System and method for safety syringes

Abstract

To provide a system for mixing and injecting drug products.SOLUTION: A system is provided, including: a syringe body 34; proximal and distal stopper members 32, 36 disposed in the syringe body; a plunger member; and a needle hub assembly coupled to a distal needle interface of the syringe body. The proximal and distal stopper members form a proximal drug chamber 40 therebetween and form a distal drug chamber 42 between the distal stopper member and a distal end of the syringe body. The plunger member includes a needle retention feature, an energy-storage member, and an energy-storage member latching member, all disposed in a plunger interior. First and second sizes of the respective proximal and distal drug chambers can be modified by movement of the proximal and distal stopper members relative to the syringe body. The needle is at least partially retractable into the plunger interior upon manipulation of the plunger member relative to the syringe body.SELECTED DRAWING: Figure 6-1

Description

Technical Field

[0001] The present invention generally relates to injection systems, devices, and processes that facilitate various levels of over-infusion control, and more particularly, to systems and methods related to multi-chamber safety syringes in a healthcare environment.

Background Art

[0002] Millions of syringes, such as those shown in Figure 1A(2), are consumed daily in the medical setting. A typical syringe (2) comprises a cylindrical body (4), a plunger (6), and an injection needle (8). As shown in Figure 1B, such syringes (2) can be used not only to inject fluids into patients but also to draw fluids from or dispense fluids into containers such as vials, bags, or other drug packaging systems (10). In fact, in some countries, such as the United States, due to regulatory constraints and concerns about maintaining sterility, when using vials (10) with syringes (2), as shown in certain patient environments, such vials must be used for one patient and then disposed of, resulting in a considerable amount of medical waste from the bottles, the disposal of remaining medication, and even contributing to regular shortages of certain essential medications. Referring to Figure 2A, three Luer-type syringes (12) are shown. These each have a Luer fitting geometry (14) positioned distally, and can be connected to other devices having a similar mating geometry, such as the Luer manifold assembly (16) shown in Figure 2B. The Luer manifold assembly in Figure 2B can be used for intravenous administration of medication to a patient, with or without an intravenous infusion bag. The Luer fitting (14) on the syringe in Figure 2A is called a “male” Luer fitting, and the one in Figure 2B (18) is called a “female” Luer fitting. One of the interfaces of the Luer is threaded so that two sides are joined by relative rotation (in this case, this configuration can be called a “Luer lock” configuration), and can be combined with compressive loads. In other words, in one embodiment of a Luer lock, rotation, and possibly compression, can be used to engage the threads in the male fitting (14), which is configured to engage with the flange of the female fitting (18), thereby fluid-seal coupling the devices to each other. In another embodiment, a tapered interface shape can be used to engage the lure using compression without threading or rotation (such a configuration is called a “slip-on” or “conical” lure configuration).While such Luer couplings are considered relatively safe for the operator, there is a risk of drug spillage / leakage and component damage during assembly. On the other hand, the use of needle injection structures carries the risk of sharp needles coming into contact with or piercing unintended persons or structures. For these reasons, so-called "safety syringes" have been developed.

[0003] One embodiment of a safety syringe (20) is shown in Figure 3, in which a tubular shield member (22) is spring-biased relative to the syringe body (4) to cover the needle (8) when released from the locked position. Another embodiment of a safety syringe (24) is shown in Figures 4A and 4B. In such a configuration, after the plunger (6) has been fully inserted into the syringe body (4), the retractable needle (26) is retracted to a safe position within the tubular body (4), as shown in Figure 4B (28, 26). Such configurations, which are configured to collapse themselves, may lead to problems with blood splashing / aerosolization, malfunction and safe storage of pre-loaded energy that may be activated before desired, loss of accuracy when injecting the entire volume due to dead space in the remaining space within the spring-compressed volume, and / or loss of retraction velocity control associated with pain and patient anxiety.

[0004] Further complicating the syringe market is the growing demand for pre-filled syringe assemblies, as shown in Figures 5A and 5B, which typically comprise a syringe body, or “drug containment delivery system” (34), a plunger tip, a plug or stopper (36), and a distal seal or cap (35) that can be fitted onto a Luer-type interface. (Figure 5A shows the cap 35 in position; Figure 5B shows the cap removed to show the Luer interface 14.) The liquid drug is contained within the volume between the distal seal and the distal end (37) of the plunger tip (36), or within the drug reservoir. The plunger tip (36) is made of standard butyl rubber material and is coated with a biocompatible lubricating coating (e.g., polytetrafluoroethylene ("PTFE")) to facilitate favorable sealing and relative motion characteristics with respect to the associated syringe body structure and materials. The proximal end of the syringe body (34) in Figure 5B is provided with a conventional one-piece syringe flange (38) integrally formed with the material of the syringe body (34). This flange (38) is configured to extend radially from the syringe body (34) and can be configured to surround all or part of the syringe body (34). Partial flanges are called “clip flanges,” and others are called “full flanges.” The flange is used to provide support for gripping the syringe with your fingers and pushing the plunger to inject. The syringe body (34) is preferably made of a translucent material such as glass or polymer. The plunger tip (36) can be positioned within the syringe body (34) to form a containment volume within the drug chamber or reservoir (40) and to assist in the release of the associated fluid through the needle. The syringe body (34) may be configured to define a substantially cylindrical shape (i.e., the plunger tip 36 having a circular cross-sectional shape can establish a seal with the syringe body (34)), or it may have another cross-sectional shape such as an ellipse.

[0005] Such assemblies are desirable because they can accommodate all the constantly changing global regulations regarding filling, packaging, and the selection of interface materials and component use for pharmaceuticals / pharmaceuticals, and can be standardized and mass-produced precisely by a small number of manufacturers worldwide. However, such simple configurations will generally not meet the new global standards regarding single use, safety, auto-deactivation, and needle stick prevention. Therefore, certain suppliers are moving towards more “vertical” solutions, such as those shown in Figure 5C, which are attempts to meet all, or at least some, criteria in a single solution. As a result of attempting to meet these criteria for many different scenarios, such products have significant limitations (including some of those mentioned above with reference to Figures 3-4B) and have relatively high inventory and utilization costs.

[0006] Furthermore, many injectable liquids (e.g., drugs) have the additional requirement that two or more components must be combined to form an injectable combination or solution immediately before delivery to the patient. While multiple components can be mixed in separate open containers before being drawn into a syringe to form an injectable combination, mixing in open containers and drawing them into a syringe is inaccurate and can lead to the loss of components or the injectable combination. Moreover, drawing an injectable combination into a syringe unnecessarily exposes the user to an uncapped needle.

[0007] Furthermore, many injectable fluids (e.g., drugs) have yet another requirement: minimizing the time the injectable fluid is exposed to metal (e.g., the stainless steel of the needle).

[0008] There is a need for an injection system that addresses the shortcomings of currently available configurations. In particular, there is a need for a multi-chamber safety injection system that can utilize the existing, relatively well-controlled supply chain of conventionally supplied pre-filled syringe assemblies, as illustrated with reference to Figures 5A and 5B. [Overview of the project]

[0009] Embodiments relating to injection systems are described. In particular, these embodiments relate to a multi-chamber safety injection system that moves the needle into a protective structure to minimize accidental user injury and contamination by used needles.

[0010] In one embodiment, a system for mixing and injecting pharmaceuticals comprises a syringe body defining a proximal opening and a distal needle interface at its distal end. The system also comprises proximal and distal stopper members located within the syringe body, forming a proximal drug chamber between the proximal and distal stopper members, and a distal drug chamber between the distal stopper member and the distal end of the syringe body. The system further comprises a plunger member that defines the interior of the plunger and is configured to be manually operated to insert the proximal stopper member into the syringe body. The plunger member comprises a needle holding mechanism located within the plunger, an energy storage member located within the plunger, and an energy storage member latch member located within the plunger. The system further comprises a needle hub assembly connected to the distal needle interface of the syringe body. The needle hub assembly comprises a needle having a needle proximal end mechanism, a hub, and a needle latch member configured to connect the needle to the hub. The first and second sizes of the proximal and distal drug chambers, respectively, can be modified by moving the proximal and distal stopper members relative to the syringe body. When the plunger member is operated relative to the syringe body, the needle becomes retractable into the plunger, at least partially, and the energy storage member latch member changes from a latched state to an unlocked state.

[0011] In another embodiment, a system for mixing and injecting a pharmaceutical product comprises a cartridge body defining a proximal opening and a distal needle interface at its distal end. The system also comprises proximal and distal stopper members located within the cartridge body, forming a proximal drug chamber between the proximal and distal stopper members, and a distal drug chamber between the distal stopper member and the distal end of the cartridge body. The system further comprises a plunger member that defines the interior of the plunger and is configured to be manually operated to insert the proximal stopper member into the cartridge body. The plunger member comprises a needle holding mechanism located within the plunger, an energy storage member located within the plunger, and an energy storage member latch member located within the plunger. The system further comprises a needle hub assembly connected to the distal needle interface of the cartridge body. The needle hub assembly comprises a needle having a needle proximal end mechanism, a hub, and a needle latch member configured to connect the needle to the hub. The first and second sizes of the proximal and distal drug chambers, respectively, can be modified by moving the proximal and distal stopper members relative to the cartridge body. When the plunger member is operated relative to the cartridge body, the needle becomes at least partially retractable into the plunger, changing the energy storage member latch member from a latched state to an unlocked state.

[0012] In one or more embodiments, the needle is configured to be retracted into the plunger, at least completely penetrating the distal stopper member. An energy storage member latch can be interconnected between the inner surface of the plunger member and the needle holding mechanism. The proximal and distal drug chambers may each contain first and second components of a drug to be mixed together before injection into the patient.

[0013] In one or more embodiments, the system comprises a transport configuration in which the proximal end mechanism of a needle is located in the distal drug chamber; a transfer configuration in which the proximal end mechanism of a needle at least partially penetrates a distal stopper member and is at least partially located in the proximal drug chamber; and a mixing configuration in which the proximal and distal stopper members are in contact with each other, thereby transferring a first drug component from the proximal drug chamber to the distal drug chamber and mixing the first drug component with a second drug component in the distal drug chamber. The needle comprises a distal end opening, an intermediate opening located in the distal drug chamber when the system is in the transport, transfer, and mixing configuration, and a proximal opening located in the proximal drug chamber when the system is in the transport and transfer configuration.

[0014] In one or more embodiments, the needle has a plurality of proximal openings, where the proximal opening is one of the plurality of proximal openings. When the system is in a transport configuration and a transfer configuration, at least some proximal openings are located in the proximal drug chamber, and when the system is in a mixing configuration, at least some proximal openings are blocked by a proximal stopper member. The proximal stopper member comprises a plug configured to block at least some proximal openings when the system is in a mixing configuration. The length of this plug is greater than the distance between the most proximal opening of the plurality of proximal openings and the most distal opening of the plurality of proximal openings.

[0015] In one or more embodiments, the syringe or cartridge body includes a position indicator configured to be adjacent to the distal end of a distal stopper when the system is in a mixed configuration. The plunger member may include a retaining clip configured to selectively connect to the syringe or cartridge body when the system is in a mixed configuration and to prevent proximal movement of the plunger member relative to the syringe or cartridge body. The retaining clip may be configured to generate an audible signal when the retaining clip is selectively connected to the syringe or cartridge body.

[0016] In one or more embodiments, the proximal and distal stoppers have first and second polymer coatings on their distal and proximal surfaces, respectively, and the proximal drug chamber is defined by the syringe or cartridge body and the first and second polymer coatings. The distal stopper may have a funnel that is tapered in the proximal direction and a space located at the tapered proximal end of the funnel.

