present invention in conjunction with the accompanying drawings.

[0009] In the picture:

[0010] Figure 1 This is a top perspective view of a therapeutic agent delivery system according to an embodiment of the present disclosure.

[0011] Figure 2 yes Figure 1 A partial exploded view of the therapeutic agent delivery system.

[0012] Figure 3 yes Figure 1 A longitudinal cross-sectional view of the therapeutic agent delivery system.

[0013] Figure 4 yes Figure 1 Top perspective view of the proximal housing portion of the housing of the therapeutic agent delivery system.

[0014] Figure 5 yes Figure 4 Bottom perspective view of the near-side shell portion.

[0015] Figure 6 It is along Figure 4 A longitudinal sectional view of the near-side outer shell portion along line 6-6.

[0016] Figure 7 yes Figure 1 Top perspective view of the distal housing portion of the housing of the therapeutic agent delivery system.

[0017] Figure 8 yes Figure 7 Bottom perspective view of the distal shell portion.

[0018] Figure 9 yes Figure 1 Top perspective view of the user input device support of the therapeutic agent delivery system.

[0019] Figure 10 yes Figure 1 Top perspective view of the user input device of the therapeutic agent delivery system.

[0020] Figure 11 yes Figure 1 Top perspective view of the input driver of the therapeutic agent delivery system.

[0021] Figure 12 yes Figure 1 Bottom perspective view of the pressure generation actuator of the therapeutic agent delivery component of the therapeutic agent delivery system.

[0022] Figure 13 yes Figure 12 Top perspective view of the pressure generating actuator.

[0023] Figure 14 yes Figure 12 A partial exploded perspective view of the pressure generating actuator.

[0024] Figure 15 It is along Figure 12 Longitudinal sectional view of the pressure generating actuator along line 15-15.

[0025] Figure 16 yes Figure 1 A side view of the syringe component of the therapeutic agent delivery component of the therapeutic agent delivery system.

[0026] Figure 17 It is along Figure 16 The longitudinal sectional view of the syringe assembly is shown in line 17-17.

[0027] Figure 18 yes Figure 1 A schematic diagram of the retraction mechanism of a therapeutic agent delivery system.

[0028] Figure 19 yes Figure 1 Top perspective view of the expandable device of the therapeutic agent delivery system.

[0029] Figure 20 It is in the initial or first configuration. Figure 1 A longitudinal cross-sectional view of the therapeutic agent delivery system.

[0030] Figure 21 It is in the first configuration Figure 1 Enlarged top perspective view of the proximal portion of the therapeutic agent delivery system; several external components are shown with hidden lines to illustrate the internal components.

[0031] Figure 22 It is a cross-sectional view of the reciprocating component of the therapeutic agent delivery system passing through the input device driver and the pressure generating actuator when the user input device is actuated.

[0032] Figure 23 When the spring extends and the therapeutic agent delivery component moves distally relative to the housing, Figure 1 Enlarged top perspective view of the therapeutic agent delivery system; several external components are shown with hidden lines to show the internal components.

[0033] Figure 24 When the therapeutic agent delivery component moves to the unfolded configuration Figure 1 A partial longitudinal cross-sectional view of the therapeutic agent delivery system.

[0034] Figure 25 It is a longitudinal sectional view of the pressure generating actuator, showing the reciprocating component rotating relative to the first and second mixing chambers of the pressure generating actuator and thereby actuating the actuator.

[0035] Figure 26 It is a longitudinal sectional view of the reciprocating component and the mixing piston of the pressure generating actuator in an unfolded configuration.

[0036] Figure 27 yes Figure 1 A longitudinal cross-sectional view of a therapeutic agent delivery system as the syringe piston moves through the syringe passage to expel the therapeutic agent from the needle.

[0037] Figure 28 yes Figure 1 The therapeutic agent delivery system has its needle in a retracted configuration in a longitudinal cross-sectional view.

[0038] In all the views, corresponding reference numerals indicate corresponding parts. The examples set forth herein illustrate exemplary embodiments of the invention, and such examples should not be construed as limiting the scope of the invention in any way. Detailed Implementation

[0039] This disclosure relates to systems, apparatus, and methods for parenteral delivery of therapeutic agents (e.g., high-viscosity therapeutic fluids). Such systems and apparatus are illustratively provided with a relatively compact outline.

[0040] 1. Drugs / Therapeutic Agents

[0041] The systems and devices according to this disclosure can carry and facilitate the delivery of drugs to subjects. The term "drug" refers to one or more therapeutic agents, including but not limited to insulin, insulin analogs (e.g., insulin lispro or insulin glargine), insulin derivatives, GLP-1 receptor agonists (e.g., duraglutide or liraglutide), glucagon, glucagon analogs, glucagon derivatives, gastric inhibitory peptides (GIPs), GIP analogs, GIP derivatives, combined GIP / GLP-1 agonists (e.g., tirzepatide), gastrin analogs, gastrin derivatives, therapeutic antibodies, and any therapeutic agent capable of being delivered by a device according to this disclosure. Drugs may be formulated with one or more excipients. Devices according to this disclosure are typically operated by a patient, caregiver, or healthcare professional in the manner described herein to deliver drugs to subjects.

