Patent Description:
Protein therapeutics is an emerging class of drug therapy that provides treatment for a broad range of diseases, such as autoimmune disorders, cardiovascular diseases, diabetes, and cancer. A common delivery method for some protein therapeutics, such as monoclonal antibodies, is through intravenous infusion, in which large volumes of dilute solutions are delivered over time. Intravenous infusion usually requires the supervision of a doctor or nurse and is performed in a clinical setting. This can be inconvenient for a patient, and so efforts are being made to permit the delivery of protein therapeutics at home. Desirably, a protein therapeutic formulation can be administered using a syringe for subcutaneous delivery instead of requiring intravenous administration. Subcutaneous injections are commonly administered by laypersons, for example in the administration of insulin by diabetics.

Transitioning therapeutic protein formulations from intravenous delivery to injection devices like syringes and injection pens requires addressing challenges associated with delivering high concentrations of high molecular weight molecules in a manner that is easy, reliable, and causes minimal pain to the patient. In this regard, while intravenous bags typically have a volume of <NUM> liter, the standard volume for a syringe ranges from <NUM> milliliters up to <NUM> milliliters. Thus, depending on the drug, to deliver the same amount of therapeutic proteins, the concentration may have to increase by a factor of <NUM> or more. Also, injection therapy is moving towards smaller needle diameters and faster delivery times for purposes of patient comfort and compliance.

Delivery of protein therapeutics is also challenging because of the high viscosity associated with such therapeutic formulations, and the high forces needed to push such formulations through a parenteral device. Formulations with absolute viscosities above <NUM>-<NUM> centipoise (cP) may be difficult to deliver by conventional spring driven auto-injectors for multiple reasons. Structurally, the footprint of a spring for the amount of pressure delivered is relatively large and fixed to specific shapes, which reduces flexibility of design for delivery devices. Next, auto-injectors are usually made of plastic parts. However, a large amount of energy must be stored in the spring to reliably deliver high-viscosity fluids. If not properly designed, this stored energy may cause damage to the plastic parts due to creep, which is the tendency of the plastic part to permanently deform under stress. An auto-injector typically operates by using the spring to push a needle-containing internal component towards an outer edge of the housing of the syringe. The sound associated with the operation of a spring-based auto-injector may cause patient anxiety, potentially reducing future compliance. The generated pressure versus time profile of such a spring driven auto-injector cannot be readily modified, which prevents users from fine tuning pressure to meet their delivery needs.

It would be desirable to provide processes and devices by which a therapeutic fluid, in particular a high-viscosity fluid, could be self-administered in a reasonable time and with a limited injection space. These processes and devices could be used to deliver high-concentration protein, high-viscosity pharmaceutical formulations, or other therapeutic fluids. <CIT> discloses an auto-injector for administration of a medicament within a prefilled syringe. The apparatus includes a housing, a carrier, and an expandable assembly. The housing defines an opening configured to selectively place a gas chamber of the housing in fluid communication with an exterior volume. The carrier is movably disposed within the housing and is coupled to a medicament container. A proximal surface of the carrier defines a portion of a boundary of the gas chamber. The expandable assembly has a first member and a second member. The first member is coupled to an elastomeric member disposed within the medicament container, and the second member includes a valve portion. The expandable assembly transitions from a collapsed configuration to an expanded configuration when the elastomeric member moves within the medicament container. The valve portion moves relative to the opening when the expandable assembly transitions from the first to the second configuration, placing the gas chamber in fluid communication with the exterior volume. <CIT> discloses an apparatuses for automatic medicament injection. An apparatus includes a housing, a needle, an energy storage member, an actuator, a locking member, and a needle guard. The needle is configured to move between a first position and a second position. In its first position, the needle is contained within the housing. In its second position, at least a portion of the needle extends from the housing. The energy storage member has a first configuration and a second configuration and is configured to produce a force when moving between its first configuration and its second configuration to move the needle from its first position to its second position. The actuator is configured to move the energy storage member from its first configuration to its second configuration. The locking member is movably coupled to the distal end portion of the housing such that the locking member can be moved between a first position and a second position. In its first position, the locking member is configured to engage the actuator to prevent the actuator from moving the energy storage member to the second configuration. The needle guard is removably coupled to at least one of the distal end portion of the housing or a base movably coupled to the distal end portion of the housing. <CIT> discloses a pneumatically-actuated retractable-needle syringe. <CIT> discloses processes and devices for delivering a fluid by chemical reaction. A chemical reaction is initiated in a reaction chamber to produce a gas, and the gas acts upon a piston to deliver the fluid. Preferred devices typically include an upper chamber, a lower chamber, a fluid chamber, a piston between the lower chamber and the fluid chamber, and a barrier between the upper chamber and the lower chamber. When the barrier is broken, reagents in the upper chamber and the lower chamber are mixed together to generate the gas.