[0017] In one or more embodiments, the hub comprises a collet and a sleeve. The collet may be configured to removably connect the needle hub assembly to the distal needle interface of the cartridge body when the sleeve is positioned around the collet. The hub may also include a sealing member configured to surround the outer surface of the needle and form a liquid-tight seal around it.

[0018] In one or more embodiments, the system further comprises a transfer pipe located within the distal drug chamber. The needle and the transfer pipe are detachably connected when the needle hub assembly is detachably connected to the distal needle interface of the cartridge body. The transfer pipe has a small-diameter portion at its distal end, which can be configured to secure the needle.

[0019] In yet another embodiment, the injection system comprises a syringe body defining a proximal opening and a distal needle interface at its distal end. The system also comprises proximal and distal stopper members located within the syringe body, forming a drug chamber between these proximal and distal stopper members. The system further comprises a plunger member that defines the interior of the plunger and is configured to be manually operated to insert the proximal stopper member into the syringe body. The plunger member comprises a needle holding mechanism located within the plunger, an energy storage member located within the plunger, and an energy storage member latch member located within the plunger. The system further comprises a needle hub assembly connected to the distal needle interface of the syringe body. The needle hub assembly comprises a needle having a needle proximal end mechanism, a hub, and a needle latch member configured to connect the needle to the hub. The needle proximal end mechanism is configured such that the distal stopper member penetrates the drug chamber when the system is in an injection configuration. When the plunger member is operated relative to the syringe body, the needle can be retracted into the plunger at least partially, changing the energy storage member latch from a latched state to an unlocked state.

[0020] In one or more embodiments, the drug chamber contains a drug that is sensitive to degradation during storage due to contact with the metal material of the needle. The proximal and distal stoppers are provided with first and second polymer coatings on their respective distal and proximal surfaces, and the drug chamber is defined by the syringe body and the first and second polymer coatings.

[0021] In one or more embodiments, the system comprises a transport configuration in which the needle proximal end mechanism is not located inside the drug chamber. The needle proximal end mechanism may penetrate a distal stopper and be located inside the drug chamber, thereby providing a drug exit path for injecting the drug into the patient when the system is in injection configuration.

[0022] In one or more embodiments, the needle comprises a distal end opening, an intermediate opening positioned within the drug chamber when the system is in a transport and injection configuration, and a proximal opening positioned within the drug chamber when the system is in an injection configuration.

[0023] In yet another embodiment, a method for mixing and injecting a drug into a patient comprises the step of providing a system comprising a syringe body defining a proximal opening and a distal needle interface at its distal end. The system also comprises proximal and distal stopper members positioned on the syringe body, forming a proximal drug chamber between the proximal and distal stopper members, and a distal drug chamber between the distal stopper member and the distal end of the syringe body. The system further comprises a plunger member that defines the interior of the plunger and is configured to be manually operated to insert the proximal stopper member into the syringe body. Furthermore, the system comprises a needle member comprising a distal needle tip, a drug passage, a plurality of transfer openings, and a proximal end. This method also includes the step of advancing the plunger member so that the proximal end of the needle member pierces the distal stopper, sending the first drug component from the proximal drug chamber through the drug passage into the distal drug chamber, and mixing the first drug component and the second drug component in the distal drug chamber to form a mixed drug.

[0024] In another embodiment, a method for mixing drugs and injecting them into a patient comprises the step of providing a system comprising a cartridge body defining a proximal opening and a distal needle interface at its distal end. The system also comprises proximal and distal stopper members positioned within the cartridge body, forming a proximal drug chamber between the proximal and distal stopper members and a distal drug chamber between the distal stopper member and the distal end of the cartridge body. The system further comprises a plunger member that defines the interior of the plunger and is configured to be manually operated to insert the proximal stopper member into the cartridge body. Furthermore, the system comprises a needle member comprising a distal needle tip, a drug passage, a plurality of transfer openings, and a proximal end. The method also comprises the step of advancing the plunger member so that the proximal end of the needle member pierces the distal stopper, allowing a first drug component to pass from the proximal drug chamber through the drug passage, and mixing the first drug component and a second drug component in the distal drug chamber to form a mixed drug.

[0025] In one or more embodiments, the method further comprises the step of advancing a plunger member to inject the mixed drug into the patient. The method may also comprise the step of automatically retracting the distal needle tip into the syringe body once the mixed drug has been injected into the patient.

[0026] In yet another embodiment, a method of injecting a drug into a patient comprises providing a system having a syringe body defining a proximal opening and a distal needle interface at its distal end. The system also comprises proximal and distal stopper members disposed within the syringe body, forming a drug chamber between the proximal stopper member and the distal stopper member, and forming a distal drug chamber between the distal stopper member and the distal end of the syringe body. The system further comprises a plunger member defining an interior and manually operable to insert the proximal stopper member into the syringe body. Additionally, the system comprises a needle member having a distal needle tip, a drug passageway, a plurality of transfer openings, and a proximal end. The method also comprises advancing the plunger member to impale the proximal end of the needle member against the distal stopper, passing the drug from the proximal drug chamber through the drug passageway into the distal drug chamber.

[0027] In one or more embodiments, the method also comprises advancing the plunger member to inject the drug into the patient. The method further comprises automatically retracting the distal needle tip into the syringe body when the admixture is injected into the patient.

[0028] In yet another embodiment, a system for mixing and injecting pharmaceuticals comprises a syringe body defining a proximal opening and a distal needle interface at its distal end. This system also comprises proximal and distal stopper members located within the syringe body, forming a proximal drug chamber between the proximal and distal stopper members and the distal end of the syringe body. This system further comprises a plunger member that defines the interior of the plunger and is configured to be manually operated to insert the proximal stopper member into the syringe body. The plunger member comprises a needle holding mechanism located within the plunger, an energy storage member located within the plunger, and an energy storage member latch member located within the plunger. Furthermore, this system comprises a needle hub assembly connected to the distal needle interface of the syringe body. This needle assembly comprises a needle having a needle proximal end mechanism, a hub, and a needle latch member configured to connect the needle to the hub. The first and second sizes of the proximal and distal drug chambers, respectively, can be modified by moving the proximal and distal stopper members relative to the syringe body. When the plunger member is operated relative to the syringe body, the needle can be retracted at least partially into the plunger, changing the energy storage member latch from a latched state to an unlocked state. The distal drug chamber is provided with a partial vacuum.

[0029] In one or more embodiments, the distal stopper member includes a proximal gate, and the needle proximal end mechanism has a closed configuration in which it cannot pass through the proximal gate and an open configuration in which it can pass through the proximal gate. The proximal gate includes a pair of movable arms operably coupled to a pair of spring elements. The pair of spring elements biases the proximal gate in the closed configuration. The needle proximal end structure may include a proximal shoulder that cannot pass through the proximal gate in the closed configuration but can pass through the proximal gate in the open configuration. The needle includes a distal shoulder that cannot pass through the proximal gate in the closed configuration but can pass through the proximal gate in the open configuration, and the distal shoulder is distal to the proximal shoulder. The proximal gate may include a pair of movable arms operably coupled to a self-biasing hinge pair.

[0030] In another embodiment, a method of mixing a medicament and injecting it into a patient includes providing a system having a syringe body defining a proximal opening and a distal needle interface at its distal end. The system also includes proximal and distal stopper members disposed in the syringe body, forming a proximal medicament chamber between the proximal and distal stopper members and a distal medicament chamber between the distal stopper member and the distal end of the syringe body. The system further includes a plunger member defining an interior of the plunger and configured to be manually operated to insert the proximal stopper member into the syringe body. Additionally, the system includes a needle member having a distal needle tip, a medicament passage, a plurality of transfer openings, and a proximal end. The distal medicament chamber contains a partial vacuum. The method also includes advancing the plunger member to pierce proximally through the distal stopper member and into the needle member, such that the partial vacuum in the distal medicament chamber draws a first medicament component from the proximal medicament chamber through the medicament passage and into the distal medicament chamber, enabling the first medicament component and a second medicament component to be mixed in the distal medicament chamber to form a mixed medicament.

[0031] In one or more embodiments, the method also comprises the step of moving a distal stopper member distally to compress the space in the distal drug chamber, allowing injection to be performed in the system without purging the system. The method may also comprise the step of advancing a plunger member to inject the drug into the patient. The method may further comprise the step of automatically retracting the distal needle tip into the syringe body once the drug has been injected into the patient.

[0032] The aforementioned embodiments and other embodiments of the present invention are described in the following detailed description. [Brief explanation of the drawing]

