Injection system and method

Abstract

The infusion system includes an infusion system body that defines a proximal opening at its proximal end and a distal needle interface at its distal end. The system also includes a stopper member and an open separator disposed within the infusion system body, forming a proximal drug chamber between the stopper member and the open separator, and a distal drug chamber between the open separator and the distal end of the infusion system body. The system also includes a plunger member configured to be operable for inserting the stopper member into the infusion system body. The open separator forms an openable and closable barrier between the proximal drug chamber and the distal drug chamber. The open separator is configured to allow flow from the proximal drug chamber to the distal drug chamber due to an increase in pressure in the proximal drug chamber relative to the distal drug chamber.

Description

Technical Field

[0001] The present disclosure generally relates to infusion systems, devices, and processes for facilitating various levels of control over fluid infusion, and more particularly, to systems and methods related to continuous infusion and pre-infusion liquid mixing in a medical environment, with or without safety features.

Background Art

[0002] Millions of syringes, as shown in Figure 1A(2), are consumed daily in the healthcare setting. A typical syringe (2) includes a tubular 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 into containers such as vials, bags, or other drug storage systems (10). In fact, in some countries, such as the United States, due to concerns about maintaining sterility and regulatory constraints, if a vial (10) is used with a syringe (2), as shown in certain patient settings, such a vial must be used for only one patient and then disposed of, resulting in a large amount of medical waste from the discarded vials and remaining medication, and also causing periodic shortages of certain essential medications. Referring to Figure 2A, three Luer syringes (12) are shown, each having a Luer connector shape (14) located distally, which are connected to other devices having similar connector shapes, such as the Luer manifold assembly (16) shown in Figure 2B. The Luer manifold assembly in Figure 2B can be used to intravenously administer liquid medication to a patient, with or without the use of an intravenous infusion bag. The Luer connector (14) of the syringe in Figure 2A is sometimes called a “male” Luer connector, and the Luer connector (18) in Figure 2B is sometimes called a “female” Luer connector, and one of the Luer interfaces has a threaded surface (in this case, the configuration is sometimes called a “Luer lock” configuration) so that the two are connected by relative rotation, which may also be combined with a compressive load. In other words, in one embodiment of a Luer lock, rotation, sometimes along with compression, is used to engage the threads of a male fitting (14), which then engage with a flange on a female fitting (18) to form a fluid-sealed coupling of the devices. In another embodiment, a tapered interface shape may be used to provide a Luer engagement using compression without the use of threads or rotation (such configurations may be referred to as “slip-on” or “conical” Luer configurations).While such Luer connectors are considered relatively safe for operators, there is a risk of drug spillage, leakage, or component damage during assembly. On the other hand, using needle injection configurations carries the risk of sharp needles coming into contact with or puncturing people or undesirable structures. For these reasons, so-called "safety syringes" have been developed.

[0003] One embodiment of the safety syringe (20) is shown in Figure 3, in which a tubular shielding member (22) is spring-biased to cover the needle (8) when released from the locked position relative to the syringe body (4). Another embodiment of the safety syringe (24) is shown in Figures 4A and 4B. In this configuration, after the plunger (6) is fully inserted into the syringe body (4), a retractable needle (26) is retracted (28, 26) into a safe position within the tubular body (4), as shown in Figure 4B. Such a self-contained configuration may be associated with issues of blood splatter / aerosolization, safe storage of pre-loaded energy which could malfunction and cause premature activation, loss of precision when delivering the full dose due to residual dead space in the spring-compressed volume, and / or loss of retraction speed control which may be associated with pain or patient anxiety.

[0004] The increasing demand for pre-filled syringe assemblies, as shown in Figures 5A and 5B, is further complicating the syringe market, which generally comprises a syringe body or “drug containment delivery system” (34), a plunger tip, plug or stopper (36), and a distal seal or cap (35) attached to a Luer interface (Figure 5A shows the cap 35 in position, while Figure 5B shows the cap removed to illustrate the Luer interface 14). The liquid drug resides in the volume between the distal seal and the distal end (37) of the plunger tip (36) or in a drug reservoir (40). The plunger tip (36) may include standard butyl rubber material and may be 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 material. The proximal end of the injection system body (34) in Figure 5B includes a conventional integrated syringe flange (38) formed integrally with the material of the injection system body (34). The flange (38) is configured to extend radially from the injection system body (34) and to be the entire circumference or part of the circumference around the injection system body (34). A partial flange is known as a "clipped flange," and the other The flange is known as a “full flange.” The flange is used to grip the syringe with the fingers and provides support for pushing the plunger to perform the injection. The injection system body (34) preferably comprises a translucent material such as glass or polymer. The plunger tip (36) can be positioned within the injection system body (34) to form a sealed volume within the chamber or reservoir (40) and to assist in the discharge of the associated fluid through the needle. The injection system body (34) can be defined as substantially cylindrical (i.e., so that the plunger tip 36 having a circular cross-sectional shape establishes a seal against the injection system body (34)) or can be configured to have other cross-sectional shapes such as elliptical.

[0005] Such assemblies are desirable because they can be standardized and precisely mass-produced by a few manufacturers in the world that can afford to meet all of the world's ever-changing regulations regarding filling, packaging, and the selection of materials that come into contact with pharmaceuticals / medicines, as well as the use of components. However, such simple configurations generally cannot meet the new global standards for single use, safety, auto-deactivation, and needle-stick prevention. For this reason, certain suppliers have moved towards more “vertically integrated” solutions, such as those shown in Figure 5C (41), which attempt to meet all or at least some of the standards in a single solution, and as a result of trying to meet those standards in a variety of situations, such products have significant constraints (including the constraints mentioned above with reference to Figures 3-4B), and can have relatively high inventory and usage costs.