[0042] In some embodiments, the therapeutic agent is a protein, such as a monoclonal antibody or some other protein that is therapeutically useful. In some embodiments, the concentration of the protein in the fluid can be from about 75 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the protein can be about 150 mg / mL, 200 mg / mL, 250 mg / mL, or higher. The drug may also contain a solvent or non-solvent, such as water, perfluoroalkane solvents, safflower oil, or benzyl benzoate.

[0043] The drug can be a fluid, more specifically a high-viscosity fluid, and can have an absolute viscosity of about 5 cP to about 1000 cP. In some embodiments, the high-viscosity fluid has an absolute viscosity of at least about 10 cP, 20 cP, 30 cP, 40 cP, 50 cP, 60 cP or higher.

[0044] 2. Therapeutic agent delivery system

[0045] Figure 1-3 A therapeutic agent delivery system 10 according to one embodiment of the present disclosure is shown. Illustratively, the therapeutic agent delivery system 10 generally includes the outline of an auto-injection pen, although other outlines may be used alternatively. Typically, the therapeutic agent delivery system 10 includes an elongated housing 12 along a longitudinal axis 14. The housing 12 carries a therapeutic agent delivery assembly 16. The therapeutic agent delivery assembly 16 includes a therapeutic agent 17 (see [link to original document]). Figure 3) and needle 18, and the therapeutic agent delivery component 16 relative to the housing 12 from the storage configuration (e.g. Figure 1-3 As illustrated, the needle 18 is translated from a configuration fully contained within the housing 12 to an unfolded configuration (shown elsewhere—for example, a configuration in which the needle 18 is at least partially exposed at the distal portion 20 of the housing 12 and configured to engage with the subject and deliver the therapeutic agent to the subject). The proximal portion 22 of the therapeutic agent delivery system 10 includes a user input device 24 (illustratively, a pressable button) actuated to activate the therapeutic agent delivery assembly 16 (i.e., to move the needle 18 from the storage configuration to the unfolded configuration and deliver the therapeutic agent to the user). Upon actuation, the therapeutic agent delivery assembly 16 is translated relative to the housing 12 from the unfolded configuration to a retracted configuration (shown elsewhere—for example, configuration 10 in which the needle 18 is fully contained within the therapeutic agent delivery system). The therapeutic agent delivery system 10 includes a retraction mechanism (shown elsewhere) that translates the therapeutic agent delivery assembly 16 relative to the housing 12 from the unfolded configuration to the retracted configuration. After reaching the retracted configuration, the therapeutic agent delivery component 16 is prevented from translating to the deployed configuration (in other words, the system 10 is "locked"). These aspects, features, and components of the therapeutic agent delivery system 10 are described in more detail below.

[0046] Figure 4-6 The proximal housing portion 26 of the housing 12 is shown. The proximal housing portion 26 includes a body 28 having a generally cylindrical shape. The body 28 includes an internal passage 34 carrying other components of the therapeutic agent delivery system 10. Adjacent to this internal passage 34, the inner surface 32 of the proximal housing portion 26 carries an actuation feature structure as described in more detail below (illustratively, two helically extending ramps 34, one of which in…). Figure 6 (As shown in the diagram), this actuation feature selectively engages with and facilitates the actuation of the therapeutic agent delivery assembly 16. The inner surface 32 of the proximal housing portion 26 has translational features (illustratively, two pairs of axially extending ridges 36, one pair of which is located in...). Figure 6 (As shown in the diagram), this pair of translational features facilitates the translation of the therapeutic agent delivery assembly 16 relative to the proximal housing portion 26. The inner surface 32 also features a biasing platform (illustratively, a radially inwardly extending flange 38), as described in more detail below, which carries other components and facilitates the translation of the therapeutic agent delivery assembly 16 from an unfolded configuration to a retracted configuration. The proximal housing portion 26 includes coupling features (illustratively, multiple snap-fit ​​couplings 40) for engagement with another portion of the housing 12.

[0047] Figure 7 and Figure 8The distal housing portion 42 of the housing 12 is shown. The distal housing portion 42 includes a body 44 having a generally conical shape with an outwardly flared distal portion 20. The body 44 includes an internal passage 46 that carries the therapeutic agent delivery assembly 16 (shown elsewhere). The distal housing portion 42 also includes coupling features (illustratively, the inner surface 48 of the internal passage 46) for coupling to a proximal housing portion 26 (illustratively, a plurality of snap-fit ​​connectors 40). In other embodiments, different arrangements of the distal housing portion 42 are possible. For example, the distal housing portion 42 may be integrally formed with the proximal housing portion 26.

