Fluid barrier with destructive punch for large volume drug delivery device

Abstract

Devices and methods for providing a fluid path barrier in an injection device, such as a reservoir-type injection device, are provided. The fluid path barrier can be used to preferentially connect the injection device at the time of use to support an appropriate fluid delivery environment.

Description

[0001] This application claims the benefit of priority to European Patent Application No. 24315119.8, filed April 4, 2024, and U.S. Provisional Patent Application No. 63 / 604,471, filed November 30, 2023, the entire contents of which are incorporated herein by reference in their entirety.

[0002] This disclosure generally relates to apparatus and methods for providing barriers to fluid path connections in injection devices, and more specifically to apparatus and methods for large-volume injection devices.

[0003] Injection devices can be used to deliver fluids containing pharmaceutical drugs or agents to a patient. For example, agents can be delivered to a patient via needles, cannulas, catheters, microneedle arrays, or other routes using an injection device.

[0004] One type of syringe used to deliver this medication is the large-volume device (LVD), which can also be called a push syringe or reservoir syringe. A large-volume device can deliver a relatively large volume of medication, typically at least 1 ml or more. The large-volume device is typically positioned against or held against the skin at a suitable injection site, and when activated, the medication is injected through the patient's skin.

[0005] The medication must be provided to and made accessible to the injection device so that the device can deliver the medication to the patient. The medication will be provided in vials or containers, and is always sterilized within the vials or containers. Loading the vials or containers into a bulk delivery device, and when the device is ready for use, a connection must be formed between the delivery flow path and the medication in the container. However, assembling the device in a sufficiently clean (e.g., sterile) manner so that the final device, including the medication container, is substantially free of microorganisms, can be complex and expensive. Furthermore, the assembled device must have mechanisms to maintain sterility or prevent the introduction of microorganisms, and also allow for the formation of a connection between the medication container and the fluid flow path. Achieving these goals is challenging, and current devices used for bulk delivery have various drawbacks. Therefore, there remains a need for devices and methods for establishing a fluid connection with the medication reservoir in an injection device in a sterile or aseptic manner. This disclosure provides devices, systems, and methods for providing a sterile or aseptic connection for medication delivery in a drug delivery device. Summary of the Invention

[0006] This disclosure provides systems, apparatus, and methods for providing fluid path connections in injection devices, such as large-volume or reservoir-type injection devices, for the delivery of pharmaceutical agents using large-volume devices.

[0007] In this embodiment, the disclosure relates to a fluid path connector for a large-volume delivery device. The fluid path connector may include a medication container comprising a cap having a first raised section, a stopper, and an internal volume for containing the medication. The cap may form a first region between the cap and the stopper. The fluid path connector may include a needle assembly operable to connect with the medication container. The needle assembly may include a needle and a needle assembly cap having a second raised section. The needle assembly cap may form a second region between the needle assembly cap and the needle.

[0008] The fluid path connector may include a movable punch. This movable punch can disrupt the first raised section and the second raised section. The movable punch can provide an unobstructed path between the needle and the plug.

[0009] The relative positions of the needle and the medication container can move between a first position and a second position. In the second position, the needle can pass through the plug and form a fluid connection with a fluid path configured to deliver fluid to the patient. In the second position, the needle can extend through the unobstructed path. In the first position, the needle assembly cap can cover the needle. The first raised section and the second raised section can protrude toward each other.

[0010] The movable punch can be configured to move between a first punch position, a second punch position, and a third punch position. In the first punch position, the movable punch may not contact the first protruding segment or the second protruding segment. In other embodiments, the movable punch may contact the first protruding segment, the second protruding segment, or both, without displacing the first protruding segment, the second protruding segment, or both. In the second punch position, the movable punch may contact the first protruding segment and the second protruding segment and may begin to displace the first protruding segment, the second protruding segment, or both. In the third punch position, the movable punch may at least partially displace or move the first protruding segment and the second protruding segment.

[0011] The movable punch can move perpendicular to the longitudinal axis of the path from the first position to the second position and the third position. The movable punch may include a concave end section and an orifice. In the second position, the orifice of the movable punch can be positioned along the path.

[0012] At the second punch position, the movable punch can engage the first sidewall of the first protruding section and the second sidewall of the second protruding section. Each of the first and second sidewalls may include a convex section. The movable punch may include a concave end section configured to mate with the convex sections of the first and second sidewalls.

[0013] The movable punch may include a cutting arm having one or more blades configured to at least partially remove the first protruding segment and the second protruding segment. The movement of the cutting arm can at least partially remove the first and second protruding segments. The movement of the cutting arm can provide an unobstructed path between the needle and the stopper.

[0014] In an embodiment, this disclosure relates to an apparatus for delivering a pharmaceutical agent. The apparatus may include a housing, a pharmaceutical container, a needle assembly, and a movable punch. The pharmaceutical container may include a cap having a first raised section, a stopper, and an internal volume for containing the pharmaceutical agent. The cap may form a first region between the cap and the stopper. The needle assembly may be operable to connect with the pharmaceutical container. The needle assembly may include a needle and a needle assembly cap. The needle assembly cap may include a second raised section. The needle assembly cap may form a second region between the needle assembly cap and the needle. The movable punch may disrupt the first and second raised sections. The movable punch may provide an unobstructed path between the needle and the stopper.