[0006] Furthermore, many injectable liquids (e.g., pharmaceuticals) have the additional requirement that two or more components should be injected sequentially (e.g., into the patient) within a short time interval (e.g., within a few seconds). Multiple components can be injected sequentially using separate injection devices (e.g., pre-loaded syringes), or sequentially by aspirating multiple components from separate open containers using the same injection device. However, such sequential injections using separate injection devices or methods of sequentially aspirating and injecting multiple components inevitably result in multiple needle sticks to the patient, potentially leading to inaccuracies or component loss. Moreover, sequential injections using separate injection devices or methods of sequentially drawing multiple components into a syringe may unnecessarily expose the user to an uncapped needle. Furthermore, sequential injections using separate injection devices or methods of sequentially drawing multiple components may result in unacceptable delays between the injections of multiple components. Existing continuous injection systems utilize transfer tubes with various openings that work in conjunction with various stopper members to enable continuous injection. However, various openings can become clogged, and injection errors can occur due to malfunctions in the complex coordination between the openings and the stopper members.

[0007] In some cases, chemical reactions can occur between the components of multi-component infusions. Conventional dual-chamber syringes mix the components within the syringe, which may make them unsuitable for combined use with reactive components, potentially rendering the mixed components unsuitable for infusion. An example of this phenomenon is that mixing components can increase the overall viscosity of the drug, making it difficult to inject easily through the needle. Other reactions, such as exothermic or endothermic reactions, may also occur, potentially interfering with the use of conventional dual-chamber infusion systems.

[0008] Furthermore, many injectable fluids (e.g., pharmaceuticals) have another requirement: minimizing the time the fluid is exposed to metal (e.g., the stainless steel of the needle). Yet another requirement is that the system be suitable for patient self-injection.

[0009] Furthermore, it is desirable to incorporate needle-stick prevention technology into the injection system. A function that retracts at least partially the sharp tip of the needle into the syringe protects both the person administering the injection and the patient from accidental needle-stick injuries.

[0010] By retracting the needle assembly, the distal end of the sharp needle moves into the needle hub or the infusion system body / syringe body, preventing accidental needle stick injuries.

[0011] Similar problems exist in known systems where two or more liquids are mixed before the mixed liquid is injected.

[0012] 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 continuous injection, and liquid mixing and injection solution with precise control that can utilize the existing, relatively well-controlled supply chain of conventionally supplied prefilled syringe assemblies, as illustrated with reference to Figures 5A and 5B. [Overview of the project]

[0013] The embodiments relate to injection systems. In particular, the embodiments relate to continuous injection, liquid mixing, and injection systems that precisely control the handling, mixing, and delivery of continuous injection agents.

[0014] In one embodiment, the infusion system includes an infusion system body that defines a proximal opening at its proximal end and a distal needle interface at its distal end. The system also includes a stopper member and an open separator disposed within the infusion system body, forming a proximal drug chamber between the stopper member and the open separator, and a distal drug chamber between the open separator and the distal end of the infusion system body. The system also includes a plunger member configured to be operable for inserting the stopper member into the infusion system body. The plunger may be operated manually by the user or by a device such as an automatic injector or a pen-type injector. The open separator forms an openable and closable barrier between the proximal drug chamber and the distal drug chamber. The open separator is configured to allow flow from the proximal drug chamber to the distal drug chamber when the pressure in the proximal drug chamber relative to the distal drug chamber increases.

[0015] In one or more embodiments, the perforated separator is configured to move longitudinally within the injection system body. The perforated separator may include proximal and distal gaskets, which are positioned adjacent to the proximal and distal ends of the perforated separator, respectively, and extend radially from the perforated separator. The perforated separator may be configured to maintain contact between the inner surface of the injection system body and the proximal gasket, and between the inner surface of the injection system body and the distal gasket, as it moves longitudinally within the injection system body. The proximal and distal gaskets may be separated by a minimum longitudinal distance.

[0016] In one or more embodiments, proximal and distal circumferential gaskets are configured to form first and second fluid-tight seals, respectively, with the inner surface of the injection system body. The proximal and distal circumferential gaskets can be made from an elastic material. The elastic material may be rubber, thermoplastic elastomer, butyl rubber, or polyisoprene elastomer. The perforated separator may include a port configured to open in response to an increase in pressure in the proximal drug chamber relative to the distal drug chamber.

[0017] In one or more embodiments, the perforated separator includes a rigid portion and an elastic portion. The elastic portion may define a pocket configured to receive the rigid portion. The rigid portion may be made from a cyclic olefin copolymer. The elastic portion may be made from rubber, a thermoplastic elastomer, butyl rubber, or a polyisoprene elastomer.

[0018] In one or more embodiments, the elastic portion includes an annular flap configured to be positioned adjacent to the distal surface of the rigid portion. The elastic portion also includes a ring configured to support the annular flap. The elastic portion further includes proximal and distal circumferential gaskets extending from the outer circumference of the ring. The proximal and distal circumferential gaskets may be configured to form first and second fluid-tight seals, respectively, with the inner surface of the injection system body. The rigid portion may include an annular portion. The annular portion may define a through port. The port may be configured to be closed in an openable and closable manner by the annular flap of the elastic portion. The annular flap of the elastic portion may be biased to close the port in an openable and closable manner and may be configured to deform away from the port defined by the annular portion of the rigid portion due to an increase in pressure in the proximal drug chamber relative to the distal drug chamber, thereby opening the port.