[0048] Figure 9 A user input device support 50 of the therapeutic agent delivery system 10 is shown. The user input device support 50 is coupled to a proximal housing portion 26 (both shown elsewhere) opposite the distal housing portion 42. The user input device support 50 includes a body 52, and the body 52 has coupling features for coupling to the proximal housing portion 30 (illustratively, a plurality of snap-fit ​​connectors 54, one of which is in…). Figure 9 (Shown elsewhere). The body 52 includes an internal passage 56 for receiving a user input device 26 (shown elsewhere). Adjacent to this internal passage 56, the inner surface 58 of the user input device support 50 has translational features (illustratively, a plurality of axially extending ridges 60, one of which is in...). Figure 9 (As shown in the figure), this translational feature facilitates the translation of the user input device 24 relative to the user input device support 50. In other embodiments, different arrangements of the user input device support 50 are possible.

[0049] Figure 10 A user input device 24 is shown in the therapeutic agent delivery system 10. The user input device 24 includes translational features (illustratively, a plurality of axially extending channels 62, one of which is in…) Figure 10(Shown elsewhere—illustratively, a plurality of axially extending ridges 60) for engagement with translational features of the user input device support 50 to facilitate translation of the user input device 24 relative to the user input device support 50 and the housing 12 (shown elsewhere). Adjacent to this translational feature, the user input device 24 includes an exposed portion 64 that the user presses to cause translation of the user input device 24 relative to the user input device support 50 and the housing 12. The user input device 24 also includes an actuation feature that facilitates actuation of the therapeutic agent delivery assembly 16. Illustratively, the actuation feature includes two arms 66 disposed opposite to the exposed portion 64. Each arm 66 includes an actuation surface (illustratively, a helically extending surface 68). The interaction of the arms 66 with other components of the therapeutic agent delivery system 10 is described in more detail below. In other embodiments, different arrangements of the user input device 24 are possible.

[0050] Figure 11 An input driver 70 of a therapeutic agent delivery system 10 is shown. The input driver 70 includes an actuation feature structure configured to interact with an actuation feature structure of a user input device 24 (shown elsewhere). Illustratively, the actuation feature structure of the input driver 70 includes two partial flanges 72 and two openings 74 disposed between the partial flanges 72. Each partial flange 72 includes an actuating surface (illustratively, a fillet 76 adjacent to one of the openings 74) that engages with one of the actuating surfaces 68 of the user input device 26 to facilitate rotation of the input driver 70 relative to the housing 12 (shown elsewhere) when the user input device 26 is translated relative to the housing 12. Opposite the actuation feature structure, the input driver 70 includes a detachable coupling feature structure (illustratively, a plurality of crossbars 78 or radially outwardly extending L-shaped protrusions 78) that detachably couples the input driver 70 to the therapeutic agent delivery assembly 16 (shown elsewhere). In other embodiments, different arrangements of the input driver 70 are possible.

[0051] Figure 12-15 The pressure-generating actuator 80 of the therapeutic agent delivery assembly 16 and the fluid passage 136, described in more detail below (see below) are shown. Figure 12 Typically, the pressure generating actuator 80 is actuated by the user input device 24 via the input driver 70 (both shown elsewhere) to facilitate the mixing of internally carried chemical reagents, which produces one or more pressurized fluids (e.g., one or more gases). Examples of suitable reagents and generated gases are provided below. As described in more detail below, the pressurized fluid is delivered to other parts of the therapeutic agent delivery assembly 16 and facilitates its movement.

[0052] The pressure generating actuator 80 includes a first mixing chamber 82 and a second mixing chamber 84, which are illustratively integrally formed with each other. The first mixing chamber 82 and the second mixing chamber 84 externally include translational features (illustratively, two axially extending ridges 86) for translationally engaging with a translational feature of the proximal housing portion 26 (shown elsewhere—illustratively, each axially extending ridge 86 is translationally received by one pair of axially extending ridges 36 of the proximal housing portion 40). Thus, the pressure generating actuator 80 is translationally carried by the proximal housing portion 26. At the outlet end portion 88, the mixing chambers 82, 84 include an outlet connection feature (illustratively, an externally threaded surface 90) for engagement with another component of the therapeutic agent delivery assembly 16. The outlet end portion 148 also includes an actuator outlet 92 (illustratively shown for conveying absorbent material 93, as described in more detail below). Pressurized fluid is discharged from the pressure generating actuator 80 via the outlet 92.