[0033] The embodiments described above and other embodiments of the embodiment will be described in further detail with reference to the accompanying drawings. The same elements in the drawings will be described with common reference numerals. [Figure 1] Figure 1A shows a conventional syringe configuration. Figure 1B shows a conventional syringe configuration. [Figure 2] Figure 2A shows a conventional syringe configuration. Figure 2B shows a conventional syringe configuration. [Figure 3] Figure 3 shows a conventional syringe configuration. [Figure 4] Figure 4A shows a conventional syringe configuration. Figure 4B shows a conventional syringe configuration. [Figure 5] Figure 5A shows a conventional syringe configuration. Figure 5B shows a conventional syringe configuration. Figure 5C shows a conventional syringe configuration. [Figure 6]Figure 6A shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6B shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6C shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6D shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6E shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6F shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6G shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6H shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6I shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6J shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6K shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6L shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6M shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use.Figure 6N shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6O shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 6P shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. [Figure 7]Figure 7A shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7B shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7C shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7D shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7E shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7F shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7G shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7H shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7I shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7J shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7K shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7L shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7M shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use.Figure 7N shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7O shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. Figure 7P shows various embodiments of a syringe-based two-chamber safety injection system in which the distal needle end / tip can be retracted into a protective configuration after use. [Figure 8] Figure 8A shows two embodiments of harpoon coupling interfaces that can be used with various two-chamber safety injection systems. Figure 8B shows two embodiments of harpoon coupling interfaces that can be used with various two-chamber safety injection systems. [Figure 9] Figure 9A shows various configurations of a mixed-configuration latch according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. Figure 9B shows various configurations of a mixed-configuration latch according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. [Figure 10] Figure 10A shows various aspects of a mixed-component indicator according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. Figure 10B shows various aspects of a mixed-component indicator according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. [Figure 11]Figure 11A is a diagram illustrating in detail various aspects of the two-chamber safety injection system shown in Figures 6A to 10B in order to demonstrate various aspects of the system. Figure 11B is a diagram illustrating in detail various aspects of the two-chamber safety injection system shown in Figures 6A to 10B in order to demonstrate various aspects of the system. Figure 11C is a diagram illustrating in detail various aspects of the two-chamber safety injection system shown in Figures 6A to 10B in order to demonstrate various aspects of the system. Figure 11D is a diagram illustrating in detail various aspects of the two-chamber safety injection system shown in Figures 6A to 10B in order to demonstrate various aspects of the system. Figure 11E is a diagram illustrating in detail various aspects of the two-chamber safety injection system shown in Figures 6A to 10B in order to demonstrate various aspects of the system. [Figure 12] Figure 12A shows various embodiments of a distal stopper bush according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. Figure 12B shows various embodiments of a distal stopper bush according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. Figure 12C shows various embodiments of a distal stopper bush according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. Figure 12D shows various embodiments of a distal stopper bush according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. Figure 12E shows various embodiments of a guide disc according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. Figure 12F shows various embodiments of a guide disc according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. [Figure 13] Figure 13A shows various forms of a proximal stopper screw according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. Figure 13B shows various forms of a proximal stopper screw according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. Figure 13C shows various forms of a proximal stopper screw according to one embodiment, which can be used with a two-chamber safety injection system according to various embodiments. [Figure 14]Figure 14A shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 14B shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 14C shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 14D shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 14E shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 15A shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 15B shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 15C shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 15D shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 15E shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 15F shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. [Figure 16]Figure 16A shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 16B shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 16C shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 16D shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 16E shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 16F shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 16G shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. Figure 16H shows various embodiments of a cartridge-type two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use. [Figure 17]Figure 17A is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 17B is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 17C is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 17D is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 17E is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 17F is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 17G is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 17H ​​shows various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 17I shows various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 17J shows various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 17K shows various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. [Figure 18]Figure 18A is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 18B is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 18C is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 18D is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 18E is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 18F is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. Figure 18G is a diagram showing various embodiments of a two-chamber safety injection system configured to have a user-attachable needle using a Luer-type coupling. [Figure 19] Figure 19A shows a two-chamber drug mixing and delivery system that delivers drugs to a patient via an IV port or via other delivery methods that do not involve injection into the patient. Figure 19B shows a two-chamber drug mixing and delivery system that delivers drugs to a patient via an IV port or via other delivery methods that do not involve injection into the patient. Figure 19C shows a two-chamber drug mixing and delivery system that delivers drugs to a patient via an IV port or via other delivery methods that do not involve injection into the patient. Figure 19D shows a two-chamber drug mixing and delivery system that delivers drugs to a patient via an IV port or via other delivery methods that do not involve injection into the patient. [Figure 20]Figure 20A shows a safety injection system for storing and delivering drugs sensitive to contact with stainless steel, according to one embodiment. Figure 20B shows a safety injection system for storing and delivering drugs sensitive to contact with stainless steel, according to one embodiment. Figure 20C shows a safety injection system for storing and delivering drugs sensitive to contact with stainless steel, according to one embodiment. Figure 20D shows a safety injection system for storing and delivering drugs sensitive to contact with stainless steel, according to one embodiment. [Figure 21] Figure 21A shows a needle latch mechanism with an adjustable force for releasing the needle. Figure 21B shows a needle latch mechanism with an adjustable force for releasing the needle. Figure 21C shows a needle latch mechanism with an adjustable force for releasing the needle. Figure 21D shows a needle latch mechanism with an adjustable force for releasing the needle. [Figure 22] Figure 22A shows one embodiment of the internal mechanism of a safety injection system for storing and delivering drugs sensitive to contact with stainless steel. Figure 22B shows one embodiment of the internal mechanism of a safety injection system for storing and delivering drugs sensitive to contact with stainless steel. Figure 22C shows one embodiment of the internal mechanism of a safety injection system for storing and delivering drugs sensitive to contact with stainless steel. Figure 22D shows one embodiment of the internal mechanism of a safety injection system for storing and delivering drugs sensitive to contact with stainless steel. [Figure 23] Figure 23 shows an embodiment of a vacuum-assisted two-chamber safety injection system in which the distal needle end / tip can be withdrawn to a protective configuration after use according to various embodiments. [Figure 24] Figure 24 shows an embodiment of a vacuum-assisted two-chamber safety injection system in which the distal needle end / tip can be withdrawn to a protective configuration after use according to various embodiments. [Figure 25] Figure 25 shows an embodiment of a vacuum-assisted two-chamber safety injection system that allows the distal needle end / tip to be withdrawn into a protective configuration after use according to various embodiments. This system includes an exemplary distal stopper bushing. [Figure 26] Figure 26 shows an embodiment of a vacuum-assisted two-chamber safety injection system that allows the distal needle end / tip to be withdrawn into a protective configuration after use according to various embodiments. This system includes an exemplary distal stopper bushing. [Figure 27] Figure 27 shows an embodiment of a vacuum-assisted two-chamber safety injection system in which the distal needle end / tip can be withdrawn to a protective configuration after use according to various embodiments. [Figure 28] Figure 28 shows an embodiment of a vacuum-assisted two-chamber safety injection system in which the distal needle end / tip can be withdrawn to a protective configuration after use according to various embodiments. [Figure 29] Figure 29 shows an embodiment of a vacuum-assisted two-chamber safety injection system in which the distal needle end / tip can be withdrawn into a protective configuration after use according to various embodiments. [Figure 30] Figure 30 shows an embodiment of a vacuum-assisted two-chamber safety injection system in which the distal needle end / tip can be withdrawn to a protective configuration after use according to various embodiments. [Figure 31] Figure 31 shows an embodiment of a vacuum-assisted two-chamber safety injection system in which the distal needle end / tip can be withdrawn to a protective configuration after use according to various embodiments. [Figure 32] Figure 32 shows an embodiment of a vacuum-assisted two-chamber safety injection system in which the distal needle end / tip can be withdrawn to a protective configuration after use according to various embodiments. [Figure 33] Figure 33 shows an embodiment of a vacuum-assisted two-chamber safety injection system in which the distal needle end / tip can be withdrawn to a protective configuration after use according to various embodiments. [Figure 34] Figure 34 shows an embodiment of a vacuum-assisted two-chamber safety injection system that allows the distal needle end / tip to be withdrawn into a protective configuration after use according to various embodiments. This system includes an exemplary distal stopper bushing.

[0034] To better understand how the above and other advantages and objectives of various embodiments are achieved, the embodiments will be described in more detail with reference to the attached drawings. Note that the drawings are not drawn to a fixed scale, and elements of similar structure or function are represented by the same reference numerals throughout. It is obvious that these drawings are for illustrative purposes only and should not be considered to limit the scope of the embodiments. [Modes for carrying out the invention]

[0035] Exemplary two-chamber safety syringe system Referring to Figures 6A and 6B, perspective and longitudinal section views are shown of a two-chamber safety injection system comprising a conventional commercially available pre-filled syringe body (34) with conventional proximal and distal stoppers (32, 36) installed inside. The proximal and distal stopper members (32, 36), together with the syringe body (34), define the proximal and distal drug chambers (40, 42). The proximal and distal stopper members (36, 37) close the proximal and distal ends of the proximal drug chamber (40). The distal stopper member (36) closes the proximal end of the distal drug chamber (42). The needle coupling assembly (606), together with a needle cover member (63) installed for storage, is located at the distal end of the distal drug chamber (42). The two-chamber safety injection system controls the transfer of a first drug component from a proximal drug chamber (40) to a distal drug chamber (42), and the discharge of a mixed / combined drug from the distal drug chamber (42) after the user has continuously inserted a plunger assembly into the syringe body (34) to varying degrees. The plunger assembly comprises a proximal stopper member (32), a plunger housing member (69), and a plunger operating interface (128). The first drug component located in the proximal drug chamber (40) may be a liquid such as an aqueous or oil-based drug solution or gel, or the first drug component may be a diluent to be mixed with a second drug component in the distal drug chamber (42). The second drug component in the distal drug chamber (42) may be a dry drug such as a powder, microspheres, emulsion, lyophilized drug, or freeze-dried drug, or a cake-like drug such as a solid drug. The second drug component in the distal drug chamber (42) may be a liquid that is mixed with the first drug component from the proximal drug chamber (40).

[0036] The two-chamber safety injection system has a steakd needle configuration, and when presented to the user, the needle assembly, comprising a needle coupling assembly (606), the distal end / tip of the needle (48), a needle coupling member (83, see, e.g., Figure 6E), and the proximal end of the needle (50), is mounted in a ready-to-inject position after removal of the needle cover member (63). The cover member has an elastomer sealing material on its inner surface and is bonded to the distal end (48) or distal housing portion (610) of the needle during storage. Alternatively, the needle cover member (63) may have a vent (not shown) to release pressure resulting from the movement and mixing of drug components from the inside of the syringe body (34) while preventing contamination from entering the syringe body (34). Although the steakd needle is depicted as being fixed in place, it may also be detachably connected to the syringe body (34) via a Luer interface, along with the proximal end (50) of the needle member that extends into the distal drug chamber (42) through the Luer interface. In the embodiments shown in Figures 6A to 22D, most of the safe needle retraction hardware is located within the plunger housing.

[0037] Referring to Figures 6C and 6D, during the initial assembly (i.e., in the factory or processing facility - not on site for the “steaked needle” configuration), the proximal housing assembly (608) is configured to snap into a slightly recessed radial portion (602) of the syringe body that is formed within the syringe body during the manufacture of the syringe body (i.e., by having the proximal housing assembly or by using a snap ring element 604 connected thereto).

[0038] Referring to Figures 6E and 6F, the needle spine assembly (76) comprises an injection member having a distal needle end (48) and a proximal needle end (50) connected to a needle connecting member (83). The needle connecting member (83) is configured to have a constricted or radially narrowed portion (111) that connects with the latch member (612) and the movable block member (614). During injection, the distal end of the needle (48), the needle connecting member (83), and the proximal end of the needle (50) remain fixed in place relative to the syringe body (34). After the plunger assembly is fully inserted into the small diameter flange (80) (33 - see, for example, Figure 7N) (i.e., before or after the complete release of the drug contained in the distal drug chamber 42 of the syringe body 34), the movable block member (614) advances relative to the distal housing portion (610), pressing the multiple cantilever latch members (616) (two are shown) out of the way of the movable housing. In particular, the needle spine assembly (76) receives a distal force due to the full advancement of the plunger assembly, which advances the movable block member (614) and moves the cantilever latch member (616). By moving the cantilever latch member (616), the distal end (48), connecting member (83), and proximal end (50) of the needle can be retracted through their connection, thereby safely positioning the distal end (48) of the needle within the plunger housing member (69). Alternatively, the distal end (48) of the needle can be retracted to a position below the outer surface of the distal housing portion (610) to safely protect the sharp tip from the user. In other words, the cantilever latch member (616) holds the position of the needle / syringe assembly and the distal end (48) of the needle during injection until it is pushed out of the way by the movable block member (614) when the plunger is fully inserted. After the plunger has been fully inserted, the needle is free to automatically withdraw when triggered by further distal movement of the needle spine assembly (76), as described in U.S. Patent Applications No. 09 / 099,952, No. 14 / 696,342 and No. 62 / 416,102.These U.S. patent applications are incorporated herein by reference.

[0039] In one embodiment, the plunger assembly includes a connecting member that forms a gap within the plunger assembly, allowing the plunger operating interface to continue moving distally after the distal stopper member has reached the distal end of the syringe body and almost all of the mixed drug has been discharged from the syringe body. In this embodiment, after complete injection, the plunger operating interface is pushed slightly distally to break the connecting member and gap, release the cantilevered latch member, connect the needle spine assembly to the energy storage member, release the energy storage member, and retract the connected needle spine assembly at least into the syringe body. This embodiment is described in more detail in U.S. Patent Application No. 62 / 416, 102, which is incorporated herein by reference.

[0040] Figure 6E shows an embodiment of a needle spine assembly (76) comprising elements of a needle assembly without a needle connecting assembly (606). The distal portion (48) of the needle spine assembly (76) comprises a sharp subcutaneous injection needle tip formed on the injection member (78). As shown in Figures 6G and 6H, the proximal end (50) of the needle also comprises a sharp tip (86) formed on the connecting member that forms the distal portion. A substantially hollow connecting member (83) connects the connecting member to the tubular injection member (78). The injection member (78), the sharp tip (86) on the proximal end (50) of the needle, and the hollow connecting member (83) are held together by interference fit, welding, and / or adhesive. In the embodiment shown in the figure, the most proximal end (84) of the needle proximal end (50) has a “harpoon” geometric shape, which is configured to pierce and hold the joining dependent member in order to draw the needle spine assembly (76) into the plunger housing member (69). The needle proximal end (50) can be made from a thin sheet metal part using, for example, laser cutting, etching, punching, and / or machining techniques. Other embodiments of the needle spine assembly (76), such as the flow channels and flow occlusions through it, are shown in at least Figures 6M to 6O and will be described below.