[0019] In one or more embodiments, the annular portion defines a plurality of ports through which it passes. Each of the plurality of ports may be configured to be closed in an openable and closable manner by an annular flap of the elastic portion. The annular flap of the elastic portion may be biased to close each of the plurality of ports in an openable and closable manner, and may be configured to deform away from each of the plurality of ports defined by the annular portion of the rigid portion as the pressure of the proximal drug chamber increases relative to the distal drug chamber, thereby opening each of the plurality of ports.

[0020] In one or more embodiments, the rigid portion includes a distally extending portion coupled to the annular portion. The elastic portion may have a radially inward circumferential surface defining a central port. The radially inward circumferential surface of the elastic portion is configured to form a fluid-tight seal around the distally extending portion of the rigid portion, thereby closing the central port of the elastic portion. The elastic portion can be biased to close the central port by the distally extending portion of the rigid portion. An increase in pressure in the proximal drug chamber relative to the distal drug chamber can cause the elastic portion to deform away from the distally extending portion of the rigid portion, thereby releasing the fluid-tight seal around it and opening the central port of the elastic portion. The distally extending portion of the rigid portion may define a circumferential groove configured to accommodate the radially inward circumferential surface of the elastic portion.

[0021] In one or more embodiments, a rigid portion defines a first port, and an elastic portion defines a second port. The perforated separator can have a closed configuration and an open configuration. In the closed configuration, both the first and second ports are closed, and in the open configuration, both the first and second ports are open. In the open configuration, the flow path can fluidly connect the proximal and distal drug chambers through the first and second ports. The elastic portion can be biased to close the first and second ports, thereby giving the perforated separator a closed configuration. The perforated separator can be configured to deform from a closed configuration to an open configuration due to an increase in pressure in the proximal drug chamber relative to the distal drug chamber.

[0022] In another embodiment, the infusion method includes the step of providing a pre-filled infusion system. The infusion system includes an infusion system body that defines a proximal opening at its proximal end and a distal needle interface at its distal end. The infusion system also includes a stopper member and an open separator disposed within the infusion system body, forming a proximal drug chamber between the stopper member and the open separator and a distal drug chamber between the open separator and the distal end of the infusion system body. The infusion system further includes a first drug and bubbles disposed within the distal drug chamber. Furthermore, the infusion system includes a second drug disposed within the proximal drug chamber. Furthermore, the infusion system includes a plunger member coupled to the stopper member. The method also includes the step of agitating the pre-filled infusion system to mix the first drug. The method further includes the step of attaching a needle assembly having a needle to the distal needle interface at the distal end of the infusion system body. Furthermore, the method includes the step of positioning the infusion system body so that the needle faces upward. Furthermore, the method includes the step of moving the plunger and the stopper member coupled thereto distally within the infusion system body with the needle facing upward, thereby removing at least a portion of the air bubbles from the distal drug chamber. The method also includes the steps of moving the plunger and the stopper member coupled thereto further distally within the infusion system body, thereby discharging at least a portion of the first drug from the distal drug chamber via the needle and moving the perforated separator longitudinally toward the distal end of the infusion system body; and moving the plunger and the stopper member coupled thereto further distally within the infusion system body, thereby opening the perforated separator and transferring at least a portion of the second drug from the proximal drug chamber to the distal drug chamber. Furthermore, the method includes the step of moving the plunger and the stopper member coupled thereto further distally within the infusion system body, thereby discharging at least a portion of the second drug from the distal drug chamber via the needle.

[0023] In one or more embodiments, after at least a portion of the first drug has been discharged from the distal drug chamber via the needle, the plunger and the stopper member coupled thereto are moved further distally within the infusion system body to increase the pressure in the proximal drug chamber relative to the distal drug chamber, thereby opening the perforated separator. The method may further include the steps of moving the perforated separator to contact the distal end of the infusion system body and moving the stopper member to contact the perforated separator, thereby completing the infusion.

[0024] In another embodiment, the infusion system includes an infusion system body that defines a proximal opening at its proximal end and a distal needle interface at its distal end. The system also includes a proximal stopper member, an intermediate perforated member, and a distal stopper member, all located within the infusion system body. The proximal stopper member, the intermediate perforated member, the distal stopper member, and the infusion system body form a proximal drug chamber between the proximal stopper member and the intermediate perforated separator, an intermediate drug chamber between the intermediate perforated separator and the distal stopper member, and a distal drug chamber between the distal stopper member and the distal end of the infusion system body. The system further includes a plunger member configured to be operable for inserting the proximal stopper member into the infusion system body. The plunger may be operated manually by the user or by a device such as an automatic injector or a pen-type injector. The perforated separator forms an openable and closable barrier between the proximal drug chamber and the intermediate drug chamber. The perforated separator is configured to selectively allow flow from the proximal drug chamber to the intermediate drug chamber.