[0015] In embodiments, this disclosure relates to a method for establishing a fluid path connection in a drug delivery device. The drug delivery device may include a drug container with a cap and a needle assembly with a needle assembly cap. The method may include operations to initiate the drug delivery device. The method may include deploying a movable punch to disrupt a first protruding section of the cap of the drug container and a second protruding section of the needle assembly cap. The method may include changing the relative position of the needle of the needle assembly to the drug container such that the needle contacts the drug container. The movable punch may be deployed by applying a force along a main axis or plane of the movable punch to displace the movable punch. The main axis may be perpendicular to the path axis. The first protruding section may include a first substantially flat outer surface. The second protruding section may include a second substantially flat outer surface. The first substantially flat outer surface and the second substantially flat outer surface may be substantially parallel. The path axis may be perpendicular to both the first substantially flat outer surface and the second substantially flat outer surface. The movable punch may extend on each of the first substantially flat outer surface and the second substantially flat outer surface. Changing the relative position of the needle of the needle assembly to the drug container may include moving the needle, moving the drug container, or moving both.

[0016] In one embodiment, a method for forming a connection in a large-volume delivery device is provided. The method may include: providing a pharmaceutical container having a sterilizing agent and a first cap having a first raised section surrounding a stopper of the container; providing a proximal needle assembly including a second cap having a second raised section surrounding a needle tip, the first and second raised sections being proximal and aligned with each other; and disrupting the first raised section and the raised section to open a passage between the needle assembly and the pharmaceutical container. Attached Figure Description

[0017] Exemplary embodiments of this disclosure are illustrated in conjunction with the accompanying drawings, which are included and form part of this specification, and together with the description, are used to explain the principles of this disclosure.

[0018] Figure 1 This is a cross-sectional view of a large-volume injection device.

[0019] Figure 2A This is a perspective cross-sectional view showing a fluid path connector according to some embodiments.

[0020] Figure 2B This is a cross-sectional view showing a fluid path connector with a movable punch according to some embodiments.

[0021] Figure 3 This is a perspective sectional view showing a movable punch according to some embodiments.

[0022] Figure 4 This is a perspective view showing a fluid path connector according to some embodiments.

[0023] Figure 5A This is a cross-sectional view showing a fluid path connector with a movable punch having a cutting arm according to some embodiments.

[0024] Figure 5B This is a cross-sectional view showing a movable punch with a cutting arm according to some embodiments.

[0025] Figure 5C This is a cross-sectional view showing a movable punch with a cutting arm according to some embodiments.

[0026] Figure 5D This is a cross-sectional view showing a fluid path connector with a movable punch having a cutting arm according to some embodiments.

[0027] Figure 6A This is a perspective view showing an example movable punch with a cutting arm according to some embodiments.

[0028] Figure 6BIt is a perspective view showing a damaged raised section according to some embodiments.

[0029] Figure 6C It is a perspective view showing a movable punch with a cutting arm according to some embodiments.

[0030] Figure 6D It is a perspective view showing a damaged raised section according to some embodiments. Detailed Implementation

[0031] Reference will now be made in detail to certain exemplary embodiments pursuant to this disclosure, with some examples of these embodiments illustrated in the accompanying drawings. Where possible, the same reference numerals will be used throughout the drawings to refer to the same or similar parts.

[0032] In this application, unless otherwise expressly stated, the use of the singular includes the plural. In this application, unless otherwise stated, the use of "or" means "and / or". Furthermore, the use of the term "including" and other forms such as "includes" and "included" is non-limiting. Any scope described herein will be understood to include all values ​​between endpoints.

[0033] The section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described. All references or portions thereof cited in this application, including but not limited to patents, patent applications, articles, books, and papers, are expressly incorporated in their entirety by reference for any purpose.

[0034] The apparatus, methods, and systems discussed here can be used to load pharmaceutical containers into large-volume delivery devices in a convenient and cost-effective manner, while maintaining a high level of hygiene for critical components.

[0035] This disclosure describes the provision of “sterile” connectors for drug delivery devices. As used herein, “sterile” should be understood to mean that the device is substantially free of all, but not necessarily all, microorganisms (such as bacteria, viruses, or fungi). As used herein, a “sterile connector” is a component that allows a fluid flow path to connect to the drug container of the device while preventing the introduction of microorganisms. A “connector” does not need to be already connected, but can be formed when ready for use. The terms “sterile” or “sterile connector” may not necessarily require the device to be sterile or free of all microorganisms (as sterilization can be defined by regulatory requirements), but “sterile” and “sterile connector” will be understood to encompass devices that are sterile or maintain sterility.

[0036] Typical injection volumes can range from about 1 mL to over 10 mL. These devices can produce a wide range of injection rates from 0.2 mL / min to 204.0 mL / min. Such injection profiles can be generally constant in flow rate, generally continuous in duration, or both generally constant and generally continuous. These injections can also occur in a single administration step. Such injection profiles can be referred to as bolus injections.

[0037] Delivery devices that work with such medications can utilize needles, cannulas, or other injection elements configured to deliver medications to a patient. Such injection elements may, for example, have an external size or diameter of 27 G or less. Further, the injection element can be rigid, flexible, and formed using one or more materials. And in some embodiments, the injection element may include two or more components. For example, a rigid cannula can be operated in conjunction with a flexible cannula. Initially, both the cannula and cannula can be moved together to puncture the skin. The cannula can then be retracted, while the cannula remains at least partially within the target tissue. Subsequently, the cannula can be retracted separately into the delivery device.

[0038] Example drug delivery devices may involve needle-based injection systems as described in ISO 11608-1:2022. Needle-based injection systems can be broadly categorized into multiple-dose container systems and single-dose (partially or completely emptied) container systems. The container may be a replaceable container or an integral, non-replaceable container.

[0039] Multiple-dose container systems can relate to needle-based injection devices with replaceable containers. In such systems, each container holds multiple doses, the size of which can be fixed or variable (preset by the user). Another type of multiple-dose container system can relate to needle-based injection devices with an integrated, non-replaceable container. In such systems, each container holds multiple doses, the size of which can be fixed or variable (preset by the user).

