Anti-reflux mechanism for drug delivery devices

Abstract

The drug delivery device includes a housing defining a shell and an internal volume, a container, a drive mechanism, a needle assembly, a fluid flow connection, and a backflow prevention mechanism. The container has an internal volume for containing a medication to be administered to a user. The drive mechanism is at least partially disposed within the housing and applies a force to expel the medication from the container. The fluid flow connection is coupled to the container and the needle assembly and allows the medication to flow from the container to the needle assembly for administration. The backflow prevention mechanism is associated with at least one of the container, the fluid flow connection, or the needle assembly and includes at least one flow restrictor for restricting fluid flow from the needle assembly to the container.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 62 / 640,934, filed March 9, 2018, which is expressly incorporated herein by reference in its entirety.

[0002] The present disclosure relates to drug delivery devices, and more particularly to drug delivery devices having an anti-reflux mechanism to assist in the flow of the drug. [Background technology]

[0003] Drug delivery devices, such as injectors, are used to deliver liquid medication to patients. When activated, the drug delivery device expels a drug stored in an internal reservoir through a needle, cannula, or other delivery member into the patient. Some drug delivery devices, such as on-body injectors, can be temporarily attached to a patient to deliver the drug over an extended period of time via an injection needle or other means. The drug delivery device can be adhesively attached to tissue in the patient's abdomen, thigh, arm, or other part of the patient's body.

[0004] Delayed delivery devices can enhance the therapeutic effect of certain drugs while preventing adverse side effects. Such devices may be initially activated by medical personnel to insert a needle and / or cannula into a patient's tissue, but may not actually administer the drug for an extended period of time. In some cases, backflow of bodily fluids into the drug delivery device can result in blockage of the fluid path. Backflow of blood or other fluids can result in the formation of clots along the fluid path of the drug delivery device. The clot can prevent the drug from being delivered if the pressure required to force the agent through (or displace) the clot exceeds the driving force capabilities of the device. Thus, the device may stall, which can adversely affect the delivery of the drug to the user. Summary of the Invention [Means for solving the problem]

[0005] One aspect of the present disclosure provides a drug delivery device including a housing defining a shell and an interior volume, a container, a drive mechanism, a needle assembly, a fluid flow connection, and a backflow prevention mechanism. The container has an interior volume for containing a medication to be administered to a user. The drive mechanism is at least partially disposed within the housing and applies a force to expel the medication from the container. The fluid flow connection is coupled to the container and the needle assembly and allows the medication to flow from the container to the needle assembly for administration. The backflow prevention mechanism is associated with at least one of the container, the fluid flow connection, or the needle assembly and includes at least one flow restrictor for restricting fluid flow from the needle assembly toward the container.

[0006] In some examples, the at least one flow restrictor may include a one-way valve. In some examples, the flow restrictor may be any one of a slit valve, an umbrella valve, a ball valve, a duckbill valve, or a flap valve. In some examples, any number of these valves may be used in combination with each other.

[0007] In some embodiments, the backflow prevention mechanism may be disposed in a coupling region where the fluid flow connection is coupled to the needle assembly. The coupling region may include a ball and reservoir receiver adapted to seal against the needle assembly. In other embodiments, the backflow prevention mechanism is at least partially disposed within the needle assembly.

[0008] In some embodiments, the fluid flow connections may be made from flexible tubing (e.g., polymeric materials). Additionally, other suitable materials may be used.

[0009] A second aspect of the present disclosure provides an anti-reflux mechanism for a drug delivery device. The anti-reflux mechanism is associated with at least one of a container, a fluid flow connection, or a needle assembly of the drug delivery device. In this aspect, the anti-reflux mechanism may include at least one flow restrictor that restricts fluid flow from the needle assembly to the container.

[0010] A third aspect of the present disclosure provides a method for preventing backflow in a drug delivery device having a housing defining a shell and an interior volume, and a container disposed at least partially within the interior volume of the housing and adapted to hold a medication to be administered to a user. A drive mechanism is disposed at least partially within the housing and applies a force to expel the medication from the container. A needle assembly is also disposed at least partially within the housing. A fluid flow connection is coupled to the container and the needle assembly to allow the medication to flow from the container to the needle assembly. A backflow prevention mechanism is associated with at least one of the container, the fluid flow connection, or the needle assembly. The backflow prevention mechanism includes at least one flow restrictor for restricting fluid flow from the needle assembly to the container.

[0011] The above needs are met, at least in part, by the provision of an anti-reflux mechanism in a drug delivery device as described in the detailed description below, particularly when studied in conjunction with the drawings.

[0012] The accompanying drawings illustrate embodiments in accordance with the present disclosure and are by way of example rather than limitation. [Brief explanation of the drawings]

[0013] [Figure 1] 1 shows a schematic cross-sectional view of one embodiment of a drug delivery device according to various embodiments. [Figure 2] 2 shows a perspective view of the drug delivery device of FIG. 1 illustrating the connection of the fluid flow path to the needle assembly, according to various embodiments. [Figure 3A] 1 illustrates a perspective view of a fluid flow path coupled to a needle hub assembly of a drug delivery device according to various embodiments. [Figure 3B] FIG. 3B illustrates a cross-sectional side view of a fluid flow path coupled to the needle hub assembly shown in FIG. 3A, according to various embodiments. [Figure 4A] 1A-1C show cross-sectional side and top views, respectively, of an exemplary arrangement of an anti-reflux mechanism in a drug delivery device according to various embodiments. [Figure 4B] 1A-1C show cross-sectional side and top views, respectively, of an exemplary arrangement of an anti-reflux mechanism in a drug delivery device according to various embodiments. [Figure 5] 1 illustrates a perspective view of a first exemplary backflow prevention mechanism in the form of a slit valve, according to various embodiments. [Figure 6A] 1 illustrates a cross-sectional side view of a second exemplary backflow prevention mechanism in the form of an umbrella valve, according to various embodiments. [Figure 6B] 1 illustrates a cross-sectional side view of a second exemplary backflow prevention mechanism in the form of an umbrella valve, according to various embodiments. [Figure 7A] 10 illustrates a cross-sectional side view of a third exemplary backflow prevention mechanism in the form of a ball valve, according to various embodiments. [Figure 7B] 10 illustrates a cross-sectional side view of a third exemplary backflow prevention mechanism in the form of a ball valve, according to various embodiments. [Figure 8A] 10 illustrates a cross-sectional side view of a fourth exemplary backflow prevention mechanism in the form of a duckbill valve, according to various embodiments. [Figure 8B] 10 illustrates a cross-sectional side view of a fourth exemplary backflow prevention mechanism in the form of a duckbill valve, according to various embodiments. [Figure 8C] 8C shows a perspective view of the fourth exemplary backflow prevention mechanism of FIGS. 8A and 8B, according to various embodiments. [Figure 8D] 8C shows a perspective view of the fourth exemplary backflow prevention mechanism of FIGS. 8A and 8B, according to various embodiments. [Figure 9A] 10 illustrates a cross-sectional side view of a fifth exemplary backflow prevention mechanism in the form of a flap valve, according to various embodiments. [Figure 9B] 10 illustrates a cross-sectional side view of a fifth exemplary backflow prevention mechanism in the form of a flap valve, according to various embodiments. [Figure 10A]10 illustrates a cross-sectional side view of a sixth alternative backflow prevention mechanism in the form of a flap valve, according to various embodiments. [Figure 10B] 10 illustrates a cross-sectional side view of a sixth alternative backflow prevention mechanism in the form of a flap valve, according to various embodiments. [Figure 10C] 10 illustrates a cross-sectional side view of a sixth alternative backflow prevention mechanism in the form of a flap valve, according to various embodiments. [Figure 11A] 10A and 10B show perspective and side cross-sectional views, respectively, of a seventh alternative backflow prevention mechanism using air displacement in accordance with various embodiments. [Figure 11B] 10A and 10B show perspective and side cross-sectional views, respectively, of a seventh alternative backflow prevention mechanism using air displacement in accordance with various embodiments. [Figure 12] 10A-10C illustrate side cross-sectional views of alternative arrangements of exemplary backflow prevention mechanisms using air displacement in accordance with various embodiments. [Figure 13A] 10A and 10B show perspective and rear views, respectively, of an eighth alternative backflow prevention mechanism using a normally open clamp assembly in accordance with various embodiments. [Figure 13B] 10A and 10B show perspective and rear views, respectively, of an eighth alternative backflow prevention mechanism using a normally open clamp assembly in accordance with various embodiments. [Figure 13C] 10A and 10B show perspective and rear views, respectively, of an eighth alternative backflow prevention mechanism using a normally open clamp assembly in accordance with various embodiments. [Figure 13D] 10A and 10B show perspective and rear views, respectively, of an eighth alternative backflow prevention mechanism using a normally closed clamp assembly in accordance with various embodiments. [Figure 13E] 10A and 10B show perspective and rear views, respectively, of an eighth alternative backflow prevention mechanism using a normally closed clamp assembly in accordance with various embodiments. [Figure 13F] 10A and 10B show perspective and rear views, respectively, of an eighth alternative backflow prevention mechanism using a normally closed clamp assembly in accordance with various embodiments. [Figure 14A] 10A-10C show side and cross-sectional views of a ninth alternative backflow prevention mechanism using a sleeve valve assembly according to various embodiments. [Figure 14B]10A-10C show side and cross-sectional views of a ninth alternative backflow prevention mechanism using a sleeve valve assembly according to various embodiments. [Figure 14C] 10A-10C show side and cross-sectional views of a ninth alternative backflow prevention mechanism using a sleeve valve assembly according to various embodiments. [Figure 15A] 13A-13C show side and cross-sectional views of a tenth alternative backflow prevention mechanism using a sleeve valve assembly according to various embodiments. [Figure 15B] 13A-13C show side and cross-sectional views of a tenth alternative backflow prevention mechanism using a sleeve valve assembly according to various embodiments. [Figure 15C] 13A-13C show side and cross-sectional views of a tenth alternative backflow prevention mechanism using a sleeve valve assembly according to various embodiments. [Figure 15D] 13A-13C show side and cross-sectional views of a tenth alternative backflow prevention mechanism using a sleeve valve assembly according to various embodiments. [Figure 15E] 13A-13C show side and cross-sectional views of a tenth alternative backflow prevention mechanism using a sleeve valve assembly according to various embodiments. [Figure 15F] 13A-13C show side and cross-sectional views of a tenth alternative backflow prevention mechanism using a sleeve valve assembly according to various embodiments. [Figure 15G] 13A-13C show side and cross-sectional views of a tenth alternative backflow prevention mechanism using a sleeve valve assembly according to various embodiments. [Figure 15H] 13A-13C show side and cross-sectional views of a tenth alternative backflow prevention mechanism using a sleeve valve assembly according to various embodiments. [Figure 16A] 11 illustrates an eleventh backflow prevention mechanism using an alternative air displacement device according to various embodiments. [Figure 16B] 11 illustrates an eleventh backflow prevention mechanism using an alternative air displacement device according to various embodiments. [Figure 16C] 11 illustrates an eleventh backflow prevention mechanism using an alternative air displacement device according to various embodiments. [Figure 16D]11 illustrates an eleventh backflow prevention mechanism using an alternative air displacement device according to various embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0014] Those skilled in the art will understand that elements in the figures are drawn for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions and / or relative positions of some of the elements in the figures may be exaggerated relative to other elements to improve understanding of various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in commercially feasible embodiments are often not shown in order to so as not to overly distract from the illustrations of these various embodiments. Furthermore, it will be appreciated that certain acts and / or steps may be described or shown in a particular chronological order, although those skilled in the art will understand that such specificity with respect to order is not actually required. It will also be understood that the terms and phrases used herein have the ordinary technical meaning, as set forth above, that would be given to such terms and phrases by those skilled in the art, unless a different specific meaning is explained herein.