[0025] In one or more embodiments, a separator with an intermediate aperture is configured to move longitudinally within the injection system body. The separator with an intermediate aperture can include proximal and distal gaskets that are disposed adjacent to the proximal and distal ends of the separator with an intermediate aperture, respectively, and extend radially from the separator with an intermediate aperture. The separator with an intermediate aperture can be configured to maintain contact between the inner surface of the injection system body and the proximal gasket and between the inner surface of the injection system body and the distal gasket when moving longitudinally within the injection system body. The proximal and distal gaskets can be separated by a minimum longitudinal distance.

[0026] In one or more embodiments, proximal and distal circumferential gaskets are configured to form first and second fluid-tight seals with the inner surface of the injection system body, respectively. The proximal and distal circumferential gaskets can be made of an elastic material. The elastic material can be rubber, a thermoplastic elastomer, butyl rubber, or a polyisoprene elastomer.

[0027] In one or more embodiments, a separator with an intermediate aperture defines an intermediate port and includes a plug configured to be removably disposed within the intermediate port to seal the intermediate port. The injection system can further include a needle having a proximal end of the needle, and the plug can be configured to be disengaged from the intermediate port by the proximal end of the needle. The separator with an intermediate aperture can define a distal-facing funnel configured to direct the proximal end of the needle to the plug within the intermediate port.

[0028] The above-described and other embodiments of the present invention are described in the following detailed description.

Brief Description of the Drawings

[0029] This patent or application file contains at least one drawing created in color. Copies of this patent or patent application publication that include color drawings are provided by the United States Patent and Trademark Office upon payment of the fee for the claims and the necessary fees. [Figure 1] Figures 1A and 1B illustrate one aspect of a conventional injection syringe configuration. [Figure 2] Figures 2A and 2B illustrate one aspect of a conventional injection syringe configuration. [Figure 3] Figure 3 illustrates one aspect of a conventional injection syringe configuration. [Figure 4] Figures 4A and 4B illustrate one aspect of a conventional injection syringe configuration. [Figure 5] Figures 5A - 5C illustrate one aspect of a conventional injection syringe configuration. [Figure 6] Figure 6 is a perspective view showing a dual - chamber continuous injection system according to some embodiments. [Figure 7] [[ID=Z1]]Figure 7 is an exploded view showing a dual - chamber continuous injection system according to some embodiments. [Figure 8] Figure 8 is a perspective view showing a pre - filled dual - chamber continuous injection system according to some embodiments. [Figure 9] Figures 9A and 9B are a perspective view and an exploded view showing a separator with apertures according to some embodiments. [Figure 10] Figures 10A - 10D are a side view (Figure 10A), a side cross - sectional view (Figure 10B), a left - hand / distal view (Figure 10C), and a right - hand / proximal view (Figure 10D) showing the elastic portion of a separator with apertures according to some embodiments. [Figure 11] Figures 11A - 11D are a side view (Figure 11A), a left - hand / distal view (Figure 11B), a right - hand / proximal view (Figure 11C), and a side cross - sectional view (Figure 11D) showing the rigid portion of a separator with apertures according to some embodiments. [Figure 12] Figure 12 is a side cross - sectional view showing a separator with apertures (900) in a closed configuration. [Figure 13]Figure 13 is a side cross-sectional view of an open-configured separator with openings according to several embodiments. [Figure 14] Figure 14 is a perspective view of an open-configured separator with openings according to several embodiments. [Figure 15] Figures 15A and 15B are detailed side cross-sectional views showing the opening and closing of a perforated separator in a continuous injection system according to several embodiments. [Figure 16] Figures 16A and 16B are detailed side cross-sectional views showing the opening and closing of a perforated separator in a continuous injection system according to several embodiments. [Figure 17] Figures 17A and 17B are detailed side cross-sectional views showing the opening and closing of a perforated separator in a continuous injection system according to several embodiments. [Figure 18] Figure 18 is a side cross-sectional view showing various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 19] Figure 19 is a side cross-sectional view showing various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 20] Figure 20 is a side cross-sectional view showing various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 21] Figure 21 is a side cross-sectional view showing various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 22] Figure 22 is a side cross-sectional view showing various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 23] Figure 23 is a side cross-sectional view showing various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 24]Figure 24 is a side cross-sectional view showing various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 25] Figure 25 is a side cross-sectional view showing various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 26] Figure 26 is a side cross-sectional view showing various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 27] Figure 27 is a side cross-sectional view showing various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 28] Figure 28 is a side cross-sectional view showing various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 29] Figure 29 is a side cross-sectional view showing various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 30] Figures 30A to 30D schematically illustrate various steps in a continuous injection method using a dual-chamber continuous injection system according to several embodiments. [Figure 31] Figure 31 is a side view illustrating various steps in a liquid mixing and injection method using a triple-chamber injection system according to several embodiments. [Figure 32] Figure 32 is a side cross-sectional view showing various steps in a liquid mixing and injection method using a triple-chamber injection system according to several embodiments. [Figure 33] Figure 33 is a side cross-sectional view showing various steps in a liquid mixing and injection method using a triple-chamber injection system according to several embodiments. [Figure 34] Figure 34 is a side cross-sectional view showing various steps in a liquid mixing and injection method using a triple-chamber injection system according to several embodiments. [Figure 35] Figure 35 is a side view illustrating various steps in a liquid mixing and injection method using a triple-chamber injection system according to several embodiments. [Figure 36] Figure 36 is a side view illustrating various steps in a liquid mixing and injection method using a triple-chamber injection system according to several embodiments. [Figure 37] Figure 37 is a side view illustrating various steps in a liquid mixing and injection method using a triple-chamber injection system according to several embodiments. [Figure 38] Figure 38 is a side view illustrating various steps in a liquid mixing and injection method using a triple-chamber injection system according to several embodiments. [Figure 39] Figure 39 is a detailed side view of a triple-chamber injection system according to several embodiments. [Figure 40] Figure 40 is a detailed view of a separator with an intermediate opening for use with a triple-chamber injection system according to several embodiments. [Figure 41] Figure 41 is a detailed view of a separator with an intermediate opening for use with a triple-chamber injection system according to several embodiments. [Figure 42] Figure 42 is a detailed view of a separator with an intermediate opening for use with a triple-chamber injection system according to several embodiments. [Figure 43] Figure 43 is a side cross-sectional view of an open separator with a closed configuration according to several embodiments. [Figure 44] Figure 44 is a side cross-sectional view of an open-configured separator with openings according to several embodiments.