[0040] As further described in ISO 11608-1:2022, a single-dose container system can relate to a needle-based injection device having a replaceable container. In one example of such a system, each container contains a single dose, in which the entire deliverable volume is discharged (completely emptied). In another example, each container contains a single dose, in which a portion of the deliverable volume is discharged (partially emptied). A single-dose container system can also relate to a needle-based injection device having an integral, non-replaceable container. In one example of such a system, each container contains a single dose, in which the entire deliverable volume is discharged (completely emptied). In another example, each container contains a single dose, in which a portion of the deliverable volume is discharged (partially emptied).

[0041] The insertion mechanism for inserting the needle can take any suitable form. It can be a spring-based mechanical mechanism. Alternatively, the insertion element mechanism can include, for example, an electric motor and a gear mechanism that causes the insertion element to be inserted into the user's body. Needle insertion can also be part of a manual action performed by the user before the drug delivery begins. Alternatively, the insertion mechanism can be a gas or fluid pressure-operated mechanism, in which case the needle-driving energy source is a reservoir of pressurized gas or a chemical system in which two or more chemicals are mixed together to generate gas or fluid pressure.

[0042] One type of delivery device includes a large volume device (LVD). LVD delivery devices are configured to dispense relatively large doses of medication, particularly at least 1 ml, and typically up to 2.5 ml, but possibly up to 10 ml. LVDs can also be configured for bolus delivery or basal delivery.

[0043] A bolus-type LVD injector device is configured to deliver a bolus of a specific drug to a patient within a predetermined time. The injection rate may not be critical; that is, it may not require strict control. However, there may be an upper limit (physiological upper limit) to the delivery rate to avoid damage to tissues surrounding the delivery site. The time taken to deliver the bolus dose can range from minutes to hours, depending on several factors, including the amount (volume) of the drug, its viscosity, and the nature of the injection site where the injector is intended to be used.

[0044] From the perspective of users or healthcare professionals, it is desirable that the injection device be configured to minimize disruption to the patient's lifestyle and schedule, thus providing minimal reminders of his or her condition between injections. Treatment schedules for therapies are often intermittent, meaning they may be administered weekly, every other week, or monthly. Therefore, patients typically lack fixed routines for managing their condition and thus have minimal established habits / experience with receiving the required injections. Consequently, it is highly desirable that the injection device's configuration simplify patient operation.

[0045] If an LVD is intended for bolus administration, its configuration differs considerably from that of an LVD injection device designed for basal administration. Furthermore, its usage is quite different. For example, basal insulin pumps are typically relatively expensive because they include many complex diabetes-specific features, such as programmable delivery rate curves, bolus calculators, etc. Moreover, the connection to the body via the infusion assembly allows the patient to handle and manipulate the pump within his / her field of vision while treatment is in progress. Furthermore, diabetic patients often have established habits of setting up the infusion assembly, connecting and operating the pump, and temporarily disconnecting the pump during events such as bathing to avoid exposing it to water. In contrast, the aforementioned bolus injector device can be a relatively simple and inexpensive device. They can be supplied as disposable devices that cannot be refilled, further reducing complexity and cost.

[0046] To use an LVD injection device, it is first positioned at a suitable injection site on the patient's skin. The device typically adheres to the patient's skin throughout the drug delivery process. Injection is usually initiated by the patient or another person (the user). Typically, initiation is done by the user, such as pressing a switch (mechanical or electrical) or by placing the LVD on the patient's body and pressing a lever on the underside of the device. If the LVD includes electronics, a controller can operate the device. The operation involves first injecting the needle into the user's body, and then injecting the drug into the user's tissues. The delivery process can take anywhere from several minutes to several hours. The LVD can then be removed from the injection site and discarded.

[0047] Biologics are increasingly being developed that include injectable liquids with higher viscosity and will be administered in larger volumes than long-known liquid medications. LVDs for administering such biologics may include pre-filled single-use drug delivery devices, or alternatively, single-use drug delivery devices in which the patient or healthcare professional must insert the cartridge before use.

[0048] In some embodiments, agents of various viscosities can be injected. For example, the viscosity can range from about 3 cP to about 50 cP. In other embodiments, the viscosity can be less than about 3 cP or greater than about 50 cP. The injection may further include delivery of the agent to a subcutaneous, intramuscular, or percutaneous site within the patient's body. The agent can be in the form of a liquid, gel, serous solution, suspension, granules, powder, or other type.

[0049] In some embodiments, the bulk device may include: a housing configured to remain against a user's body when the device is in use; a medication cartridge; and a fluid passage connected to the medication cartridge and extending to an insertion mechanism, such as a needle insertion mechanism or a cannula and catheter insertion mechanism. The medication can be drawn or expelled from the medication cartridge by any method (e.g., via a plunger mechanism or pump) and injected into the user's body by the same force or via a separate plunger or pump. In some embodiments, the plunger may be driven by one or more springs, a drive screw, a motor, or any other suitable drive mechanism.

[0050] In this document, the terms “drug,” “medicament,” or “pharmaceutical”, used interchangeably, refer to a pharmaceutical preparation comprising at least one pharmaceutically active compound, which may be, for example, a small molecule or a bioactive pharmaceutical ingredient. Further descriptions of the envisioned drug, medicament, or pharmaceutical are provided below.