[0015] The present disclosure generally relates to a backflow prevention mechanism for a drug delivery device. Generally, the drug delivery device includes a housing defining a shell, a container, a drive mechanism, a needle assembly having a first end and a second end, a fluid flow connection, and a backflow prevention mechanism, each of which is at least partially disposed within the housing. The container has first and second ends and an interior volume for containing a medication to be administered to a user. The drive mechanism is adapted to apply a force to the first end of the container to force the medication within the container toward the second end. The fluid flow connection is coupled to the second end of the container and the first end of the needle assembly and is adapted to allow the medication to flow from the container to the needle assembly.

[0016] An anti-reflux mechanism is a fluid path element disposed within the fluid path. The anti-reflux mechanism allows fluid flow in a first direction (i.e., from the container to the needle assembly so that the medication can be administered to the patient) while restricting fluid flow in a second direction (i.e., from the needle assembly back to the container). Blocking fluid flow in the second direction reduces and / or eliminates the possibility of clot formation, thereby allowing fluid to flow at predetermined flow rates. As a result, the anti-reflux mechanism can eliminate the need for expensive, high-power drive mechanisms required to overcome flow path obstructions or even obstructions that completely prevent drug delivery. Furthermore, anti-reflux mechanisms can be readily used in delayed-delivery injectors that do not immediately deliver medication to the patient when the device is activated and / or when the needle and / or cannula is inserted into the patient.

[0017] FIG. 1 is a schematic diagram of one embodiment of a drug delivery device 10 constructed in accordance with the principles of the present disclosure. The drug delivery device 10 may operate to deliver a drug subcutaneously or transdermally to a patient. In the illustrated embodiment, the drug delivery device 10 is configured as a wearable drug delivery device, such as an on-body injector or a portable infusion pump, and is removably attached to the patient's tissue 11 (e.g., the patient's skin). The drug delivery device 10 may also be configured to automatically deliver a fixed or patient / operator-settable dose of a drug over a controlled or selected time period. Furthermore, the drug delivery device 10 may be for self-administration by the patient or may be operated by formally trained medical personnel or other caregivers to administer the injection.

[0018] Generally, the drug delivery device 10 may include a needle assembly (also referred to as an insertion mechanism) 12, a reservoir 14, a fluid path assembly 22, a drive mechanism 24, and a controller 26, each of which may be disposed within the interior space of a main housing 29 that defines a shell. An actuator 28 (e.g., a user-depressible button, touchscreen, microphone, etc.) may protrude from or be disposed on an exterior surface of the housing 29 and may be configured to initiate operation of the drug delivery device 10 by activating the needle assembly 12, the fluid path assembly 22, the drive mechanism 24, the controller 26, and / or other mechanisms and / or electronics by mechanical and / or electrical means (shown in dashed lines in FIG. 1 ). In some examples, wireless communication may be used to activate the device 10. In embodiments in which the actuator 28 is a button that is pressed or otherwise physically operated by a user or patient, the actuator 28 may be configured to apply the motive force necessary to activate the needle assembly 12, the fluid path assembly 22, the drive assembly 24, the controller 26, and / or other mechanisms. In such embodiments, actuator 28 may be physically connected, either directly or indirectly via a mechanical linkage, to needle assembly 12, drive mechanism 24, fluid path assembly 22, and / or other mechanisms, such that manually pushing or otherwise interacting with actuator 28 provides the motive force necessary to activate needle assembly 12, drive mechanism 24, fluid path assembly 22, and / or other mechanisms. For example, in some embodiments, manually pushing actuator 28 may move fluid path assembly 22 toward first end 36 of fixed container 14 or move container 14 toward fixed fluid path assembly 22, thereby causing container access needle 60 to pierce seal member 40 and enter reservoir or interior volume 30 of container 14.Additionally or alternatively, the actuator 28 may operate as an input device that sends electrical and / or mechanical signals to the controller 26, which may further execute programmable instructions for controlling the operation of the needle assembly 12, drive mechanism 24, fluid path assembly 22, and / or other mechanisms. In such embodiments, the controller 26 may include a processor (e.g., a microprocessor) and non-transitory memory for storing the programmable instructions executed by the processor. Further, in such embodiments, the drug delivery device 10 may include an internal actuator (e.g., an electric motor, a pneumatic or hydraulic pump, and / or a source of pressurized gas or liquid) separate from the actuator 28 that applies the motive force necessary to activate the needle assembly 12, drive mechanism 24, fluid path assembly 22, and / or other mechanisms in response to electrical control signals received from the controller 26.

[0019] 1 , the housing 29 may include a bottom wall 25 configured to be removably attached (e.g., adhered by an adhesive) to the patient's tissue 11 and a top wall 27 including one or more visual indicators 42 (e.g., lights, graphical displays, etc.) and / or a window 35 for viewing the container 14 and the medication 32 contained therein. The one or more visual indicators 42 may be used to communicate information to a user regarding the operational status of the drug delivery device 10 and / or the status of the medication or medication 32. An opening 31 may be formed in the bottom wall 25, and optionally, a pierceable sterile barrier 33, such as a pierceable septum, may extend across the opening 31 to seal the interior of the housing 29 prior to use. In some embodiments, the pierceable sterile barrier 33 may be omitted, and instead, a removable sealing member (not shown) may cover and seal close the opening 31 prior to use.

[0020] After the bottom wall 25 of the housing 29 is attached to the patient's skin 11, the needle assembly 12 may be actuated to move the delivery member from a retracted position within the housing 29 to a deployed position extending outside the housing 29. In this embodiment, this may involve the needle assembly 12 inserting the needle or trocar 21 and hollow cannula 23 surrounding the trocar 21 through a pierceable sterile barrier 33 and into the patient's skin 11 and subcutaneous tissue 13, as shown in FIG. 1 . Immediately or shortly thereafter, the needle assembly 12 may automatically retract the needle 21, leaving the open distal end of the cannula 23 inside the patient for subcutaneous delivery of the drug 32. The needle 21 may be solid and have a sharpened end for piercing the patient's skin 11. Additionally, the needle 21 may be made of a more rigid material than the cannula 23. In some embodiments, the needle 21 may be made of metal and the cannula 23 may be made of plastic or another polymer. The relative flexibility of cannula 23 may allow cannula 23 to be placed subcutaneously within the patient's tissue 11 for a period of time without causing pain or significant discomfort to the patient.

[0021] In some embodiments, needle assembly 12 may include one or more springs (e.g., coil springs, torsion springs, etc.) that are initially held in a biased state and are released upon depression of actuator 28 to insert needle 21 and cannula 23 or a hollow needle into a patient. Additionally, retraction of needle 21 may be achieved by automatic release of another spring after needle 21 and cannula 23 are inserted into a patient. Other power sources for insertion and / or retraction are also contemplated, including, for example, an electric motor, a hydraulic or pneumatic pump, or a canister that releases pressurized gas or liquid to provide actuation energy.

[0022] The container 14, which may be referred to in some contexts as a primary container, may include a wall 38 having an interior surface 43 and an exterior surface 47 that define a reservoir 30 that is filled with the drug 32. In some embodiments, the reservoir 30 may be pre-filled with the drug 32 by the drug manufacturer prior to attachment of the container 14 to the drug delivery device 10. In some embodiments, the container 14 may be rigidly connected to the housing 29 such that the container 14 cannot move relative to the housing, while in other embodiments, the container 14 may be slidably connected to the housing 29 such that the container 14 can move relative to the housing 29 during operation of the drug delivery device 10. The container 14 may have an elongated, barrel-like or cylindrical shape extending along a longitudinal axis A. In embodiments in which the drug delivery device 10 is configured as an on-body injector, the longitudinal axis A of the container 14 may be perpendicular, substantially perpendicular, or otherwise non-parallel to the direction in which the needle assembly 12 inserts a delivery member, such as the cannula 23, into a patient. This configuration may allow the on-body injector to have a generally flat, low-profile shape that can be worn by a patient without interfering with patient movement. Initially, a stopper 34 or other piston member may be disposed within the reservoir 30 at a first end 36 of the container 14. The stopper 34 may sealingly and slidably engage an interior surface 43 of a wall 38 of the container 14 and may be movable relative to the wall 38 of the container 14.