[0053] The mixing chambers 82 and 84 internally carry an axially stacked actuator spring 94, a mixing piston 96, and a rotatable reciprocating member 98. The rotatable reciprocating member 98 includes a recess 100, and the recess 100 has a detachable connection feature (illustratively, a plurality of crossbars 102 or radially outwardly extending L-shaped protrusions 102, one of which is in…) Figure 15 (shown elsewhere), it engages with a detachable coupling feature structure (illustratively, multiple crossbars 78) of the input driver 70. The first mixing chamber 82 and the reciprocating member 98 form a helical connection for movably engaging with each other. Illustratively, the reciprocating member 98 includes a helically extending ridge 104, and the first mixing chamber 82 includes a helically extending groove 106 receiving the ridge 104. The reciprocating member 98 includes an actuation feature structure (illustratively, two radially outward extending fingers 108), which, as described in more detail below, engages with and is driven by an actuation feature structure of the proximal housing portion 26 (shown elsewhere—illustratively, two helically extending ramps 34). The reciprocating member 98 internally includes a first constraint feature structure (illustratively, eight radially inward extending tabs 110, four of which are in the mixing piston 96) that engages with the mixing piston 96. Figure 15 (Selected from the bid). Illustratively, the reciprocating component 98 also includes channels 112 disposed between adjacent tabs 110 (three of which are in... Figure 15 (Pointed out). The hybrid piston 96 includes a second constraint feature structure (illustratively, eight radially outwardly extending tabs 114) that engages with the first constraint feature structure of the reciprocating member 98. Initially and as Figure 19As shown, the first constraint feature engages with the second constraint feature (illustratively, the radially inwardly extending tab 110 of the reciprocating member 98 is angularly aligned and engaged with the radially outwardly extending tab 114 of the mixing piston 96) to hold the mixing piston 96 in a position between the first mixing chamber 82 and the second mixing chamber 84. The mixing piston 96 thus keeps the reagents in the first mixing chamber 82 and the second mixing chamber 84 separated. Initially, the actuator spring 94 is also compressed in the second mixing chamber 84 against the mixing piston 96. In a subsequent configuration, as described in more detail below, the reciprocating member 98 rotates relative to the first mixing chamber 82 and the second mixing chamber 84 to disengage the first constraint feature from the second constraint feature (illustratively, the radially inwardly extending tab 110 of the reciprocating member 98 is angularly misaligned or angularly offset from the radially outwardly extending tab 114 of the mixing piston 96, while the channel 126 is angularly aligned with the radially outwardly extending tab 114 of the mixing piston 96). As a result, the actuator spring 94 extends and moves the mixing piston 96 into the reciprocating member 98 and the first mixing chamber 82, which allows the reagents in the first mixing chamber 82 and the second mixing chamber 84 to mix. The mixing of the reagents produces one or more pressurized fluids (e.g., one or more gases), and the pressurized fluids are delivered to other parts of the therapeutic agent delivery assembly 16.

[0054] In some embodiments, the pressure generating actuator 80 has different structures. For example, suitable pressure generating actuators 80 include those described in the following documents: U.S. Patent 9,795,740 entitled "Chemical Powered Device and Method Therefor Including Injection of Highly Viscous Fluids"; U.S. Patent Application Publication No. US2020 / 0030537 entitled "Method and Apparatus for Delivering Fluids by Chemical Reaction"; and International Publication No. WO2019 / 050791 entitled "System for Controlling Gas Generation in a Drug Delivery Device," the disclosures of which are expressly incorporated herein by reference in their entirety.

[0055] One or more pressurized fluids can be generated in the pressure generating actuator 80 of this disclosure using any suitable chemical reagent. Examples of generated gases include carbon dioxide, nitrogen, oxygen, chlorine, etc. Ideally, the generated gases are inert and non-flammable. The amount of gas required to facilitate movement of other components of the therapeutic agent delivery assembly 16 may influence the type, amount, and concentration of each reagent used in the pressure generating actuator 80. Reagents can be in dry form (e.g., powder, tablet) and / or liquid form.

[0056] In one exemplary embodiment, a bicarbonate (which may be present in dry form) reacts with an acid (which may be present in liquid form) to generate carbon dioxide gas in a pressure generating actuator 80. Examples of suitable bicarbonates include sodium bicarbonate, potassium bicarbonate, and ammonium bicarbonate. Other components may also be present with the bicarbonate, such as diatomaceous earth. Examples of suitable acids include acetic acid, citric acid, potassium hydrogen tartrate, disodium pyrophosphate, and calcium dihydrogen phosphate. In a particular example, the bicarbonate is potassium bicarbonate, and the acid is an aqueous solution of citric acid, which can react to produce carbon dioxide gas and a liquid mixture of water and dissolved potassium citrate.