The invention is defined in claims <NUM> and <NUM>. Any aspects, embodiments and examples of the present disclosure which do not fall under the scope of the appended clams do not form part of the invention and are merely provided for illustrative purposes.

In addition to the abovementioned devices of the invention, there is hereinafter disclosed a method (not claimed) for delivering a therapeutic fluid by chemical reaction from a device comprising a barrel having a first chamber, an actuator assembly coupled to the barrel and including a first reagent and a second reagent separated by a barrier, a syringe coupled to the barrel, the syringe containing the therapeutic fluid and including a needle, a plunger disposed in the syringe, and a shield coupled to the barrel and surrounding the syringe. The method includes actuating the actuator assembly, at least partially removing the barrier between the first reagent and the second reagent, generating a gas from a reaction of the first reagent and the second reagent, pressurizing the first chamber of the barrel with the generated gas, displacing the syringe, the plunger, and the needle in a first direction via a force created by the generated gas, displacing the plunger within the syringe via the force created by the generated gas, delivering the therapeutic fluid from the needle, releasing the generated gas from the first chamber within the barrel, and displacing the needle and the syringe in a second direction after releasing the generated gas form the first chamber.

In one example of the method, the needle of the syringe is positioned within the shield prior to displacement of the syringe, the plunger, and the needle in the first direction via the force created by the generated gas.

In another example of the method, the method further comprises exposing the needle of the syringe outside of the shield when the syringe, the plunger, and the needle are displaced in the first direction.

In a further example of the method, the second direction is opposite the first direction.

In yet another example of the method, the device further includes an air passageway, the step of releasing the generated gas from the first chamber including the generated gas entering the air passageway after the plunger is displaced within the syringe.

In a further example of the method, displacement of the syringe and the needle in the second direction occurs after the generated gas enters the air passageway.

The above-mentioned and other features and advantages of this disclosure, and the manner of attaining them, will become more apparent and will be better understood by reference to the following description of embodiments of the invention taken in conjunction with the accompanying drawings, wherein:.

Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set out herein illustrate exemplary embodiments of the invention and such exemplifications are not to be construed as limiting the scope of the invention in any manner.

The present disclosure provides auto-injectors and methods that operate using gas-generating chemical reactions. The generated gas may place the auto-injector in a punctured configuration to puncture a patient's skin with a needle, an injected configuration to deliver a therapeutic fluid through the needle and into the puncture site, and/or a retracted configuration to withdraw the needle from the puncture site. Unless specifically noted or clearly implied otherwise, the term "about" refers to a range of values of plus or minus <NUM>%, e.g., about <NUM> refers to the range <NUM> to <NUM>.

The therapeutic fluid to be dispensed from the devices of the present disclosure may take various forms, such as a solution, dispersion, suspension, emulsion, or another suitable fluid form.

The therapeutic fluid may contain a therapeutically useful agent. The therapeutic agent may include insulin, insulin analog such as insulin lispro or insulin glargine, insulin derivative, GLP-<NUM> receptor agonist such as dulaglutide or liraglutide, glucagon, glucagon analog, glucagon derivative, gastric inhibitory polypeptide (GIP), GIP analog, GIP derivative, oxyntomodulin analog, oxyntomodulin derivative, therapeutic antibody and any therapeutic agent that is capable of transport or delivery by the devices of the present disclosure. The therapeutic agent as used in the device may be formulated with one or more excipients.

In certain embodiments, the agent is protein, such as a monoclonal antibody or some other protein which is therapeutically useful. In some embodiments, the protein may have a concentration of from about <NUM>/mL to about <NUM>/mL in the therapeutic fluid. In certain embodiments, the protein may have a concentration of about <NUM>/mL, <NUM>/mL, <NUM>/mL, or more. The therapeutic fluid may further contain a solvent or non-solvent, such as water, perfluoroalkane solvent, safflower oil, or benzyl benzoate.

The therapeutic fluid may be considered a high-viscosity fluid and may have an absolute viscosity of from about <NUM> cP to about <NUM> cP. In certain embodiments, the high-viscosity fluid has an absolute viscosity of at least about <NUM> cP, <NUM> cP, <NUM> cP, <NUM> cP, <NUM> cP, <NUM> cP, or more.

Any suitable chemical reagent or reagents may be used to generate a gas in the devices of the present disclosure. Examples of generated gases include carbon dioxide gas, nitrogen gas, oxygen gas, chlorine gas, etc. Desirably, the generated gas is inert and non-flammable. The amount of gas needed to operate the device may impact the type, amount, and concentration of each reagent used in the device. The reagents may be in dry form (e.g., powdered form, tablet form) and/or in liquid form.

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 produce carbon dioxide gas in the device. Examples of suitable bicarbonates include sodium bicarbonate, potassium bicarbonate, and ammonium bicarbonate. Other ingredients may also be present along with the bicarbonates, such as diatomaceous earth. Examples of suitable acids include acetic acid, citric acid, potassium bitartrate, disodium pyrophosphate, and calcium dihydrogen phosphate. In one particular example, the bicarbonate is potassium bicarbonate and the acid is aqueous citric acid, which may react to produce carbon dioxide gas and a liquid mixture of water and dissolved potassium citrate.