[0023] The amount of drug 32 contained within reservoir 30 prior to delivery can be any amount within the range of about (e.g., ±10%) 0.5 to 20 mL, or any amount within the range of about (e.g., ±10%) 0.5 to 10 mL, or any amount within the range of about (e.g., ±10%) 1 to 10 mL, or any amount within the range of about (e.g., ±10%) 1 to 8 mL, or any amount within the range of about (e.g., ±10%) 1 to 5 mL, or any amount within the range of about (e.g., ±10%) 1 to 3.5 mL, or any amount within the range of about (e.g., ±10%) 1 to 3 mL, or any amount within the range of about (e.g., ±10%) 1 to 2.5 mL, or any amount within the range of about (e.g., ±10%) ) 1-2 mL, or any amount up to about (e.g., ±10%) 4 mL, or any amount up to about (e.g., ±10%) 3.5 mL, or any amount up to about (e.g., ±10%) 3 mL, or any amount up to about (e.g., ±10%) 2.5 mL, or any amount up to about (e.g., ±10%) 2 mL, or any amount up to about (e.g., ±10%) 1.5 mL, or any amount up to about (e.g., ±10%) 1 mL, or any amount up to about (e.g., ±10%) 2 mL, or any amount up to about (e.g., ±10%) 2.5 mL, or any amount up to about (e.g., ±10%) 3 mL. Reservoir 30 may be fully or partially filled with drug 32. Drug 32 may be one or more of the drugs listed below under the heading "Drug Information," such as, for example, granulocyte colony-stimulating factor (G-CSF), PCSK9 (human proprotein convertase subtilisin / kexin type 9)-specific antibody, sclerostin antibody, or calcitonin gene-related peptide antibody (CGRP).

[0024] During operation of the drug delivery device 10, the drive mechanism 24 may apply a force to the first end 36 of the container 14. For example, the drive mechanism 24 may push the stopper 34 along the longitudinal axis A from the first end 36 of the container 14 to the second end 37 of the container 14 to expel or push the drug 32 from the container 14. In some embodiments, the drive mechanism 24 may include one or more springs (e.g., coil springs, torsion springs, etc.) that are initially held in a biased state and released upon pressing the actuator 28. After their release, the springs may expand or contract to move the stopper 34 within the reservoir 30 along the longitudinal axis A from the first end 36 of the container 14 to the second end 37 of the container 14. In other embodiments, the drive mechanism 24 may include an electric motor (not shown) that rotates a gear mechanism, for example, including one or more sprocket gears, to cause axial movement of the stopper 34 within the reservoir 30. In yet another embodiment, drive mechanism 24 may include both an electric motor and a spring, with the electric motor adjusting the tension of the spring via a tether or pulley system. In yet another embodiment, drive mechanism 24 may include a canister that releases pressurized gas or liquid to provide actuation energy. Other examples are possible.

[0025] The fluid pathway assembly 22 may be configured to establish fluid communication between the container 14 and the needle assembly 12 via a sterile fluid flow path during operation of the drug delivery device 10. The first end 44 of the fluid pathway assembly 22 may include a container access needle 60 and an overmold member 62. Generally, the overmold member 62 may serve as a mounting member or connection hub for the container access needle 60 and may provide an enlarged outer dimension, such as an enlarged outer diameter, to a portion of the container access needle 60 that does not access the reservoir 30. The container access needle 60 may have a sharpened end or tip 63 corresponding to the first end of the container access needle 60 and a second end 64 in fluid communication with a fluid flow connection.

[0026] The fluid path assembly 22 may include a first end 44 connected to the second end 37 of the container 14 and a second end 48 connected to the first end of the needle assembly 12, with a fluid flow connection 50 extending between the first end 44 and the second end 48, and a backflow prevention mechanism 70 associated with at least one of the container 14, the fluid flow connection 50, or the needle assembly 12. In the illustrated example, the backflow prevention mechanism 70 is disposed within the fluid flow connection 50. As described in further detail below, in some embodiments, the first end 44 of the fluid path assembly 22 may be connected to the container 14 by a clip member 53. The fluid flow connection 50 may be sterilized and may be partially or completely made of flexible tubing 52, such as a polymer or other material. Initially, there may be slack in the flexible tubing 52 to allow the fluid path assembly 22 to move relative to the housing 29 and / or to allow components of the needle assembly 12 to which the fluid path assembly 22 is attached to move relative to the housing 29. As shown in Figure 2, the second end 48 of the fluid flow connection 50 may have a ball or plug 49 that can be inserted into a reservoir receiving portion in the needle assembly 12 to create a seal between the fluid flow connection 50 and the needle assembly 12. As shown in Figures 2, 3A, and 3B, the ball or plug 49 may be disposed at the second end 48 of the fluid flow connection 50. Additionally, as shown in Figures 2 and 3B, the plug 49 may include an opening or bore 49a that allows the fluid flow connection 50 to pass through to create a complete fluid flow path to the needle assembly 12.

[0027] 3A and 3B illustrate an exemplary needle assembly (also referred to as an insertion mechanism) 120 corresponding to the needle assembly 12 shown in FIGS. 1 and 2. The needle assembly 120 may be incorporated into a drug delivery device, such as the drug delivery device 10 shown in FIG. 1. The needle assembly 120 includes a needle hub 122, a needle or trocar 121 coupled to the needle hub 122, a boot 130 removably coupled to the needle hub 122, a cannula 140 at least partially disposed within the interior volume 131 of the flexible boot 130, and a spring 150 coupled to the needle hub 122. The needle 121 may have a hollow interior to allow the drug 32 to flow. The needle assembly 120 may include any number of additional components and / or features to aid operation. In some examples, delivery of the drug 32 may be delayed until a time after the needle assembly 120 has inserted the needle 121 and / or cannula 140 into the user. In some instances, drug delivery may be either incremental or as a bolus.

[0028] 3A and 3B, second end 48 of fluid flow connection 50 is inserted into or coupled to reservoir receiving portion or opening 124 of needle hub 122 at coupling region 71. Medication 32 enters cannula 140 where fluid flow connection 50 terminates and flows through the hollow interior of needle 121 for delivery to the user.

[0029] 2-4B, the backflow prevention mechanism 70 may be located, disposed, and / or coupled at a coupling region 71 where the fluid flow connection 50 is coupled to the needle assembly 12. In other examples, the backflow prevention mechanism 70 may be located elsewhere along the fluid path within the device 10 (e.g., at a location within the needle assembly 12). In one example, the backflow prevention mechanism 70 may be coupled to the needle hub 122 via a press-fit connection. Other suitable techniques may be used to couple the backflow prevention mechanism 70 at the coupling region 71. The backflow prevention mechanism 70 may include at least one flow restrictor 72 that restricts fluid flow from the needle assembly 12 through the fluid flow connection 50 to the container 14.

[0030] 5 shows an example of a flow restrictor 172 corresponding to the flow restrictor 72 shown in FIGS. 4A and 4B. In the example shown, the flow restrictor 172 is in the form of a one-way slit valve having an inlet portion 174, an outlet portion 176, a valve disc 178 extending between the inlet portion 174 and the outlet portion 176, and one or more slits or openings 180 defined by the valve disc 178 for allowing the drug 32 to pass through the valve disc 178. The flow restrictor 172 may also include a groove 182 for receiving a corresponding protrusion (not shown) in the coupling region 71 to couple the flow restrictor 172 to the protrusion. The flow restrictor 172 may be made partially and / or completely from an elastic and / or flexible material, such as rubber and / or a polymeric material.

[0031] The flow restrictor 172 is positioned within the device 10 such that the inlet portion 174 is located upstream of the outlet portion 176. In other words, the inlet portion 174 of the flow restrictor 172 is positioned closer to the container 14, while the outlet portion 176 of the flow restrictor 172 is positioned closer to the needle assembly 12. Configured in this manner, when it is desired to deliver the medication 32 to a user, the device 10 is actuated and the medication 32 flows from the container 14 along the fluid flow connection 50, through the inlet portion 174 of the flow restrictor 172 and the outlet portion 176 of the flow restrictor 172, and through the slit or opening 180.

[0032] In the illustrated example, the outlet portion 176 of the flow restrictor 172 opens at a slit 180, allowing the medicament 32 to pass and be delivered into the needle assembly 12. Once delivery of the medicament 32 is complete, the inherent resiliency of the flow restrictor 172 causes the slit 180 to close, thus restricting the medicament 32 or other fluid from flowing from the outlet portion 176 of the flow restrictor 172 to the inlet portion 174 of the flow restrictor 172.

[0033] In some of these instances, it may be desirable to prevent unintended forward flow. Changes in environmental pressure due to altitude can cause air bubbles in the reservoir 14 or fluid flow connection 50 of these devices to expand. This expansion can force the drug out of the needle, resulting in unintended delivery. Using a one-way valve with a cracking pressure that exceeds the naturally occurring pressure differential can prevent these occurrences. Thus, the cracking pressure of the flow restrictor 172 may also be configured to be greater than about 2 psi to prevent forward flow of air or drug when it is not desired.