[0057] In some embodiments, other reactions may be used. In one example, a metal carbonate such as copper carbonate or calcium carbonate is thermally decomposed in pressure generating actuator 80 to produce carbon dioxide gas and the corresponding metal oxide. In another example, 2,2'-azobisisobutyronitrile (AIBN) is heated to produce nitrogen gas in pressure generating actuator 80. In yet another example, an enzyme (e.g., yeast) reacts with sugar to produce carbon dioxide gas in pressure generating actuator 80. Some substances readily sublimate, changing from a solid to a gas. These substances include, but are not limited to, naphthalene and iodine. In yet another example, hydrogen peroxide is decomposed by a catalyst such as an enzyme (e.g., catalase) or manganese dioxide to produce oxygen in pressure generating actuator 80. In yet another example, silver chloride decomposes by exposure to light to generate gas in pressure generating actuator 80. Suitable reagents, chemicals and reactions are further described in the above-incorporated U.S. Patent 9,795,740, U.S. Patent Application Publication No. US2020 / 0030537 and International Publication No. WO2019 / 050791.

[0058] As briefly described above, the outlet 92 of the pressure generating actuator 80 may carry one or more absorbent materials 93. This absorbent material 93 can absorb excess liquid supplied by mixing reagents within the pressure generating actuator 80. Suitable absorbent materials are further described in the appended U.S. Patent Publication No. US 2020 / 0030537.

[0059] Figure 16 and Figure 17 A syringe assembly 116 of a therapeutic agent delivery assembly 16 is shown. The syringe assembly 116 includes an inlet portion 118, and the inlet portion 118 includes an inlet connection feature structure (illustratively, an internally threaded surface 120, such as...). Figure 17As shown elsewhere—illustratively, external threaded surface 90—it is coupled to the outlet connection feature of the pressure generating actuator 80. The inlet portion 118 also includes an inlet 122 for receiving pressurized fluid from the outlet 92 of the pressure generating actuator 80. The inlet portion 118 is coupled to a syringe chamber 124, and the syringe chamber 124 includes a syringe passage 126 that receives pressurized fluid from the inlet portion 118. The syringe passage 126 carries a syringe piston 128, and when the syringe passage 126 receives pressurized fluid, the syringe piston 128 moves away from the inlet portion 118 and translates toward the outlet portion 130 of the syringe assembly 116. Illustratively and as described in further detail below, the syringe piston 128 carries a magnetic component 132, which may also be referred to as a target, which facilitates determining the position of the syringe piston 128 within the syringe passage 126. Syringe passage 126 also delivers therapeutic agent 18 (shown elsewhere—illustratively, 2.25 mL of therapeutic agent, though other volumes may be delivered alternatively, including, for example, 0.5 mL, 1.0 mL, 3.0 mL, or 5.0 mL) between syringe piston 128 and outlet portion 130, more specifically needle 18. Therefore, translation of syringe piston 128 within syringe passage 126 causes needle 18 to expel therapeutic agent therefrom. In other embodiments, different arrangements are feasible. For example, inlet portion 118 and syringe chamber 124 may be integrally formed with each other, or syringe assembly 116 may be replaced by another type of therapeutic agent container, such as a bellows or sac-like structure. Below inlet portion 118, syringe assembly 116 includes a retractable surface (illustratively, as shown in the image). Figure 2 and Figure 3 The retraction ring 133 is located between the inlet portion 118 and the syringe chamber 124 (as shown).

[0060] Figure 18A retraction mechanism 134 of the therapeutic agent delivery system 10 is schematically shown. Typically, the retraction mechanism 134 is actuable to translate the therapeutic agent delivery assembly 16 relative to the housing 12 (both shown elsewhere) from an deployed configuration to a retracted configuration. The retraction mechanism 134 includes a passage 136 coupled at a first end 140 to a first chamber 138. The passage 136 is in fluid communication with and receives fluid from the first chamber 138. The first chamber 138 may include, for example, a second mixing chamber 84 of the therapeutic agent delivery assembly 16 (shown elsewhere), and the fluid may include, for example, pressurized fluid generated by the therapeutic agent delivery assembly 16, as described in more detail below. The passage 136 is also coupled at a second end 144 to a second chamber 142. The passage 136 is in fluid communication with and delivers fluid to the second chamber 142. As described in more detail below, the second chamber 142 receives fluid to increase its volume and thereby drive the therapeutic agent delivery assembly 16 relative to the housing 12 from an expanded configuration to a retracted configuration. The second chamber 142 may be, for example, part of an expandable device (shown elsewhere) as described in more detail below.

[0061] The retraction mechanism 134 also includes a valve 148 for selectively allowing fluid to flow from the first chamber 138 to the second chamber 142. In other words, the valve 148 is actuable from a closed position to an open position. In the closed position, the valve 148 prevents fluid communication between the first chamber 138 and the second chamber 142. In the open position, the valve 148 allows fluid communication between the first chamber 138 and the second chamber 142, such that the first chamber 138 delivers fluid to the second chamber 142.