[0041] Figure 6P is a detailed cross-sectional view of the needle coupling assembly (606) snap-fitted onto the syringe body (34). Figures 6I to 6L are partial perspective wireframe diagrams that provide a more direct visualization of the latch member (612) and cantilever latch member (616) relative to the needle portions (48, 83, 50, 111). The functions of the latch member (612) and cantilever latch member (616) in the retracted needle position are described in U.S. Patent Applications No. 14 / 696,342 and No. 62 / 416,102, which are incorporated herein by reference.

[0042] Figure 6P shows a distal seal (620) configured to seal between the distal drug chamber (42) in the drug container (e.g., syringe body (34)) and the outer surface of the needle spine assembly (76). Preferably, this distal seal (620) is configured to seal around the outside of the needle coupling member (83). This seal is further configured to seal between the distal drug chamber (42) and the inner surface of the needle coupling assembly (606). Figure 6P also shows a snap fit (630) between the distal end of the drug chamber (e.g., syringe body (34)) and the proximal end of the needle coupling assembly (606).

[0043] Returning to Figures 6A and 6B, for example, a two-chamber safety injection system comprises a conventional syringe body (34) fitted with proximal and distal plunger tips (32, 36) configured such that the proximal needle end (50) penetrates at the appropriate time to assist in drug transfer and needle retraction. The proximal plunger tip (32) is connected to a plunger operating interface (128) by a plunger housing member (69) which defines the internal volume occupied by various other parts of the assembly, as will be described later, and these are configured to retract the needle at the appropriate time in the usage sequence. The needle coupling assembly (606) described above is included in the embodiment shown in the figure, and other embodiments may include a Luer-type needle assembly that connects to the syringe body (34). The syringe body (34) of the version shown in the figure has a small diameter flange (33) connected to a conventional one-piece syringe flange (38), which has a geometric shape that can be operated or engaged between the operator's index and middle fingers, for example, while the operator's thumb is engaged with the plunger operating interface (128). Figures 6A and 6B show a pre-use assembly with a needle cover (63) in place to mechanically isolate the distal needle end (48). The needle cover (63) is removed to prepare the assembly for injection into the patient.

[0044] As shown in Figure 6M, the proximal and distal stopper members (32, 36), together with the syringe body (34), define the proximal drug chamber (40) with a two-chamber safety injection system configured for transport. In particular, the distal end of the proximal stopper member (32) and the proximal end of the distal stopper member (36) are coated with a lubricating polymer coating (e.g., PTFE), so that the first and second polymer coatings of the proximal and distal stopper members (32, 36), together with the syringe body (34), define the proximal drug chamber (40). The lubricating polymer coating also acts to isolate the rubber of the proximal and distal stopper members (32, 36) from the drug and drug components. The proximal and distal stopper members (32, 36) may be oriented as shown in Figure 6M, or the distal stopper may be inverted so that the lubricating coating faces the distal drug chamber (42) so that the second drug component in the distal drug chamber (42) comes into contact with the lubricating coating for preservation. When the stopper is inverted, the needle guide assembly is shown in Figure 12F and can be held in place by a centering guide disc, which will be described below. In an alternative embodiment, the proximal and distal stopper members (32, 36) are rubber without a lubricating polymer coating.

[0045] Since the proximal stopper member (32) is connected to the plunger housing member (69) and the plunger operating interface (128), a distal force applied to the plunger operating interface (128) moves the proximal stopper member (32) distally relative to the syringe body (34). The proximal drug chamber (40) is pre-filled with substantially incompressible liquid, and in the transport configuration shown in Figure 6M, there is no escape route for the incompressible liquid from the proximal drug chamber (40). Therefore, the distal movement of the proximal stopper member (32) results in the distal movement of the distal stopper member (36).

[0046] As shown in Figure 6N, in order to configure the two-chamber safety injection system for transfer, the distal stopper member (36) moves distal to the syringe body (34), after which the proximal end of the needle (50) pierces the distal stopper member (36) and partially enters the proximal drug chamber (40). In fact, in the transfer configuration shown in Figure 6N, the transfer pipe (46) portion of the proximal end (50) of the needle forms a fluid path between the proximal and distal drug chambers (40, 42). This transfer pipe (46) has multiple proximal openings (270) and intermediate openings (266). The transfer pipe (46) is hollow and forms a flow path between the most proximal opening (270) located in the proximal drug chamber (40) and the central opening (266) located in the distal drug chamber (42). The transfer pipe (46) shown in Figures 6M to 6O has four proximal openings (270) and intermediate openings (266), but other embodiments may have more or fewer proximal and intermediate openings. Increasing the number of proximal and intermediate openings increases the positioning tolerance of the transfer pipe (46) / needle proximal end (50) relative to the distal stopper member (42) while maintaining an open flow path between the proximal drug chamber and the distal drug chamber (40, 42).

[0047] After the two-chamber safety injection system is configured as shown in Figure 6N, more force is applied to the plunger operating interface (128), allowing the proximal stopper member (32) to move proximal to the distal stopper member (36). This is because the liquid in the proximal drug chamber (40) can move to the distal drug chamber (42) via the transfer pipe (46). Once the liquid is transferred to the distal drug chamber (42), it is mixed with the contents of the distal drug chamber (42). In the embodiments shown in Figures 6A and 6B, the liquid in the proximal drug chamber (40) in the transport configuration (Figures 6A, 6B, and 6M) is initially the first liquid component of the drug. The contents of the distal drug chamber (42) are the second component of the drug. By transferring the liquid from the proximal drug chamber (40) to the distal drug chamber (42), the first and second components are mixed to create the injectable drug.

[0048] As shown in Figure 6O, a continuous force applied from the transfer configuration to the plunger operating interface (128) completes the transfer of the liquid from the proximal drug chamber (40) to the distal drug chamber (42), forming a mixed configuration of the two-chamber safety injection system. In the mixed configuration, the first and second components are mixed, and the drug is ready for injection into the patient. The mixed drug is placed in the distal drug chamber (42). The distal movement of the proximal stopper member (32) relative to the distal stopper member (36) brings the proximal and distal stopper members (32, 36) into contact, reducing the volume of the proximal drug chamber (40) to virtually zero. Therefore, when a continuous force is applied to the plunger operating interface (128), the proximal and distal stopper members (32, 36) move together, and the mixed drug is released through the distal opening / outlet port at the distal end of the transfer pipe (46), exiting the distal drug chamber (42) through the needle and entering the patient. The transfer pipe (46) also includes a lumen plug (268) positioned between the proximal and distal ends of the lumen. This lumen plug (268) prevents the mixed drug from being forced retrogradely through the flow channel while the mixed drug is being injected into the patient.

[0049] Referring to Figures 7A to 7L, various embodiments of configurations designed to facilitate the injection of multi-drug formulations and the retraction of the needle into the syringe body, in which two or more drug components are combined to form an injectable or solution before delivery to the patient. In one modification, immediately before injection, a liquid first drug component / diluent (252) can be combined with a substantially non-liquid second drug component (254), such as a drug in powder form, like a lyophilized or freeze-dried drug. Referring to Figures 7A to 7L, the configurations described herein are two-chambered, utilizing two or more chambers within the same syringe body (34) to carry, mix, and inject the injectable solution.

[0050] Referring to Figures 7A and 7B, the proximal and distal drug chambers (40, 42) are formed by a distal stopper member (36) between two parts inside the syringe body (34). The distal drug chamber (42) contains an air or gas gap, as well as a non-liquid drug (254). The proximal drug chamber (40), opposite the distal stopper member (36), contains a liquid diluent (252) housed proximal to the proximal stopper member (32). This liquid diluent (252) is the first component of the drug, and the non-liquid drug (254) is the second component of the drug.

[0051] Referring to the relevant cross-sectional views in Figures 7C and 7D, various components of the needle coupling assembly are shown (a so-called "steak-type" needle coupling assembly (606) is shown here, but other needle assembly lures described below may be used, including those coupled with lures similar to the steak-type structure). The lug mechanism (258) is configured to assist in coupling the needle coupling assembly (606) to the needle cover member (63), as shown, for example, in Figure 7A. A small O-ring can be used as a sealing member (260) around the needle shaft, and a larger O-ring can be used as a sealing member (262) at the syringe body (34) / needle coupling assembly (606) interface. Alternatively, the small O-ring (260) and the large O-ring (262) may be combined to form a single seal that performs both O-ring sealing functions. Alternatively, the small O-ring (260) can be used to seal both around the needle shaft and the syringe body (34).

[0052] The needle comprises multiple (e.g., four) proximal openings / ports (270) configured to hold a liquid diluent and release it from a more distally located central opening / port (266); a lumen plug (268) occludes the needle lumen to form a flow path from the proximal opening (270) to the central opening (266) under the conditions described above with reference to Figures 6N and 7H. The needle also comprises a distal opening (264) opposite the lumen plug (268) from the central opening (266). The distal opening (264) is fluid-connected to the distal end (48) of the needle through the needle to inject the liquid into the patient.

[0053] Referring to Figure 7E, the proximal harpoon interface (84) is configured to sequentially penetrate the proximal and distal stopper members (32, 36) and connect a coupling mechanism (e.g., the needle holding mechanism, element 712, etc., as shown in Figures 7N and 7P) into the plunger rod. Figure 7F shows a spike-style harpoon coupling interface (85) which sequentially penetrates both the proximal and distal stopper members (32, 36) and is configured to connect with a coupling mechanism in the plunger rod after injection into the patient, thereby retracting the needle member at least partially into the plunger rod.

[0054] Figures 7A, 7B, and 7G through 7P illustrate a series of operations in an injection procedure using the two-chamber safety injection system described above. Referring to Figures 7A and 7B, the injection assembly is in a stable structure and can be shipped or brought into the treatment scenario of a patient to be injected. The first drug component / liquid diluent (252) is isolated from the second non-liquid drug component (254), both located in the syringe body on either side of the distal stopper member (36).

[0055] Figures 7G and 7H show the initial insertion motion of the plunger assembly (44) which advances the distal stopper member (36) and the proximal stopper member (32) together relative to the syringe body (34). Referring to Figure 7H, by advancing the distal stopper member (36) sufficiently and piercing the proximal end (50) of the needle assembly, a fluid path is formed between the two pre-isolated chambers (40, 42) of the syringe body (34). As a result, the liquid first drug component (252) in the proximal drug chamber (40) flows through the transfer pipe (46) into at least one of the proximal openings (270), exits through the more distal intermediate opening (266), and reaches the non-liquid second drug component (254) in the distal drug chamber (42).

[0056] Figures 7I and 7J show the state in which the stopper members (36, 32) are further inserted until they are directly adjacent to each other, causing the liquid first drug component / diluent (252) to move into the distal drug chamber (42) and merge with the non-liquid second drug component (254). Figures 7K and 7L show the state in which, by time and / or manual stirring, the liquid first drug component / diluent (252) and the non-liquid second drug component (254) are mixed to form a mixed drug administration solution (272).