[0034] 6A and 6B show a second example of a flow restrictor 272 corresponding to the flow restrictor 72 shown in FIGS. 4A and 4B. In the illustrated example, the flow restrictor 272 is in the form of a one-way (normally closed) umbrella valve having an inlet portion 274, an outlet portion 276, a valve disc 278 extending between the inlet portion 274 and the outlet portion 276, and one or more openings 280 defined by the valve disc 278 for allowing the drug 32 to pass through the valve disc 278. The flow restrictor 272 also includes an umbrella member 282 operatively coupled to the valve disc 278 using any number of suitable techniques (e.g., via a press-fit connection, a threaded connection, etc.). The flow restrictor 272 may also include a groove (not shown) or other coupling mechanism used to couple the flow restrictor 272 at the coupling region 71.

[0035] The umbrella member 282 includes a base portion 282 a and a flap portion 282 b and may be partially and / or completely made from a resilient and / or flexible material, such as a rubber and / or polymeric material, to enable movement between a first configuration and a second configuration. Similarly, the valve body 278 may be partially and / or completely made from a resilient and / or flexible material, such as a rubber and / or polymeric material.

[0036] Flap portion 282b of umbrella member 282 includes a first surface 282c and a second surface 282d and is movable between a first, closed position (FIG. 6A) and a second, open position (FIG. 6B) to selectively cover opening 280. Flap portion 282b may include any number of support structures to help maintain its shape and / or configuration. In some examples, flap portion 282b is integrally formed with base portion 282a, and in some examples, flap portion 282b is a separate component.

[0037] Flow restrictor 272 is positioned within device 10 such that inlet portion 274 is located upstream of outlet portion 276. In other words, inlet portion 274 of flow restrictor 272 is positioned closer to container 14, while outlet portion 276 of flow restrictor 272 is positioned closer to needle assembly 12. Configured in this manner, and as shown in FIG. 6B , when it is desired to deliver medication 32 to a patient, device 10 is actuated and medication 32 flows from container 14 along fluid flow connection 50, through inlet portion 274 of flow restrictor 272 and outlet portion 276 of flow restrictor 272, and through opening 280. The cracking pressure of flow restrictor 272 may also be configured to be greater than about 2 psi to prevent forward flow of air or medication when such flow is not desired.

[0038] 6B, as the medicament 32 flows through the opening 280, it exerts pressure on the first surface 282c of the flap portion 282b, which pressure further urges the flap portion 282b to a second, open position, allowing the medicament 32 to pass and be delivered (as indicated by the arrow in FIG. 6B) into the needle assembly 12. In some instances, the inherent resiliency of the umbrella member 282 may return the flap portion 282b to the closed configuration (FIG. 6A). In other instances, the flap portion 282b may maintain the open configuration until a counter pressure is exerted on the flap portion 282b.

[0039] 6A, if the medicament 32 or other fluid flows in the opposite direction (e.g., from the outlet portion 276 of the flow restrictor 272 to the inlet portion 274 of the flow restrictor 272), the medicament 32 or other fluid contacts the second surface 282d of the flap portion 282b, thereby returning the flap portion 282b to the closed configuration. Thus, and as indicated by the arrow in FIG. 6A, the flap portion 282b restricts the medicament 32 or other fluid from flowing through the opening 280.

[0040] 7A and 7B show a third example of a flow restrictor 372 corresponding to the flow restrictor 72 shown in FIGS. 4A and 4B. In the illustrated example, the flow restrictor 372 is in the form of a one-way ball valve having an inlet portion 374, an outlet portion 376, a generally hollow valve body 378 extending between the inlet portion 374 and the outlet portion 376, and any number of elongated ledges 380 defined by the valve body 378 and forming a channel 381 allowing the drug 32 to pass from the inlet portion 374 to the outlet portion 376. The flow restrictor 372 also includes a ball member 382 disposed within the valve body 378 that is movable between a first, closed position ( FIG. 7A ) and a second, open position ( FIG. 7B ) to selectively restrict or allow fluid flow. The flow restrictor 372 may also include a groove (not shown) or other coupling mechanism used to couple the flow restrictor 372 at the coupling region 71. The components of the flow restrictor 372 may be made from any number of suitable materials.

[0041] A ledge 380 in the disc 378 extends at least partially into the outlet portion 376 of the disc 378 but terminates before reaching the inlet portion 374 of the disc 378. As a result, as shown in FIG. 7B , when the ball member 382 is disposed in the second, open position ( FIG. 7B ), the ball member 382 abuts the ledge 380, thereby maintaining a gap to accommodate the channel 381, thus allowing flow from the inlet portion 374, through the flow channel or channels 381, and through the outlet portion 376. Conversely, when the ball member 382 is disposed in the first, closed position ( FIG. 7A ), the ball member 382 contacts the disc 378 and creates a seal, thereby restricting flow from the outlet portion 376 to the inlet portion 374.

[0042] Flow restrictor 372 is positioned within device 10 such that inlet portion 374 is located upstream of outlet portion 376. In other words, inlet portion 374 of flow restrictor 372 is positioned closer to container 14, while outlet portion 376 of flow restrictor 372 is positioned closer to needle assembly 12. Configured in this manner, and as shown in FIG. 7B , when it is desired to deliver medication 32 to a user, device 10 is actuated and medication 32 flows from container 14, along fluid flow connection 50, and through inlet portion 374 of flow restrictor 372. As medication 32 flows through inlet portion 374, it exerts pressure on ball member 382, ​​thereby moving ball member 382 toward outlet portion 376 and into a second, open configuration that allows medication 32 to be delivered through channel 381 (as shown by the arrow in FIG. 7B ) and into needle assembly 12.

[0043] 7A, if the drug 32 or other fluid flows in the opposite direction (e.g., from the outlet portion 376 of the flow restrictor 372 to the inlet portion 374 of the flow restrictor 372), the drug 32 or other fluid will contact the ball member 382 and urge the ball member 382 toward the inlet portion 374 and into the first, closed configuration. Thus, and as indicated by the arrow in FIG. 7A, the ball member 382 seals against the valve disc 378, preventing the drug 32 or other fluid from flowing back through the inlet portion 374.

[0044] 8A-8D show a fourth example of a flow restrictor 472 corresponding to the flow restrictor 72 shown in FIGS. 4A and 4B. In the illustrated example, the flow restrictor 472 is in the form of a one-way (normally closed) duckbill valve having an inlet portion 474, an outlet portion 476, and a generally hollow valve body 478 extending between the inlet portion 474 and the outlet portion 476, the valve body 478 defining an opening 480 that allows the drug 32 to pass from the inlet portion 474 to the outlet portion 476. The flow restrictor 472 also includes a duckbill member 482 disposed within the valve body 478 and operatively coupled to the valve body 478 using any number of suitable techniques (e.g., via a press-fit connection, a threaded connection, etc.). The flow restrictor 472 may also include a protrusion 473, groove (not shown), or other coupling mechanism that is used to couple the flow restrictor 472 at the coupling region 71. The components of flow restrictor 472 may be made from any number of suitable materials, such as, for example, a rigid material for valve body 478 and a resilient material for duckbill member 482 .

[0045] Duckbill member 482 includes a base portion 482a and a flap portion 482b. Flap portion 482 includes an inner surface 482c and an outer surface 482d. Further, outlet portion 484 is disposed at or near the downstream end of flap portion 482b. In some examples, flap portion 482b is integrally formed with base portion 482a, and in some examples, flap portion 482b is a separate component. Duckbill member 482 may be partially and / or completely constructed from a resilient and / or flexible material, such as rubber and / or a polymeric material.

[0046] The duckbill member 482 is movable between a first, closed position ( FIGS. 8A and 8C ) and a second, open position ( FIGS. 8B and 8D ). The duckbill member 482 remains in the first, closed position until the pressure differential across the flow restrictor 472 (the difference between the pressure in the inlet portion 474 and the pressure in the outlet portion 476) exceeds the cracking pressure of the valve. When the duckbill member 482 is in the first, closed position, the inner surfaces 482c of the flap portions 482b contact each other, forming a seal at the outlet portion 484. When the pressure differential across the flow restrictor 472 exceeds the cracking pressure, the duckbill member moves to the second, open position, and the inner surfaces 482c of the flap portions 482b move apart, forming an opening at the outlet portion 484.

[0047] Flow restrictor 472 is positioned within device 10 such that inlet portion 474 is located upstream of outlet portion 476. In other words, inlet portion 474 of flow restrictor 472 is positioned closer to container 14, while outlet portion 476 of flow restrictor 472 is positioned closer to needle assembly 12. Configured in this manner, and as shown in Figures 8B and 8D, when it is desired to deliver medication 32 to a user, device 10 is actuated and medication 32 flows from container 14, along fluid flow connection 50, through inlet portion 474 of flow restrictor 472, and to flap portion 482b of duckbill member 482. The medication 32 then exerts pressure on the inner surface 482c of the flap portion 482b, thereby moving the duckbill member 482 to a second, open position and widening the outlet portion 484 of the duckbill member 482, allowing the medication 32 to pass through the outlet portion 476 of the flow restrictor 472 (as shown by the arrow in FIG. 8B) and be delivered. When the pressure difference across the flow restrictor 472 is less than the cracking pressure, the inherent resiliency of the duckbill member 482 causes the duckbill member 482 to return to the first, closed position, closing the outlet portion 484 of the duckbill member 482 and forming a seal. The cracking pressure of the flow restrictor 472 may be configured to be (or exceed) approximately 2 psi to prevent the forward flow of air or medication when this is not desired.

[0048] 8A, if the drug 32 or other fluid flows in the opposite direction (e.g., from the outlet portion 476 of the flow restrictor 472 to the inlet portion 474 of the flow restrictor 472), the drug 32 or other fluid will contact the outer surface 482d of the flap portion 482b of the duckbill member 282. Thus, and as indicated by the arrows in FIG. 8A, the duckbill member 482 restricts the drug 32 or other fluid from flowing back through the outlet portion 476 to the inlet portion 474.