[0062] Continue to refer to Figure 18Valve 148 includes a valve element 150 and a valve actuator 152. Valve element 150 is reconfigurable from a closed position to an open position to selectively block and allow fluid flow in passage 136, respectively. Valve actuator 152 actuates valve element 150 from the closed position to the open position. Valve element 150 and valve actuator 152 can take various forms. For example, valve element 150 may include a consumable element, and valve actuator 152 may actuate valve element 150 by damaging or destroying the consumable element. As a more specific example, valve element 150 may include a fusible element initially disposed in passage 136, and valve actuator 152 may include a heating element. In these embodiments, valve actuator 152 actuates valve element 150 by transferring heat from heating element to fusible element, thereby melting fusible element. As a more specific example, the fusible element may include a wax plug, the heating element may be an electrical conductor coupled to carbon nanotube paper or nichrome wire wound around the passage 136 and the fusible element, and the passage 136 may contain a thermally conductive material, such as stainless steel. Alternatively, the carbon nanotube paper or nichrome wire may be disposed within the passage 136 and surrounding the fusible element, or a wire may be disposed within the fusible element. As another alternative, the heating element may include an electrical conductor coupled to the passage 136, such that the passage 136 itself acts as part of the heating element. In this alternative, the passage 136 may contain titanium, an austenitic nickel-chromium-based superalloy, other high-temperature alloys, etc. As yet another example, the valve 148 may be an electromechanical valve, such as a solenoid valve. That is, the valve actuator 152 may include a solenoid coil, and the valve element 150 may include a valve seat actuated by the solenoid coil to allow flow through the valve body.

[0063] Further reference Figure 18The retraction mechanism 134 also includes an electronic component assembly 154 operatively coupled to the valve 148. The electronic component assembly 154 includes an electronic controller 156 operatively coupled to and receiving power from a power source 158 (illustratively, a battery). The controller 156 sends a retraction signal to the valve 148 to actuate the valve 148. The retraction signal may include, for example, a current sufficient to heat and thereby melt the valve element 150, which is provided as a fusible element, via a valve actuator 152 provided as a heating element. The controller 156 may send a retraction signal to the valve 148 in response to receiving a sensor signal from a sensor 160 operatively coupled to the controller 156. The sensor 160 may send a sensor signal in response to sensing various types of input. For example, the sensor 160 may be configured to determine the position of the syringe piston 128 in the syringe chamber 124 (e.g., to determine whether the syringe piston 128 has moved toward the syringe outlet portion 130, thereby indicating that therapeutic agent has been expelled from the needle 18). More specifically, sensor 160 may be a Hall effect sensor configured to sense the magnetic component 132 carried by syringe piston 128. As another example, sensor 160 and / or target 132 may be an optical sensor or a vibration sensor. As yet another example, sensor 160 may be configured to sense when user input device 24 is actuated, and controller 156 may subsequently send a retraction signal after a predetermined time period. In these embodiments, sensor 160 may, for example, be an electrical switch.

[0064] Figure 19 An inflatable device 146 is shown that provides a second chamber 142 (both shown elsewhere) for a retraction mechanism 134. The inflatable device 146 is shown as an inflatable bellows having a generally semi-annular shape. The inflatable device 146 can alternatively take many other forms. For example, the inflatable device 146 can be an inflatable bellows with different shapes. As another example, the inflatable device 146 can be an inflatable pouch, an inflatable balloon, etc. The inflatable device 146 has an inflation port 147 in fluid communication with passage 136 (shown elsewhere). The inflatable device 146 is carried within the housing 12 between an inwardly extending crossbar 38 of the proximal housing portion 26 and the retraction ring 133 of the syringe assembly 116 (both shown elsewhere). Therefore, and as described in more detail below, the expansion of the inflatable device 146 facilitates relative movement between the syringe assembly 116 and the housing 12, which facilitates the movement of the needle 18 (shown elsewhere) from an expanded configuration to a retracted configuration.

[0065] Illustratively, the actuation of the therapeutic agent delivery system 10 is as follows. (Refer to...) Figure 20The therapeutic agent delivery system 10 is shown in an initial or first configuration. In the first configuration, the therapeutic agent delivery component 16 is in a storage configuration (illustratively, a configuration in which the needle 18 is completely within the housing 12).

[0066] Reference Figure 21 User input device 24 and input driver 70 are shown in a first configuration. In this configuration, user input device 24 can be actuated by a user to actuate therapeutic agent delivery system 10. More specifically, user input device 24 can be pressed and translated relative to housing 12 in direction D1 (e.g., substantially parallel to longitudinal axis 14 (i.e., parallelism ± 5 degrees)). This action causes actuation surface 68 of user input device 24 to engage with actuation surface 76 of input driver 70. User input device 24 thereby causes input driver 70 to rotate in direction D2. Figure 22 As shown, this action causes the crossbar 78 of the input driver 70 to begin sliding on and disengaging from the crossbar 102 of the reciprocating member 98.