[0051] Standards or best practices for designing drug delivery devices may require or require an unobstructed path from the drug container to the needle or cannula used to deliver the drug to the user. Additionally, standards or best practices for manufacturing and assembling drug delivery devices (such as large-volume or reservoir-type injection devices) may require certain steps in the assembly process to be performed in a cleanroom or sterile facility, or may require the sterilization of certain components. According to this disclosure, embodiments can provide a sterile path from the drug container to the needle or cannula without requiring all aspects of assembly to be performed in a cleanroom or hypersterilized environment. Embodiments can provide flexibility and cost savings in manufacturing by allowing sterility to be maintained within the device without the need for cleanrooms or other hypersterilized environments throughout all steps of the manufacturing process. For example, the drug container can be inserted into the injection device outside of a cleanroom or hypersterilized environment while still providing a sterile connection. Another advantage is that the manufacturing of the injection device and the loading of the drug container into the injection device can be performed independently, and the reservoir can be added to a wider range of facilities. For example, the reservoir can be supplied in a separate manufacturing process, or it can be supplied by a healthcare professional, pharmacy, or user without requiring a cleanroom or hypersterilized environment.

[0052] Figure 1 An exemplary bulk device 100 is shown, which includes a housing 110, a needle insertion mechanism 120, a release mechanism 130, a drive mechanism 135, a cartridge holder 140, a needle 145, and a fluid path 147. The release mechanism 130 includes a button 131, a button biasing member or other power source (not shown), and a release member 133. The drive mechanism 135 includes a drive mechanism biasing member or other power source (not shown) and a piston 137.

[0053] The reagent container 200 is included within the bulk device 100. The reagent container 200 includes a plunger 210, a stopper 215 (which may alternatively be referred to as a diaphragm), and a cap 217 (e.g., a crimp cap), and has an internal volume 220 at least partially filled with reagent 221. The container 200 may be, for example, a glass vial with a polymer plunger and diaphragm. Typically, the container will comprise a standard reagent container, allowing the disclosed device and fluid path connections to be used with existing standard containers without requiring the development of a dedicated container or reagent cartridge. The plunger 210 may be actuated by a piston 137.

[0054] Figure 1 This should be understood as an exemplary device. The drive mechanism 135 may include one or more springs, but other drive mechanisms or power sources are also possible. Other drive mechanisms may include other biasing elements, screw drives, gear drives, gas or chemical sources, or electric motors. The pharmaceutical container 200 should be understood as exemplary only. For example, different types of containers or vials may be used, including containers with different stopper or piston arrangements, or containers without stoppers or pistons.

[0055] By loading the reagent container 200 and setting the drive mechanism 135 to the energized state (e.g.) Figure 1 As shown, the bulk device 100 is ready for use. The drive mechanism biasing member 136 is held in the activated state by the engagement of the release member 133 with the pawl 138 of the piston 137. To operate the bulk device 100, the bulk device 100 is positioned such that the needle insertion mechanism 120 is against the user's skin. The bulk device 100 can be attached to the user's skin by removing a removable cover mounted on the housing 145 to expose the adhesive on the housing 110. The user or an assistant presses the button 131 of the release mechanism 133 to remove the release member 133 from the pawl 138 and release the drive mechanism biasing member 136, which then drives the piston 137 against the plunger 210 of the medicine container 200, forcing the plunger 210 into the medicine container 200 and pressurizing the internal volume 220 with the medicine 221. The action of the mass-volume device 100 causes the needle 145 to pierce the stopper 215 and access the medication 221 within the medication container 200. Pressurized medication flows from the medication container 200 into the needle 145 and then along the fluid path 147 to the needle insertion mechanism 120. The action of the mass-volume device 100 causes the needle insertion mechanism 120 to insert the needle and / or cannula into the user's body. The medication 221 is delivered to the patient via the needle or cannula.

[0056] The bulk device 100 also includes a fluid path connector 300. The fluid path connector 300 is positioned near the stopper 215 and the needle 145, and allows the needle 145 to travel through an unobstructed path to the stopper 215 to establish a fluid path connection with the medication container 200. In some embodiments, the fluid path connector 300 is a connector configured to isolate the fluid path and maintain a sterile or sterile fluid path during storage and / or use.

[0057] Figure 2A and Figure 2B A fluid path connector 300 according to some embodiments is shown. The fluid path connector 300 can be used in a large-volume device 100. The fluid path connector 300 includes a pharmaceutical container 200, which includes a cap 217 having a first raised section 310, a stopper 215, and an internal volume 220 for containing the pharmaceutical agent. The cap 217 may form a first region 311 between the cap 217 and the stopper 215.

[0058] The fluid path connector 300 may include a needle assembly 320 operable to connect with a pharmaceutical container 200. The needle assembly 320 includes a needle 145 and a needle assembly cap 322 having a second raised section 324. The needle assembly cap 322 forms a second region 326 between the needle assembly cap 322 and the needle 145.

[0059] Needle assembly cap 322 and cap 217 cover needle assembly 320 and medication container 200, thereby forming areas 311, 326. These areas are thus isolated from potential contaminants, ensuring that the needle 145 and stopper 215 of container 200 are not accidentally contaminated once the components of the mass delivery device are assembled in a sterile or sufficiently clean environment, or sterilized after assembly. Furthermore, the fluid path connector 300 includes a component (i.e., a punch) configured to break or remove a portion (a raised section) of needle assembly cap 322 and cap 217 to form an opening or channel that allows needle 145 to advance through stopper 215, thereby forming a sterile or sufficiently clean fluid connection between the medication container and fluid path 147 to allow medication delivery to the patient. In this way, the various components of mass delivery device 100 can be assembled, and a sterile or sufficiently clean connection between the medication container and fluid path 147 can be achieved even if small amounts of contaminants are introduced outside needle assembly 320 and cap 217.