Other reactions may be used to drive the devices of the present disclosure. In one example, a metal carbonate, such as copper carbonate or calcium carbonate, is thermally decomposed to produce carbon dioxide gas and the corresponding metal oxide in the device. In another example, <NUM>,<NUM>'-azobisisobutyronitrile (AIBN) is heated to produce nitrogen gas in the device. In yet another example, enzymes (e.g. yeast) are reacted with sugar to produce carbon dioxide gas in the device. Some substances readily sublime, going from solid to gas. Such substances include but are not limited to naphthalene and iodine. In still yet another example, hydrogen peroxide is decomposed with catalysts such as enzymes (e.g. catalase) or manganese dioxide to produce oxygen gas in the device. In still yet another example, silver chloride is decomposed through exposure to light to generate a gas in the device.

Suitable reagents, chemical formulations, and reactions used to operate the devices of the present disclosure are further described in the following references: <CIT>, and titled "Process and Device for Delivery of Fluid by Chemical Reaction"; <CIT> (<CIT>, and titled "Chemical Engines and Methods for Their Use, Especially in the Injection of Highly Viscous Fluids"; and International Patent Application No. <CIT>, and titled "Processes and Devices for Delivery of Fluid by Chemical Reaction".

<FIG> and <FIG> show a first exemplary delivery device <NUM> of the present disclosure. The illustrative device <NUM> is an elongate structure that extends along longitudinal axis L from a first, distal end <NUM> (illustratively, a lower end) to a second, proximal end <NUM> (illustratively, an upper end). Advantageously, device <NUM> may have a compact construction and a relatively short length. Distal end <NUM> of device <NUM> includes a syringe <NUM>, a plunger <NUM>, and a shield <NUM>. Proximal end <NUM> of device <NUM> includes barrel <NUM>, an actuator assembly <NUM>, a first piston <NUM>, a second piston <NUM>, and an airway <NUM>. Each component of device <NUM> is described further below with continued reference to <FIG> and <FIG>.

The illustrative syringe <NUM> contains a therapeutic fluid <NUM>, as discussed above. At distal end <NUM>, syringe <NUM> includes a needle <NUM> configured to puncture a patient's skin. At its other end, syringe <NUM> includes a rim <NUM> configured to interact with shield <NUM>. In use, syringe <NUM> is configured for longitudinal movement with first piston <NUM> relative to shield <NUM> and barrel <NUM>.

The illustrative plunger <NUM> is disposed within syringe <NUM> and coupled to the distal end of first piston <NUM>. In use, plunger <NUM> is configured for longitudinal movement with first piston <NUM>.

The illustrative shield <NUM> is disposed around syringe <NUM> and is coupled (e.g., threaded, welded) to barrel <NUM>. It is also within the scope of the present disclosure for shield <NUM> to be integrally formed with barrel <NUM>. Shield <NUM> includes an interior shoulder <NUM> configured to contact rim <NUM> of syringe <NUM> to limit distal movement of syringe <NUM>.

The illustrative barrel <NUM> is substantially cylindrical in shape, although this shape may vary. Barrel <NUM> includes an upper chamber <NUM> having a relatively small internal diameter and a lower chamber <NUM> having a relatively large internal diameter.

The illustrative actuator assembly <NUM> includes a button <NUM> having a sharp distal tip <NUM>. The illustrative actuator assembly <NUM> also includes a housing <NUM> having an interior barrier <NUM> (e.g., film). In the illustrated embodiment of <FIG>, housing <NUM> of actuator assembly <NUM> is integrally formed with barrel <NUM>, but it is also within the scope of the present disclosure for housing <NUM> of actuator assembly <NUM> and barrel <NUM> to be separate components. In the configuration shown in <FIG>, interior barrier <NUM> divides housing <NUM> into a first actuation chamber <NUM> that contains a first reagent <NUM> (e.g., aqueous citric acid) and a second reaction chamber <NUM> that contains a second reagent <NUM> (e.g., potassium bicarbonate).

The illustrative first piston <NUM> includes a head <NUM> disposed in upper chamber <NUM> of barrel <NUM> and a shaft <NUM> disposed in syringe <NUM>. As indicated above, longitudinal movement of the first piston <NUM> may be transferred to plunger <NUM>.

The illustrative second piston <NUM> includes a head <NUM> disposed in lower chamber <NUM> of barrel <NUM>. As shown in <FIG>, second piston <NUM> surrounds shaft <NUM> of first piston <NUM> beneath head <NUM> of first piston <NUM>. In use, second piston <NUM> is configured to slide axially across shaft <NUM> of first piston <NUM>. The surface area of head <NUM> of second piston <NUM> may exceed the surface area of head <NUM> of first piston <NUM>.