[0049] 9A and 9B show a fifth example of a flow restrictor 572 corresponding to the flow restrictor 72 shown in FIGS. 4A and 4B. In the illustrated example, the flow restrictor 572 is in the form of a one-way flap, plate, or diaphragm valve having an inlet portion 574, an outlet portion 576, a generally hollow valve body 578 extending between the inlet portion 574 and the outlet portion 576, and a cap member 579 having one or more openings 579 a in fluid communication with the valve body 578. The valve body 578 includes any number of ledges 580 defined by the valve body 578 to form channels 581 that allow the drug 32 to pass from the inlet portion 574 to the outlet portion 576. In some examples, the cap member 579 is integrally formed with the ledges 580. The flow restrictor 572 also includes a flap, plate, and / or diaphragm member 582 disposed within the cap member 579 and movable between an open position ( FIG. 9A ) and a closed position ( FIG. 9B ) to selectively allow or restrict fluid flow. The flow restrictor 572 may also include a groove (not shown) or other coupling mechanism used to couple the flow restrictor 572 at the coupling region 71. The components of the flow restrictor 572 may be made from any number of suitable materials.

[0050] A ledge 580 in the valve disc 578 extends at least partially into the outlet portion 576 of the valve disc 578. A flap member 582 is movable between an upper surface 580 a of the ledge 580 and an inner surface 579 b of the cap member 579. As shown in FIG. 9A , when the flap member 582 is positioned against the upper surface 580 a of the ledge 580, fluid can flow from the inlet portion 574 through the cap member opening 579 a and through the channel 581 to the outlet portion 576. In some examples, the outer diameter of the flap member 582 may be smaller than the inner diameter of the cap 579, thus allowing fluid to flow to the outlet portion 576. Conversely, when the flap member 582 is positioned in the closed position ( FIG. 9B ), the flap member 582 contacts the inner surface 579 b of the cap member 579 to create a seal, thereby restricting flow from the outlet portion 576 to the inlet portion 574.

[0051] The flow restrictor 572 is positioned within the device 10 such that the inlet portion 574 is located upstream of the outlet portion 576. In other words, the inlet portion 574 of the flow restrictor 572 is positioned closer to the container 14, while the outlet portion 576 of the flow restrictor 572 is positioned closer to the needle assembly 12. Configured in this manner, and as shown in FIG. 9A , when it is desired to deliver a medication 32 to a user, the device 10 is actuated and the medication 32 flows from the container 14, along the fluid flow connection 50, and through the inlet portion 574 of the flow restrictor 572. As the medication 32 flows through the inlet portion 574, it exerts pressure on the flap member 582, causing the flap member 582 to move toward the outlet portion 576 and rest on the upper surface 580 a of the ledge 580 to an open configuration that allows the medication 32 to pass through the channel 581 (as indicated by the arrow in FIG. 9A ) and be delivered to the needle assembly 12.

[0052] 9B, if the medicament 32 or other fluid flows in the opposite direction (e.g., from the outlet portion 576 of the flow restrictor 572 to the inlet portion 574 of the flow restrictor 572), the medicament 32 or other fluid will contact the flap member 582 and urge the flap member 582 toward the inner surface 579b of the cap member 579 and thus into a closed configuration in which the flap member 582 seals the opening 579a in the cap member 579. Thus, and as shown by the arrow in FIG. 9B, the flap member 582 restricts the medicament 32 or other fluid from flowing back through the opening 579a of the cap member 579 and the inlet portion 574.

[0053] Figures 10A-10C show a sixth example of a flow restrictor 672 corresponding to flow restrictor 72 shown in Figures 4A and 4B. Flow restrictor 672 is in the form of another one-way flap, plate, or diaphragm valve having similar features as flow restrictor 572 shown in Figures 9A and 9B. Therefore, for the sake of brevity, features of flow restrictor 672 having the same two-digit suffix as those shown in flow restrictor 572 of Figures 9A and 9B will not be described.

[0054] The flow restrictor 672 further includes a protruding member 685 disposed within the valve body 678. In the illustrated example of FIG. 10A, in a first, open (resting) configuration, the flap member 682 abuts the protruding member 685. In this configuration, the channel 681 allows fluid to flow between the inlet portion 674 and the outlet portion 676. In a second, deflected configuration, as shown in FIG. 10B, pressure exerted on the flap member 682 by the drug 32 deflects the flap member toward the outlet portion 676, providing complete fluid flow through the flow restrictor 672. As shown in FIG. 10C, if the drug 32 or other fluid attempts to flow in the opposite direction (e.g., from the outlet portion 676 to the inlet portion 674), the flap member 682 moves to abut against the inner surface 679b of the cap member 679, sealing the opening 679a. Thus, and as indicated by the arrows in FIG. 10C, the flap member 682 restricts the backflow of the medication 32 or other fluid through the opening 679a and inlet portion 674 of the cap member 679.

[0055] 11A and 11B show a seventh example of a backflow prevention mechanism 770 in the form of an air exclusion device 772 corresponding to the backflow prevention mechanism 70. In some cases, when the container 14 is filled with the drug 32 through the fill port 776, air can be introduced into the fluid path (container 14, fluid pathway assembly 22, and / or fluid flow path 50), increasing the compliance of the fluid path compared to an air-free / bubble-free fluid path. In the case of delayed delivery, this added compliance can allow blood or other fluids to enter (backflow) into the needle assembly 12, fluid flow path 50, or container 14, increasing the likelihood of forming clots in the fluid path. Removing air entrained during the filling process can help prevent clots in the device fluid path 50. To accomplish this, the air exclusion device 772 includes a bubble removal membrane or filter plate 774 coupled to the fluid flow path 50 using any suitable technique, such as, for example, a press-fit connection, a threaded connection, a clamp, and / or other coupling.

[0056] The bubble removal membrane 774 may be made from a hydrophobic material such as microporous PTFE. Additionally, other suitable materials may be used. In some examples, the bubble removal membrane 774 may be positioned at or near the fill port 776 of the device 10 to remove air during the filling process. In these examples, and as shown in FIG. 11A , the air removal device 772 is positioned within the fluid flow path 50 at a location downstream (relative to the flow during the filling process) of the fill port 776. In other examples, and as shown in FIG. 12 , the air removal device 772 is positioned within the fill port 776 of the device. Other locations are possible. In some examples, the use of a bubble-free pre-filled syringe (not shown) can also help eliminate and / or reduce the amount of air introduced into the fluid path during the filling process. Furthermore, in some examples, a removable cap or seal may be used to aid in the process of filling the device with a drug. Specifically, the removable cap limits the drug from flowing out of the needle assembly 12 during filling of the primary container 14.

[0057] 11B, the air exclusion device 772 may be formed by drilling channels (e.g., microchannels) 778 in the filter plate 774 for passing air bubbles in any radial direction of the filter plate 774. In some examples, the flow rate during filling of the container 14 with the drug 32 is reduced by using any number of flow restrictors (not shown) to allow more air to escape through the air exclusion device 772. If there is a large flow resistance downstream of the air exclusion device 772, the pressure inside the air exclusion device 772 increases during filling. This increased pressure encourages air to pass through the filter plate 774 to the environment, thereby reducing the amount of air introduced into the fluid path during the filling process.

[0058] During the filling process, as the medication 32 flows through the filling port 776 and enters the air exclusion device 772, the pressure differential between the interior of the air exclusion device and the environment causes entrained air to be expelled through the bubble removal membrane 774 while the medication 32 continues to flow within the fluid flow path 50 to the container 14. The air exclusion device 772 may be used with any number of additional backflow prevention mechanisms 70 described herein.

[0059] The efficiency of the air exclusion device 772 may depend on the ratio between the liquid flow and the gas flow. In some examples, the maximum removable bubble size for a given liquid flow rate can be determined if the airflow resistance of the filter plate 774 is known. In some examples, the channel 778 may have a diameter of approximately 0.25 mm and a length of approximately 5 mm, thus resulting in a channel volume of approximately 0.25 μL. This channel 778 design results in the air exclusion device 772 having a low (sub-microliter) internal volume, which is desirable for minimizing the amount of medication 32 not delivered to the patient while providing high air exclusion efficiency and a high flow rate during filling of the container 14. Furthermore, in some examples, the air exclusion device 772 may further include a hydrophilic element (not shown) that prevents entrained air from exiting the air exclusion device 772 via the liquid flow.

[0060] 13A-13F show an eighth example of a flow restrictor 872 corresponding to the flow restrictor 72 shown in Figures 4A and 4B. In the example shown, the flow restrictor 872 is in the form of a clamp valve 873 located on the lower portion of the needle assembly 120, through whose opening the needle 121 and cannula 140 protrude and are inserted into the patient's tissue, although other locations are possible. The clamp valve 873 has a clamp mechanism 874 that includes any number of movable elements or jaws 875 in communication with the cannula 140 or other portions of the fluid flow connection 50, any number of pivot members 876, a resilient member 878, and a drive mechanism or actuator 880. Each jaw 875 includes a first end 875a, a second end 875b, a length 875c extending between the first and second ends 875a and 875b, and a contact surface 875d disposed adjacent the cannula 140 (or other portion of the fluid flow connection 50). Additionally, one or both jaws 875 include a stop 875e that defines and limits the minimum clamp opening to prevent damage (i.e., excessive compression) to the cannula 140. The pivot member 876 is disposed along the length 875c and, in some examples, may be in the form of an integral protrusion formed along the length 875c that rotatably couples to the needle assembly 120. In other examples, the pivot member 876 may be in the form of a post or protrusion extending from the needle assembly 120 and inserted into an opening or bore formed along the length 875c of the jaw 875. Other examples are possible.

