Sequential delivery system and method

Abstract

An automatic and / or semi-automatic sequential drug delivery syringe system in which energy provided for dispensing drugs from multiple containers or cartridges can be repeatedly applied to deliver drugs in each separate step without mixing the drug components within the device. A pressurized gas source can drive a flow through multiple valves to sequentially dispense doses or distinct drugs from each of the multiple containers arranged within the device. The administration needle, when in its nominal state, is in fluid communication with a flow path connecting adjacent drug containers.

Description

TECHNICAL FIELD

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application No. 63 / 590,958 filed on October 17, 2023, and U.S. Provisional Application No. 63 / 622,886 filed on January 19, 2024, the entire contents of each of which are incorporated herein by reference in their entirety.

[0002] FIELD OF THE SUBJECT MATTER OF THE PRESENT DISCLOSURE The present invention generally relates to dual container devices for sequentially delivering pharmaceutical components (e.g., different pharmaceutical components, or multiple doses of a single pharmaceutical component). In addition to functioning well for large quantities of active pharmaceutical ingredient(s), including high viscosity ones that require large forces or APIs that require extensive agitation for maximum effectiveness. The devices disclosed herein can be resized or dimensioned to accommodate standard drug cartridges, for example, each with a volume of 1 mL to 5 mL, though cartridges of less than 1 mL and greater than 5 mL are also contemplated.

BACKGROUND ART

[0003] Dual container / cartridge syringes / autoinjectors are typically known to store drug components separately until reconstitution or combination at the time of use, or to be co-administered separately from two containers. Therapeutic agents that may preferably be provided in a multi-chamber format offer various advantages. Drugs may have low thermal stability, short shelf life, or other issues that are present in aqueous forms. Solubilization of a drug in a liquid formulation, suspension of dry particles in a liquid, or combination of a liquid-liquid solution or suspension thereof may be required for similar reasons. In other cases, multiple liquid drugs that need to be co-administered may not be suitable for storage in the same container due to issues of stability, different requirements around pH, or molecular interactions that could affect the efficacy of the drug itself.

SUMMARY OF THE INVENTION

PROBLEMS TO BE SOLVED BY THE INVENTION

[0004] In some cases, speed and ease of use can be critical for rescue applications where emergency treatment needs to be delivered very quickly and in very few steps. Preparation may also require multiple steps, including changing needles or manually transferring drugs and diluents from one container to another. Furthermore, if a second drug, and / or a second dose of a common drug, is required, conventional devices may require a second injection procedure and, potentially, a separate needle assembly for administration.

[0005] As a result of these additional steps required of the user, the user may experience delays in treatment time, insufficient dosage, or general dissatisfaction with the product experience. In other cases, drugs may be formulated in less-than-ideal ways, requiring the user to inject higher doses, tolerate more uncomfortable dosage forms, use larger-than-desirable dosing needles, be exposed to additional solubilizers or stabilizers added to the formulation, or be required to administer injections more frequently. There is a strong motivation to create devices that can improve the sequential delivery of drugs that cannot be co-formulated in other ways and are difficult to solubilize, reconstitute, or suspend by resynthesis alone.

[0006] This application seeks to solve some of these identified problems, as well as other problems that would be apparent to those skilled in the art. [Means for solving the problem]

[0007] The objectives and merits of the subject matter of this disclosure are set forth in the following description, are evident from the following description, and will be understood through the implementation of the subject matter of this disclosure. Additional merits of the subject matter of this disclosure are realized and achieved by the methods and systems specifically indicated in this specification and its claims in the document, and by the accompanying drawings.

[0008] To achieve these and other advantages, and in accordance with the objectives of the disclosed subject matter, as embodied and broadly described, the disclosed subject matter is a drug delivery system comprising a housing configured to hold a first container and a second container, the first container containing a first drug component and the second container containing a second drug component; a first seal associated with the first container and a second seal associated with the second container; and a fluid communication assembly having a fluid channel between the first container and the second container, wherein the fluid communication assembly is located in the housing at a first position within the housing. A drug delivery system comprising: a fluid communication assembly configured to be displaced from a first position to a second position, thereby opening, removing, or otherwise puncturing a first seal and a second seal to provide a fluid path between a first container and a second container; at least one actuator which may be a storage energy source configured to discharge first and second drug components; and a needle delivery assembly including a dosing needle having a first end and a second end, wherein the first end of the dosing needle is in fluid communication with a fluid channel in a first position.

[0009] In some embodiments, at least one energy storage source includes a spring that engages with a first plunger of a first container and a second spring that engages with a second plunger of a second container.

[0010] In some embodiments, the system further comprises a plate coupled to the first and second plungers, the plate restricting the displacement of at least one of the first and second plungers.

[0011] In some embodiments, at least one of the first plunger and the second plunger includes a structural feature configured to displace a plate, thereby enabling the displacement of the other plunger.

[0012] In some embodiments, the storage energy source includes at least one pressurized gas chamber, the at least one pressurized gas chamber communicating with a first vessel via a first path and with a second vessel via a second path.

[0013] In some embodiments, the system further comprises at least one gas chamber and a valve positioned between it and at least one of a first and / or second vessel, the valve selectively opening the flow of pressurized gas to one of the first and / or second vessels.

[0014] In some embodiments, the system further comprises at least one pressurized gas chamber and a third path communicating with at least one of the first and second paths.

[0015] In some embodiments, at least one pressurized gas displaces a plunger in the first container by a predetermined distance, opening a second path to the second container.

[0016] In some embodiments, the gas chamber includes at least one gas chamber that is in fluid communication with a first vessel and a second gas chamber that is in fluid communication with a second vessel.

[0017] In some embodiments, the first gas chamber displaces the first plunger in the first container by a predetermined distance, thereby opening the second gas chamber and displacing the second plunger in the second container.

[0018] In some embodiments, a predetermined distance is detected by a sensor.

[0019] According to another aspect of the present disclosure, a drug delivery system includes a housing configured to hold a first container and a second container, the first container containing a first drug component and the second container containing a second drug component; a first seal associated with the first container and a second seal associated with the second container; and a fluid communication assembly having a fluid channel between the first container and the second container, the fluid communication assembly being configured to be displaced from a first position to a second position within the housing, thereby opening, removing the first seal and the second seal. A drug delivery system is provided, comprising: a fluid communication assembly that provides a fluid path between a first container and a second container by puncturing or otherwise; a pressurized gas chamber at least partially located in the housing and in fluid communication with the first and second containers; an operating mechanism configured to open or otherwise puncture the pressurized gas chamber; at least one valve configured to release a portion of the pressurized gas to facilitate the discharge of first and second drug components; and a needle delivery assembly configured to be in fluid communication with the first and second containers during the delivery phase.

[0020] In some embodiments, pressurized gas flows through a first pressurized gas path to displace a plunger in the first container by a predetermined distance, thereby opening a second pressurized gas path to the second container.

[0021] In some embodiments, the pressurized gas remains in the first pressurized gas path while the pressurized gas flows into the second pressurized path.

[0022] In some embodiments, the first drug and the second drug are dispensed sequentially and automatically.

[0023] In some embodiments, the pressurized gas chamber is located above the first and second vessels.

[0024] According to another aspect of the present disclosure, a drug delivery system is a housing configured to hold a first container and a second container, wherein the first container contains a first pharmaceutical component, and the second container contains a second pharmaceutical component; a first seal associated with the first container; a second seal associated with the second container; a fluid communication assembly having a fluid channel between the first container and the second container, the fluid communication assembly being configured to be displaced from a first position to a second position within the housing, thereby opening, removing, or otherwise puncturing the first seal and the second seal to provide a fluid path between the first container and the second container; a pressurized gas chamber disposed at least partially in the housing and in fluid communication with the first container and the second container; an actuation mechanism configured to open or otherwise puncture the pressurized gas chamber; at least one valve configured to release a portion of the pressurized gas that facilitates expulsion of the first and second pharmaceutical components; a needle delivery assembly configured to be in fluid communication with the first and second containers during a delivery phase; and a valve disposed in the fluid channel between the first container and the second container.

[0025] In some embodiments, the valve closes the fluid channel to the second container while the medicament from the first container is being expelled.

[0026] In some embodiments, the valve is a ball valve, and the first pharmaceutical component displaces the ball valve in a first direction to close the fluid channel of the second container.