[0030] To better understand how the above and other advantages and objectives of various embodiments are obtained, a more detailed description of the embodiments is provided with reference to the accompanying drawings. Note that the drawings are not drawn to a fixed scale, and elements of similar structure or function are indicated by the same reference numerals throughout. It should be understood that these drawings merely illustrate specific exemplary embodiments and should not be considered to limit the scope of the embodiments. [Modes for carrying out the invention]

[0031] Exemplary multi-chamber continuous injection system and method Figures 6 and 7 are perspective and exploded views showing a dual-chamber continuous infusion system (100) according to several embodiments. Figure 8 is a perspective view of a dual-chamber continuous infusion system (100) pre-filled with first and second liquids (252, 254), which are first and second drugs for continuous infusion according to several embodiments. The dual-chamber continuous infusion system (100) includes a conventional off-the-shelf infusion system body (34) in which a conventional off-the-shelf stopper member (32) is disposed. The dual-chamber continuous infusion system (100) also includes a perforated separator (900) located at a distance distal to the stopper member (32) within the infusion system body (34). The stopper member (32) and the perforated separator (900), together with the infusion system body (34), define the proximal and distal drug chambers (40, 42). The first and second liquids (252, 254) are contained in distal and proximal drug chambers (42, 40), respectively (see Figure 8). A stopper member (32) and an open separator (900) close the proximal and distal ends of the proximal drug chamber (40). The open separator (900) closes the proximal end of the distal drug chamber (42). In some embodiments, the distal surface of the stopper member (32) and the proximal surface of the open separator (900) are coated with a lubricating polymer coating (e.g., PTFE or ETFE), and the polymer coating of the stopper member (32) and the open separator (900), together with the infusion system body (34), defines the proximal drug chamber (40). The lubricating polymer coating also serves to isolate the rubber of the stopper member (32) and the perforated separator (900) from the second liquid (254). In other embodiments, the perforated separator (900) may be made of uncoated butyl rubber such as chlorobutyl rubber and / or bromobutyl rubber. Alternatively, the perforated separator (900) may be made of other elastomer materials such as TPE, TPU, silicone rubber, or other elastomers.

[0032] The dual-chamber continuous injection system (100) further includes a plunger member (44) which is coupled to a stopper member (32) and configured to insert the stopper member (32) distally within the injection system body (34).

[0033] The dual-chamber continuous infusion system (100) enables continuous infusion by injecting a first fluid (252) from the distal drug chamber (42) and then a second fluid (254) from the proximal drug chamber (40) by the user progressively pushing a plunger assembly (44) against the infusion system body (34). The plunger assembly (44) includes a plunger housing member (69) coupled to a stopper member (32) and a plunger operating interface (128). The plunger operating interface (128) may be configured to be pushed by an operator or to be configured to connect to a device such as an automatic injector or a pen-type injector. In some embodiments, including an automatic injector, a linear motor or one or more compression springs are configured to apply distally directed and / or proximal directed forces to the plunger operating interface to operate the plunger assembly (44). The first and second liquids (252, 254) located in the distal and proximal drug chambers (42, 40), respectively, may be any liquid or gel, such as an aqueous or oily drug solution.

[0034] The infusion system body (34) includes a distal needle interface (810) at its distal end. In some embodiments, the distal needle interface (810) may be a female Luer connector. The dual-chamber continuous infusion system (100) also includes a distal seal or cap (35), which is removably coupled to the distal needle interface (810) to fluidize the distal needle interface (810). Although the dual-chamber continuous infusion system (100) is depicted as having a distal needle interface (810), in other embodiments, a fixed needle may be attached to the distal end of the infusion system body (34). The infusion system body (34) shown in Figures 6 to 8 is a syringe body, but the infusion system body (34) may be a cartridge body instead of a syringe.

[0035] 1. Separator with opening Figures 9A to 12 show perforated separators (900) for use with a dual-chamber continuous infusion system (100) according to several embodiments. The perforated separators (900) are positioned within the infusion system body (34) and configured to define the proximal and distal drug chambers (40, 42) as described above. The perforated separators (900) have a closed configuration (see Figure 12) in which the flow of fluid through the perforated separators (900) is blocked, and an open configuration (see Figures 13 and 14) in which fluid is allowed to flow through the perforated separators (900) from the proximal drug chamber (40) to the distal drug chamber (42). The perforated separators (900) are configured to change from the closed configuration to the open configuration due to an increase in pressure in the proximal drug chamber (40) relative to the distal drug chamber (42).