[0060] The cap 217 and the needle assembly cover 322 may be formed of an elastomer material, such as natural rubber, styrene-butadiene block copolymer, polyisoprene, polybutadiene, ethylene propylene rubber, ethylene propylene diene rubber, silicone elastomer, fluoroelastomer, polyurethane elastomer and nitrile rubber; or a metal material, such as metal foil.

[0061] The fluid path connector 300 includes a movable punch 330. The movable punch 330 is operable to disrupt a first raised section 310 and a second raised section 324. The operation of the movable punch provides an unobstructed path 350 between the needle 145 and the plug 215. Figure 3 (As shown). Specifically, as described below, the movable punch 330 is operable to disrupt or partially displace the cap 217 and the needle assembly cover 322, thereby providing an open path for relative movement of the needle 145 and the stopper 215, allowing the needle 145 to pierce the stopper 215. The movable punch 330 has a circular shape corresponding to the shape of the first raised section 310 and the second raised section 324, such that the movable punch 330 can engage the first raised section 310 and the second raised section 324. Although shown as circular, different shapes may be used in different embodiments, such as flat, full circle, semicircle, oval, partially oval, square, or other geometries. The movable punch 330 is mounted on the arm 332 and driven by a spring 334 to cause rotation of the movable punch 330 when movement of the movable punch 330 is activated. In some embodiments, other biasing devices may be used to power the movable punch 330. The movable punch 330 may be driven by a main drive spring. Furthermore, although springs are specifically described as the driving mechanism, other types of power sources besides springs are envisioned, including, for example, electromechanical, chemical, or gas-based mechanisms.

[0062] Figure 3 The fluid path connector 300 is shown after the movable punch 330 has been driven through the first protruding section 310 and the second protruding section 324 and the needle 145 has extended through the stopper 215 to reach the internal volume 220 of the medicine container 200. The first protruding section 310 and the second protruding section 324 are cleared by the movable punch 330 to provide an unobstructed path 350 along which the needle 145 extends.

[0063] The fluid path connector 300 can be used to establish an unobstructed connection in a drug delivery device (e.g., a bulk device 100) including a drug container 200 with a cap 217 and a needle assembly 320 with a needle assembly cap 322. The method may include an operation to activate the drug delivery device 100. The movable punch 330 may be in a first position, such as... Figures 2A to 2B As shown. The method may include deploying a movable punch 330 to break a first protruding segment 310 of the cap 217 of the medicine container 200 and a second protruding segment 324 of the needle assembly cap 322 by moving through a second punch position. The movable punch 330 can then be in a third punch position, such as Figure 3 What is shown.

[0064] The method may further include changing the relative position of the needle 145 of the needle assembly 320 with respect to the medication container 200, such that the needle 145 contacts the medication container 200. This movement may be made along axis 338. The relative position of the needle 145 may be changed by moving the needle toward the medication container, or by moving the medication container more toward the needle, or both. In any case, "advancing the needle" into or through the stopper 215 will be understood to include any action that causes the needle to penetrate the stopper 215 to form a fluid connection with the medication container.

[0065] The method may include deploying the movable punch 330 by applying a force along the main axis of the movable punch 330 (e.g., along the direction of arrow 337) to displace the movable punch 330. The main axis may be perpendicular to the axis 338 of the unobstructed path 350, wherein the first raised section 310 includes a first substantially flat outer surface 312, the second raised section 324 includes a second substantially flat outer surface 325, the first substantially flat outer surface 312 and the second substantially flat outer surface 325 are substantially parallel, and the path axis 338 is perpendicular to both the first substantially flat outer surface 312 and the second substantially flat outer surface 325, and wherein the movable punch 330 extends on each of the first substantially flat outer surface and the second substantially flat outer surface. Although described as a substantially flat outer surface, the outer surface may have a circular, convex, concave, or other shape. Figures 2A to 3 As shown, the movement of the movable punch 330 can be axial. Changing the relative position of the needle 145 of the needle assembly 320 with respect to the drug container 200 can include moving the needle 145, moving the drug container 200, or moving both.

[0066] Figure 4 A fluid path connector 300 according to some embodiments is shown, comprising a movable punch 330' having a first cavity 335 and a second cavity 336, a first raised section 310 and a cap 217 of a needle assembly 320, and a second raised section 324 and a needle assembly cap 322 of a medicine container 200. The movable punch 330' is characterized by the first cavity 335, the shape of which corresponds to the shape of the first raised section 310 and the second raised section 324. As the movable punch 330' moves in the direction indicated by arrow 337, the first cavity 335 engages with and breaks the first and second raised sections 310 and 324. As the movable punch 330' continues to move in the direction indicated by arrow 337, the second cavity 336 moves to align with the center of the cap 217 and the needle assembly cap 322 for the needle 145 (in... Figure 4 (Not visible in the middle) provides an unobstructed path 350 to the medicine container 200.

[0067] The movable punch is shown to move by translation, but it is contemplated that the movement of the punch could be translation, rotation, or some combination of both, as long as the punch moves to cause damage to the raised section. Furthermore, the punch could move suddenly, forcefully, and rapidly to damage or cut these raised sections, or the punch could move more slowly but with sufficient force to cut the raised section.

[0068] Although not shown, the movement of the punch can be activated in several ways. For example, the punch can be activated by pushing the main release mechanism of the device, which in turn activates the entire device. Alternatively, the punch can be operatively connected to a separate activation mechanism (e.g., a separate button or pull-out safety tab). Furthermore, the punch can be activated by a switch when the device 100 is positioned to contact the patient's skin.

[0069] The raised sections 310 and 324 can be broken in a variety of ways. For example, the raised sections can be formed of a variety of different materials, and such materials can be configured to be broken or fractured by the movement of a punch. For example, the raised sections can include metallic or polymeric materials that are impermeable to liquids or microorganisms. The material can be selected such that it can be cut or broken by a punch and pushed out of place. Thus, the punch can include blunt or sharp edges, depending on the mechanism for removing the raised section.