The illustrative airway <NUM> connects upper chamber <NUM> of barrel <NUM> with lower chamber <NUM> of barrel <NUM>. Although the illustrative airway <NUM> is an external tube that extends outside of barrel <NUM>, it is within the scope of the present disclosure that airway <NUM> may be incorporated into barrel <NUM>. In use, when airway <NUM> is open, airway <NUM> is configured to direct gas from upper chamber <NUM> of barrel <NUM> into lower chamber <NUM> of barrel <NUM>.

Referring next to <FIG>, an exemplary method is shown and described for operating device <NUM>.

In <FIG>, device <NUM> is shown in a loaded configuration. It is within the scope of the present disclosure for device <NUM> to be locked in this loaded configuration until device <NUM> is ready for use. At distal end <NUM> of device <NUM>, syringe <NUM> and needle <NUM> are withdrawn into and concealed by shield <NUM>. At proximal end <NUM> of device <NUM>, interior barrier <NUM> of actuator assembly <NUM> separates first reagent <NUM> (e.g., aqueous citric acid) in first actuation chamber <NUM> from second reagent <NUM> (e.g., potassium bicarbonate) in second reaction chamber <NUM>.

In <FIG>, device <NUM> is shown in an actuated configuration. Button <NUM> of actuator assembly <NUM> has been pressed to pierce interior barrier <NUM> with tip <NUM>. As a result, interior barrier <NUM> between first reaction chamber <NUM> and second reaction chamber <NUM> is at least partially removed such that first reagent <NUM> (e.g., aqueous citric acid) in first actuation chamber <NUM> is exposed to second reagent <NUM> (e.g., potassium bicarbonate) in second reaction chamber <NUM>.

Additional details regarding actuator assembly <NUM> and other suitable actuator assemblies are described in <CIT>; <CIT>; and International Application No. <CIT>. For example, in one alternative embodiment disclosed in <CIT>, the actuator assembly includes a piston (not shown) and a spring (not shown). In the loaded configuration, the piston compresses the spring and creates a sealed interface between the first and second chambers <NUM>, <NUM>. In the actuated configuration, the spring releases and moves the piston to break the sealed interface between the first and second chambers in <NUM>, <NUM>.

In <FIG>, device <NUM> is shown in a punctured configuration. At proximal end <NUM> of device <NUM>, first and second reagents <NUM>, <NUM> react and generate gas. The gas pressurizes upper chamber <NUM> of barrel <NUM> and applies force to head <NUM> of first piston <NUM>, which causes first piston <NUM> to move distally through barrel <NUM>. Due to frictional forces between syringe <NUM> and plunger <NUM>, the initial distal movement of first piston <NUM> causes distal movement of syringe <NUM>, until rim <NUM> of syringe <NUM> abuts interior shoulder <NUM> of shield <NUM>. At distal end <NUM> of device <NUM>, needle <NUM> protrudes from shield <NUM> to puncture the patient's skin.

In <FIG>, device <NUM> is shown in an injected configuration. At proximal end <NUM> of device <NUM>, first and second reagents <NUM>, <NUM> continue to react and generate gas. With rim <NUM> of syringe <NUM> abutting interior shoulder <NUM> of shield <NUM>, the continued distal movement of first piston <NUM> overcomes frictional forces between plunger <NUM> and syringe <NUM> and causes distal movement of plunger <NUM> through syringe <NUM> to deliver therapeutic fluid <NUM> from syringe <NUM>, through needle <NUM>, and into the puncture site. When first piston <NUM> reaches the end of its distal stroke, as shown in <FIG>, head <NUM> of first piston <NUM> moves past and exposes airway <NUM>.

In <FIG>, device <NUM> is shown in a retracted configuration. To reach this configuration, the gas from upper chamber <NUM> of barrel <NUM> is released from upper chamber <NUM> and travels through the exposed airway <NUM> and into lower chamber <NUM> of barrel <NUM>. Eventually, because the surface area of head <NUM> of second piston <NUM> exceeds the surface area of head <NUM> of first piston <NUM>, the proximal force on second piston <NUM> may overcome the distal force on first piston <NUM>, even when the pressure in lower chamber <NUM> is equal to or less than the pressure in upper chamber <NUM>. When the proximal force eventually exceeds the distal force after a certain delay time, second piston <NUM> moves proximally through lower chamber <NUM> of barrel <NUM> toward first piston <NUM>. The proximal movement of second piston <NUM>, including the delay time before movement, may be controlled by adjusting the size and shape of first piston <NUM>, the size and shape of second piston <NUM>, and the size of airway <NUM>, for example. When second piston <NUM> reaches head <NUM> of first piston <NUM>, the continued proximal movement of second piston <NUM> causes proximal movement of first piston <NUM>. Due to frictional forces between syringe <NUM> and plunger <NUM>, the proximal movement of first piston <NUM> causes proximal movement of syringe <NUM>. At distal end <NUM> of device <NUM>, needle <NUM> withdraws from the puncture site and retracts into shield <NUM>. Needle <NUM> may have the same position in the retracted configuration of <FIG> as the loaded configuration of <FIG>. First piston <NUM> and/or second piston <NUM> may be captured at the end of the proximal stroke, such as using an expanding C-ring, to maintain needle <NUM> in the retracted configuration.