[0067] like Figure 23 As shown, the compression spring 162 disposed between the input driver 70 and the reciprocating member 98 is relatively unrestrained when the input driver 70 and the reciprocating member 98 are disengaged. Therefore, the compression spring 162 extends and... Figure 24 The therapeutic agent delivery assembly 16 is driven distally relative to the housing 12. The therapeutic agent delivery assembly 16 thus moves from a storage configuration to an unfolded configuration (illustratively, a configuration in which the needle 18 is partially exposed at the distal portion 20 of the housing 12 and configured to engage with and deliver the drug to the subject). Illustratively, the needle 18 translates from the storage configuration to the unfolded configuration in a direction D3 substantially parallel to the longitudinal axis 14 (i.e., parallelism ± 5 degrees).

[0068] Refer again Figure 23 The distal translation of the therapeutic agent delivery assembly 16 relative to the housing 12 also causes the radially outwardly extending fingers 108 of the reciprocating member 98 to engage with and slide on the helically extending ramp 51. This engagement causes the reciprocating member 98 to rotate relative to the mixing chambers 82, 84 of the pressure generating actuator 80 (illustratively, about an axis substantially parallel to the longitudinal axis 14 (i.e., parallelism ±5 degrees)), which actuates the pressure generating actuator 80. More specifically and as Figure 25 As shown, rotating the reciprocating member 98 relative to the first mixing chamber 82 and the second mixing chamber 84 causes the radially inwardly extending tab 110 of the reciprocating member 98 to be angularly misaligned with the radially outwardly extending tab 114 of the mixing piston 96, and angularly aligns the channel 112 of the reciprocating member 98 with the radially outwardly extending tab 114 of the mixing piston 96. Therefore, the actuator spring 94 is relatively unconstrained, and as... Figure 26As shown, the actuator spring 94 extends and translates the mixing piston 96 into the reciprocating member 98 and the first mixing chamber 82. The reagents in the first mixing chamber 82 and the second mixing chamber 84 then mix and react to provide a pressurized gas, which is delivered from the actuator outlet 92 by the pressure generating actuator 80.

[0069] Reference Figure 27 The pressure generating actuator 80 delivers pressurized gas to the syringe passage 126, which causes the syringe piston 128 to translate distally within the syringe passage 126. Thus, the syringe piston 128 pushes the treatment fluid distally toward the needle 18, and the needle 18 expels the treatment fluid and delivers it to the subject. After the treatment fluid has been delivered to the subject (illustratively determined by the sensor 182, shown elsewhere, sensing that the magnetic component 132 and the syringe piston 128 are near the outlet portion 130 of the syringe assembly 116), the electronic component assembly 154 actuates the valve 148. This action causes the pressure generating actuator 80 to deliver pressurized fluid through passage 136 to the expandable device 146.

[0070] Reference Figure 28 The pressurized fluid causes the expandable device 146 to increase the volume between the inwardly extending flange 38 of the proximal housing portion 26 and the retracted ring 133 of the syringe assembly 116, which in turn causes the syringe assembly 116 and the pressure generating actuator 80 to translate proximally relative to the housing 12. This action causes the needle 18 to translate from an deployed configuration to a retracted configuration. Illustratively, the therapeutic agent delivery system 10 cannot be re-actuated (i.e., the therapeutic agent delivery system 10 can be “locked”) and the therapeutic agent delivery system 10 can be discarded.

[0071] While the invention has been described as having an exemplary design, it may be further modified within the spirit and scope of this disclosure. Therefore, this application is intended to cover any variations, uses, or adaptations of the invention using its general principles. Furthermore, this application is intended to cover such deviations from this disclosure that fall within the known or customary practice in the field to which this invention pertains and are limited by the appended claims.

Claims

1. A therapeutic agent delivery system, comprising: A housing with a distal portion; A therapeutic agent delivery assembly carried by the housing, the therapeutic agent delivery assembly comprising: A chamber, which includes a first pathway configured to deliver therapeutic agents; A needle connected to the first pathway; The therapeutic agent delivery assembly is translatable relative to the housing from a storage configuration to an unfolded configuration, in which the needle extends at least partially distally from a distal portion of the housing, and the therapeutic agent delivery assembly is translatable relative to the housing from the unfolded configuration to a retracted configuration, in which the needle is positioned proximally relative to the distal portion of the housing. A user input device configured to be actuated by a user, wherein actuation of the user input device translates the therapeutic agent delivery component from the storage configuration to the unfolded configuration; A retraction mechanism, actuable to translate the therapeutic agent delivery assembly from the deployed configuration to the retracted configuration, the retraction mechanism comprising: First chamber; The fluid transported in the first chamber; An expandable device including a second chamber; A valve actuable from a closed position to an open position, in which the valve prevents fluid communication between the first chamber and the second chamber, and in the open position, the valve allows fluid communication between the first chamber and the second chamber, such that the first chamber delivers fluid to the second chamber, and the expandable device thereby expands and translates the therapeutic agent delivery assembly from the deployed configuration to the retracted configuration.