[0070] Figures 5A to 5D A fluid path connector 300' including a cutting arm 370 is shown according to some embodiments. The cutting arm 370 has one or more blades 371 configured to at least partially remove the first protruding section 310 and the second protruding section 324 when the cutting arm 370 is driven across the first protruding section 310 and the second protruding section 324. The cutting arm 370 at least partially removes the first protruding section 310 and the second protruding section 324 to provide an unobstructed path 350 between the needle 145 and the plug 215. A spring 373 biases the cutting arm 370 toward an extended position to provide force to drive the cutting arm 370 through the first protruding section 310 and the second protruding section 324.

[0071] Figure 5A and Figure 5B A fluid path connector 300 is shown, with the cutting arm 370 in its initial position, i.e., before the cutting arm 370 is deployed to clear the first raised section 310 and the second raised section 324. Figure 5C and Figure 5D In the middle, the cutting arm 370 has passed through the first protruding section 310 and the second protruding section 324, thereby clearing both and providing an unobstructed path 350. Figure 5C and Figure 5DA pair of bias springs 373 are shown, which are used to bias the cutting arm 370 toward the extended position and help drive the cutting arm 370 through the first protruding section 310 and the second protruding section 324.

[0072] Figure 6A A first cutting arm 370' is shown, which is a flat-ended blade. The first cutting arm 370' is used to break the first protruding section 310' of the cap 217', as... Figure 6B As shown. The first raised section 310' is made of metal foil.

[0073] Figure 6B A second cutting arm 370'' is shown, which is a curved blade. The second cutting arm 370'' is used to break the first protruding section 310'' of the cap 217'', as... Figure 6D As shown. The first raised section 310'' is made of metal foil. According to the embodiments herein, the first cutting arm 370' and the second cutting arm 370'' demonstrate that the first raised section 310', 310'' made of metal foil can be destroyed and removed from the caps 217', 217''.

[0074] The first cutting arm 370' and the second cutting arm 370'' only illustrate exemplary methods. Other cutting methods and configurations of the first cutting arm 370'' and the second cutting arm 370'' can be used, including cutting arms with different blade shapes, different numbers of blades, or different cutting surface positions. Exemplary drugs or pharmaceuticals

[0075] The terms “drug” or “pharmaceutical” are used synonymously herein and describe pharmaceutical preparations comprising one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally pharmaceutically acceptable carriers. In the broadest sense, an active pharmaceutical ingredient (“API”) is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or pharmaceutical preparation is used to treat, cure, prevent, or diagnose a disease or to otherwise enhance physical or mental health. Drugs or pharmaceutical preparations may be used for a limited duration or periodically for chronic disorders.

[0076] As described below, a drug or pharmaceutical agent may include at least one API or combination thereof in different types of formulations for the treatment of one or more diseases. Examples of APIs may include small molecules (having a molecular weight of 500 Da or less); polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids (such as antisense DNA and RNA (including RNAi and siRNA)), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems (such as vectors, plasmids, or liposomes). Mixtures of one or more drugs are also considered.

[0077] Drugs or pharmaceutical preparations may be contained in primary packaging or "drug containers" suitable for use with drug delivery devices. Drug containers may be, for example, cartridges, syringes, reservoirs, or other robust or flexible vessels configured to provide suitable chambers for storing (e.g., short-term or long-term storage) one or more drugs. For example, in some cases, the chambers may be designed to store a drug for at least one day (e.g., 1 day to at least 30 days). In other examples, the container may be made of a flexible elastomeric material and designed to be loaded by a healthcare provider or patient and then placed on the body for administration. In some cases, the chambers may be designed to store a drug for approximately 1 month to approximately 2 years. Storage may be performed at room temperature (e.g., approximately 20°C) or at refrigerated temperatures (e.g., approximately -4°C to approximately 4°C). In some cases, drug containers may be or may include dual-chamber cartridges configured to separately store two or more components of the pharmaceutical preparation to be administered (e.g., an API and a diluent, or two different drugs), one component in each chamber. In such a configuration, the two chambers of a dual-chamber cartridge can be configured to allow mixing of two or more components before and / or during dispensing into a human or animal. For example, the two chambers can be configured such that they are in fluid communication with each other (e.g., through a catheter between the two chambers), allowing the user to mix the two components as needed before dispensing. Alternatively or additionally, the two chambers can be configured to allow mixing during dispensing of the components into a human or animal.

[0078] The drugs or agents contained in the drug delivery devices described herein can be used to treat and / or prevent many different types of medical disorders. Examples of disorders include, for example, diabetes or diabetes-related complications (such as diabetic retinopathy), and thromboembolic disorders (such as deep vein or pulmonary thromboembolism). Other examples of disorders include acute coronary syndrome (ACS), angina pectoris, myocardial infarction, tumors, macular degeneration, inflammation, hay fever, atherosclerosis, and / or rheumatoid arthritis.