[0057] In some embodiments, particularly with a lyophilized non-liquid second drug component, the mixed drug solution (272) can be formed with minimal agitation, without any agitation, or over time. In other embodiments, particularly with drugs or emulsifiers held in suspension, vigorous shaking may be necessary to facilitate mixing. When vigorous shaking is required, it is convenient for the user to be able to remove their thumb from the plunger operating interface (128). While the liquid first drug component (252) is transferred from the proximal drug chamber (40, 42) to the distal drug chamber (40, 42), pressure may build up in the distal drug chamber (42). This pressure acts on the proximal and distal stopper members (32, 36) to resist the movement of the stoppers. The pressure rise also moves the stopper members (32, 36) and, if the user is not holding the plunger assembly (44) with their thumb, the plunger operating interface (128) to the proximal side. A mixing configuration latch or “mixing click” (shown in Figures 9A and 9B and described below) in the plunger assembly (44) is used to provide resistance to the movement of the plunger operating interface (128) due to increasing pressure, allowing the user to release their thumb from the plunger operating interface (128) for shaking or mixing the drug. The mixing click may also provide an audible and / or tactile indication that the transfer of the liquid first pharmaceutical component (252) is complete. The distal drug chamber (42) may be equipped with a stirring device to assist in the mixing of the drug components.

[0058] With the assembly ready to inject the mixed solution (272), the needle cover member (63) is removed, and the plunger assembly (44) and associated stopper members (36, 32) are pushed in / inserted, as shown in Figures 7M and 7N, to inject the exposed distal end (48) of the needle into the patient. Referring to Figures 7O and 7P, when the plunger assembly (44) and associated stopper members (32, 36) are fully pushed in / inserted, the distal end / tip (48) of the sharp needle automatically retracts to a safe position within the syringe body (34), the needle coupling assembly (606), or at least partially within the plunger assembly (44), passing at least partially through the distal and proximal ends. The automatic retraction of at least partially the needle within the plunger is described in U.S. Patent Applications 14 / 696,342 and 62 / 416,102.

[0059] Existing freeze-drying manufacturing processes freeze-dry a solution (e.g., a liquid drug) inside a syringe chamber sealed near the drug with a stopper. The distal tip of the syringe remains open during freeze-drying, allowing the drug to pass through the inner diameter ("ID") of the syringe tip into the freeze-drying process. This existing method requires the needle to be positioned before freeze-drying due to the adhesive curing process, and traditional glued staked needles are usually not usable. Traditional 25-gauge to 34-gauge staked needles have an ID of approximately 0.010 to 0.003 inches. This range of ID is usually too small to freeze-dry the drug within a reasonable time. The staked needle assemblies shown in Figures 6A to 7P use Luer tapered tip syringes with a tip ID of approximately 0.040 inches that are freeze-dryable. After freeze-drying, the staked needles in Figures 6A to 7P are attached to the syringe by snap-fitting to seal the drug container and allow use of the existing freeze-drying process.

[0060] The embodiments shown in Figures 6A to 7P transport the liquid through a transfer pipe (46), but in other two-chamber embodiments, the liquid can be transported through a bypass channel / passage formed in the syringe body. The bypass channel can be formed in or near the wall of the glass syringe using a mandrel during syringe formation. The bypass channel has an opening to the syringe body, which can be selectively closed by proximal and distal stopper members to control liquid movement. Such embodiments are described in further detail in U.S. Patent Application No. 14 / 696,342.

[0061] A. Exemplary harpoon coupling interface Figures 8A and 8B show two embodiments of a two-chamber safety syringe system having different harpoon coupling interfaces (87, 88). The embodiment shown in Figure 8A has an articulated needle coupling interface (87). The embodiment shown in Figure 8B has a tree-like harpoon coupling interface (88). For clarity, the spring is omitted from Figure 8B. These coupling interfaces (87, 88), their corresponding needle retention mechanisms (712), and their use for selectively retracting the needle are described in U.S. Patent Application No. 62 / 416,102, which is prior to this specification. These different harpoon coupling interfaces (87, 88) can be used in conjunction with those shown in Figures 6A to 7P.

[0062] B. Mixed configuration latch Figures 9A and 9B show a mixed configuration latch (300) on the plunger assembly (44) that can be used with the embodiments shown in Figures 6A to 8B. The mixed configuration latch (300) is tapered distally and is biased (e.g., by a spring) to extend radially from the plunger assembly (44). The mixed configuration latch (300) is configured to move distally beyond the stopper (302) on the small diameter flange (33) connected to the syringe body (34) when the two-chamber safety syringe system is in a mixed configuration (i.e., when the proximal and distal stopper members are in contact with each other), as shown in Figure 9B. At that point, the mixed configuration latch (300) extends radially from the plunger assembly (44), preventing proximal movement of the plunger assembly (44) relative to the syringe body (34).

[0063] By preventing the plunger assembly (44) from moving proximal, the user can release the pressure at the plunger operating interface (128) without the pressure accumulated in the distal drug chamber driving the plunger assembly (44) proximal when the liquid first drug component is pushed from the proximal drug chamber (40) to the distal drug chamber (42).

[0064] The radial extension of the mixing configuration latch (300) after radial compression by the tapered portion passing through the stopper (302) generates an audible or tactile signal (i.e., a click). This audible or tactile signal indicates to the user that the two-chamber safety syringe system is in a mixing configuration and that the user may release the pressure on the plunger operating interface (128). The user may also agitate and / or invert the two-chamber safety syringe system to mix the drug components (252, 254) after hearing or feeling the audible or tactile signal.

[0065] C. Mixed Configuration Indicator Figures 10A and 10B show a portion of the two-chamber safety injection system shown in Figures 6A to 9B, which comprises proximal and distal stopper members (32, 36) having a transport configuration (Figure 10A) and a mixing configuration (Figure 10B). Comparing Figures 10A and 10B, it can be seen that the proximal drug chamber (40) in the system in the transport configuration folds when the system becomes the mixing configuration. As described above, the liquid first drug component (252) in the proximal drug chamber (40) in the system in the transport configuration is transported through at least one proximal opening (270), a distal drug chamber (42), a transport pipe (46), and a central opening (266).

[0066] For optimal performance, the pressure applied by the user to the plunger operating interface (128) to move the proximal stopper member (32) distally relative to the distal stopper member (36) must not exceed the pressure required to transfer the liquid through the transfer pipe (46) at the maximum speed ("maximum transfer pressure"). The maximum transfer pressure is determined by various system parameters, including but not limited to the cross-sectional area, length, and liquid viscosity of the transfer pipe. If the applied pressure exceeds the maximum transfer pressure, the incompressible liquid remaining in the proximal drug chamber (40) transfers the applied pressure to the distal stopper member (36), moving the distal stopper member (36) and the needle spine assembly (76) connected to it distal to the syringe body.

[0067] By moving the distal stopper member (36) relative to the needle spine assembly (76) before reaching the mixed configuration, the transfer of liquid can be stopped early by moving the distal opening member (36) beyond the central opening (266) before all the drug in the proximal drug chamber (40) has been transferred to the distal drug chamber (42). Since the lumen plug (268) prevents the transfer of liquid from the proximal and central openings (270, 266) to the distal opening (264), the distal stopper member (36) closes the intermediate opening (266), effectively stopping the transfer of liquid before completion. If even greater pressure is applied, the distal stopper member (36) can be moved further distally to position the intermediate opening (266) within the proximal drug chamber (40) before the transfer of liquid is complete. This also stops the transfer of liquid before completion. Therefore, applying a pressure greater than the maximum transfer pressure results in incomplete liquid transfer, which affects the dissolution of the second drug component (254), which is substantially not a liquid, and / or the concentration of the mixed drug solution (272).

[0068] To address the issue of users applying pressure higher than the maximum transfer pressure, the embodiments shown in Figures 10A and 10B include a mixed configuration indicator (304), which is a visual indicator placed on the syringe body (34). The mixed configuration indicator (304) in Figures 10A and 10B is a ring (e.g., painted, etched, etc.) placed on the syringe body (34) that indicates the approximate optimal position of the distal edge of the distal stopper member (36) when the system is in a mixed configuration. This visual indication / signal allows the user to visually detect when the distal stopper member (36) has moved too far distally relative to the syringe body (34) before the system reaches its mixed configuration. When the user detects such movement, the user reduces the pressure on the plunger operating interface (128) to stop / decelerate the distal movement of the distal stopper member (36). In some embodiments, an audible or tactile signal from the mixed configuration latch (300) indicates to the user that the system has reached a mixed configuration and that it is safe to push the distal stopper member (36) distally beyond the mixed configuration indicator (304).

[0069] A two-chamber safety injection system having a mixing configuration indicator (304) may include instructions for use that instruct the user to "not allow the forward / distal stopper to pass the mixing line until a click is heard." The mixing configuration indicator (304) allows the user to change the applied pressure so that the system can transfer the liquid with minimal movement of the distal stopper member (36). The mixing configuration indicator (304) can control the movement of the stopper during the liquid transfer phase of the mixing process, eliminating the need for various friction-increasing mechanisms previously used.

[0070] D. Distal stopper bush and proximal stopper screw Figures 11A to 11E provide a more detailed view of the two-chamber safety injection system shown in Figures 6A to 10B to demonstrate various features of the system. As best shown in Figure 11E, the proximal and distal stopper members (32, 36) start as off-the-shelf stoppers for conventional injection systems, but each of the proximal and distal stopper members (32, 36) is modified with additional components to optimize the performance of the two-chamber safety injection system.

[0071] Figure 11E shows that the distal stopper member (36) is positioned within the syringe body (34) in the opposite orientation to that of a typical stopper. In this reverse orientation, the lubricating coating (308) on the distal stopper member (36) faces the proximal drug chamber (40), and the internal threads on the inner surface of the distal stopper member (36) face the distal drug chamber (42). On the other hand, the proximal stopper member (32) is positioned within the syringe body (34) in the typical orientation, with its lubricating coating (306) facing the proximal drug chamber (40) and its internal threads facing the plunger assembly (44). The internal threads on the proximal and distal stopper members (32, 36) are configured for mounting. Typically, the internal threads are used for mounting the plunger assembly. However, the two-chamber safety injection system described herein takes advantage of the benefits of internal threads to mount additional components and optimize performance. The lubricating coating (306, 308) may be PTFE, which acts as a fluid barrier protecting the proximal and distal stopper members (32, 36) (e.g., made of butyl rubber) from the first drug component (40) in the proximal drug chamber, or vice versa.

[0072] The distal stopper bush (310) is fixed to the distal stopper member (36) by utilizing the interaction between a male thread (312) on the distal stopper bush (310) and a distally oriented female thread on the distal stopper member (36). The distal stopper bush (310) is shown separately in Figures 12A to 12D. As shown in Figures 11E and 12D, the distal stopper bush (310) defines a distally oriented alignment funnel (314) when the distal stopper bush (310) is attached to the distal stopper member (36) which is attached to the two-chamber safety injection system. The distally oriented alignment funnel (314) is configured to guide the proximal end (50) of the needle into position when assembling the two-chamber safety injection system. As also shown in Figures 11E and 12D, the distal stopper bush (310) also defines a containment space (316) configured to receive the proximal end (50) of the needle when assembling the two-chamber safety injection system into a transport configuration. This containment space (316) is located adjacent to the “through” portion of the rubber distal stopper bush (310), into which the proximal end (50) of the needle is inserted, with at least one proximal opening (270) exposed into the proximal drug chamber (40) to allow the liquid to move. During assembly, an alignment funnel (314) facing distally guides the proximal end (50) of the needle into the containment space (316), which secures the proximal end (50) of the needle during transport and storage of the two-chamber safety injection system. The alignment funnel (314) also guides the proximal end (50) of the needle during liquid transfer and / or needle retraction to ensure that the proximal end (50) of the needle enters the funnel of the plunger rod for needle retraction (U.S. Patent Application No. 62 / 416,102, incorporated herein by reference). The distal stopper bushing (310) also defines a bushing flange (318) that seals against the distal-facing surface of the distal stopper member (36) to limit contact between the second drug component in the distal drug chamber (42) and the distal stopper member (36) during transport and storage of the two-chamber safety injection system.The bush flange (318) also prevents fluid leakage between the distal stopper bush (310) and the distal stopper member (36) under pressure. In an alternative embodiment, the distal stopper bush (310) and the distal stopper member (36) are integrated into a solid rubber stopper member with a "through" section and a funnel shape. A lubricating coating can be applied to the distal end, the distal stopper member (36), and / or the proximal and / or circumferential sides of the aligned funnel (314).