[0027] In some embodiments, the second pharmaceutical component displaces the ball valve in a second direction to close the fluid channel of the first container.

[0028] It is to be understood that both the foregoing summary and the following detailed description for carrying out the invention are exemplary and are intended to provide further explanation of the claimed subject matter of the present disclosure.

[0029] The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to illustrate the methods and systems of the presently disclosed subject matter and to provide a further understanding thereof. Together with the specification, the drawings serve to explain the principles of the presently disclosed subject matter.

[0030] A detailed description of various aspects, features, and embodiments of the subject matter described in this specification is provided with reference to the accompanying drawings, which are briefly described below. The drawings are illustrative and are not necessarily drawn to scale, with some components and features exaggerated for clarity. The drawings illustrate various aspects and features of the present subject matter and may illustrate one or more embodiments or examples of the present subject matter in whole or in part. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] [Figure 1] FIG. 1 is a schematic diagram of an exemplary large volume dual chamber (LVDC) primary drug container (PDC) architecture and dual cartridge holder (DCH) in accordance with the presently disclosed subject matter. Note that references to "dual cartridge holder" and "cartridge holder" are used interchangeably herein. [Figure 2] FIG. 2 is a schematic diagram of an exemplary large volume dual chamber (LVDC) primary drug container (PDC) architecture and dual cartridge holder (DCH) in accordance with the presently disclosed subject matter. Note that references to "dual cartridge holder" and "cartridge holder" are used interchangeably herein. [Figure 3] FIG. 3 is a schematic diagram of an exemplary stored energy source (e.g., a spring) for driving a plunger and dispensing medicament(s). [Figure 4] FIG. 4 is a schematic diagram of an exemplary stored energy source (e.g., a spring) for driving a plunger and dispensing medicament(s). [Figure 5] FIG. 5 is a schematic diagram of an exemplary stored energy source (e.g., a spring) for driving a plunger and dispensing medicament(s). [Figure 6]This is a schematic diagram of an additional exemplary stored energy source (e.g., a gas canister) for driving a plunger and dispensing the drug(s). [Figure 7] This is a schematic diagram of an additional exemplary stored energy source (e.g., a gas canister) for driving a plunger and dispensing the drug(s). [Figure 8] This is a schematic diagram of an additional exemplary stored energy source (e.g., a gas canister) for driving a plunger and dispensing the drug(s). [Figure 9] This is a schematic diagram of an additional exemplary stored energy source (e.g., a gas canister) for driving a plunger and dispensing the drug(s). [Figure 10] This is a schematic diagram of an additional exemplary stored energy source (e.g., a gas canister) for driving a plunger and dispensing the drug(s). [Figure 11] This is a schematic diagram of an additional exemplary stored energy source (e.g., a gas canister) for driving a plunger and dispensing the drug(s). [Figure 12] This is a schematic diagram of an exemplary actuator (e.g., electrically controlled) for driving a plunger and dispensing a drug(s). [Figure 13] This is a schematic diagram of an exemplary device operating feature (e.g., a needle shield). [Figure 14] This is a schematic diagram illustrating exemplary device operating features (e.g., a needle shield). [Figure 15] These are schematic diagrams of exemplary device operating features (e.g., needle shields (Figures 13-15) and buttons (Figure 16)). [Figure 16] This is a schematic diagram of an example device operating feature (e.g., a button). [Figure 17] This is a schematic diagram of a sequential delivery autoinjector (SDA) according to another aspect of the subject matter of this disclosure. [Figure 18] Figure 17 shows a series of front views of the SDA in use. [Figure 19] Figure 17 is a schematic exploded view of the SDA with component identifiers. [Figure 20] This is a cross-sectional view of the SDA in Figure 17, which has a part identifier. [Figure 21] This is a cross-sectional view of the DCH. [Figure 22] This is a cross-sectional view of the distal end of the SDA in its nominal state. [Figure 23] This is a cross-sectional view illustrating the safety cap and sterile barrier removed from the SDA. [Figure 24] This is a schematic isometric view of the internal frame impact snap arm array interacting with the corresponding ramps on the housing. [Figure 25] This is a schematic front view of the translation of the internal frame that rotates the spring release cam. [Figure 26] This is a schematic diagram of a dual-lamp gas-operated system. [Figure 27] This is a schematic isometric view (shown as transparent) of a pneumatic manifold. [Figure 28] This is a schematic cross-sectional view showing the exposure and introduction of the administration needle to the intended site. [Figure 29] This is a schematic cross-sectional view illustrating a needle shield that presses a delivery hub to the delivery position. [Figure 30] This is a schematic cross-sectional view of a pneumatic manifold (pressurized volume shown in blue) and a DCH illustrating a drug delivered from a first drug cartridge via a fluid channel. [Figure 31] This schematic cross-sectional view illustrates how the translation of the first piston reveals the pneumatic path within the pneumatic manifold and reroutes the pressurized gas to the top of the second piston. [Figure 32] This is a schematic cross-sectional view of a pneumatic manifold (pressurized volume shown in blue) and a DCH illustrating a drug delivered from a second drug cartridge via a fluid channel. [Figure 33] This schematic cross-sectional view illustrates how the translation of the second piston exposes the pneumatic vent in the pneumatic manifold, releasing gas and depressurizing the pneumatic manifold. [Figure 34]This is a schematic isometric view showing the internal frame and the compression needle shield return spring that indirectly pushes the needle shield (not shown). [Figure 35] This is a schematic isometric view showing the relative motion between the needle shield and the delivery hub, and how the compliant member falls into the recess and transitions to a lockout state. [Figure 36] This is a side view of another embodiment of a sequential drug delivery device. [Figure 37] Figure 36 is an exploded view of the device's components. [Figure 38] This is a schematic cross-sectional view of the distal end of the device in Figure 36 in its nominal state. [Figure 39] This is a schematic diagram of the device with the cap removed. [Figure 40] This is a schematic diagram of the impact mechanism. [Figure 41] This is a schematic diagram of the operation steps of the primary drug container. [Figure 42] This is a schematic diagram of the gas operation. [Figure 43] This is a schematic cross-sectional view of the gas flow path and piston motion. [Figure 44] This is a schematic cross-sectional view of the mixing prevention mechanism. [Figure 45] This is a schematic cross-sectional view of the lockout function. [Figure 46] This is a schematic cross-sectional view of the lockout function. [Figure 47] This is a schematic cross-sectional view of the lockout function. [Figure 48] This is a schematic diagram illustrating the various operating states of the device. [Modes for carrying out the invention]

[0032] Hereinafter, exemplary embodiments of the subject matter of this disclosure are given in detail, and these embodiments are illustrated in the accompanying drawings. The methods and corresponding steps of the subject matter of this disclosure are described in conjunction with a detailed description of the system.

[0033] For clarification, the applicant wishes to provide context for certain terms used throughout this specification, in addition to their usual meanings.

[0034] The distal or distal end primarily refers to the end of a syringe system that has components and functions for driving a plunger. In contrast, the proximal or proximal end refers to the end of the device into which the plunger is pushed. For example, in all disclosed embodiments, the dosing needle is located at the proximal end of the syringe system. Furthermore, the distal end of the dosing needle is the end that receives the drug component, while the proximal end of the dosing needle is injecting the drug component into the recipient or otherwise releasing the drug component.

[0035] For the purposes of this application, the term "container" can include any component configured to hold a volume. For example, cartridges, pre-filled syringes, vials, etc., would be considered containers. Containers may have associated mounting points, removable or puncturable seals, and may contain pharmaceutical components stored therein.

[0036] As mentioned above, sequential delivery devices need to be improved to enable the delivery of large quantities of drug formulations through a single device. The inventors who have prepared the embodiments herein have provided solutions to at least this mentioned problem, and to other problems that may become apparent from reading this specification.

[0037] In many embodiments provided herein, a fluid communication system is provided comprising a pair of cartridge access / puncture needles, a fluid channel, and a frame. This system can be positioned within a housing in a fixed manner, with other systems engaging with the housing, or the housing can be movable distally and / or proximally to engage with a container and needle delivery system. Further details and examples of this fluid communication system can be found in U.S. Patent Applications Publication Nos. 2022 / 0001112A1, 2022 / 0379033, and / or 2022 / 0001112, each of which is incorporated herein by reference in whole.