[0036] Figures 9A and 9B are perspective and exploded views of perforated separators (900) according to several embodiments. The perforated separator (900) includes a rigid portion (910) disposed within an elastic portion (950). The elastic portion (950) defines a pocket (952) in which the rigid portion (910) is disposed. The rigid portion (910) can be made from a polymer such as a cyclic olefin copolymer (COC) and / or a cyclic olefin polymer (COP). Alternatively, the rigid portion (910) may be made from glass, ceramic, metal, or other material that does not react with the drug in the distal drug chamber (42). The elastic portion (950) can be made from rubber, thermoplastic elastomer (TPE), butyl rubber such as chlorobutyl or bromobutyl, silicone rubber, and / or polyisoprene elastomer.

[0037] Furthermore, the perforated separator (900) is configured to move longitudinally within the injection system body (34). The elastic portion (950) of the perforated separator (900) includes a proximal gasket (954) and a distal gasket (956). The proximal and distal gaskets (954, 956) are annular bodies extending radially outward from the proximal and distal ends, respectively, of the elastic portion (950) of the perforated separator (900). The proximal and distal gaskets (954, 956) are made of an elastic material and are configured to form first and second fluid-tight seals with the inner surface of the injection system body (34). The elastic material can be rubber, thermoplastic elastomer (TPE), butyl rubber, silicone rubber, or polyisoprene elastomer. The perforated separator (900) may be coated with PTFE on one or both of the proximal and distal drug chambers (40, 42).

[0038] While the perforated separator (900) moves longitudinally within the injection system body (34), the perforated separator (900) is configured to maintain contact between the inner surface of the injection system body (34) and both the proximal and distal gaskets (954, 956). To this end, the proximal and distal gaskets (954, 956) are separated by the minimum longitudinal distance. By maintaining contact between the inner surface of the injection system body (34) and both the proximal and distal gaskets (954, 956), the perforated separator (900) is prevented from twisting or inverting around its diameter, thereby maintaining the respective first and second fluid-tight seals.

[0039] Figures 10A to 10D are side views (Figure 10A), side section views (Figure 10B), left / distal side views (Figure 10C), and right / proximal side views (Figure 10D) of the elastic portion (950) of an open separator (900) according to several embodiments. As described above and as shown in Figure 10B, the elastic portion (950) defines a pocket (952) in which the rigid portion (910) is located. Figures 10A and 10B also show proximal and distal gaskets (954, 956). The elastic portion (950) of the open separator (900) also defines an annular flap (958) supported by a ring (960), as shown in Figures 10B, 10C, and 10D. As shown in Figure 10B, the annular flap (958) of the elastic portion (950) has a radially inward circumferential surface (962) that defines a central port (964) that penetrates the annular flap (958).

[0040] Figures 11A to 11D are side views (Figure 11A), left / distal side view (Figure 11B), right / proximal side view (Figure 11C), and side cross-sectional view (Figure 11D) of the rigid portion (910) of the perforated separator (900) according to several embodiments. The rigid portion (910) of the perforated separator (900) defines an annular portion (912) that defines a pair of through ports (914), as shown in Figures 11B, 11C, and 11D. When the rigid portion (910) is positioned within the pocket (952) of the elastic portion (950), the annular flap (958) of the elastic portion (950) is biased to fluid-seal / close the ports (914) of the annular portion (912) of the rigid portion (910). As shown in Figures 11A, 11B, and 11D, the rigid portion (910) also defines a distally extending portion (916), which extends distally from approximately the center of the distal surface of the annular portion (912) of the rigid portion (910). The distally extending portion (916) defines a circumferential groove (918) configured to receive the radially inward circumferential surface (962) of the annular flap (958). When the rigid portion (910) is positioned within the pocket (952) of the elastic portion (950), the radially inward circumferential surface (962) of the annular flap (958) of the elastic portion (950) is biased to form a fluid-tight seal around the distally extending portion (916) of the rigid portion (910), thereby fluid-sealing / closing the central port (964) of the annular flap (958) of the elastic portion (950).

[0041] Figure 12 is a side cross-sectional view of an open separator (900) in a closed configuration according to several embodiments. In the closed configuration, the port (914) of the annular portion (912) of the rigid portion (910) is fluid-sealed / closed by the annular flap (958) of the elastic portion (950). Similarly, in the closed configuration, the central port (964) of the annular flap (958) of the elastic portion (950) is fluid-sealed / closed by the distally extending portion (916) of the rigid portion (910). Thus, in the open separator (900) in a closed configuration, the flow of fluid from the proximal drug chamber (40) to the distal drug chamber (42) is blocked.

[0042] Figures 13 and 14 are side and perspective views of an open-configured perforated separator (900) according to several embodiments. In the open configuration, the increase in pressure within the proximal drug chamber (40) relative to the distal drug chamber (42) causes the annular flap (958) of the elastic portion (950) to deform / dome-shaped so as to move distally away from the annular portion (912) of the rigid portion (910). As a result, the port (914) of the annular portion (912) of the rigid portion (910) is opened. Similarly, in the open configuration, the radially inward circumferential surface (962) of the annular flap (958) moves distally away from the groove (918) of the distally extending portion (916) of the rigid portion (910). As a result, the central port (964) of the annular flap (958) of the elastic portion (950) is opened. Therefore, in an open-configuration separator with openings (900), the fluid flow path (1300) from the proximal drug chamber (40) to the distal drug chamber (42) is opened.