[0061] Actuator 880 is disposed at or near first end 875a of jaw 875 and is configured to rotate jaw 875 about pivot member 876. In some examples, actuator 880 may be in the form of a pulley mechanism that generates relative motion of jaw 875. Other actuator mechanisms may be used, such as magnetic mechanisms, gear mechanisms, etc. Resilient member 878 is disposed at or near second end 875b of jaw 875 and is configured to exert a force opposite to the force exerted by actuator 880 (depending on the configuration of the clamping mechanism, whether normally open (as shown in FIGS. 13A-13C) or normally closed (as shown in FIGS. 13D-13F)).

[0062] Specifically, as shown in FIGS. 13A-13C, a normally open clamp valve 873 is provided in which a resilient member 878 exerts a force on jaws 875 to position jaws 875 in an open configuration (as shown in FIGS. 13A and 13B) that allows fluid to flow out of cannula 140 and / or fluid flow connection 50. As shown in FIG. 13C, upon actuation of actuator 880, actuator 880 exerts a clamping force on jaws 875 that is greater than the force exerted by resilient member 878. As a result, jaws 875 rotate about pivot member 876, crushing or clamping cannula 140 and / or fluid flow connection 50 at contact surface 875d of jaws 875, thus restricting fluid flow in either direction. By way of example, if a delay is desired before drug delivery, actuator 880 may transition clamping mechanism 874 to a closed configuration. When administration of the medication 32 is desired, the actuator 880 may cease exerting force on the jaws 875, thus causing the resilient member 878 to transition the jaws 875 to the open configuration.

[0063] 13D-13F, a normally-closed clamp valve 873 is provided in which a resilient member 878 exerts a force on jaws 875 to position jaws 875 in a closed configuration (see FIGS. 13D and 13E) that restricts fluid from flowing in either direction through cannula 140 and / or fluid flow connection 50. As shown in FIG. 13F, upon actuation of actuator 880, actuator 880 exerts a clamping force on jaws 875 that is greater than the force exerted by resilient member 878. As a result, jaws 875 rotate about pivot member 876, releasing their grip or clamp on cannula 140 and / or fluid flow connection 50 at contact surface 875d, thus allowing fluid flow in either direction, and specifically, allowing delivery of drug 32 to the patient. As an example, if a delay is desired before drug delivery, actuator 880 exerts no force on jaws 875, and thus clamping mechanism 874 is positioned in the closed configuration. When administration of the medication 32 is desired, the actuator 880 may exert a force on the jaws 875, thus overcoming the force exerted by the resilient member 878 and causing the jaws 875 to transition to the open configuration.

[0064] 14A-14C show a ninth example of a flow restrictor 972 corresponding to the flow restrictor 72 shown in FIGS. 4A and 4B. In the illustrated example, the flow restrictor 972 is in the form of a one-way (normally closed) sleeve valve 973 having an inlet portion and an outlet portion disposed at or near the tip of a needle 921. In this example, the sleeve valve 973 includes a rigid hollow needle 921 having at least one side fluid port 921a connecting the inlet portion to the outlet portion, a flexible sleeve member 974, and a needle tip closure member 976. The flexible sleeve 974 is dimensioned to at least partially surround and / or enclose the outer diameter of the needle 921 and may be operatively coupled to the needle 921 using any number of suitable techniques (e.g., by an interference fit connection, an adhesive connection, etc.). The needle tip closure member 976 has an outer diameter that is equal to or exceeds the outer diameter of the flexible sleeve 974. In this example, the needle tip closure 976 is an accessory device attached to the needle 921. In another example, the needle tip closure 976 may be integrally formed as a feature of the needle 921. The needle 921 may include any number of side fluid ports 921 a to adjust fluid resistance and drug infusion time. The components of the flow restrictor 972 may be made from any number of suitable materials, such as, for example, a rigid material for the needle 921 and tip closure 976 and an elastic material for the flexible sleeve member 974.

[0065] The flexible sleeve 974 is movable between a first, closed position (FIGS. 14A and 14B) and a second, open position (FIG. 14C). The flexible sleeve 974 remains in the first, closed position until the pressure differential across the flow restrictor 972 (the difference between the pressure at the inlet and outlet ports) exceeds the valve's cracking pressure. When the flow restrictor 972 is in the first, closed position, the inner surface of the flexible sleeve 974 covers and seals the side fluid port 921a. The needle tip closure 976 is dimensioned to have an outer diameter equal to or greater than the outer diameter of the flexible sleeve 974, so that during insertion of the needle 921 by the needle assembly 120, the needle tip closure 976 prevents the leading edge of the flexible sleeve 974 from catching on the patient's tissue during needle insertion. When the pressure difference across the flow restrictor 972 exceeds the cracking pressure, the flexible sleeve member 974 transitions to a second, open position, and the inner surface of the flexible sleeve member 974 moves away from the outer surface of the needle 921, exposing the fluid side port 921a.

[0066] The flow restrictor 972 is positioned within the device 10 such that its inlet portion is located upstream of its outlet portion. In other words, the inlet portion of the flow restrictor 972 is positioned closer to the container 14, while the outlet portion of the flow restrictor 972 is positioned closer to the needle assembly 12. Configured in this manner, and as shown in FIG. 14C , when it is desired to deliver a medication 32 to a patient, the device 10 is actuated and the medication 32 flows from the container 14, along the fluid flow connection 50, through the inlet portion of the flow restrictor 972, through the fluid side port 921 a, and to the needle 921 until it contacts the inner surface of the flexible sleeve member 974. The medication 32 then exerts pressure on the inner surface of the flexible sleeve member 974, transitioning the flexible sleeve member 974 to a second, open position, exposing the fluid side port 921 a and allowing delivery of the medication 32 (as indicated by the arrow in FIG. 14C ). When the pressure differential across the flow restrictor 972 is less than the cracking pressure, the inherent resiliency of the flexible sleeve member 974 causes it to return to the first, closed position, covering the fluid side port 921a of the needle 921 and forming a seal. Thus, the flow restrictor 972 self-closes after each increment or bolus of medication 32 is delivered. The cracking pressure of the flow restrictor 972 may be configured to be (or exceed) approximately 2 psi to prevent the forward flow of air or medication when this is not desired.

[0067] 14B, if the drug 32 or other fluid flows in the opposite direction (e.g., from the outlet portion of the flow restrictor 972 to the inlet portion of the flow restrictor 972), the drug 32 or other fluid will contact the outer surface of the flexible sleeve member 974. Thus, and as shown by the arrows in FIG. 14A, the flexible sleeve member 974 restricts the drug 32 or other fluid from flowing back through the outlet portion to the inlet portion.

[0068] 15A-15H show a tenth example of a flow restrictor 1072 corresponding to the flow restrictor 72 shown in FIGS. 4A and 4B. In the illustrated example, the flow restrictor 1072 is in the form of an integrated sliding sleeve valve disposed in the lower portion of the needle assembly 120, specifically around a portion of the needle 1021. In this example, the flow restrictor 1072 includes a rigid needle 1021 and a flexible cannula 1040 having a valve chamber 1074. The needle 1021 includes at least one fluid port 1021a and has a closed tip portion. In these examples, the needle 1021 and cannula 1040 are coupled together via a frictional, interference fit that covers the fluid port 1021a during any delay before drug delivery. In other words, the cannula 1040 prevents blood or other fluids from entering the needle 1021. In some examples, the clearance between the outer diameter of the needle 1021 and the inner diameter of the cannula 1040 is dimensioned to provide a complete seal for the fluid port 1021a while allowing smooth movement of the needle 1021 within the cannula 1040.

[0069] As shown in FIG. 15A , the needle 1021 is used to insert the cannula 1040 through the skin 11 and into the subcutaneous tissue 13. After the cannula 1040 is inserted into the subcutaneous tissue 13, the needle is retracted into a “valve closed” position, where its fluid port 1021 a is sealed by the inner surface of the cannula, restricting fluid flow in either direction. In some examples, the needle 1021 may be left in this state to provide additional rigidity to the cannula 1040 and prevent kinking due to relative movement between the patient and the device during any delay before drug delivery. Such kinking could disrupt delivery by either occluding the cannula 1040 or removing the cannula 1040 from the skin 11 or subcutaneous tissue 13, resulting in delivery of the drug 32 at an incorrect location / depth (e.g., on the skin 11 rather than at a specific depth within the subcutaneous tissue 13).

[0070] As shown in FIG. 15B, if desired, the needle 1021 may be moved to a "valve open" position, with the fluid port 1021a located within the cannula valve chamber 1074. The medication 32 may then be delivered to the patient either incrementally or as a bolus. More specifically, as shown in FIG. 15C, in an initial, pre-actuation state, the needle 1021 and cannula 1040 are both positioned above the patient's skin 11. As shown in FIG. 15D, when the needle assembly 120 is actuated, the needle 1021 and cannula 1040 are inserted into the skin 11 and subcutaneous tissue 13. The cannula 1040 includes a latching ledge 1076 that mates with any number of tabs 25a located on the bottom wall 25 of the device 10 to secure the cannula 1040 in place.

[0071] As shown in Figure 15E, the needle 1021 is then moved to a "valve closed" position in which the fluid port 1021a is sealed against the inner surface of the cannula 1040. When delivery of the drug 32 is desired, the needle 1021 is moved to a position in which the fluid port 1021a is disposed within the valve chamber 1074, as shown in Figure 15F. As a result, the fluid line 50 is once again hydraulically connected to the cannula 1040, thus allowing administration of the drug 32.