[0038] For illustrative and illustrative purposes only, without limitation, exemplary embodiments of a system in accordance with the subject matter of this disclosure are shown in Figure 1. Among the various figures and drawings presented herein, similar reference numerals (distinguished by leading numerals) may be provided to indicate functionally corresponding but not necessarily identical structures.

[0039] The methods and systems presented herein may be used in a large-volume dual-chamber (LVDC) primary drug container (PDC) used to facilitate the storage and delivery of pharmaceutical components. Two pharmaceutical components are held in separate drug cartridges 102, 104 within the device. Note that the references to drug “cartridge” and drug “container” are used interchangeably herein. In exemplary embodiments, the PDC is dimensionally modified to accommodate, but is not limited to, standard drug cartridges with volumes ranging from about 1 mL to about 10 mL. In another embodiment (not shown), the cartridge may be a pre-filled syringe.

[0040] Drug cartridges 102, 104 are held within a cartridge holder 200 to prevent them from moving during storage or use. The cartridges may be held in place by "tight fit" or friction with adjacent structures / surfaces of the housing, and / or by mating engagements (e.g., mechanical interlocks such as male / female complementary surface features) to maintain a fixed orientation relative to the cartridge holder.

[0041] The cartridge holder 200 is fitted within a hub 300 so that the two components can be displaced relative to each other (e.g., slide or translate perpendicularly), and the walls of the hub 300 help maintain a particular orientation of the cartridge holder. For example, the upward-extending walls of the hub 300 surround at least a portion of the cartridge holder 200, thereby orienting the two components to have a position-aligned central axis. In some embodiments, the hub 300 contains at least one (e.g., two equally spaced) cartridge lancets 302, 304 fixed to the base of the components (e.g., adhesively fixed, insert-molded, or integrally formed). Each cartridge lancet 302, 304 can be positioned below the central longitudinal axis of the drug cartridge 102, 104. Corresponding through-holes concentric with the cartridge access / lancets 302, 304 are included at the bottom of the hub so that what flows through the needles can also flow through the hub 300. Therefore, these components form a fluid communication assembly for cartridges 102, 104. In embodiments using pre-filled syringes instead of a cartridge-based design, partitions 152, 154 are positioned opposite the cartridge access / puncture needles 302, 304. That is, the needles 302, 304 are fastened directly to the drug cartridges 102, 104 (which may be glass or plastic) with seals 152, 154 fixed and attached to the channel inlets.

[0042] Additional embodiments of cartridges 102, 104, cartridge holder 200, and hub 300 are provided in international patent application PCT / US24 / 23643, which is incorporated herein by reference in its entirety.

[0043] In some embodiments, the cartridge access / puncture needles 302, 304 can be seated in a needle receptacle 306 that extends upward within the base of a missing hub, which is sized to have an inner diameter sufficient to accommodate the outer diameter of the needles 302, 304.

[0044] The drug / medicine delivery fluid channel 310 encompasses a groove connecting the cartridge access / puncture needles 302, 304 in the hub 300. In operation, the drugs / medicines from each container 102, 104 travel through this channel, albeit at separate times to avoid mixing of the drugs within the channel. As long as there is residual drug in the fluid channel 310 from the discharge of the first drug, the high viscosity and laminar flow of the drug prevents the second drug from mixing with the residual first drug within the fluid channel 310. This feature is applicable to all embodiments disclosed herein. To ensure that fluid does not leak from this groove in the fluid channel 310, there is a second concentric groove surrounding the central groove. This groove encompasses an O-ring 320 or other sealing surface that is compressed between the fluid channel 310 and the hub 300 to create a seal. In another embodiment, the O-ring may be a two-shot molded elastomer molded directly into the cartridge holder 200 or the hub 300.

[0045] Furthermore, the through-hole 315 is in fluid communication with the fluid channel 310 and is located beneath the fluid channel 310, which separates the fluid channel 310 from the dosing needle 600 until the partition wall 340 is punctured by the dosing needle 600, allowing fluid to exit the fluid channel 310 (and enter the dosing needle downwards). In the exemplary embodiment shown, the through-hole is located in the center of the device, equally spaced between the two needles 302, 304, and is perpendicularly aligned with the dosing needle 600. At the end of the through-hole is a partition wall 340 (which may be formed from an elastic elastomer material) which is compressed against the fluid channel 310 by a partition wall cap 350. The partition wall seals the through-hole of the fluid channel 310 (until it is punctured or opened by the dosing needle 600, as described below).

[0046] The hub 300 (which can be referred to as the “release” hub, as the drugs from each container 102, 104 are first released into the fluid channel 310 of this hub 300) fits into the delivery hub 400 together with the fluid channel 310 and the partition cap 350. Similar to the hub 300 and the cartridge holder 200, the upward-extending walls of the delivery hub help guide the other components so that they can slide relative to each other in a particular orientation. In an exemplary embodiment, the delivery hub 400 has upward-extending side walls surrounding at least a portion of the hub 300 received therein, and the hub 300 then receives the cartridge holder 200 (containing the drug cartridges 102, 104) therein, as described above. Thus, the device can be configured in a nested configuration, in a cascaded order of drug cartridges, cartridge holders, hubs, and delivery hubs.

[0047] Furthermore, the delivery hub 400 has a dosing needle 600 fixed into its base (e.g., bonded, insert-molded, or fixed in some other way) which is used to deliver the drug component to its intended target. The dosing needle 600 may be located at the center of the delivery hub and extend upward into the interior of the delivery hub 400 and downward beyond the lower boss on the bottom surface of the delivery hub 400. In another embodiment, the dosing needle is not located at the center of the delivery hub but is offset to some extent.

[0048] Aseptic function The devices disclosed herein incorporate many features specifically designed for sterile purposes. When stored, primary drug containers prevent the entry of particles and bacteria, or sometimes other bioloading substances or endotoxins, from reaching critical interfaces that could introduce such bacteria, bioloading substances, or endotoxins into the patient.

[0049] The primary area for ensuring sterility is the hub compartment 300, created by the void in the space between the bottom of the cartridge holder 200 and the inner surface of the hub 300. The seal is created to prevent particles from reaching the top of the needle or drug cartridge. Cartridges 102 and 104 are press-fitted into the cartridge holder 200 to create a radial seal from which particles cannot bypass.

[0050] In some embodiments, a seal is established between the cartridge holder 200 and the hub 300. For illustrative purposes rather than limiting, in an exemplary embodiment, an O-ring groove 319, in which an O-ring 320 is positioned, runs along the outer wall of the cartridge holder 200, creating a seal between the cartridge holder 200 and the hub 300. It should be noted that any reference to any type of O-ring may be two-shot molded into another part and may not be an isolated O-ring, but simply may indicate a sealing surface for the purpose of preventing foreign particulate matter, bioloads, or endotoxins from passing through the interface.

[0051] The second compartment is the delivery hub compartment, created by the inner walls of the hub 300 and the delivery hub 400. The administration needle 600 is fixed (e.g., glued) into the delivery hub, which prevents particles from bypassing the outer surface of the needle.

[0052] The delivery hub 400 has a hole in its lower surface that establishes a delivery hub compartment vent 430. This vent is initially covered with a cover or film (e.g., Tyvec or other foil) which can be inserted into plastic (e.g., ultrasonically welded) to create a seal. The intention of the lower surface of the delivery hub is for a safety cap to fit over the needle 600, which is press-fitted around a lower boss from which the dosing needle 600 protrudes. This seals the delivery hub compartment 400 and the dosing needle 600, creating a final seal to ensure that everything remains sterile before use.

[0053] Device operating status The devices disclosed herein have multiple (e.g., four) different device states throughout their entire operating lifecycle, namely nominal, operational, first drug delivery, and second drug delivery. In the nominal state, all components are assembled together as described above in relation to Figures 1 and 2, and all different compartments are sealed and sterile.

[0054] As the hub 300 moves vertically upward relative to the cartridge holder 200, the needles 302, 304 puncture the standard drug cartridge container closure partitions (152, 154), opening a fluid pathway between the two cartridges 102, 104 via the fluid channel 310. The partition 340 below the fluid channel 310 prevents any fluid from being released while also providing an access point for the non-patient end of the administration needle. The partition cap 350 ensures that the partition 340 remains compressed to prevent leakage. The delivery hub 400 seats around the hub 300 and the other components to which it is fixed, holding the administration needle 600. As the delivery hub 400 moves vertically upward relative to the rest of the assembly, the non-patient proximal end of the administration needle 600 punctures the partition 340, forming a fluid pathway between the fluid channel 310 and the patient.