[0073] Figures 12E and 12F show a guide disc (320) according to another embodiment having similar features to the distal stopper bush (310) described above. The guide disc (320) also defines an alignment funnel (314') tapered proximal to the housing space (316'). The guide disc (320) defines a radial spring arm (321) which connects to the inner surface of the syringe body (34) and centers the guide disc (320) while passing through the distal stopper member (36) and guiding the proximal end (50) of the needle into the plunger rod assembly (44), thereby releasing and / or retracting the latch of the needle (as described in U.S. Patent Application No. 62 / 416,102, which is incorporated herein by reference). As shown in Figure 12E, the guide disc (320) can be used with a distal stopper member (36') installed in a conventional manner (i.e., facing distally).

[0074] The proximal stopper screw (322) is fixed to the proximal stopper member (32) by utilizing the interaction between the male thread (324) on the proximal stopper screw (322) and the proximal-facing female thread on the proximal stopper member (32). The proximal stopper screw (322) is shown alone in Figures 13A to 13C. As shown in Figures 11E and 13C, the proximal stopper screw (322) defines the alignment funnel (326) and the seal space (328). The seal space (328) is greater than or equal to the distance between the most proximal opening (270) and the intermediate opening (266) (see Figures 6N and 6O).

[0075] The alignment funnel (326) is configured to guide the proximal end of the needle (50) into the sealing space (328) after the needle proximal end (50) has passed through both the distal and proximal stopper members (36, 32). During the early injection phase, the intermediate opening (266) remains in the distal drug chamber (42), providing a fluid path to the plunger assembly (44) through the transfer pipe (46). The sealing space (328) of the proximal stopper screw (322) is configured to prevent liquid (e.g., mixed drug solution (272)) from flowing backward through the transfer pipe (46) into the intermediate opening (266) and out of the opening (270) from the proximal end. The proximal stopper screw (322) has a proximal partition (330) that maintains the seal and prevents the movement of the backward-flowing liquid until the intermediate opening (266) is positioned within the proximal stopper screw (322) and thereby sealed. The proximal stopper screw (322) can be made of a hard plastic portion (equipped with a male thread (324)) and a rubber or elastomer portion defining the alignment funnel (326) and the sealing space (328), and is equipped with a proximal partition (330).

[0076] Exemplary two-chamber safety cartridge system Figures 14A and 14B show cartridges (134) and syringe bodies (34) of similar size, respectively. Both the cartridge (134) and syringe bodies (34) may be made of glass. The syringe body (34) is configured for use in an injection system, while the cartridge (134) is configured for storing a substance (e.g., a drug). This results in several differences between the cartridge (134) and the syringe body (34). For example, the proximal end of the syringe body (34) has a conventional integrated syringe flange (38), while the proximal end of the cartridge (134) does not have an integrated flange. Furthermore, the distal end of the syringe body (34) has a Luer taper configured to allow snap engagement of a needle coupling assembly (606), while the distal end of the cartridge (134) has a flange (102) configured to secure a conventional cartridge seal (not shown). Conventional cartridge seals comprise an elastically compressible sealing member that is at least partially surrounded by an elastically deformable closure (e.g., an aluminum ring). As shown in Figures 14A and 14B, the distal opening of the cartridge (134) is considerably larger than the corresponding distal opening of the syringe body (34). This provides more airflow for freeze-drying, as described above.

[0077] Figures 14C and 14D show a two-chamber safety injection system constructed around a cartridge (134) instead of a syringe body (34). Using a cartridge (134) instead of a syringe body (34) results in two changes to the two-chamber safety injection system. First, the small diameter flange (33) is bonded or press-fitted to the cartridge (134) rather than being connected to the syringe flange.

[0078] A second difference in the two-chamber safety injection system constructed around the cartridge (134) is the connection of the needle coupling assembly (606) to the distal end of the cartridge (134), as shown in Figures 14C to 16H. As shown in Figure 14E, the needle coupling assembly (606) is coupled to the distal end of the cartridge (134) using a collet (104) and a sleeve (106). The collet (104) can be welded onto the base plate of the needle coupling assembly (606). Figures 15A and 15B illustrate the system assembly process, with the distal needle portion (50) of the needle coupling assembly (606) inserted into the distal drug chamber (42). As shown in Figures 15B and 15D, the collet (104) is expandable to partially pass proximal over the flange (102) at the distal end of the cartridge (134). As shown in Figures 15D and 15E, after the proximal end (108) of the collet (104) passes the proximal side of the flange (102), the sleeve (106) can be slid proximal on the collet (104) to prevent the collet (104) from opening and being released from the flange (102). The needle coupling assembly (606) is secured to the distal end of the cartridge (134) by fixing the sleeve (106) that covers the collet (104) on the flange (102).

[0079] Figures 16A to 16C also show the attachment of the coupling assembly (606) to the distal end of the cartridge (134). Figures 16A and 16B also show the proximal end of the needle (50) and the alignment funnel (314) on the distal stopper bush (310) that guides the proximal end of the needle (50) into the receiving space (316) during the assembly of the two-chamber safety injection system. Figure 16D shows the attachment of the small diameter flange (33) to the proximal end of the cartridge (134), the insertion of the plunger assembly (44), and the fixing of the proximal stopper member (32) to the cartridge (134). The two-chamber safety injection system with the cartridge (134) shown in Figure 16D is ready for transport, storage, preservation, and use (i.e., mixing, injection, and automatic dispensing). The following steps are exactly the same as those shown in Figures 7A to 7P for the two-chamber safety injection system with a syringe.

[0080] Figures 16G and 16H show in detail the interface between the collet (104) and the flange (102) with and without the sleeve (106G) (Figure 16G). Figures 16G and 16H show a needle seal (110) positioned within the needle coupling assembly (606) and configured to fluidly seal the annular space between the inner diameter of the opening at the distal end of the cartridge (134) and the outer diameter of the needle spine assembly (76). The needle seal (110) can be made from an elastically deformable material such as rubber. The needle seal (110) also comprises a pair of gland (112) extending within the inner diameter of the needle seal (110). These gland (112) function like two O-rings sealing the needle spine assembly (76).

[0081] The various features of the two-chamber safety injection system constructed around the cartridge (134) can also be used with an auto-syringe or a pen-type syringe. The cartridges of these systems may incorporate a one-piece glass or plastic finger flange similar to those employed in syringe-based systems.

[0082] Exemplary two-chamber safety injection system with Luer connector Figures 17A to 19D show various two-chamber safety injection systems having a Luer connector (114) at the distal end. As shown in Figures 17A to 17H, a female Luer lock connector (114) with internal threads is attached to a collet (104) and sleeve (106) as shown in Figure 14A and described above to form a needle hub (116) for use with a cartridge (134). The collet (104) and sleeve (106) can be used to attach the needle hub (116) to the distal end of the cartridge (134) as shown in Figures 14A to 16H, as described above for attaching the needle coupling assembly (606) to the cartridge (134). The distal end of the female Luer lock connector (114) is temporarily sealed with a removable Luer cap (118). Once the needle hub (116) is attached to the cartridge (134), the Luer cap (118) can be removed, and the Luer needle (120) can be attached to the needle hub (116) and the two-chamber safety injection system via the female Luer lock connector (114) as shown in Figure 17E.

[0083] After the Luer needle (120) is attached to the needle hub (116) and the two-chamber safety injection system, the system is ready for transport, storage, and use (i.e., mixing, injection, and automatic retraction) and performs the exact same steps as shown for the two-chamber safety injection system with syringes in Figures 7A to 7P. The mixing, injection, and retraction steps, similar to those shown in Figures 7A to 7P, are shown for the two-chamber safety injection system with a female Luer lock connector (114) in Figures 17A to 17H.

[0084] Further problems arise when using a Luer needle (120) interchangeable with a female Luer lock connector (114). The proximal end (122) of the Luer needle (120) must be connected to a transfer pipe (46), and the Luer needle (120) must be connected to a female Luer lock connector on a needle hub (116). During installation of the Luer needle (120), a needle cover member (63) guides the Luer needle (120) into the needle hub (116), thereby aligning the proximal end (122) of the Luer needle (120) with the transfer pipe (46) and improving the connectivity between the Luer needle (120) and the transfer pipe (46). The guidance of the needle cover member is described in U.S. Patent Application No. 14 / 696,342, which is incorporated herein by reference. Figures 17J and 17K, and Figures 18C through 18F, show the connection between the Luer needle (120) and the transfer pipe (46). As seen in these figures, the male Luer lock connector (124) with external threads on the Luer needle (120) has a proximal end (122) that guides the proximal end (122) of the Luer needle (120) into the transfer pipe (46) to ensure the connection between them. The threads of the Luer lock connector (114, 124) push the proximal end (122) of the Luer needle (120) into the transfer pipe (46) for airtight press-fit or snap-fit. The distal end of the transfer pipe (46) also has a latch groove (111) configured to interact with one or more cantilever latch members (616) to prevent the transfer pipe from being pushed proximal into the cartridge (134) during installation.

[0085] Figures 19A to 19D show embodiments of a two-chamber safety injection system having a female Luer lock connector (114) at the distal end, used for mixing (with or without a Luer cap (118)) and injection without a Luer needle. The connector (114) may be a Luer taper, a Luer slip, or other fluid connector. As shown in Figure 19D, the two-chamber safety injection system can be connected to any Luer lock access port (130), such as those connected to an IV pipe and IV bag. In such embodiments, since there is no sharp needle, a retraction mechanism is not required, and therefore the two-chamber safety injection system does not retract. In this case, a transfer pipe (46) allows for the transfer of liquid from the proximal drug chamber (40) to the distal drug chamber (42), and then the mixed drug (272) can be injected into an IV pipe or other injection system.

[0086] The two-chamber safety injection system equipped with a Luer connector, as shown in Figures 17A to 19D, includes a cartridge, but the Luer connector can also be used with syringes and other two-chamber safety injection systems.

[0087] Exemplary safety injection system for metal-sensitive drugs Many injectable drugs (e.g., pharmaceuticals) are sensitive to degradation during storage due to contact with metal, such as that found in needles. Figures 20A to 20D illustrate the use of a pre-filled two-chamber safety injection system designed to minimize exposure of such sensitive drugs to metal during storage. For example, as shown in Figure 20A, which illustrates a transport configuration for a two-chamber safety injection system, the sensitive drug (132) can be pre-filled into the system and stored in the proximal drug chamber (40). Thus, during transport and storage, the sensitive drug (132) is exposed only to the glass of the syringe body (34) on the proximal and distal stopper members (32, 36) and to a hydrophilic or lubricating coating (e.g., PTFE). The distal drug chamber (42) contains only the proximal end of the needle (50) and does not contain the injectable drug. In fact, the distal stopper member (36) separates the sensitive drug (132) from the proximal end (50) of the sensitive metal needle.