[0072] As shown in Figures 15G and 15H, an alternative flow restrictor 1072' is provided that uses a solid trocar 1021' instead of the needle 1021 described in Figures 15A-15F. In these examples, the flow of the drug is selectively enabled or blocked by an engagement between the trocar 1021' and the cannula 1040'. In these examples, there is no fluid path in the trocar 1021'; rather, the drug 32 flows around the exterior surface of the trocar 1021' and is delivered to the patient. As a result, the trocar 1021' functions as a stopper or seal operable with the cannula 1040'.

[0073] 16A-16D illustrate an eleventh example of a flow restrictor 1172 corresponding to the flow restrictor 72 shown in FIGS. 4A and 4B, and more specifically, the flow restrictor 772 shown in FIGS. 11A-12. Generally, air contained within the drug reservoir 30 can allow blood and interstitial fluid to enter the fluid path 50 after needle insertion. Breaking of capillaries during needle insertion and the formation of clots that can block the fluid path 50 can adversely affect successful dose delivery. Requiring medical personnel to purge air from a pre-filled syringe used to add the drug 32 to the reservoir can be time-consuming and may result in the drug 32 being ejected from the syringe, resulting in waste.

[0074] In the illustrated example, the flow restrictor 1172 is in the form of a multi-chamber air filter mechanism having a primary chamber 1174, a secondary chamber 1176, an inlet 1173, and an outlet 1182. Additionally, positioned adjacent to the first chamber 1174 is a first membrane 1178 made from a hydrophilic material. The flow restrictor 1172 further contains a second membrane 1180 made from a hydrophobic material. Hydrophobic membranes have a critical water break-through pressure below which water (and therefore the medicament 32) cannot pass. Similarly, hydrophilic membranes also have a critical pressure below which air cannot pass. This critical pressure is known as the boiling point pressure. The flow restrictor 1172 is designed to ensure that the medicament 32 does not leak out of the air filter outlet and that air bubbles are not extruded along with the medicament 32 during delivery. Additionally, elimination of air bubbles can minimize retention volume, ie, drug retained within the device (eg, less than about 20 μL in some embodiments).

[0075] 16A and 16B, during filling of device 10, drug 32 and air enter primary chamber 1174 through inlet 1173. Drug 32 passes through first, hydrophilic membrane 1178 to secondary chamber 1176 and then passes to outlet 1182 for delivery (e.g., pushed through a needle (not shown)). Air is filtered through secondary, hydrophobic membrane 1180 and exits to atmosphere through atmosphere outlet 1184.

[0076] By using the described air exclusion device 1172, air is removed from the fluid line 50, thus resulting in a fully primed fluid line 50 with no air bubbles in the drug reservoir. Such a fully primed fluid line 50 increases the reliability of the device by reducing failure due to clot obstruction and ensures successful delivery of the entire dose of drug 32.

[0077] In some forms, the air exclusion device 1172 can be incorporated directly into the device (e.g., coupled to an inlet port of the reservoir 30 within the housing), or alternatively, in some examples, the air exclusion device 1172 can be selectively coupled to a drug delivery port external to the device 10 that is in fluid communication with the reservoir 30. For example, as shown in FIGS. 16C and 16D , the air exclusion device 1172 can be affixed to the tip of a filling syringe 1185. The outlet 1182 of the air exclusion device 1172 can have a needle 1186 that is inserted into the device 10 to fill the reservoir 30 with the drug 32. The air exclusion device 1172 can include a luer lock mechanism that is used to secure it to the filling syringe 1185. Other examples are possible.

[0078] In some instances, additional strategies may be employed to reduce and / or eliminate clot formation. For example, a desired pressure may be applied via device 10 to remove any potential clots. In some approaches, using a primed fluid path, any potential clots may be removed after a desired delay (e.g., about 25 to about 30 hours) by applying a pressure of approximately 10 psi. Note that the location of the clot may affect the required pressure needed to remove the clot. For example, if the clot is located only within the cannula (as opposed to the cannula and needle), the clot is more likely to be removed using a pressure of approximately 10 psi. However, if the clot extends upstream of the needle or forms within flexible tubing 52, the clot is less likely to be removed by applying pressure.

[0079] The above description describes various devices, assemblies, components, subsystems, and methods of use related to drug delivery devices. The devices, assemblies, components, subsystems, methods, or drug delivery devices may further include or be used in conjunction with drugs, including, but not limited to, the drugs identified below and their generic and biosimilar equivalents. As used herein, the term drug may be used interchangeably with other similar terms and may refer to any type of pharmaceutical or therapeutic material, including traditional and non-traditional medicines, nutraceuticals, supplements, biologics, biologically active agents and compositions, large molecules, biosimilars, bioequivalents, therapeutic antibodies, polypeptides, proteins, small molecules, and generic drugs. Non-therapeutic injectable materials are also included. Drugs may be in liquid form, lyophilized form, or reconstituted from a lyophilized form. The following list of exemplary drugs should not be considered exhaustive or limiting.

[0080] The drug is placed in a reservoir. In some cases, the reservoir is a primary container that is either filled or pre-filled with the drug for treatment. The primary container can be a vial, cartridge, or pre-filled syringe.

[0081] In some embodiments, the reservoir of the drug delivery device may be loaded with, or the device may be used in conjunction with, a colony-stimulating factor such as granulocyte colony-stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, Neulasta® (pegfilgrastim, PEGylated filgastrim, PEGylated G-CSF, PEGylated hu-Met-G-CSF) and Neupogen® (filgrastim, G-CSF, hu-Met-G-CSF).

[0082] In other embodiments, the drug delivery device may contain or be used in conjunction with an erythropoiesis-stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates red blood cell production. In some embodiments, the ESA is an erythropoiesis-stimulating protein. As used herein, "erythropoiesis-stimulating protein" refers to any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to the receptor and causing receptor dimerization. Erythropoiesis-stimulating proteins include erythropoietin and variants, analogs, or derivatives thereof that bind to and activate the erythropoietin receptor; antibodies that bind to and activate the erythropoietin receptor; or peptides that bind to and activate the erythropoietin receptor. Erythropoiesis-stimulating proteins include Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methoxypolyethylene glycol epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), and Binocrit® (epoetin alfa). Epoetin alpha, epoetin beta, epoetin iota, epoetin omega, epoetin delta, epoetin zeta, epoetin theta, and epoetin delta, PEGylated erythropoietin, carbamylated erythropoietin, and molecules or variants or analogs thereof.