[0055] The LVDC PDC provides the opportunity to complete the sequential delivery of two medications stored separately in each cartridge. It should be noted that while "two" medications are mentioned, this can include two distinct / different medications having different formulations and active ingredients (as well as diluents or other components). Furthermore, two doses (of equivalent or different volumes) of the same medication can be provided in two cartridges 102, 104. In addition, an additional medication container (i.e., larger than the two adjacent cartridges 102, 104 shown) can be incorporated into the housing so that the device can automatically and sequentially deliver any desired amount / number of medications to the patient.

[0056] This is useful when you want to package different medications together for delivery to a patient while maintaining only a single administration needle. PDC also allows for the simultaneous delivery of multiple standard cartridges of the same medication, thus increasing the total deliverable volume within a single device. If desired, PDC / DCH can also be used to simultaneously inject any similar or different medications stored in each medication cartridge.

[0057] According to one aspect of the present disclosure, and as shown in the exemplary embodiment shown in Figure 2, the delivery hub 400 can be formed in a complementary shape such that the upper part of the delivery hub 400 forms the geometric shape of the channel 310, and the slots allow fluid access to both drug cartridges 102, 104. Here, the non-patient proximal end of the administration needle 600 is already in the fluid flow path 310, i.e., it does not need to puncture the partition 340 as shown in Figure 1. The user or device does not need to apply any force or displace any components for the administration needle 600, which is positioned to fluidly communicate with the channel 310, as this is the default position of the needle 600. In this exemplary embodiment, once the hub 400 moves vertically and the needles 302, 304 puncture the drug cartridges 102, 104, delivery can be achieved. It should be noted that the reference to “mixing” in relation to channel 310 does not mean that drugs from one cartridge are mixed or transferred and blended with drugs in an adjacent cartridge, but rather that each drug travels through the same physical channel 310 in a separate sequence of delivery.

[0058] power source There are many different power sources that can facilitate the sequential delivery of multiple drugs stored in separate cartridges 102, 104. For example, the devices disclosed herein may utilize a stored energy source (which may include springs, pressurized gas canisters, mechanical and / or electric actuators). References to “actuator” and “stored energy source” may be used interchangeably throughout this disclosure. In some embodiments, spring-based mechanisms (e.g., compression springs, tension springs, constant-load springs, torsion springs, and coil springs) may be used. A dedicated spring may exist for each to drive the movement of a separate plunger in each individual cartridge 102, 104. Alternatively, a single spring may be used that is coupled to a mechanism (e.g., a plate) that controls the movement of both plungers.

[0059] In the exemplary embodiment shown in Figure 3, two plunger rods 112, 114 are each driven by individual (e.g., constant-load) springs 122, 124. The proximal ends of the springs 122, 124 can abut against the flange of the drug cartridge or cartridge holder 200, and the distal ends of the springs engage with the plunger rods to drive the rod distally into the drug container (the springs remain outside the drug container to avoid drug contamination and / or spring degradation). The plunger rods may include a tab 126 at the proximal end that locks into the cartridge holder 200 when in storage but can flex inward to release the plunger in order to advance under spring force and dispense the drug from the container.

[0060] The plunger rod 112 may include a latch at its proximal end that releasably engages with the actuator 113. When the actuator is pushed downward (as the user presses the device against a target area of ​​skin and compresses the device), the latch (which may be formed as an inclined ramp) is pushed together, disengaging from the actuator sidewall 113, at which point the spring 122 releases its force, driving the plunger rod 112 downward to dispense the drug from the container 102.

[0061] As shown in the third stage of Figure 3, these release tabs 126 can operate independently so that the first plunger 112 can be released while the release tab of the second plunger remains engaged / locked. This allows for sequential dispensing of the drug(s) while the dispensing of each drug container is a separate operation.

[0062] In the exemplary embodiment shown in Figure 4, a mechanical coupling can connect two plunger rods. For example, a plate 132 having an opening for receiving the distal ends of plunger rods 112, 114. In the initial (i.e., storage) state, the plungers are engaged / locked on the plate 132 to prevent them from moving. The plate 132 has a notch (132a) from which the plungers 112, 114 can move to initiate delivery. For example, the plungers 112, 114 may be formed to have spherical distal ends having a diameter larger than the notch 132a portion of the plate 132 so that the plungers are restricted from longitudinal movement. To initiate discharge, the proximal ends of the plungers are displaced laterally through the notch 132a to a portion of the notch having an opening equal to (or larger than) the thickness / diameter of the spherical plunger head, so that a spring force displaces the plungers longitudinally (as shown in the third paragraph of Figure 4).

[0063] Furthermore, or alternatively, plate 132 can be displaced to actuate and release plunger rods 112, 114. As shown in the second and third stages of Figure 4, plate 132 can be tilted or pushed down on one side to align a larger opening of the notch 132 with the plunger rod retaining feature (e.g., a spherical head, but other geometric shapes are within the scope of this disclosure), thereby releasing the spring force to displace the plunger rod through the drug container and dispense the drug. Once the first plunger rod 112 reaches the end of its movement, a structural feature (e.g., a protruding ramp) slides the locking plate 132 horizontally. The second plunger rod 114, which was resting on top of plate 132 during the operation / movement of the first plunger rod 112, is then released, and the drug in the second container 114 is delivered.

[0064] Another exemplary embodiment of a spring power source for driving sequential drug delivery is shown in Figure 5. The spring may be contained within the plunger rod (as shown by step 1), and the plate 132 may have a notch (e.g., a rectangular groove) (shown as step 2) having an opening larger in size (or shape) than the rest of the plate. Furthermore, the plate 132 may be positioned near the distal ends of the plungers 112, 114.

[0065] As shown in step 1 of Figure 5, the first plunger rod 112 is released to dispense the drug. The first plunger rod 112 may include a trigger structural feature 112b (e.g., a rib or projection tapering or outward near the proximal end of the plunger rod) to displace the plate 132 (e.g., laterally) and release the second plunger rod 114 for dispensing the drug in the second container. That is, the operation of the second plunger 114 is inhibited until the first plunger rod 112 is displaced a sufficient distance distally so that the trigger geometric feature 112b engages with the plate 132 and moves the plate (e.g., laterally), aligning the notch 132b with the second plunger rod, thereby releasing the second plunger rod due to the displacement (via spring force). These structural features ensure sequential delivery of dose / drug within each cartridge and inhibit or inhibit dose / drug mixing in situ. Displacement of plate 132 (e.g., lateral) causes notch 132b to align with the second plunger rod 114 (shown as step 3) to allow the second plunger rod 114 to pass through plate 132, thereby driving the dispensing of the drug (shown as step 4).

[0066] Gas power source In some embodiments of this disclosure, the power source is gas power contained within a pressurized gas chamber or canister (e.g., a cylinder). For each of the embodiments disclosed herein, the gas chamber / canister used may contain a two-phase gas (e.g., one stored as a liquid and converted to a gas when it leaves the chamber / canister and expands to a larger volume) or a single-phase gas (e.g., nitrogen). A mechanism (e.g., a pin) is used to puncture the gas chamber and power the movement of a plunger in a drug cartridge as the pressurized gas expands. However, to do so effectively, the pressure is controlled, for example, via a regulator to reduce the pressure, using an expansion volume to reduce the pressure, using components that can operate at high pressure in a cylinder, and / or limiting the flow rate to the cartridge to prevent a rapid increase in pressure.

[0067] In the exemplary embodiment shown in Figure 6, a compressed gas chamber 700 is included above the plungers 112, 114, and a valve 712 acts to open a first air passage 701 that delivers a first dose through plunger 112, while a second air passage 702 to a second plunger 114 is blocked via a barrier / seal 714 (as shown on the left side of Figure 6). As shown, the first plunger rod 712 can extend upward beyond the cartridge 102 (and the gas manifold as well). Once the first plunger 112 has been displaced a sufficient distance (e.g., to the end of cartridge 102), a lever 713 on the proximal end of the first plunger rod 112 can be actuated and pushed to the right to switch or displace the seal 714, i.e., in the exemplary embodiment shown, to open the passage 702 to the second vessel 104. The pressurized gas is continuously released from the gas chamber 700, causing the pressure in the manifold, including the valve 712, to gradually increase, thereby supplying the pressurized gas to the first vessel 102 via path 701. Additionally, the displacement of the seal 714 (laterally to the right in the center image of Figure 6) opens the second path 702, allowing the pressurized gas to be delivered to the second vessel 104 via the second path 702.