[0043] Figures 12, 13, and 14 also show that in some embodiments, a distal radial extension (920) is provided at the distal end of the distally extending portion (916). The distal radial extension (920) increases the mechanical interference between the elastic portion (950) and the rigid portion (910), thereby increasing the pressure difference between the proximal and distal chambers (40, 42) required to convert the perforated separator (900) from a closed configuration to an open configuration. In some embodiments, the distal radial extension (920) prevents the seal between the elastic portion (950) and the rigid portion (910) from accidentally opening during shipping, handling, or transport. For example, in some embodiments, changes in ambient air pressure may cause the perforated separator to accidentally deform from a closed configuration to an open configuration. Some embodiments are made without a distal radial extension at the distal end of the distally extending portion (see, for example, Figure 11).

[0044] Figures 43 and 44 show perforated separators (4300) for use with multi-chamber continuous infusion or mixed infusion systems according to various embodiments. The perforated separators (4300) are located within the infusion system body (34) as described above and are configured to define the proximal and distal drug chambers (40, 42). The perforated separators (4300) have a closed configuration (see Figure 43) in which the flow of fluid through the perforated separators (4300) is blocked, and an open configuration (see Figure 44) in which the fluid is allowed to flow through / across the perforated separators (4300) from the proximal chamber to the distal chamber (from right to left in Figures 43 and 44). The perforated separators (4300) are configured to change from the closed configuration to the open configuration when the pressure in the proximal chamber (right side in Figures 43 and 44) ​​increases compared to the pressure in the distal chamber (left side in Figures 43 and 44).

[0045] The perforated separator (4300) includes a rigid portion (4310) disposed within an elastic portion (4350). The elastic portion (4350) defines a pocket (4352) in which the rigid portion (4310) is placed. The rigid portion (4310) can be made from a polymer such as a cyclic olefin copolymer (COC) and / or a cyclic olefin polymer (COP). Alternatively, the rigid portion (4310) can be made from glass, ceramic, metal, or other material that does not react with the drug in the distal drug chamber (42). The elastic portion (4350) can be made from rubber, thermoplastic elastomer (TPE), butyl rubber such as chlorobutyl or bromobutyl, silicone rubber, and / or polyisoprene elastomer.

[0046] Furthermore, the perforated separator (4300) is configured to move longitudinally within the injection system body (34; see, for example, Figures 6 and 8). The elastic portion (4350) of the perforated separator (4300) includes a proximal gasket (4354) and a distal gasket (4356). The proximal and distal gaskets (4354, 4356) are annular bodies extending radially outward from the proximal and distal ends, respectively, of the elastic portion (4350) of the perforated separator (4300). The proximal and distal gaskets (4354, 4356) are made of an elastic material and are configured to form first and second fluid-tight seals with the inner surface of the injection system body (34). Examples of elastic materials include rubber, thermoplastic elastomer (TPE), butyl rubber, silicone rubber, or polyisoprene elastomer. The perforated separator (4300) may be coated with PTFE on one or both of the proximal and distal drug chambers (40, 42; see, for example, Figures 6 and 8).

[0047] While the perforated separator (4300) moves longitudinally within the injection system body (34), the perforated separator (4300) is configured to maintain contact between the inner surface of the injection system body (34) and both the proximal and distal gaskets (4354, 4356). To this end, the proximal and distal gaskets (4354, 4356) are separated by the minimum longitudinal distance. By maintaining contact between the inner surface of the injection system body (34) and both the proximal and distal gaskets (4354, 4356), the perforated separator (4300) is prevented from twisting or inverting around its diameter, thereby maintaining the respective first and second fluid-tight seals.

[0048] The elastic portion (4350) of the perforated separator (4300) defines an annular flap (4358) supported by a ring (4360). The annular flap (4358) of the elastic portion (4350) has a radially inward circumferential surface (4362) that defines a central port (4364) passing through the annular flap (4358). The perforated separator (4300) can be positioned around an elongated member (4316). The elongated member (4316) may be a needle of the injection system and may be retractable to keep the injection system safe after injection. The rigid portion (4310) of the perforated separator (4300) may define a proximal funnel (not shown) to guide the elongated member (4316) and facilitate assembly.

[0049] The annular flap (4358) defines a radially inward circumferential surface (4362). When the rigid portion (4310) is positioned within the pocket (4352) of the elastic portion (4350), the radially inward circumferential surface (4362) of the annular flap (4358) of the elastic portion (4350) is biased to form a fluid-tight seal around the outer surface of the elongated member (4316), thereby fluid-sealing / closing the central port (4364) of the annular flap (4358) of the elastic portion (4350).

[0050] Figure 43 is a side cross-sectional view of an open separator (4300) in a closed configuration according to several embodiments. In the closed configuration, the radially inward circumferential surface (4362) of the annular flap (4358) of the elastic portion (4350) is aligned relative to the longitudinal axis of the elongated member (4316), and fluid seals / closes the periphery of the outer surface of the elongated member (4316). As a result, in the open separator (4300) in a closed configuration, fluid flow from the proximal chamber (right side in Figures 43 and 44) ​​to the distal chamber (left side in Figures 43 and 44) ​​is blocked.