<FIG> show a second exemplary delivery device <NUM> of the present disclosure. The illustrative device <NUM> is similar to delivery device <NUM> described above, except that first piston <NUM> and second piston <NUM> are coupled or fixed together or integral to form a dual-piston body <NUM> including both first piston <NUM> and second piston <NUM>. Piston body <NUM> is positioned within proximal end <NUM> of device <NUM>. In order for the pistons <NUM>, <NUM> to be integrally formed, device <NUM> is slightly elongated along longitudinal axis L compared to device <NUM>. Similar to device <NUM>, distal end <NUM> of device <NUM> includes a syringe <NUM>, a plunger <NUM>, and a shield <NUM>, and proximal end <NUM> of device <NUM> includes barrel <NUM>, an actuator assembly <NUM>, and an airway <NUM>. Each component of device <NUM> is described further below with continued reference to <FIG>.

The illustrative syringe <NUM> contains a therapeutic fluid <NUM>, as discussed above. At distal end <NUM>, syringe <NUM> includes a needle <NUM> configured to puncture a patient's skin. At its other end, syringe <NUM> includes a rim <NUM> configured to interact with shield <NUM>. In use, syringe <NUM> is configured for longitudinal movement with piston body <NUM> relative to shield <NUM> and barrel <NUM>.

The illustrative plunger <NUM> is disposed within syringe <NUM> and coupled to the distal end of piston body <NUM>. In use, plunger <NUM> is configured for longitudinal movement with piston body <NUM>.

The illustrative piston body <NUM> includes first piston <NUM> having a head <NUM> disposed in upper chamber <NUM> of barrel <NUM>, a second piston <NUM> having a head <NUM> disposed in lower chamber <NUM> of barrel <NUM>, and a shaft <NUM> coupling first and second piston <NUM> and <NUM>. The upper end of shaft <NUM> is coupled beneath head <NUM> of first piston <NUM>, and the lower end of shaft <NUM> extends past second piston <NUM> and into syringe <NUM>. In use, second piston <NUM> and first piston <NUM> are configured to slide longitudinally simultaneously. The surface area of head <NUM> of second piston <NUM> may exceed the surface area of head <NUM> of first piston <NUM>. As indicated above, longitudinal movement of the piston body <NUM> may be transferred to plunger <NUM>.

The illustrative airway <NUM> connects upper chamber <NUM> of barrel <NUM> with lower chamber <NUM> of barrel <NUM>. Although the illustrative airway <NUM> is an external tube that extends outside of barrel <NUM>, it is within the scope of the present disclosure that airway <NUM> may be incorporated into barrel <NUM>. In use, when airway <NUM> is open, airway <NUM> is configured to direct gas from upper chamber <NUM> of barrel <NUM> into lower chamber <NUM> of barrel <NUM>. Due to the extended length of device <NUM>, airway <NUM> may also be extended in length to properly couple upper chamber <NUM> and lower chamber <NUM>.

Additional details regarding actuator assembly <NUM> and other suitable actuator assemblies are described in <CIT>; <CIT>; and International Application No. <CIT>, as discussed above.

In <FIG>, device <NUM> is shown in a punctured configuration. At proximal end <NUM> of device <NUM>, first and second reagents <NUM>, <NUM> react and generate gas. The gas pressurizes upper chamber <NUM> of barrel <NUM> and applies force to head <NUM> of first piston <NUM> of piston body <NUM>, which causes piston body <NUM> to move distally through barrel <NUM>, and thus first and second pistons <NUM> and <NUM> to move distally through barrel <NUM> and lower chamber <NUM>, respectively. Due to frictional forces between syringe <NUM> and plunger <NUM>, the initial distal movement of piston body <NUM> causes distal movement of syringe <NUM>, until rim <NUM> of syringe <NUM> abuts interior shoulder <NUM> of shield <NUM>. At distal end <NUM> of device <NUM>, needle <NUM> protrudes from shield <NUM> to puncture the patient's skin.

In <FIG>, device <NUM> is shown in an injected configuration. At proximal end <NUM> of device <NUM>, first and second reagents <NUM>, <NUM> continue to react and generate gas. With rim <NUM> of syringe <NUM> abutting interior shoulder <NUM> of shield <NUM>, the continued distal movement of piston body <NUM> overcomes frictional forces between plunger <NUM> and syringe <NUM> and causes distal movement of plunger <NUM> through syringe <NUM> to deliver therapeutic fluid <NUM> from syringe <NUM>, through needle <NUM>, and into the puncture site. When piston body <NUM> reaches the end of its distal stroke, as shown in <FIG>, head <NUM> of first piston <NUM> moves past and exposes airway <NUM>.