[0068] Once the second passage 702 is opened, the pressurized gas in the manifold drives the second piston / plunger 114 downward to discharge the drug from the second container. In some embodiments, the first fluid passage 701 can be closed while the pressurized gas displaces the seal 714 to open the second fluid passage 702 and drives the plunger to discharge the drug into the second container.

[0069] Furthermore, as shown in Figure 6, the first container may include a plunger rod 712, and the pressurized gas acts on the plunger rod to drive the rod (and a piston located at its end) to discharge the drug from the first container 102, while the pressurized gas acts directly on the piston in the second container 104. In other words, the second container 104 does not have a plunger rod, only a piston. In each embodiment disclosed herein that uses pressurized gas to discharge a drug(s), the gas may act on the plunger rod and / or directly on the piston or plunger head itself (where the plunger rod is not present in that particular container).

[0070] In the exemplary embodiment shown in Figure 7, the gas chamber 700 delivers pressurized gas to the first container 102 via the first fluid path 701 while the second fluid path is closed. The pressure continues to increase after the first plunger 112 has discharged the agent, increasing the pressure in the third path 703, which eventually opens the valve (as shown in the center of Figure 7), allowing air to enter the second fluid path 702, thereby driving the second plunger and discharging the second agent. The third path 703 is oriented vertically and may extend between the midpoint of the first path 701 and the second path 702.

[0071] In the exemplary embodiment shown in Figure 8, the gas canister 700 delivers pressurized gas to the first container via the first fluid path 701 while the second fluid path 702 is closed (as shown in step 1 of Figure 8). A third path 703, located between the first two paths 701, 702, drives a pilot valve to restrict the airflow and gradually increase the pressure in this line (as shown in step 2 of Figure 8). As the pressure in the third path 703 increases, the force applied to the shuttle piston 714 increases until the shuttle piston 714 is displaced (to the right, as shown in step 4 of Figure 8). Once the shuttle piston is displaced (to the right in the drawn embodiment), the second path 702 is opened, and the pressurized gas then displaces the second plunger to discharge the second agent (as shown in step 5 of Figure 8).

[0072] Gas pressure can be utilized in a variety of different ways for injecting medication. Gas pressure can be applied directly to the proximal end of a cartridge to push a plunger. Alternatively, gas pressure can drive a piston or other mechanical mechanism that propels the plunger downward. Alternatively, the gas cylinder itself can be used as a piston, so that when the pressure is released behind it, the cylinder pushes down the plunger or piston, driving the plunger's movement.

[0073] In the exemplary embodiment shown in Figure 9, the first container 104 and the first plunger 114 are driven downward to puncture the seal of container 104 on the needle 304. Subsequently, the second container 102 and the second plunger 112 are driven downward to puncture the seal of container 102 on the needle 302.

[0074] In the exemplary embodiment shown in Figure 10, the first plunger rod 112 is driven via pressurized air to deliver a first dose (indicated as step 1). Once the plunger rod 112 reaches the bottom of its movement, the secondary air path 712 is exposed (or opened) to the second cartridge 104 (indicated as step 2). The pressurized gas then travels through the now-accessible path 712, displacing the second plunger 114 and discharging the second drug (indicated as step 3). As described herein, some embodiments use an elongated plunger rod attached to a plunger piston head, while some embodiments use only a plunger piston / head (i.e., not an elongated plunger rod). In the exemplary embodiment shown in Figure 10, the first cartridge uses a plunger rod coupled to a plunger head, and the elongated rod acts as a seal that blocks the flow of pressurized gas to the second cartridge until the plunger rod is displaced a distance sufficient to remove the seal / block and allow the pressurized gas to reach the second cartridge. The second cartridge does not require an elongated plunger rod and therefore utilizes only the plunger 114. This saves space in the device housing and overall form factor because it does not require providing a cavity or gap to accommodate the retracted end of the plunger rod (for the second cartridge).

[0075] Similar to a spring, the device can use a single gas cylinder to drive the movement of both plungers, or it can use multiple gas cylinders to individually control separate drug cartridges. In the case of multiple gas cylinders, the device can sequentially actuate two cylinders separately to control the sequential delivery of the drug. Alternatively, after the first cylinder has been punctured, the movement of the plunger can cause a mechanical mechanism to actuate the second cylinder, then enable the delivery of the second cartridge.

[0076] In the exemplary embodiment shown in Figure 11, the sequential drug delivery device is powered by two separate gas cartridges 701 and 702. Each gas cartridge is activated individually using buttons 711 and 712, and when the first button 711 is pressed, the first gas cartridge 701 is activated to deliver a first dose (shown as step 3 in Figure 11). When the second button 702 is pressed, the second gas cartridge is activated and a second dose is delivered (shown as step 4 in Figure 11).

[0077] In some embodiments, when a single gas cylinder is used, a mechanism (e.g., a valve(s)) is used to direct the power of the pressurized gas from one cylinder to the next. Some valve options allow for automatic delivery of a second dose, such as a pilot valve or electronically controlled valve that senses the completion of the first delivery. Other valve options require user input, such as a conventional stem valve. Alternatively, the air path can also be configured such that a new air path is revealed to allow for delivery of a second dose after the first delivery is complete.

[0078] In the exemplary embodiment shown in Figure 12, drug delivery is controlled by an electronic controller (e.g., a solenoid valve 714 driven by a control board 715 and powered by a battery 716). The valve is powered / commanded to open (shown as step 1) to open a first compressed air path 701 for delivering a first dose while the second air path is blocked (shown as step 2). Once the plunger 112 reaches the bottom of its movement, it passes in front of a light source 115 that triggers a light sensor (shown as step 3). The trigger activates a solenoid that reveals the second air path 702 (shown as step 4). The pressurized gas then drives the second plunger to sequentially discharge the drug from the second container.

[0079] The exemplary embodiments shown illustrate a pressurized gas canister and a solenoid valve, but it will be apparent to those skilled in the art that other power sources, including electric motors, chemical reactions, magnets, electromagnets, or user-generated power, can be used.

[0080] Depending on the power source and desired user input, multiple options are available for device activation. The device can be activated in several different ways (the drug cartridge is opened and drug delivery is initiated). For example, the device can utilize a needle shield that, once pressed, inserts the needle into the patient, activates the hub, and performs delivery (as shown in Figure 13). Similarly, the needle shield can be used to activate the hub while a separate button inserts the needle into the patient and delivers the drug (as shown in Figure 14). The needle shield can be used to insert the needle into the patient and activate the hub with a separate button used solely for delivery (as shown in Figure 15). Furthermore, or alternatively, the button can activate the hub, insert the needle into the patient, and activate the protective needle shield at the end of treatment to perform delivery (as shown in Figure 16). All devices have an additional safety cap that must be removed before the device can be used. There is an option to activate the hub by removing this cap while a separate button inserts the needle into the patient and performs delivery.

[0081] This exemplary embodiment describes the complete depression of each plunger over the entire range of movement toward the distal end of the container, but only partial depression of either (or both) of the plungers is within the scope of this disclosure. Thus, any desired amount of drug from either container can be administered.

[0082] According to one aspect of this disclosure, an automated sequential delivery autoinjector is constructed around a large-capacity dual-chamber primary drug container configuration to enable a user to deliver large volumes of high-viscosity drugs. The user controls the actuation and delivery point, but the delivery force is controlled by the device. This design eliminates as many user steps as possible to ensure that delivery is not affected by the user.

[0083] Additional embodiments of sequential drug delivery devices According to another aspect of this disclosure, a sequential delivery device (SDA) is provided that enables a user to automatically or semi-automatically sequentially deliver two doses of a drug from a single device. The user controls the actuation and delivery point, but the delivery force is controlled by the device. Advantageously, this reduces the number of user steps for delivery and ensures that the delivery timing and execution are not influenced by the user.