[0079] Examples of APIs used to treat and / or prevent type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes include insulin (e.g., human insulin, or human insulin analogs or derivatives); glucagon-like peptide-1 (GLP-1), GLP-1 analogs or GLP-1 receptor agonists, or analogs or derivatives thereof; dipeptidyl peptidase-4 (DPP4) inhibitors, or pharmaceutically acceptable salts or solvates thereof; or any mixture of the above. As used herein, the terms “analyte” and “derivative” refer to a polypeptide having a molecular structure that is formally derived from the structure of a naturally occurring peptide (e.g., the structure of human insulin) by deletion and / or exchange of at least one amino acid residue present in a naturally occurring peptide and / or by addition of at least one amino acid residue. The added and / or exchanged amino acid residues may be encoding amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogs are also referred to as “insulin receptor ligands”. Specifically, the term "derivative" refers to a polypeptide having a molecular structure that is formally derived from the structure of a naturally occurring peptide (e.g., human insulin), wherein one or more organic substituents (e.g., fatty acids) are bound to one or more amino acids. Optionally, one or more amino acids present in a naturally occurring peptide may have been missing and / or substituted with other amino acids (including non-coding amino acids), or amino acids (including non-coding amino acids) may have been added to a naturally occurring peptide.

[0080] Examples of insulin analogs are Gly(A21), Arg(B31), Arg(B32) human insulin (glargine insulin); Lys(B3), Glu(B29) human insulin (glutamate insulin); Lys(B28), Pro(B29) human insulin (lispro insulin); Asp(B28) human insulin (aspart insulin); human insulin wherein the proline at position B28 is replaced by Asp, Lys, Leu, Val, or Ala, and wherein the Lys at position B29 can be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0081] Examples of insulin derivatives include, for instance, B29-N-myristoyl-des(B30) human insulin, Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (detemir®); B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoylLysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; and B30-N-myristoyl-ThrB29. LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-γ-glutamyl)-des(B30) human insulin, B29-N-ω-carboxypentadecanoyl-γ-L-glutamyl-des(B30) human insulin (Degludec insulin, Tresiba®); B29-N-(N-lithochyl-γ-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0082] Examples of GLP-1, GLP-1 analogs, and GLP-1 receptor agonists include, for example, lixilamide (Lyxumia®), exenatide (Exendin-4, Byetta®, Bydureon®, a 39-amino acid peptide produced by the salivary glands of the Gila monster), liraglutide (Victoza®), semaglutide, tasglutide, abiglutide (Syncria®), duraglutide (Trulicity®), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (efpeglenatide), HM-15211, CM-3, and GLP-1. Eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1 , GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Telboride (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN, and Glucagon-Xten.

[0083] Examples of oligonucleotides include, for instance, mirtamicin sodium (Kynamro®), a cholesterol-reducing antisense agent used to treat familial hypercholesterolemia, or RG012 used to treat Alport syndrome.

[0084] Examples of DPP4 inhibitors are liraliptin, vedagliptin, sitagliptin, degliptin, saxagliptin, and berberine.

[0085] Examples of hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follicle-stimulating hormone, luteinizing hormone, human chorionic gonadotropin, fertility-stimulating hormone), growth hormone (growth hormone), desmopressin, terlipressin, gosorelin, triptorelin, leuprorelin, buserorelin, nafarelin, and goserelin.

[0086] Examples of polysaccharides include glucosamine, hyaluronic acid, heparin, low molecular weight heparin or ultra-low molecular weight heparin or derivatives thereof, or sulfated polysaccharides (e.g., polysulfated forms of the above-mentioned polysaccharides), and / or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan GF 20 (Synvisc®), a sodium hyaluronate.

[0087] As used herein, the term "antibody" refers to an immunoglobulin molecule or its antigen-binding portion. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments that retain the ability to bind antigens. Antibodies can be polyclonal antibodies, monoclonal antibodies, recombinant antibodies, chimeric antibodies, deimmunized or humanized antibodies, fully human antibodies, non-human (e.g., mouse) antibodies, or single-chain antibodies. In some embodiments, antibodies have effector functions and can immobilize complement. In some embodiments, the ability of an antibody to bind to an Fc receptor is reduced or absent. For example, an antibody can be an isotype or subtype, an antibody fragment, or a mutant that does not support binding to an Fc receptor, for example, its Fc receptor-binding region has been mutagenized or deleted. The term "antibody" also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or dual variable-region antibody-like binding proteins with cross-binding region orientation (CODV).

[0088] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., antibody heavy chain and / or light chain polypeptide) derived from an antibody polypeptide molecule that does not contain the full-length antibody polypeptide but still contains at least a portion of the full-length antibody polypeptide capable of binding to an antigen. Antibody fragments may contain cleaved portions of the full-length antibody polypeptide, but the term is not limited to such cleaved fragments. Antibody fragments that can be used in this invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments (e.g., bispecific, trispecific, tetraspecific, and multispecific antibodies (e.g., double-chain, triple-chain, and quadruple-chain antibodies)), monovalent or multivalent antibody fragments (e.g., bivalent, trivalent, quadruvalent, and multivalent antibodies), microantibodies, chelated recombinant antibodies, tri- or bivalent antibodies, intracellular antibodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camel-derived antibodies, and antibodies containing VHH. Further examples of antigen-binding antibody fragments are known in the art.

[0089] The term "complementarity-determining region" or "CDR" refers to a short polypeptide sequence within the variable region of both heavy and light chain polypeptides, primarily responsible for mediating specific antigen recognition. The term "frame region" refers to an amino acid sequence within the variable region of both heavy and light chain polypeptides; it is not a CDR sequence and is primarily responsible for maintaining the correct positioning of the CDR sequence to allow antigen binding. Although frame regions, as is known in the art, typically do not directly participate in antigen binding, certain residues within the frame region of some antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in the CDR to interact with the antigen.

[0090] Examples of antibodies are anti-PCSK-9 mAb (e.g., aliximumab), anti-IL-6 mAb (e.g., thalidomumab), and anti-IL-4 mAb (e.g., dupilumab).

[0091] It is also considered that a pharmaceutically acceptable salt of any API described herein may be used in a drug or pharmaceutical preparation in a drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts.