[0088] Immediately before injection, the user applies pressure to the plunger operating interface (128), thereby pushing the proximal and distal stopper members (32, 36) and the sensitive drug (132) contained between them toward the distal end. The proximal end of the needle (50) is configured to have a single opening located immediately proximal to the distal stopper member (36) when the distal stopper member (36) is positioned at the distal end of the syringe body (34), as shown in Figure 20B. Thus, the two-chamber safety injection system is ready for injection, as shown in Figure 20B. From the configuration shown in Figure 20B, further pressure from the user on the plunger operating interface (128) injects the sensitive drug (132) through the distal end of the needle (48) and collapses the proximal drug chamber (42), as shown in Figure 20C. Moving to Figures 20C to 20D, the needle-spine assembly (76) is retracted into the syringe body (34) and at least partially into the plunger assembly (44), as described in U.S. Patent Applications No. 14 / 696,342 and No. 62 / 416,102, which are incorporated herein by reference. Thus, the time the sensitive drug (132) is exposed to the metal of the needle-spine assembly (76) is minimized to the time it takes to complete the injection.

[0089] The two-chamber safety injection system shown in Figures 20A to 20D is configured for use with a syringe, but a similar system can be configured for use with a cartridge containing a sensitive drug. The two-chamber safety injection system shown in Figures 20A to 20D features direct injection from the proximal drug chamber (40), while other systems, as shown in Figures 22A to 22D, feature the transfer of the sensitive drug from the proximal drug chamber (40) to the distal drug chamber (42) prior to injection.

[0090] Needle latch member Figures 21A to 21D show the interaction between the latch groove (111) on the distal end of the transfer pipe (46) and the needle latch member (612) that prevents the needle spine assembly (76) (including the transfer pipe (46)) from moving proximal before the injection is completed.

[0091] Figure 21A shows a transfer pipe (46) with a latch groove (111) formed thereon, into which the proximal end of the distal needle end (48) is inserted. In one embodiment, as described above, the proximal end of the distal needle end (48) may be the proximal end of the Luer needle. The transfer pipe (46) has a neck-down or radially retracting latch groove (111) configured to interact with a latch member (612) and a movable block member (614), so that during system assembly and use (e.g., mixing and injection), the needle spine assembly (76) including the transfer pipe (46) remains fixed in place relative to the syringe body (34), but after the plunger assembly is fully inserted into the small diameter flange (33 - see, for example, Figure 7N) (i.e., into the distal drug chamber 42 of the syringe body 34) When the contained drug is about to be completely released or thereafter, the needle spine assembly (76) is subjected to a distal force by the forward movement of the plunger, which moves the movable block member (614) forward relative to the distal housing portion (610), and pushes a plurality (two shown) of cantilevered latch members (616) of the latch member (612) out of the way of the movable block member (614), causing the needle spine assembly (76) (i.e., the distal end (48) of the needle, the transfer pipe (46), and the proximal end (50)) to retract. This safely positions the distal end (48) of the needle within the plunger assembly (44). Alternatively, the distal end (48) of the needle can be retracted to a position below the outer surface of the distal housing portion (610), safely protecting the sharp tip from the user. In other words, the cantilevered latch member (616) holds the distal end (48) of the needle in place during injection and needle / syringe assembly until the movable block member (614) pushes them out of the way when the plunger is fully inserted (see Figure 21D). The needle is then freely withdrawn as described in U.S. Patent Applications 14 / 696,342 and 62 / 416,102, which are incorporated herein by reference.

[0092] The movable block member (614) comprises a smaller distal portion (617) and a larger proximal portion (618) to increase the force required to release the latch of the needle spine assembly (76). The larger proximal portion (618) is configured to create a block outer diameter (622) dimension that interferes with the inner diameter (624) of the latch (612), thereby increasing the force that slides the movable block and thus increasing the force that releases the needle.

[0093] The torque applied to the cantilevered latch member (616) is reduced, thereby increasing the force required to release the latch.

[0094] Vacuum-assisted two-chamber safety injection system Figures 23 to 34 show various embodiments of a vacuum-assisted two-chamber safety injection system similar to those shown in Figures 6A to 10B. The two-chamber safety injection system has a conventional off-the-shelf pre-filled syringe body (34) having proximal and distal stopper members (32, 36) positioned therein. The proximal and distal stopper members (32, 36), together with the syringe body (34), define the proximal and distal drug chambers (40, 42). The proximal and distal stopper members (32, 36) close the proximal and distal ends of the proximal drug chamber (40). The distal stopper member (36) closes the proximal end of the distal drug chamber (42). The two-chamber safety injection system allows the user to control, to varying degrees, the transfer of a first drug component from a proximal drug chamber (40) to a distal drug chamber (42), and the discharge of a mixed / combined drug from the distal drug chamber (42), which is continuously inserted into the distal side of the plunger assembly relative to the syringe body (34). The plunger assembly comprises a proximal stopper member (32), a plunger housing member (69), and a plunger operating interface (128). The first drug component located in the proximal drug chamber (40) is a liquid such as an aqueous or oily drug solution or gel, or a diluent to be mixed with the second drug component in the distal drug chamber (42). The second drug component in the distal drug chamber (42) is a drug in a dry form, such as a powder, microspheres, emulsion, lyophilized or freeze-dried, or a cake such as a solid drug. The second drug component in the distal drug chamber (42) may also be a liquid that mixes with the first drug component from the proximal drug chamber (40).

[0095] As described above, the proximal and distal stopper members (32, 36) of the two-chamber safety injection system are configured to allow the proximal needle end (50) to penetrate in a timely manner to assist in the movement of the drug. Figure 23 shows a pre-use assembly with a needle cover (63) in place to mechanically separate the distal needle end (48). The needle cover (63) is removed to allow the assembly to be injected into the patient. In some embodiments (not shown), the needle cover member (63) is equipped with a vent (not shown) that allows pressure resulting from the movement and mixing of drug components to be released from inside the syringe body (34) while preventing contaminants from entering the syringe body (34). However, such a vented needle cover member is not always desirable.

[0096] When the first drug component moves from the proximal drug chamber (40) to the distal drug chamber (42) under pressure, pressure is generated within the distal drug chamber (42) without ventilation. When pressure is generated within the distal drug chamber (42), the liquid (e.g., mixed drugs) is released from the distal drug chamber (42) before injection (e.g., through the distal end (48) of the needle).

[0097] Therefore, the vacuum-assisted two-chamber safety injection system shown in Figure 23 creates a partial vacuum (e.g., 0.1 ATM or 90% vacuum) inside the distal medical chamber (42) before transferring the fluid from the proximal drug chamber (40). The partial vacuum assists the movement of the fluid from the proximal drug chamber (40). For example, after a portion of the transfer pipe (46) is pushed through the proximal stopper member (32) and the proximal opening (270, see Figure 29) is positioned inside the proximal drug chamber (40), the partial vacuum inside the distal drug chamber (42) draws the fluid from the proximal drug chamber (40) into the distal drug chamber (42). The partial vacuum reduces the amount of distal force that must be applied to the proximal stopper member (32) via the plunger assembly, thereby transferring the fluid from the proximal drug chamber (40) to the distal drug chamber (42). The transfer of the fluid also releases at least partially the vacuum inside the distal drug chamber (42).

[0098] As shown in Figure 24, the partial vacuum in the distal drug chamber (42) generates a force ("Fv") on the distal stopper member (36), which must be temporarily resisted in order to maintain the two-chamber safety injection system in a transport, storage, and premixing state. The distal force (Fv) on the distal stopper member (36) is approximately the difference between the pressure in the proximal drug chamber (40) and the pressure in the distal drug chamber (42) multiplied by the area of ​​the distal stopper member (36). In one embodiment, Pressure inside the proximal drug chamber (40) = 1 ATM = 14.7 psi Pressure inside the distal drug chamber (42) = 0.1 atmospheres = 0.15 psi The tip surface area of ​​a standard 3cc stopper = 0.09 in² 2 Force (Fv) acting on distal stopper member (36) = 0.09(14.7-0.15) = 1.31 pounds The resistance of the distal stopper member (36) to puncture by the harpoon coupling interface (not shown) is sufficient to overcome a force of 1.31 pounds (Fv). However, with a sharper harpoon coupling interface or a distal stopper member (36) with less puncture resistance, a partial vacuum within the distal drug chamber (42) may result in premature puncture of the distal stopper member (36) by the harpoon coupling interface or premature transfer of fluid from the proximal drug chamber (40) to the distal drug chamber (42).

[0099] Figures 25 and 26 show a distal stopper bush (310) having a proximal gate (332). The distal stopper bush (310) is configured to screw into the distal end of the distal stopper member (36). The proximal gate (332) comprises a pair of movable arms (334), each biased toward each other by a spring element (336). Thus, the proximal gate (332) has two configurations: a closed configuration in which the harpoon coupling interface cannot pass through the proximal gate (332); and an open configuration in which the harpoon coupling interface can pass through the proximal gate (332). In the open configuration, the movable arms (334) are subjected to a force that separates them from each other (for example, the gate is opened by the relative movement between the harpoon coupling interface and the distal stopper member (36), as shown below).

[0100] When the dual-chamber injection system is in the transfer / storage / premixing state (see Figures 23, 24, 27, and 28), the gate (332) is in the closed state. As shown in Figures 27 and 28, the closing member (322) prevents the harpoon coupling interface from contacting the distal stopper member (36), so the closing gate transmits the force (Fv) generated by the partial vacuum in the distal drug chamber (42) to the harpoon coupling interface and needle spine assembly (76) without penetrating the distal stopper member (36). The harpoon coupling interface (89, see Figure 28) has a proximal shoulder (90) that interferes with the closing gate (322), preventing the harpoon coupling interface (89) from passing through the gate. The harpoon coupling interface (89) has a hollow 3D arrowhead shape as described in the U.S. Patent Application “System and Method for a Safe Syringe,” filed November 1, 2017, Agent Reference No. CM20015. This application is incorporated herein by reference.

[0101] After sufficient distal force is applied to the plunger assembly, this distal force applied to the plunger, along with the force (Fv) acting on the distal stopper member (36) from the partial vacuum in the distal drug chamber (42), overcomes the biasing force of the spring element (336) in the arm (334) of the gate (332), causing the gate (332) to open from a closed configuration. Then, as shown in Figure 29, the harpoon coupling interface (89) partially penetrates the distal stopper member (36) and subsequently the transfer pipe (46). Since the outer diameter of the transfer pipe (46) is smaller than the distal end of the harpoon coupling interface (89), the gate (332) closes after the proximal end of the harpoon coupling interface (89) has passed.

[0102] The movement of the needle spine assembly (76) through the distal stopper member (36) is then temporarily stopped by the distal shoulder (92), which has a larger outer diameter than the transfer pipe (46) formed in the needle joint member (83) of the needle spine assembly (76). The distal shoulder (92) does not pass through the closed gate (322), thereby holding the needle spine assembly (76) and the distal stopper member (36) in the position shown in Figure 29. In this position, the transfer pipe (46) straddles the distal stopper member (36), allowing the liquid to move through it. Partial vacuum and distal forces within the distal drug chamber (42) are applied to the plunger assembly, drawing or pushing the liquid from the proximal drug chamber (40) to the distal drug chamber (42). Mechanical interference between the distal shoulder (92) and the closed gate (322) minimizes the movement of the distal stopper member (36) during liquid transfer.

[0103] Figure 30 shows the configuration of the two-chamber safety injection system after the transfer of liquid from the proximal drug chamber (40) to the distal drug chamber (42) is substantially complete. The proximal stopper member (32) seals the harpoon coupling interface (89, see Figure 29) and the opening of the transfer pipe (46, see Figure 29), stopping the liquid transfer. The partial vacuum in the distal drug chamber (42) provides space within the distal drug chamber (42) after the liquid transfer, allowing the user to mix the first and second drug components by agitating these components.