[0084] As shown in the exemplary embodiment of Figure 17, the device comprises a housing that functions as the body for the user to hold during use. The main contact points of this device are a safety cap, which is removed immediately before delivery, and a needle shield (hidden beneath the safety cap and therefore not shown in the figure) which is exposed when the safety cap is removed and functions as an activation trigger. The user can also obtain information about the status of the device by observing a viewing window on the side of the housing, which allows the user to look inside the drug cartridge and assess the drug components.

[0085] As shown in Figure 18, when the user removes the device from its packaging, the device is in its nominal state. Energy is stored inside the device, isolated from the drug(s), and the safety cap is placed on top of the device. To activate the device, the user removes the safety cap to expose the needle shield. The user places the needle shield on top of the patient's injection site and presses the device against the patient. This activates the device's pneumatic system, causing the administration needle to puncture the skin and open the delivery fluid pathway. Once delivery is complete, the user can withdraw the device from the patient, and the needle shield extends and locks out.

[0086] In an exemplary embodiment of the SDA, there are three main subassemblies. 1. A dual cartridge holder (DCH) consists of two drug cartridges containing a stopper or plunger, a drug (which may be the same or different formulation and quantity), a septum, and a septum crimp; a cartridge holder; two cartridge puncture needles (labeled “chamber needles” in Figure 19); a delivery hub; a fluid channel; an administration needle; and a sterile barrier. 2. The power system consists of a gas cylinder, a pneumatic manifold, two pistons, a gas operating pin, a spring release cam, a gas operating spring, a spring compressor, and a mixture prevention bracket. 3. Finally, the shroud consists of the upper housing, spring guide, needle shield return spring, internal frame, needle shield, bottom housing, and safety cap. Figures 19 and 20 illustrate the appearance of these parts and their relative positions within the assembly.

[0087] Referring to Figure 20, the drug cartridges 1102 and 1104 are held within a cartridge holder 1200 to prevent them from moving during storage or use. The cartridge holder 1200 fits into a delivery hub 1400 so that the two can slide relative to each other, although the walls of the delivery hub help maintain a specific orientation of the cartridge holder. The delivery hub contains two cartridge lancets 1302 and 1304 bonded to the base of the components. The cartridge lancets 1302 and 1304 have concentric through-holes so that whatever flows through the needles can also flow through the delivery hub. The bottom surface of the delivery hub contains four posts that help align and secure both the fluid channel 1310 and the drug cartridges 1102 and 1104.

[0088] The fluid channel 1310 contains a groove connecting the two cartridge lancets 1302 and 1304 in the delivery hub 1400. This groove allows fluid and air to flow between the two cartridge lancets 1302 and 1304 when an external force is applied to the drug cartridge stopper. To ensure that fluid does not leak from this groove, a second groove surrounding the central groove may be included. This radially outer groove contains a compressed O-ring 1320 between the fluid channel 1310 and the delivery hub 1400, creating a seal (as best seen in Figure 21).

[0089] Furthermore, a through-hole in the fluid channel 1310 allows the fluid to not only pass between the two cartridge puncture needles 102 and 1304 but also to exit the channel. At the end of the through-hole is a dosing needle 1600, which is attached to the fluid channel 1310 and used to deliver the drug to its intended target.

[0090] Figure 22 shows a sequential delivery autoinjector (SDA) in its nominal state, where the safety cap 1900 captures a sterile barrier that maintains the sterility of the dosing needle 1600 during storage. The user can inspect the drug(s) before using the device through the viewing window (as shown in Figure 17). The safety cap 1900 also prevents accidental operation of the device during inspection and preparation by preventing the user from interacting with the needle shield 1700.

[0091] Operation As shown in Figure 23, when the user is ready to administer the injection, they firmly grasp the safety cap 1900 and pull it axially against the SDA housing. Once the safety cap 1900 is removed, the sterile barrier 1910 is also removed from the administration needle 1600. Once the safety cap 1900 is removed, the SDA is ready for delivery. The needle shield 1700 still protects the user from accidental puncture by the administration needle 1600 while the user positions the SDA.

[0092] Next, the user aligns the SDA with the intended target of the patient and begins to firmly push the needle shield 1700 into the intended target. As the user pushes, the internal frame is pushed by the needle shield 1700, resisting the user's force. This is due to interference between the array of impact snap arms 1510 on the internal frame 1500 and the corresponding ramps in the device housing, as shown in Figure 24. Once a force sufficient to overcome the bending forces of all the impact snap arms 1510 is generated, the impact snap arms begin to bend around the ramps and the internal frame 1500, as well as the needle shield 1700, and begin to translate within the housing. At this point, the SDA is activated, and the next series of device states are achieved by utilizing the residual downward force provided by the user. The exact timing of each mechanism may vary compared to the other steps.

[0093] As the internal frame 1500 translates, it compresses the needle shield return spring 1710. The needle shield return spring 1710 then provides the force required to extend the needle shield 1700 again after delivery is complete.

[0094] Furthermore, as shown in Figure 25, as the internal frame 1500 translates, the ramp surface 1520 on the internal frame contacts the spring release cam 1550, causing it to rotate. In storage, the spring release cam 1550 is compressed and held between the pneumatic manifold and the gas-actuated spring 1555. After sufficient rotation, the raised feature of the spring release cam aligns with the recess in the pneumatic manifold, allowing the gas-actuated spring to push the spring release cam into the pneumatic manifold. The ramp on the spring release cam completes its rotation after aligning with the recess, preventing further obstruction of the internal frame's translation. As the spring release cam is pushed further into the pneumatic manifold, the gas-actuated pin 2000 punctures the gas cylinder 2100, releasing the gas stored inside the gas cylinder and activating the pneumatic system. A seal on the spring release cam prevents the gas from escaping from the pneumatic manifold.

[0095] In another gas-operated embodiment, a double-ramp system can be implemented, as shown in Figure 26. In this embodiment, the large ramp 1560 represents the translation of the internal frame 1500, the small ramp 1570 represents the fixed ramp on the pneumatic manifold, and the mass 1580 represents the spring release cam. There is no spring in this embodiment. As the internal frame 1500 translates, the spring release cam is double-wedge-shaped between the two ramps 1560, 1570, causing vertical translation. Alternatively, a snap release mechanism, which is described in more detail below, can also be used.

[0096] Once the gas is released, it rapidly fills the expansion volume in the pneumatic manifold (see Figure 27). This reduces the gas storage pressure to the operating pressure. Simultaneously, the pneumatic manifold arranges the gas overhead of the first piston for driving downward to discharge the drug in the first drug container 1102.

[0097] Before, after, or simultaneously with gas activation, the needle shield 1700 and internal frame are still translating. As the needle shield 1700 translates, the administration needle 1600 is exposed and introduced to its intended location, as shown in Figure 28. The exposure and introduction of the administration needle 1600 continues until the needle shield 1700 contacts the DCH delivery hub 1400, corresponding to the full exposure and introduction of the administration needle 1600. Although the drug cartridges 1101, 1102 in the DCH may be partially pressurized at this point, no drugs are delivered because the DCH is not yet activated.

[0098] Finally, during the translation of the needle shield 1700 over its final length, the DCH delivery hub 1400 is pushed into the delivery position, as shown in Figure 29. In doing so, the cartridge puncture needles 1302, 1304 puncture the septum 1340 and expose the drug to the fluid channel 1310, as described above. This marks the transition of the device from the working state to the delivery state.

[0099] Sequential delivery In some embodiments, immediately after the DCH delivery hub is activated, the pressurized first cartridge 1102 is pressurized by the pressurized first piston or plunger rod 1112 pushing the first cartridge stopper, thereby initiating delivery of the first drug / dose via the fluid channel 1310 and the administration needle 1600. Figure 30 shows an exemplary embodiment with an enlarged view showing the dispensing of the first cartridge 1102. Both cartridges 1102, 1104 can be punctured by needles 1302, 1304 at this stage, but since no pressure is applied to the plunger / piston of the second cartridge at this point, the contents of cartridge 1104 are not dispensed, but rather the plunger / piston is pushed down, dispensing the drug within it, as the path to the second container 1104 is currently closed / blocked at this stage of use.