[0083] Among certain exemplary proteins are the specific proteins described below, including fusions, fragments, analogs, variants, or derivatives thereof: OPGL-specific antibodies (also referred to as RANKL-specific antibodies, peptibodies, etc.), peptibodies, and related proteins, including fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies; myostatin-binding proteins, peptibodies, and related proteins, including myostatin-specific peptibodies; IL-4 receptor-specific antibodies, peptibodies, and related proteins, particularly those that inhibit activities mediated by binding of IL-4 and / or IL-13 to their receptors. Interleukin 1-receptor 1 ("IL1-R1") specific antibodies, peptibodies, related proteins, etc.; Ang2 specific antibodies, peptibodies, related proteins, etc.; NGF specific antibodies, peptibodies, related proteins, etc.; CD22 specific antibodies, peptibodies, related proteins, etc., especially dimers of human-mouse monoclonal hLL2 gamma chain disulfide bound to human-mouse monoclonal hLL2 kappa chain, e.g., the human form of epratuzumab (CAS Registry Number 501423-23-0). Human CD22-specific antibodies, including but not limited to, humanized and fully human antibodies, including but not limited to, humanized and fully human monoclonal antibodies, particularly including but not limited to, human CD22-specific IgG antibodies, such as CD22-specific fully humanized antibodies; IGF-1 receptor-specific antibodies, peptibodies, and related proteins, including but not limited to, anti-IGF-1R antibodies; B-7-related protein 1-specific antibodies, peptibodies, and related proteins, including but not limited to, those that inhibit the interaction of B7RP-1 with ICOS, the natural receptor for B7RP-1 on activated T cells, including but not limited to, a B7RP-specific fully human monoclonal IgG2 antibody; HuMax, e.g., 146B7; IL-15 specific antibodies, peptibodies, related proteins, etc., including, but not limited to, IL-15 antibodies and related proteins, particularly humanized monoclonal antibodies; human IFNIFN-γ specific antibodies, peptibodies, related proteins, etc., including but not limited to, IFN-γ specific antibodies, and fully human anti-IFN-γ antibodies; TALL-1 specific antibodies, peptibodies, related proteins, etc., and other TALL specific binding proteins; parathyroid hormone ("PTH") specific antibodies, peptibodies, related proteins, etc.; thrombopoietin receptor ("TPO-R") specific antibodies, peptibodies, related proteins, etc.; hepatocyte growth factor / scatter factor (HGF / SF):cMet axis (HG), such as fully human monoclonal antibodies that neutralize HGF / SF. Hepatocyte growth factor ("HGF")-specific antibodies, peptibodies, related proteins, etc., including those targeting F / SF:c-Met; TRAIL-R2-specific antibodies, peptibodies, related proteins, etc.; activin A-specific antibodies, peptibodies, related proteins, etc.; TGF-β-specific antibodies, peptibodies, related proteins, etc.; amyloid β protein-specific antibodies, peptibodies, related proteins, etc.; proteins that bind to c-Kit and / or other stem cell factor receptors c-Kit-specific antibodies, peptibodies, related proteins, etc., including but not limited to proteins that bind to OX40L and / or other ligands of the OX40 receptor; OX40L-specific antibodies, peptibodies, related proteins, etc., including but not limited to proteins that bind to OX40L and / or other ligands of the OX40 receptor; Activase® (alteplase, tPA), Aranesp® (darbepoetin alfa), Epogen® (epoetin alfa, or erythropoietin), GLP-1, Avonex® (interferon beta-1a), Bexxar® (tositumomab, an anti-CD22 monoclonal antibody), Betaseron® (interferon-beta), Campath® (alemtuzumab, an anti-CD52 monoclonal antibody), Dynepo® (epoetin delta), Velcade® (bortezomib), MLN0002 (anti-α4β7mAb), MLN1202 (anti-CCR2 chemokine receptor mAb), Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Eprex® (epoetin alfa), Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-1), Genotropin® (somatropin, human growth hormone), Herceptin® (trastuzumab, anti-HER2 / neu(erbB2) receptor mAb), Humatrope® (somatropin, human growth hormone), Humira® (adalimumab), Vectibix® (panitumumab), Xgeva® (denosumab), Prolia® (denosumab), Enbrel® (etanercept, TNF-receptor / Fc fusion protein, TNF blocker), Nplate® (romiplostim), rilotumumab, ganitumab, conatumumab, brodalumab, insulin in solution, Infergen® (interferon alfacon-1), Natrecor® (nesiritide, recombinant human B-type natriuretic peptide (hBNP), Kineret® (anakinra), Leukine® (sargamostim, rhuGM-CSF), LymphoCide® (epratuzumab, anti-CD22 mAb), Benlysta™ (lymphostat B, belimumab, anti-BlyS mAb), Metalyse® (tenecteplase, t-PA analog), Mircera® (methoxypolyethylene glycol-epoetin beta), Mylotarg® (gemtuzumab ozogamicin), Raptiva® (efalizumab), Cimzia® (certolizumab pegol, CDP870), Soliris™ (eculizumab), pexelizumab (anti-complement C5), Numax® (MEDI-524), Lucentis® (ranibizumab), Panorex® (17-1A, edrecolomab), Trabio® (lerdelimumab), TheraCimhR3 (nimotuzumab), Omnitarg (pertuzumab, 2C4), Osidem® (IDM-1), OvaRex® (B43.13), Nuvion® (vigilizumab), cantuzumab mertansine (huC242-DM1), NeoRecormon® (epoetin beta), Neumega® (oprelvekin, human interleukin-11), Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody), Procrit® (epoetin alfa), Remicade® (infliximab, anti-TNFα monoclonal antibody), Reopro® (abciximab, anti-GP IL6 receptor monoclonal antibody), Actemra® (anti-IL6 receptor mAb), Avastin® (bevacizumab), HuMax-CD4 (zanolimumab), Rituxan® (rituximab, anti-CD20 mAb), Tarceva® (erlotinib), Roferon-A® (interferon alfa-2a), Simulect® (basiliximab), Prexige® (lumiracoxib), Synagis® (palivizumab), 146B7-CHO (anti-IL15 antibody, see U.S. Pat. No. 7,153,507), Tysabri® (natalizumab, anti-α4 integrin mAb), Valortim® (MDX-1303, anti-anthrax protective antigen mAb), ABthrax™, Xolair® (omalizumab), ETI211 (anti-MRSA mAb), IL-1 trap (Fc portion of human IgG1 and extracellular domains of both IL-1 receptor components (type I receptor and receptor accessory protein)), VEGF trap (IgG1 Ig domain of VEGFR1 fused to Fc), Zenapax® (daclizumab), Zenapax® (daclizumab, anti-IL-2Rα mAb), Zevalin® (ibritumomab tiuxetan), Zetia® (ezetimibe), Orencia® (atacicept, TACI-Ig), anti-CD80 monoclonal antibody (galiximab), anti-CD23mAb (lumiliximab), BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist), CNTO148 (golimumab, anti-TNFα mAb), HGS-ETR1 (mapatuzumab, human anti-TRAIL receptor-1 mAb), HuMax-CD20 (ocrelizumab, anti-CD20 human mAb), HuMax-EGFR (zalutumumab), M200 (volociximab, anti-α5β1 integrin mAb), MDX-010 (ipilimumab, anti-CTLA-4 mAb, and VEGFR-1 (IMC-18F1), anti-BR3 mAb, anti-C. difficile toxin A and toxin BC mAbs MDX-066 (CDA-1) and MDX-1388), anti-CD22 dsFv-PE38 conjugate (CAT-3888 and CAT-8015), anti-CD25 mAb (HuMax-TAC), anti-CD3 mAb (NI-0401), adecatumumab, anti-CD30 mAb (MDX-060), MDX-1333 (anti-IFNAR), anti-CD38 mAb (HuMax CD38), anti-CD40L mAb, anti-Cripto mAb, anti-CTGF idiopathic pulmonary fibrosis stage 1 fibrogen (FG-3019), anti-CTLA4 mAb, anti-eotaxin 1 mAb (CAT-213), anti-FGF8 mAb, anti-ganglioside GD2 mAb, anti-ganglioside GM2 mAb, anti-GDF-8 human mAb (MYO-029), anti-GM-CSF receptor mAb (CAM-3001), anti-HepC mAb (HuMax HepC), anti-IFNα mAb (MEDI-545, MDX-1103), anti-IGF1R mAb, anti-IGF-1R mAb (HuMax-Inflam), anti-IL12 mAb (ABT-874), anti-IL12 / IL23 mAb (CNTO1275), anti-IL13 mAb (CAT-354), anti-IL2Ra mAb (HuMax-TAC), anti-IL5 receptor mAb, anti-integrin receptor mAb (MDX-018, CNTO95), anti-IP10 ulcerative colitis mAb (MDX-1100), BMS-66513, anti-mannose receptor / hCGβ mAb (MDX-1307), anti-mesothelin dsFv-PE38 conjugate (CAT-5001), anti-PD1 mAb (MDX-1106(ONO-4538)), anti-PDGFRα antibody (IMC-3G3), anti-TGFβmAb(GC-1008), TRAIL-2 mAb (HGS-ETR2), TWEAK mAb, VEGFR / Flt-1 mAb, ZP3 mAb (HuMax-ZP3)

[0084] In some embodiments, the drug delivery device may contain or be used in conjunction with a sclerostin antibody, such as, but not limited to, romosozumab, brosozumab, or BPS804 (Novartis), or in other embodiments, a monoclonal antibody (IgG) that binds to human proprotein convertase subtilisin / kexin type 9 (PCSK9). Such PCSK9-specific antibodies include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab). In other embodiments, the drug delivery device may contain or be used in conjunction with rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, or panitumumab. In some embodiments, the reservoir of the drug delivery device may be loaded with, or the device may be used in conjunction with, IMLYGIC® (talimogene laherparepvec) or another oncolytic HSV for the treatment of melanoma or other cancers, including but not limited to, OncoVEX GALV / CD; OrienX010; G207, 1716; NV1020; NV12023; NV1034; and NV1042. In some embodiments, the drug delivery device may contain or be used in conjunction with an endogenous tissue inhibitor of metalloproteinase (TIMP), such as, but not limited to, TIMP-3. Antagonistic antibodies of the human calcitonin gene-related peptide (CGRP) receptor, such as, but not limited to, erenumab, and bispecific antibody molecules targeting the CGRP receptor and other headache targets, may also be delivered using the drug delivery devices of the present disclosure. Additionally, bispecific T cell-engaging (BiTE®) antibodies, such as, but not limited to, BLINCYTO® (blinatumomab), can be used in or with the drug delivery devices of the present disclosure. In some embodiments, the drug delivery devices may contain or be used with APJ large molecule agonists, such as, but not limited to, apelin or analogs thereof.In some embodiments, a therapeutically effective amount of anti-thymic stromal lymphopoietin (TSLP) or a TSLP receptor antibody is used in or with the drug delivery device of the present disclosure.

[0085] The drug delivery devices, assemblies, components, subsystems, and methods have been described in terms of exemplary, but not limited to, embodiments. The detailed description is to be construed as an example only and does not describe every possible embodiment of the present disclosure. Many alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent, and such embodiments will still fall within the scope of the claims that define the invention disclosed herein.

[0086] Those skilled in the art will appreciate that numerous modifications, variations, and combinations can be made to the above-described embodiments without departing from the spirit and scope of the invention disclosed herein, and that such modifications, variations, and combinations are to be construed as falling within the scope of the inventive concept.

Claims

1. 1. A drug delivery device comprising: a housing defining a shell and an interior volume; a container at least partially disposed within the housing, the container having an interior volume adapted to contain a medication to be administered to a user; a drive mechanism at least partially disposed within the housing, the drive mechanism adapted to exert a force to expel the medicament from the container; a needle assembly at least partially disposed within the housing, the needle assembly configured to insert a needle or trocar and a hollow cannula surrounding the needle or trocar into the user's skin and then retract, thereby leaving the cannula within the user's skin for at least a period of time until the drive mechanism expels the medicament from the reservoir; a fluid flow connection coupled to the container and the needle assembly, the fluid flow connection adapted to allow the medicament to flow from the container to the needle assembly; an anti-reflux mechanism disposed within a coupling region between the reservoir and the needle assembly, the anti-reflux mechanism including at least one flow restrictor for restricting fluid flow from the cannula to the reservoir, thereby reducing and / or eliminating clot formation, at least for a period of time until the drive mechanism expels the medicament from the reservoir into the needle assembly; Including, the coupling region includes an upstream portion and a downstream portion, the upstream portion having a larger upstream diameter than the flow restrictor, and the downstream portion having a smaller downstream diameter than the flow restrictor, and the backflow prevention mechanism is positioned in the coupling region where the fluid flow connection is coupled to the needle assembly.

2. The drug delivery device of claim 1 , wherein the at least one flow restrictor comprises a one-way valve.

3. The at least one flow restrictor comprises: Slit valve, Umbrella valve, Ball valves, Duckbill valve, or Flap Valve The drug delivery device of claim 2 , comprising at least one of:

Images