2. The therapeutic agent delivery system according to claim 1, wherein, The valve includes: A valve element, in the closed position, prevents fluid communication between the first chamber and the second chamber, and in the open position, allows fluid communication between the first chamber and the second chamber; and A valve actuator connected to the valve element actuates the valve element from the closed position to the open position upon receiving a retraction signal.

3. The therapeutic agent delivery system according to claim 2, wherein, The valve element includes a consumable element, and the valve actuator actuates the valve element by destroying the consumable element.

4. The therapeutic agent delivery system according to claim 2, wherein, The valve element includes a fusible element, the valve actuator includes a heating element, and the valve actuator actuates the valve element by transferring heat from the heating element to the fusible element, thereby melting the fusible element.

5. The therapeutic agent delivery system according to any one of claims 2-4, further comprising an electronic component assembly including a sensor configured to sense the discharge of the therapeutic agent from the needle, and the electronic component assembly being configured to send a retraction signal when the sensor senses the discharge of the therapeutic agent from the needle.

6. The therapeutic agent delivery system according to any one of claims 1-4, wherein, The therapeutic agent delivery assembly further includes a pressure generating actuator comprising the first chamber, and wherein actuation of the user input device causes the pressure generating actuator to generate the fluid via a chemical reaction.

7. The therapeutic agent delivery system of claim 6, wherein, Actuation of the user input device causes the pressure generating actuator to pressurize the therapeutic agent, delivering the therapeutic agent from the passage to the needle and expelling the therapeutic agent from the needle.

8. The therapeutic agent delivery system according to any one of claims 1-4, wherein, The expandable device includes a bellows.

9. The therapeutic agent delivery system of claim 8, wherein, The bellows includes a semi-annular shape and extends around the therapeutic agent delivery assembly.

10. The therapeutic agent delivery system according to any one of claims 1-4, further comprising the therapeutic agent delivered in a first passage of the chamber.

11. A therapeutic agent delivery system, comprising: A housing with a distal portion; A therapeutic agent delivery assembly carried by the housing, the therapeutic agent delivery assembly comprising: A chamber, which includes a first pathway configured to deliver therapeutic agents; A needle connected to the first pathway; The therapeutic agent delivery assembly is translatable relative to the housing from a storage configuration to an unfolded configuration, in which the needle extends at least partially distally from a distal portion of the housing, and the therapeutic agent delivery assembly is translatable relative to the housing from the unfolded configuration to a retracted configuration, in which the needle is positioned proximally relative to the distal portion of the housing. A user input device configured to be actuated by a user, wherein actuation of the user input device translates the therapeutic agent delivery component from the storage configuration to the unfolded configuration; A retraction mechanism, actuable to translate the therapeutic agent delivery assembly from the deployed configuration to the retracted configuration, the retraction mechanism comprising: First chamber; The fluid transported in the first chamber; Second chamber; An electronic component assembly configured to send a retraction signal; A valve, operably coupled to the electronic component assembly and actuated from a closed position to an open position upon receiving the retraction signal, wherein in the closed position the valve prevents fluid communication between the first chamber and the second chamber, and in the open position the valve allows fluid communication between the first chamber and the second chamber, such that the first chamber delivers fluid to the second chamber, and the retraction mechanism thereby translates the therapeutic agent delivery assembly from the deployed configuration to the retracted configuration.

12. The therapeutic agent delivery system of claim 11, wherein, The electronic component assembly includes a sensor configured to sense the discharge of the therapeutic agent from the needle, and the electronic component assembly is configured to send a retraction signal when the sensor senses the discharge of the therapeutic agent from the needle.

13. The therapeutic agent delivery system of claim 11, wherein, The valve includes: The valve element, in the closed position, prevents fluid communication between the first chamber and the second chamber, and in the open position, allows fluid communication between the first chamber and the second chamber; and A valve actuator connected to the valve element actuates the valve element from the closed position to the open position upon receiving the retraction signal.

14. The therapeutic agent delivery system of claim 13, wherein, The valve element includes a consumable element, and the valve actuator actuates the valve element by destroying the consumable element.

15. The therapeutic agent delivery system according to any one of claims 13 and 14, wherein, The valve element includes a fusible element, the valve actuator includes a heating element, and the valve actuator actuates the valve element by transferring heat from the heating element to the fusible element, thereby melting the fusible element.

16. The therapeutic agent delivery system according to any one of claims 11-14, wherein, The therapeutic agent delivery assembly further includes a pressure generating actuator comprising the first chamber, and wherein actuation of the user input device causes the pressure generating actuator to generate the fluid via a chemical reaction.

17. The therapeutic agent delivery system of claim 16, wherein, Actuation of the user input device causes the pressure generating actuator to pressurize the therapeutic agent, delivering the therapeutic agent from the passage to the needle and expelling the therapeutic agent from the needle.

18. The therapeutic agent delivery system according to any one of claims 11-14, further comprising a therapeutic agent delivered in a first passage of the chamber.

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