[0100] As the first dose / drug is dispensed, the first cartridge stopper and the first piston translate (downward as shown in Figure 30). The gas overhead of the first piston expands to fill the volume in the pneumatic manifold 2200. Once the first plunger has moved to the bottom of the first cartridge to reach the end of the delivery of the first drug / dose, the pneumatic path 2230 in the pneumatic manifold 2200 (from the gas canister to the second cartridge 1104) is revealed or opened. In the exemplary embodiment shown in Figure 31, the pneumatic path extends laterally at the bottom between the plungers / pistons of the two drug cartridges 1102, 1104 and the vertical paths aligned in position. The pneumatic path can be formed with right-angle turns or curved / radial turns, as indicated by the arrows in Figure 31. Furthermore, the pneumatic path 2230 may have a uniform size throughout the entire path (e.g., the diameter of the gas conduit(s)), or alternatively, the size of the path may vary (e.g., the diameter of the lateral section 2233 bridging the two vertical sections 2231 and 2232 may be smaller).

[0101] The pressurized gas in the pneumatic manifold is routed through this pneumatic path 2230 over the head of the second piston / plunger 1114 (and presides over the first container to keep the first plunger fully extended / displaced). Then, and in some embodiments immediately thereafter, the second cartridge 1104, pressurized by the pressurized second piston / plunger 1114 pushing the second cartridge stopper, begins delivery of the second drug / dose through the fluid channel 1310, as shown in Figure 32.

[0102] As the second drug / dose is dispensed, the second cartridge stopper and the second piston translate (downward as shown in Figure 32). The gas overhead of the second piston expands to fill the volume in the pneumatic manifold 2200. Once the second cartridge 1104 approaches the end of delivery, the pneumatic vent 2234 in the pneumatic manifold is exposed (e.g., the plunger 1114 is displaced a sufficient distance to stop blocking the port of the vent), allowing the gas to be released and the pneumatic manifold 2200 to be depressurized. This corresponds to the end of the delivery state. In an exemplary embodiment, the pneumatic vent 2234 is in the same horizontal plane as the lateral portion 2233 of the pneumatic path 2230 bridging two vertical portions 2231, 2232.

[0103] Accordingly, according to one aspect of the present disclosure, the pneumatic path 2230 may include a plurality (e.g., three) vertically oriented conduits, as shown in Figure 33. During operation, the pressurized gas descends downward in the first vertical section 2231, then changes direction in the lateral section 2233 to reverse the direction of gas flow, moving the intermediate row upward to deliver pressurized air above the second plunger 1114 (once the path 2233 is released or opened by the movement of the first plunger 1112), at which point the pressurized gas changes direction again to flow downward (parallel to the first path 2231) in section 2232, pushing down the second plunger 1114 and dispensing the second drug / dose.

[0104] Needle Shield Lockout According to another aspect of the present disclosure, when the user begins to lift the device from a desired position, the needle shield return spring 1755, which is compressed in operation, applies an opposing force to the internal frame 1500 which is transferred to the needle shield 1700.

[0105] As shown in Figures 34 and 35, when the needle shield 1700 leaves the patient surface, the needle shield 1700 extends outward from the housing, and the compliant member 1510 fits into a recess in the delivery hub that was revealed when the delivery hub 1400 was moved during operation. At this point, the device is in a locked-out state.

[0106] Another exemplary embodiment of a sequential delivery device in accordance with this disclosure is shown in Figures 36–48. The exemplary device is a gas-driven auto-injector designed to sequentially and automatically deliver a drug(s) from two internal chambers. To use the device, the user removes the safety cap, firmly presses the needle shield against the desired delivery site until the needle shield collapses, and then waits a predetermined time for both doses to be delivered automatically. Thus, the device disclosed herein provides a two-step auto-injector using a novel solution for achieving complex internal device states with limited user input.

[0107] A side view of the device is shown in Figure 36, and exploded views of the various components of the device are shown in Figure 37.

[0108] Nominal condition In storage, the device is presented as a capped auto-injector, as shown in Figure 38. This cap 1900 captures a needle sterile barrier 1910 that maintains the sterility of the administration needle 1600 during storage. The user can inspect the drug through the windows (two sides) before using the device. The safety cap 1900 also prevents accidental activation of the auto-injector during device inspection and preparation by preventing the user from interacting with the needle shield 1700.

[0109] Ready state When the user is ready to administer the injection, they firmly grasp the safety cap 1900 and pull it axially relative to the device body, as shown in Figure 39. Once the safety cap 1900 is removed, the needle sterile barrier 1910 is also removed from the administration needle 1600. Once the safety cap 1900 is removed, the device is ready for delivery. The needle shield 1700 still protects the user from accidental puncture by the administration needle while the user positions the device.

[0110] Operation The user aligns the device with the desired delivery location and begins to firmly push the needle shield 1700 into the delivery area. As they push, the needle shield 1700 contacts the retaining ring 1740 inside the housing, as shown in Figure 40, and resists the user's force. The user must generate a downward force sufficient to overcome the resistance of the annular retaining ring. Once sufficient force is generated, the retaining ring flexes around the needle shield, allowing the needle shield to continue translating upward. This actuation function may also be included in exemplary embodiments disclosed in relation to Figures 17-35.

[0111] The first action is to see the administration needle 1600 exposed from the device and inserted into the patient (as shown in the left image of Figure 41) once the retaining arm 1740 is overcome. The needle shield then exits the bottom of the needle hub of the PDC, pushing the needles 1302 and 1304 into the drug cartridge (as shown in the center image of Figure 41). Once the needles 1302 and 1304 are fully seated, the PDC is activated. At this point, the device is activated, and the next series of device states are achieved by utilizing the residual downward force provided by the user. The exact timing of each state may vary relative to the other steps.

[0112] As shown in Figure 42, at the end of the movement, two upwardly projecting extensions on the PDC clamp together the snap arms of the snap release. Once the snap arms have finished passing the mating flat surface, the snap release is free to move. The actuating spring 1555 provides an upward force, driving the actuating release and the gas cartridge 2100 upward. The gas cartridge 2100 is opened by the actuating pin 1550, allowing gas to flow into the system. An O-ring around the neck of the gas cartridge prevents gas backflow around the gas cartridge. The sealing of the (potentially ultrasonically welded (UW)) cap prevents gas from escaping from the rear end of the device. In the exemplary embodiment shown, the snap release is designed with a double snap arm release mechanism, but other options for triggering actuating release, including cam release, are available.

[0113] Sequential delivery Once the gas is released from the cartridge, it moves across the top between the seal chamber and the sealed cap (labeled Step 1), as shown in Figure 43, and down to the inner diameter of both rods (labeled Step 2). That is, the pressurized gas moves downward within the inner diameter of the piston rod 2112, which itself is within the inner diameter of the piston 2114. As the pressurized gas exits the piston rod 2112, it is captured by a receiving portion (shown as a cup-shaped portion in the right-hand image of Figure 43), which results in relative movement between the rod 2112 and the piston 2114. Once it exits the bottom of the rod 2112, the gas fills the volume between the rod 2112 and the piston 2114. As the gas is continuously delivered, the volume of the gas expands, which displaces the piston 2114 downward (as indicated by the arrow in Figure 43), discharging the drug below and within its cartridge.

[0114] As the pressure increases, the piston 2114 of the first dose in the first cartridge 1102 begins to translate downward, delivering the first dose. The second piston 2214 is also pressurized and therefore prompted to move downward as indicated by the arrow in Figure 43, but is prevented from moving by the second dose lockout 2300. In some embodiments, the pistons may utilize a coated metal tube to eliminate draft angles on the inner diameter of the piston, allowing for a constant seal between the rod and the piston throughout the movement.

[0115] According to one aspect of the present disclosure, optional features can be incorporated into embodiments described in relation to Figures 36–43. In some embodiments, mixing prevention is achieved by a one-way valve (e.g., a ball valve) located on the PDC above the dosing needle 1600, as shown in Figure 44. During the dispensing of the first dose / drug from the first cartridge 1102, the ball 2302 is pushed against the wall of the fluid channel 1310 (e.g., below the second cartridge 1104) by the pressure of the drug fluid in the channel 1310. In some embodiments, the ball can be displaced laterally and upward (as shown on the left side of Figure 44) and is received in a socket that effectively closes the valve. This seals access to the second drug cartridge 1104 and limits or prohibits contact between the two drugs. When the first dose is completed and the second dose is initiated, the drug from the second cartridge 1104 can move around the ball and exit the dosing needle (as shown on the right side of Figure 44). The residual pressure from the first dose prevents mixing back into the first cartridge 1102. Note that the exemplary (ball) valve feature is not a requirement of the SDA, and sequential drug delivery can be achieved without using this feature, as described above in relation to Figures 36-43.