In <FIG>, device <NUM> is shown in a retracted configuration. To reach this configuration, the gas from upper chamber <NUM> of barrel <NUM> is released from upper chamber <NUM> and travels through the exposed airway <NUM> and into lower chamber <NUM> of barrel <NUM>. Eventually, because the surface area of head <NUM> of second piston <NUM> exceeds the surface area of head <NUM> of first piston <NUM>, the proximal force on second piston <NUM> may overcome the distal force on first piston <NUM>, even when the pressure in lower chamber <NUM> is equal to or less than the pressure in upper chamber <NUM>. When the proximal force eventually exceeds the distal force after a certain delay time, piston body <NUM> moves proximally through barrel <NUM>. The proximal movement of piston body <NUM>, including the delay time before movement, may be controlled by adjusting the size and shape of first piston <NUM>, the size and shape of second piston <NUM>, and the size of airway <NUM>, for example. Due to frictional forces between syringe <NUM> and plunger <NUM>, the proximal movement of piston body <NUM> causes proximal movement of syringe <NUM>. At distal end <NUM> of device <NUM>, needle <NUM> withdraws from the puncture site and retracts into shield <NUM>. Needle <NUM> may have the same position in the retracted configuration of <FIG> as the loaded configuration of <FIG>. First piston <NUM> and/or second piston <NUM> may be captured at the end of the proximal stroke to maintain needle <NUM> in the retracted configuration.

<FIG> show a second exemplary delivery device <NUM> of the present disclosure. The illustrative device <NUM> is generally similar to delivery devices <NUM> and <NUM> described above, except that device <NUM> has been configured such that airway <NUM> is positioned internally within device <NUM> between an outer housing <NUM> of device <NUM> and barrel <NUM> to act on barrel <NUM>. Distal end <NUM> of device <NUM> includes a syringe <NUM>, a plunger <NUM>, and a shield <NUM>, and proximal end <NUM> of device <NUM> includes barrel <NUM>, an actuator assembly <NUM>, a piston <NUM>, and airway <NUM>. Each component of device <NUM> is described further below with continued reference to <FIG>.

The illustrative syringe <NUM> contains a therapeutic fluid <NUM>, as discussed above. At distal end <NUM>, syringe <NUM> includes a needle <NUM> configured to puncture a patient's skin. At its other end, syringe <NUM> includes a rim <NUM> configured to interact with shield <NUM>. In use, syringe <NUM> is configured for longitudinal movement with piston <NUM> relative to shield <NUM> and barrel <NUM>.

The illustrative plunger <NUM> is disposed within syringe <NUM> and coupled to the distal end of piston <NUM>. In use, plunger <NUM> is configured for longitudinal movement with piston <NUM>.

The illustrative shield <NUM> is disposed around syringe <NUM> and is integrally formed with outer housing <NUM>. It is also within the scope of the present disclosure for shield <NUM> to be coupled (e.g., threaded, welded) to outer housing <NUM>. Shield <NUM> includes an interior shoulder <NUM> configured to contact rim <NUM> of syringe <NUM> to limit distal movement of syringe <NUM>.

The illustrative barrel <NUM> has an upper piston head <NUM> (<FIG>) and is substantially T-shaped, although this shape may vary. Barrel <NUM> is configured for longitudinal movement relative to outer housing <NUM>. Barrel <NUM> also includes an inner chamber <NUM> having a relatively small internal diameter.

The illustrative piston <NUM> has a head <NUM> disposed in inner chamber <NUM> of barrel <NUM> and a shaft <NUM> that extends downward from head <NUM> and into syringe <NUM>. As indicated above, longitudinal movement of the piston <NUM> may be transferred to plunger <NUM>.

The illustrative airway <NUM> connects inner chamber <NUM> of barrel <NUM> with outer chamber <NUM> of barrel <NUM> defined by outer housing <NUM>. Although the illustrative airway <NUM> is an internal passage that extends within of outer housing <NUM>, it is within the scope of the present disclosure that airway <NUM> may external to outer housing <NUM>. In use, when airway <NUM> is open, airway <NUM> is configured to release gas from inner chamber <NUM> of barrel <NUM> and direct the gas into outer chamber <NUM> of barrel <NUM> defined by outer housing <NUM>.

In <FIG>, device <NUM> is shown in a punctured configuration. At proximal end <NUM> of device <NUM>, first and second reagents <NUM>, <NUM> react and generate gas. The gas pressurizes inner chamber <NUM> of barrel <NUM> and applies force to head <NUM> of piston <NUM>, which causes piston <NUM> to move distally through barrel <NUM>. Due to frictional forces between syringe <NUM> and plunger <NUM>, the initial distal movement of piston <NUM> causes distal movement of syringe <NUM>, until rim <NUM> of syringe <NUM> abuts interior shoulder <NUM> of shield <NUM>. At distal end <NUM> of device <NUM>, needle <NUM> protrudes from shield <NUM> to puncture the patient's skin.