[0104] Figure 31 shows the configuration of the two-chamber safety injection system after sufficient distal force has been applied to the plunger assembly to overcome the mechanical interference between the distal shoulder (92, see Figure 29) and the closing gate (322, see Figure 322) (i.e., by opening the gate (322)). After the distal and proximal stopper members (36, 32) are no longer prevented from moving distally by the distal shoulder (92, see Figure 29) and the closing gate (322, see Figure 29), the partial vacuum collapses this space by moving the distal and proximal stopper members (36, 32). The distal force applied to the plunger assembly also helps to collapse the space within the distal drug chamber (42) (compare Figures 30 and 31).

[0105] After partial vacuum collapses the space within the distal drug chamber (42), the distal drug chamber contains small bubbles that do not need to be purged before injection. Therefore, unlike other injection systems, the vacuum-assisted double-chamber safety injection system functions without purging. Thus, the vacuum-assisted double-chamber safety injection system described herein can be used with autosyners, pens, and other "reusable" or "disposable" housing interfaces without purging.

[0106] Figure 32 shows the configuration of the two-chamber safety injection system after the needle latch member (612) has been detached from the needle spine assembly (76) and the harpoon coupling interface (89) has been fixed to the needle holding mechanism as described above. For clarity, the energy storage member has been omitted from Figure 32.

[0107] Figure 33 shows the configuration of the double-chamber safety injection system after the retraction mechanism is triggered to retract the needle spine assembly (76) proximal to the syringe body (34) until the sharp end (34) of the distal end of the needle is in a safe position within the needle hub, as described above. For clarity, the energy storage member has been omitted from Figure 33.

[0108] Figure 34 shows a distal stopper bush (310) equipped with a proximal gate (332) according to another embodiment. The difference between the distal stopper bush (310) in Figure 34 and the distal stopper bush (310) in Figures 25 to 28 is the design of the proximal gate (332). In the proximal gate (332) shown in Figure 34, when the distal shoulder (92) pushes the movable arm (334) in the proximal direction, the pair of movable arms (334) rotate around their respective self-biasing hinges (338). The force of the distal shoulder (92) on the movable arms (334) brings the arms closer to each other, thereby fixing the transfer pipe (46) to the movable arm (334). This fixes the transfer pipe (46) in an optimal position for liquid transfer. The position of the fixed transfer pipe (46) allows the axial length of the self-biasing hinge (338) to be changed, thereby adjusting the force applied to the transfer pipe (46) from the movable arm (334). After the liquid transfer is complete, the increased distal force on the plunger assembly overcomes the mechanical interference between the distal shoulder (92) and the closing gate (322), enabling injection.

[0109] The vacuum-assisted two-chamber safety injection system, shown in Figures 23 to 33 and described herein, facilitates the transfer of liquid from the proximal drug chamber (40) to the distal drug chamber (42) by drawing the liquid into the distal drug chamber (42) and minimizing the pressure rise within the distal drug chamber (42) through liquid transfer. The vacuum-assisted two-chamber safety injection system also comprises a distal stopper bush (310) having a proximal gate (332) to prevent premature movement of the distal stopper member (36) caused by partial vacuum within the distal drug chamber (42).

[0110] Various exemplary embodiments of the present invention are described herein. These embodiments are provided for non-limiting purposes. These embodiments are provided to illustrate broader applicable aspects of the present invention. Various modifications can be made to the described invention without departing from the true spirit and scope of the invention, and equivalents can be substituted. Furthermore, many modifications can be made to adapt specific situations, materials, composition of substances, processes, process actions or steps to the object, spirit or scope of the invention. Furthermore, as will be apparent to those skilled in the art, each of the modifications described and illustrated herein has separate components and features that can be readily separated or combined with features of several other embodiments without departing from the spirit and scope of the invention. All such modifications are intended to fall within the scope of the claims relating to this disclosure.

[0111] Any device described for performing the relevant diagnostic or interventional procedure may be provided in a packaged combination for use when performing such intervention. These supply “kits” may further include instructions for use and may be packaged in sterile trays or containers, as is commonly used for such purposes.

[0112] The present invention includes methods that can be carried out using the apparatus of the present invention. These methods include the act of providing such a suitable apparatus. Such provision is performed by the end user. In other words, the act of “providing” only requires the end user to acquire, access, approach, position, set up, activate, power on, or perform any other action to provide the apparatus required in the method. The methods enumerated herein can be carried out in any logically possible order of the enumerated events, as well as in the order of the enumerated events.

[0113] Exemplary embodiments of the present invention, along with details relating to the selection and manufacture of materials, are described above. Further details of the present invention can be found in relation to the patents and publications referenced above, as well as matters generally known or recognized by those skilled in the art. For example, it is obvious to those skilled in the art that one or more lubricating coatings (e.g., hydrophilic polymers such as polyvinylpyrrolidone compositions, fluoropolymers such as tetrafluoroethylene, PTFE, hydrophilic gels, or silicones) can be used, as needed, on various parts of an apparatus, such as relatively large interface surfaces of movable couplings, to facilitate low-friction operation and advancement of such objects against other parts of the instrument or nearby structural elements. The same applies to embodiments of the method of the present invention in the sense of additional actions that are generally or logically used.

[0114] Furthermore, although the present invention has been described with reference to several embodiments that optionally incorporate various features, the present invention is not limited to any modifications of the present invention that have been described or shown herein. Various modifications can be made to the present invention as described above, and equivalents (whether listed herein or otherwise) can be substituted without departing from the true spirit and scope of the invention. Furthermore, if a range of values ​​is provided, it is understood that the upper and lower limits of that range, and any intermediate values ​​within that range, or any intermediate values ​​between intermediate values ​​within that range, are encompassed in the present invention.

[0115] Furthermore, any feature of the modified invention described herein is intended to be described independently or in combination with any one or more of the features described herein, and to be claimed. References to singular items include the possibility that there may be multiple identical items. More specifically, where used herein and in the claims relating herein, the singular “a,” “an,” “the,” and “the” include multiple referents unless otherwise specified. In other words, the use of articles may mean “at least one” of the subject items in the above description and in the claims relating to this disclosure. It should be further noted that such claims may be drafted to exclude optional elements. This statement is intended to be used as an antecedent to the use of exclusive terms such as “alone,” “only,” etc., in connection with the enumeration of claim elements or the use of “negative” limitations.

[0116] Without using such exclusive technical terms, the term “encompassing” in the claims relating to this disclosure means that the inclusion of any additional element is possible, regardless of whether a given number of elements are enumerated in such claims, or whether the addition of a feature can be considered to transform the nature of the elements described in such claims. Unless specifically defined herein, all technical and scientific terms used herein are used in a way that is as broadly and generally understood as possible, while maintaining the validity of the claims.

[0117] The scope of the present invention should not be limited to the examples provided and / or this specification, but rather should be limited only by the language of the claims relating to this disclosure.

Claims

1. In a system for mixing and injecting pharmaceuticals: A cylindrical syringe body comprising a proximal opening and a distal needle interface at its distal end; Proximal and distal stopper members arranged on the cylindrical syringe body, wherein a proximal drug chamber is formed between the proximal and distal stopper members, and a distal drug chamber is formed between the distal stopper member and the distal end of the cylindrical syringe body; A plunger member configured to define the inside of the plunger and to insert the proximal stopper member into the cylindrical syringe body; A needle hub assembly connected to the distal needle interface of the syringe body, A needle having a needle proximal end structure; Hub and; A needle latch member configured to connect the needle to the hub; A needle hub assembly comprising; The first and second sizes of the proximal and distal drug chambers, respectively, can be changed by moving the proximal and distal stopper members relative to the cylindrical syringe body. The distal stopper member is a funnel positioned at its distal end, and has a tapered shape in the proximal direction such that the inner diameter of the distal end of the funnel is larger than the inner diameter of the proximal end of the funnel. The distal stopper member comprises a proximal gate having a closed configuration in which the needle proximal end structure cannot pass through the proximal gate, and an open configuration in which the needle proximal end structure can pass through the proximal gate. The proximal gate comprises a pair of movable arms operably connected to a pair of spring elements, and the pair of spring elements biases the proximal gate to the closed configuration. A system characterized in that, when a sufficiently large distal force is applied to the plunger member, the distal force exceeds the biasing force of the spring element pair that keeps the proximal gate in the closed configuration, causing the proximal gate to transition from the closed configuration to the open configuration.

2. The system according to claim 1, characterized in that the proximal drug chamber and the distal drug chamber each contain a first and second component of a drug that is mixed with each other before being injected into the patient.

3. The aforementioned system: A transport configuration in which the needle proximal end structure is placed within the distal drug chamber, allowing the system to be stored and transported; The needle proximal end structure is at least partially penetrating the distal stopper member and at least partially positioned within the proximal drug chamber, and the transfer configuration is such that the first drug in the proximal chamber can be transferred to the distal chamber; The proximal and distal stopper members come into contact with each other, eliminating the space in the proximal drug chamber, and all of the first drug component in the proximal drug chamber moves to the distal drug chamber, thereby mixing the first drug component and the second drug component in the distal chamber; The system according to claim 1, characterized by having

4. The aforementioned needle: With the distal end opening; When the system is in the transport configuration, the transfer configuration, and the mixing configuration, the central opening located in the distal drug chamber is: When the system is in the transfer configuration, the proximal opening located in the proximal drug chamber and; The system according to claim 3, characterized by comprising the following.

5. The needle further comprises a plurality of proximal openings, wherein the proximal opening is one of these plurality of proximal openings: At least some of the plurality of proximal openings are located in the proximal drug chamber when the system is in the transfer configuration; At least some of the plurality of proximal openings are closed by the proximal stopper member when the system is in the mixed configuration; The system according to claim 4, characterized in that...

6. The system according to claim 5, characterized in that the inner surface of the proximal stopper member is configured to close at least some of the plurality of proximal openings when the system is in the mixed configuration.

7. The system according to claim 6, characterized in that the length of the proximal stopper member from the distal end to the proximal end is longer than the distance between the most proximal opening among the plurality of proximal openings and the most distal opening among the plurality of proximal openings.

8. The system according to claim 3, characterized in that the cylindrical syringe body includes a mixing configuration indicator that shows the optimal position of the distal end of the distal stopper member when the system is in the mixing configuration.

9. The system according to claim 3, characterized in that the plunger member comprises a mixed configuration latch configured to prevent proximal movement of the plunger member relative to the cylindrical syringe body when the system is in the mixed configuration.

10. The system according to claim 9 is further characterized by comprising a retaining clip configured to generate an audible signal when connected to the syringe body.

11. Each of the proximal and distal stopper members has surfaces facing each other, The opposing surfaces of the proximal stopper member are facing in the distal direction. The opposing surfaces of the distal stopper member are facing in the proximal direction. The system according to claim 1, characterized in that the proximal and distal stopper members have first and second polymer coatings on their opposing surfaces, respectively, and the proximal drug chamber is defined by the cylindrical syringe body and the first and second polymer coatings.

12. The system according to claim 1, characterized in that the distal drug chamber includes a partial vacuum.

13. The system according to claim 1, characterized in that the needle proximal end structure has a proximal shoulder portion which cannot pass through the proximal gate in the closed configuration but can pass through the proximal gate in the open configuration.

14. The system according to claim 13, wherein the needle has a distal shoulder portion that cannot pass through the proximal gate in the closed configuration but can pass through the proximal gate in the open configuration, and the distal shoulder portion is located distal to the proximal shoulder portion.

15. The system according to claim 1, characterized in that the proximal gate comprises a pair of movable arms operably connected to a self-biasing hinge pair.

16. The system according to claim 1, characterized in that the funnel is configured to receive the needle proximal end structure and to guide the needle so that it is aligned coaxially with the distal stopper member.

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