[0116] In some embodiments, as shown in Figure 45, as each delivery is performed, a bend on the back of the piston 1112 runs along the edge of the ratchet, which can also be used to generate an audible click sound to indicate to the user that the device is continuing delivery. The sound stops once each dose has been fully delivered.

[0117] As shown in Figure 46, at the end of the movement of the first dose, the extended arm 1113 on the piston contacts the inclined surface on the slide lockout 2300. This moves the second dose release so that the shelf preventing the delivery of the second dose is removed from the second piston, allowing the second dose to be initiated. At the end of the second dose, the slit 2115 in the piston (best shown in Figure 37) allows any excess gas to be released.

[0118] Needle Shield Lockout Once both doses are complete, the user pulls the device away from their body. This releases the return spring 1710, which initiates the lockout operation. As the return spring 1710 extends, the snap arm on the needle shield 1700 pulls down the lockout sleeve, exposing the shelf for the needle shield 1700 to lock, as shown in Figure 47. At the end of the movement, the upper snap of the needle shield 1700 engages with the shelf, preventing it from being pushed down again. The shelf, which extends towards the bottom of the PDC, prevents the needle shield from being completely removed. As previously stated, the lockout mechanism described herein can be used in any embodiment of the SDA.

[0119] For illustrative purposes rather than limiting, Figure 48 shows various states of the operation described above.

[0120] As stated above, the exemplary embodiments of this disclosure show a two-cartridge device, but it will be apparent to those skilled in the art that additional cartridges may be included, each including a separate valve for selective opening of a valve and dispensing the contents of the associated container. For example, multiple cartridges (and valves having the necessary channels coupled to the cartridges) may be configured in a circular ring (similar to a gun barrel) to provide multiple stages and materials for dispensing.

[0121] While the subject matter of this disclosure is described herein with respect to certain preferred embodiments, those skilled in the art will recognize that various modifications and improvements can be made to the subject matter of this disclosure without departing from its scope. Furthermore, while individual features of one embodiment of the subject matter of this disclosure may be discussed herein or shown in the drawings of one embodiment but not in other embodiments, it should be apparent that individual features of one embodiment can be combined with one or more features of other embodiments, or features of multiple embodiments.

[0122] In addition to the specific embodiments claimed below, the subject matter of this disclosure also covers other embodiments having any other possible combinations of the dependent features claimed below and those disclosed above. Therefore, it should be recognized that the specific features presented in the dependent claims and disclosed above can be combined with each other in other ways within the scope of the subject matter of this disclosure, thereby specifically covering other embodiments having any other possible combinations. Accordingly, the foregoing description of specific embodiments of the subject matter of this disclosure is provided for illustrative and explanatory purposes only. The foregoing description is not intended to be exhaustive or to limit the subject matter of this disclosure to those disclosed embodiments.

[0123] Those skilled in the art will see that various modifications and variations can be made to the methods and systems of the subject matter of this disclosure without departing from the spirit or scope of the subject matter of this disclosure. Accordingly, the subject matter of this disclosure is intended to include modifications and variations that fall within the scope of the appended claims and their equivalents.

Claims

1. A drug delivery system, A housing configured to hold a first container and a second container, wherein the first container contains a first pharmaceutical component and the second container contains a second pharmaceutical component, A first seal associated with the first container, A second seal associated with the second container, A fluid communication assembly having a fluid channel between the first container and the second container, wherein the fluid communication assembly is configured to be displaced from a first position to a second position within the housing, thereby opening, removing, or otherwise puncturing the first seal and the second seal to provide a fluid path between the first container and the second container. A storage energy source configured to dispense the first and second drug components, A needle delivery assembly comprising a dispensing needle having a first end and a second end, wherein the first end of the dispensing needle is in fluid communication with the fluid channel at a first position, A drug delivery system equipped with the following features.

2. The system according to claim 1, wherein the at least one energy storage source includes a spring that engages with a first plunger of the first container and a second spring that engages with a second plunger of the second container.

3. The system according to claim 2, further comprising a plate coupled to the first and second plungers, wherein the plate restricts the displacement of at least one of the first and second plungers.

4. The system according to claim 3, wherein at least one of the first plunger and the second plunger includes a structural feature configured to displace the plate, thereby enabling the displacement of the other plunger.

5. The system according to claim 1, wherein the at least one energy storage source includes at least one pressurized gas chamber, the at least one pressurized gas chamber is in communication with the first container via a first path and is in communication with the second container via a second path.

6. The system according to claim 5, further comprising a valve positioned between the at least one gas chamber and at least one of the first and / or second vessels, wherein the valve selectively opens the flow of pressurized gas to one of the first and / or second vessels.

7. The system according to claim 6, further comprising the at least one pressurized gas chamber and a third path communicating with at least one of the first and second paths.

8. The system according to claim 5, wherein the at least one pressurized gas displaces a plunger in the first container by a predetermined distance, thereby opening the second path to the second container.

9. The system according to claim 5, wherein the at least one gas chamber includes a first gas chamber that is in fluid communication with the first container and a second gas chamber that is in fluid communication with the second container.

10. The system according to claim 5, wherein the first gas chamber displaces the first plunger in the first container by a predetermined distance, thereby opening the second gas chamber and displacing the second plunger in the second container.

11. The system according to claim 10, wherein the predetermined distance is detected by a sensor.

12. A drug delivery system, A housing configured to hold a first container and a second container, wherein the first container contains a first pharmaceutical component and the second container contains a second pharmaceutical component, A first seal associated with the first container, A second seal associated with the second container, A fluid communication assembly having a fluid channel between the first container and the second container, wherein the fluid communication assembly is configured to be displaced from a first position to a second position within the housing, thereby opening, removing, or otherwise puncturing the first seal and the second seal to provide a fluid path between the first container and the second container. A pressurized gas chamber is provided in the housing, at least partially, and is in fluid communication with the first container and the second container. An operating mechanism configured to open the pressurized gas chamber or otherwise puncture, At least one valve configured to release a portion of the pressurized gas that facilitates the discharge of the first and second drug components, A needle delivery assembly configured to be in fluid communication with the first and second containers during the delivery stage, A drug delivery system equipped with the following features.

13. The system according to claim 12, wherein the pressurized gas flows through a first pressurized gas path, displacing a plunger in the first container by a predetermined distance, thereby opening a second pressurized gas path to the second container.

14. The system according to claim 13, wherein the pressurized gas remains in the first pressurized gas path while the pressurized gas flows into the second pressurized path.

15. The system according to claim 12, wherein the first drug and the second drug are dispensed sequentially and automatically.

16. The system according to claim 12, wherein the pressurized gas chamber is positioned above the first and second containers.

17. A drug delivery system, A housing configured to hold a first container and a second container, wherein the first container contains a first pharmaceutical component and the second container contains a second pharmaceutical component, A first seal associated with the first container, A second seal associated with the second container, A fluid communication assembly having a fluid channel between the first container and the second container, wherein the fluid communication assembly is configured to be displaced from a first position to a second position within the housing, thereby opening, removing, or otherwise puncturing the first seal and the second seal to provide a fluid path between the first container and the second container. A pressurized gas chamber is provided in the housing, at least partially, and is in fluid communication with the first container and the second container. An operating mechanism configured to open the pressurized gas chamber or otherwise puncture, At least one valve configured to release a portion of the pressurized gas that facilitates the discharge of the first and second drug components, A needle delivery assembly configured to be in fluid communication with the first and second containers during the delivery stage, A valve is located in the fluid channel between the first container and the second container, A drug delivery system equipped with the following features.

18. The system according to claim 17, wherein the valve closes the fluid channel to the second container while the drug is being discharged from the first container.

19. The system according to claim 18, wherein the valve is a ball valve, and the first drug component displaces the ball valve in a first direction to close the fluid channel of the second container.

20. The system according to claim 19, wherein the second drug component displaces the ball valve in a second direction, thereby closing the fluid channel of the first container.

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