In <FIG>, device <NUM> is shown in an injected configuration. At proximal end <NUM> of device <NUM>, first and second reagents <NUM>, <NUM> continue to react and generate gas. With rim <NUM> of syringe <NUM> abutting interior shoulder <NUM> of shield <NUM>, the continued distal movement of piston <NUM> overcomes frictional forces between plunger <NUM> and syringe <NUM> and causes distal movement of plunger <NUM> through syringe <NUM> to deliver therapeutic fluid <NUM> from syringe <NUM>, through needle <NUM>, and into the puncture site. When piston <NUM> reaches the end of its distal stroke, as shown in <FIG>, head <NUM> of first piston <NUM> moves past and exposes airway <NUM>, as shown in detail in <FIG>.

In <FIG>, device <NUM> is shown in a retracted configuration. To reach this configuration, the gas from inner chamber <NUM> of barrel <NUM> is released from inner chamber <NUM> and travels through the exposed airway <NUM> and into outer chamber <NUM> of barrel <NUM> defined by outer housing <NUM>. Eventually, the proximal force on head <NUM> of barrel <NUM> is sufficient to cause proximal movement of barrel <NUM> and syringe <NUM>. When the proximal force eventually exceeds the distal force after a certain delay time, barrel <NUM> moves proximally through outer housing <NUM>. In this manner, barrel <NUM> serves as a second piston inside outer housing <NUM>. The proximal movement of barrel <NUM>, including the delay time before movement, may be controlled by adjusting the size and shape of barrel <NUM>, the size and shape of first piston <NUM>, and the size of airway <NUM>, for example. Like devices <NUM> and <NUM>, for example, the surface area of head <NUM> of barrel <NUM> may exceed the surface area of head <NUM> of piston <NUM> to promote retraction of barrel <NUM>. Due to frictional forces between syringe <NUM> and plunger <NUM>, the proximal movement of barrel <NUM> causes proximal movement of syringe <NUM>. At distal end <NUM> of device <NUM>, needle <NUM> withdraws from the puncture site and retracts into shield <NUM>. Needle <NUM> may have the same position in the retracted configuration of <FIG> as the loaded configuration of <FIG>. Body <NUM><NUM> may be captured at the end of the proximal stroke to maintain needle <NUM> in the retracted configuration.

<FIG> show a fourth exemplary delivery device <NUM> of the present disclosure. The illustrative device <NUM> is an elongate structure that extends along longitudinal axis L from a first, distal end <NUM> (illustratively, a lower end) to a second, proximal end <NUM> (illustratively, an upper end). Advantageously, device <NUM> may have a compact construction and a relatively short length. Device <NUM> includes a syringe <NUM>, a plunger <NUM>, a shield <NUM>, a barrel <NUM>, an actuator assembly <NUM>, a first piston <NUM>, an airway <NUM>, and a spring <NUM>. Each component of device <NUM> is described further below with continued reference to <FIG>.

The illustrative syringe <NUM> contains a therapeutic fluid <NUM>, as discussed above. At distal end <NUM>, syringe <NUM> includes a needle <NUM> configured to puncture a patient's skin. At its other end, syringe <NUM> includes a rim <NUM>. In use, syringe <NUM> is configured for longitudinal movement with first piston <NUM> relative to shield <NUM> and barrel <NUM>.

The illustrative plunger <NUM> is disposed within syringe <NUM>. In use, plunger <NUM> is configured for longitudinal movement within syringe <NUM>.

The illustrative shield <NUM> is disposed around syringe <NUM> and is coupled (e.g., threaded, welded) to barrel <NUM>. It is also within the scope of the present disclosure for shield <NUM> to be integrally formed with barrel <NUM>.

The illustrative barrel <NUM> is substantially cylindrical in shape, although this shape may vary. Barrel <NUM> includes an upper chamber <NUM> having a relatively large internal diameter and detent <NUM> configured to interact with first piston <NUM> surrounding syringe <NUM> to limit distal movement of first piston <NUM> and syringe <NUM>.

The illustrative actuator assembly <NUM> includes a button <NUM> having a sharp distal tip <NUM>. The illustrative actuator assembly <NUM> also includes a housing <NUM> having an interior barrier <NUM> (e.g., film). In the illustrated embodiment of <FIG>, housing <NUM> of actuator assembly <NUM> is a separate component coupled (e.g., threaded, welded) to barrel <NUM>, but it is also within the scope of the present disclosure for housing <NUM> of actuator assembly <NUM> to be integrally formed with barrel <NUM>. In the configuration shown in <FIG>, interior barrier <NUM> divides housing <NUM> into a first actuation chamber <NUM> that contains a first reagent <NUM> (e.g., aqueous citric acid) and a second reaction chamber <NUM> that contains a second reagent <NUM> (e.g., potassium bicarbonate).