[0092] Those skilled in the art will understand that modifications (additions and / or removals) can be made to the different components, formulations, devices, methods, systems, and embodiments of the API described herein without departing from the full scope and spirit of the invention, which covers such modifications and any and all equivalents thereof.

[0093] While the principles of this disclosure have been described herein with reference to illustrative embodiments of specific applications, it should be understood that this disclosure is not limited thereto. Those skilled in the art, upon receiving the teachings provided herein, will recognize that additional modifications, applications, embodiments, and equivalents fall within the scope of the embodiments described herein. Therefore, the invention should not be considered limited to the foregoing description.

Claims

1. A fluid path connector for a large-volume drug delivery device, the fluid path connector comprising: A pharmaceutical container including a cap having a first protruding section, a stopper, and an internal volume for containing a pharmaceutical agent, the cap forming a first region between the cap and the stopper; A needle assembly operable to connect with the medication container, wherein the needle assembly includes: Needle; and Needle assembly cover, the needle assembly cover having a second raised section, the needle assembly cover forming a second region between the needle assembly cover and the needle; and A movable punch is used to break the first protruding section and the second protruding section and to provide an unobstructed path between the needle and the plug.

2. The fluid path connector as described in claim 1, wherein, The relative positions of the needle and the medicine container are movable between a first position and a second position, wherein the needle in the second position passes through the plug and forms a fluid connection between the needle assembly and the medicine container.

3. The fluid path connector as described in claim 2, wherein, At this second position, the needle extends through the unobstructed path.

4. The fluid path connector as described in claim 2, wherein, In this first position, the needle assembly cover covers the needle.

5. The fluid path connector as described in claim 1, wherein, The first protruding section and the second protruding section protrude toward each other.

6. The fluid path connector as claimed in claim 1, wherein, The movable punch is configured to move between the following positions: a first punch position, in which the movable punch is not in contact with the first protruding section or the second protruding section; and a second punch position, in which the movable punch is in contact with both the first and second protruding sections. And at the third punch position, at which the movable punch has at least partially displaced the first protruding segment and the second protruding segment.

7. The fluid path connector as claimed in claim 6, wherein, The movement of the movable punch from the first position to the second position and the third position is perpendicular to the longitudinal axis of the unobstructed path.

8. The fluid path connector as claimed in claim 2, wherein, The movable punch includes a concave end section and an orifice.

9. The fluid path connector as claimed in claim 8, wherein, In this second position, the orifice of the movable punch is positioned along the unobstructed path.

10. The fluid path connector as claimed in claim 6, wherein, At the second punch position, the movable punch engages the first sidewall of the first protruding section and the second sidewall of the second protruding section.

11. The fluid path connector as claimed in claim 10, wherein, Each of the first sidewall and the second sidewall includes a convex section, and the movable punch includes a concave end section configured to mate with the convex sections of the first sidewall and the second sidewall.

12. The fluid path connector as claimed in claim 1, wherein, The movable punch includes a cutting arm having one or more blades configured to at least partially remove the first protruding section and the second protruding section.

13. The apparatus of claim 12, wherein, The cutting arm's action of at least partially removing the first and second protruding sections provides an unobstructed path between the needle and the plug.

14. A bulk delivery device for a pharmaceutical agent, the bulk delivery device comprising: case; A pharmaceutical container including a cap having a first protruding section, a stopper, and an internal volume for containing a pharmaceutical agent, the cap forming a first region between the cap and the stopper; A needle assembly operable to connect with the medication container, wherein the needle assembly includes: Needle; and A needle assembly cover having a second raised section, the needle assembly cover forming a second region between the needle assembly cover and the needle; A movable punch for breaking the first and second protruding sections and providing an unobstructed path between the needle and the plug; and A drive mechanism for driving the plunger in the pharmaceutical container.

15. A method for establishing a fluid path connection in a large-volume drug delivery device, the large-volume drug delivery device comprising a drug container with a cap and a needle assembly with a needle assembly cap, the method comprising: Initiating the operation of the drug delivery device; Deploy a movable punch to break the first protruding section of the cap of the medicine container and the second protruding section of the needle assembly cover; as well as The relative position of the needle of the needle assembly and the drug container is changed so that the needle touches the drug container.

16. The method of claim 15, wherein, Deploying the movable punch includes applying a force along the main axis of the movable punch to displace the movable punch, wherein the main axis is perpendicular to the unobstructed path axis, wherein the first protruding segment includes a first substantially flat outer surface, and the second protruding segment includes a second substantially flat outer surface, the first substantially flat outer surface and the second substantially flat outer surface are substantially parallel, and the unobstructed path axis is perpendicular to both the first substantially flat outer surface and the second substantially flat outer surface, and wherein the movable punch extends on each of the first substantially flat outer surface and the second substantially flat outer surface.

17. The method of claim 15, wherein, Changing the relative position of the needle and the drug container of the needle assembly includes moving the needle, moving the drug container, or moving both.

18. A method for forming a connection in a large-volume delivery device, the method comprising: A pharmaceutical container is provided, the pharmaceutical container having a sterilizing agent, and the pharmaceutical container having a first cap having a first protruding section surrounding a stopper of the container; Provide a proximity needle assembly, the needle assembly including a second cap having a second raised section surrounding the needle tip, the first raised section and the second raised section being close to each other and aligned; as well as The first raised section and the raised section are disrupted to open the passage between the needle assembly and the drug container.

19. The method of claim 18, wherein, The drug container and the needle assembly are housed in a shared housing.

20. The method of claim 18, further comprising advancing the needle through the plug to establish a fluid passage between the drug container and the needle assembly.

21. The method of claim 20, further comprising delivering the drug to the patient by allowing the drug to pass through the needle and into a fluid delivery pathway.

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