The illustrative first piston <NUM> surrounds syringe <NUM> below rim <NUM>. In use, first piston <NUM> is configured to interact with rim <NUM> of syringe <NUM> and a detent <NUM> of barrel <NUM>.

The illustrative airway <NUM> connects upper chamber <NUM> of barrel <NUM> to the surrounding atmosphere. It is also within the scope of the present disclosure for airway <NUM> to be an external or internal tube that extends from a portion of upper chamber <NUM> above first piston <NUM> to a portion of upper chamber <NUM> below first piston <NUM>. In use, when airway <NUM> is open, airway <NUM> is configured to direct gas from upper chamber <NUM> of barrel <NUM> into the atmosphere.

In <FIG>, device <NUM> is shown in a punctured configuration. At proximal end <NUM> of device <NUM>, first and second reagents <NUM>, <NUM> react and generate gas. The gas pressurizes upper chamber <NUM> of barrel <NUM> and applies force to first piston <NUM> and syringe <NUM>, which causes first piston <NUM> and syringe <NUM> to move distally through barrel <NUM> in turn causing spring <NUM> to compress. Due to frictional forces between syringe <NUM> and plunger <NUM>, the initial distal movement of first piston <NUM> causes distal movement of syringe <NUM>, until first piston <NUM> abuts detent <NUM> of barrel <NUM>. At distal end <NUM> of device <NUM>, needle <NUM> protrudes from shield <NUM> to puncture the patient's skin.

In <FIG>, device <NUM> is shown in an injected configuration. At proximal end <NUM> of device <NUM>, first and second reagents <NUM>, <NUM> continue to react and generate gas. With first piston <NUM> abutting an upper surface of detent <NUM> of barrel <NUM>, as shown in <FIG>, the continued pressure increase within upper chamber <NUM> of barrel <NUM> overcomes frictional forces between plunger <NUM> and syringe <NUM> and causes distal movement of plunger <NUM> through syringe <NUM> to deliver therapeutic fluid <NUM> from syringe <NUM>, through needle <NUM>, and into the puncture site. When plunger <NUM> reaches the end of its distal stroke, as shown in <FIG>, pressure within upper chamber <NUM> becomes sufficient to move first piston <NUM> down over detent <NUM>, as shown in <FIG>, and exposes airway <NUM>.

In <FIG>, device <NUM> is shown in a retracted configuration. To reach this configuration, the gas from upper chamber <NUM> of barrel <NUM> is released from upper chamber <NUM> and travels through the exposed airway <NUM> out of barrel <NUM>. Eventually, when the proximal force on first piston <NUM> from spring <NUM> exceeds the distal force on first piston <NUM> from the pressurized gas and the frictional force on first piston <NUM> from detent <NUM> after a certain delay time, first piston <NUM> and syringe <NUM> move proximally through upper chamber <NUM> of barrel <NUM> toward actuator assembly <NUM>. The proximal movement of first piston <NUM>, including the delay time before movement, may be controlled by adjusting the size, shape, and spring constant of spring <NUM>, the size and shape of detent <NUM>, and the size of airway <NUM>, for example. Due to rim <NUM> of syringe <NUM> being above first piston <NUM> within upper chamber <NUM> of barrel <NUM>, the proximal movement of first piston <NUM> causes proximal movement of syringe <NUM>. At distal end <NUM> of device <NUM>, needle <NUM> withdraws from the puncture site and retracts into shield <NUM>. Needle <NUM> may have the same position in the retracted configuration of <FIG> as in the loaded configuration of <FIG>. First piston <NUM> may be captured at the end of the proximal stroke to maintain needle <NUM> in the retracted configuration.

Claim 1:
A device for delivering a therapeutic fluid by chemical reaction, the device comprising:
a barrel (<NUM>, <NUM>, <NUM>) including a first chamber (<NUM>, <NUM>, <NUM>) and a second chamber (<NUM>, <NUM>, <NUM>);
an actuator assembly (<NUM>, <NUM>, <NUM>) coupled to the barrel and including a first reagent (<NUM>, <NUM>, <NUM>) and a second reagent (<NUM>, <NUM>, <NUM>);
a syringe (<NUM>, <NUM>, <NUM>) coupled to the barrel, the syringe containing the therapeutic fluid and including a needle (<NUM>, <NUM>, <NUM>); and
a plunger (<NUM>, <NUM>, <NUM>) disposed in the syringe;
characterized in that the device includes a first piston (<NUM>, <NUM>, <NUM>) and a second piston (<NUM>, <NUM>, <NUM>), the first piston is coupled to the plunger, and the device has:
an actuated configuration in which the first and second reagents react and generate a gas;
an injected configuration in which the gas applies a force to the first piston to move the plunger in a first direction to deliver the therapeutic fluid from the syringe; and
a retracted configuration in which, following exposure of an airway (<NUM>, <NUM>, <NUM>) by movement in the first direction of the first piston past the airway, the gas travels from the first chamber through the airway to the second chamber to apply a force to the second piston to move the syringe in a second direction opposite the first direction.