[0051] Figure 44 is a side cross-sectional view of an open-configured separator (4300) according to several embodiments. In the open configuration, the increase in pressure in the proximal chamber (right side in Figures 43 and 44) ​​relative to the distal chamber (left side in Figures 43 and 44) ​​causes the annular flap (4358) of the elastic portion (4350) to deform distally away from the rigid portion (4310) / become dome-shaped. As a result, the radially inward circumferential surface (4362) of the annular flap (4358) of the elastic portion (4350) rotates away from the longitudinal axis of the elongated member (4316) and out of alignment with the longitudinal axis. As a result, the central port (4364) of the annular flap (4358) of the elastic portion (4350) is opened. Therefore, in the open configuration of the perforated separator (4300), the fluid flow path (1300) from the proximal chamber (right side in Figures 43 and 44) ​​to the distal chamber (left side in Figures 43 and 44) ​​is opened.

[0052] 2. Operation of a separator with openings Figures 15A to 17B are detailed side cross-sectional views showing the opening and closing of a perforated separator (900) of a continuous infusion system (100) that enables continuous infusion according to several embodiments. The perforated separator (900) opens and closes in response to the force and pressure difference applied to the proximal and distal drug chambers (40, 42). In Figure 15A, first and second fluids (252, 254) are placed in the distal and proximal drug chambers (42, 40), respectively. As a result, the pressure in the distal drug chamber (42) (P1) and the pressure in the proximal drug chamber (40) (P2) are equal. In this step of the continuous infusion method, the perforated separator (900) is placed in a closed configuration by the biasing of an annular flap (958). In the closed configuration, a distal force applied to the stopper member (32) via the plunger member (44) is transmitted to the perforated separator (900) via the incompressible second liquid (254), thereby causing the perforated separator (900) to move distally along the longitudinal axis of the infusion system body (34), as shown in Figure 15B, and the first liquid (252) to be discharged from the distal drug chamber (42).

[0053] In Figure 15B, the distal movement of the perforated separator (900) causes most of the first liquid (252) to be discharged from the distal drug chamber (42). As a result, the pressure (P2) in the proximal drug chamber (40) increases relative to the pressure (P1) in the distal drug chamber (42). Consequently, the perforated separator (900) begins to deform from a closed configuration to an open configuration, as shown in Figure 16A.

[0054] In Figure 16A, when a distal force is continuously applied to the stopper member (32) via the plunger member (44), the pressure (P2) in the proximal drug chamber (40) increases relative to the pressure (P1) in the distal drug chamber (42). Due to the increase in pressure in the proximal drug chamber (40) relative to the distal drug chamber (42), the annular flap (958) of the elastic portion (950) deforms to move distally away from the annular portion (912) of the rigid portion (910) / becomes dome-shaped, and the perforated separator (900) deforms from a closed configuration to an open configuration. When the perforated separator (900) is in the open configuration, the second liquid (254) can flow from the proximal drug chamber (40) to the distal drug chamber (42) through the perforated separator (900), as shown in Figure 16B.

[0055] In Figure 16B, a portion of the second liquid (254) flows from the proximal drug chamber (40) to the distal drug chamber (42), but the pressure (P2) in the proximal drug chamber (40) remains higher than the pressure (P1) in the distal drug chamber (42). Therefore, the perforated separator (900) remains in an open configuration.

[0056] In Figure 17A, most of the second liquid (254) flows from the proximal drug chamber (40) to the distal drug chamber (42). As a result, the pressure (P1) in the distal drug chamber (42) increases, and the pressure (P2) in the proximal drug chamber (40) decreases until the pressure (P2) in the proximal drug chamber (40) becomes lower than the pressure (P1) in the distal drug chamber (42). Consequently, the perforated separator (900) changes from an open configuration to a closed configuration. In the closed configuration, a distal force applied to the stopper member (32) via the plunger member (44) is transmitted to the perforated separator (900) via the incompressible second liquid (254), thereby causing the perforated separator (900) to move distally along the longitudinal axis of the infusion system body (34), as shown in Figure 17B, and the second liquid (254) to be discharged from the distal drug chamber (42).

[0057] In Figure 17B, most of the second liquid (254) is discharged from the distal drug chamber (42). As a result, the pressure (P1) in the distal drug chamber (42) and the pressure (P2) in the proximal drug chamber (40) become equal. In this step of the continuous infusion method, the annular flap (958) biases the perforated separator (900) to maintain a closed configuration.

[0058] 3. Exemplary continuous injection method Figures 18 to 29 are side cross-sectional views illustrating various steps in a continuous infusion method using a dual-chamber continuous infusion system (100) according to several embodiments. Figure 18 shows a pre-filled dual-chamber continuous infusion system (100) in a transport / storage configuration. As described above, the dual-chamber continuous infusion system (100) includes a conventional off-the-shelf infusion system body (34), a conventional off-the-shelf stopper member (32) placed therein, a perforated separator (900), proximal and distal drug chambers (40, 42), a plunger member (44), a distal needle interface (810), and a distal seal or cap (35) that closes the distal needle interface (810). The first and second fluids (252, 254) are contained in the distal and proximal drug chambers (42, 40), respectively. The distal drug chamber (42) also contains bubbles (256) to facilitate the mixing of the first liquid (252), which is a drug suspension (e.g., an aluminum suspension).

[0059] In the step shown in Figure 19, the dual-chamber continuous injection system (100) is shaken to mix / resuspend the first liquid (252). Also, the distal sealer (35) is removed from the distal needle interface (810) in preparation for injection of the system (100).

[0060] In the step shown in Figure 20, the needle assembly (600) is coupled to the distal needle interface (810) in preparation for injection of the system (100).

[0061] In the step shown in Figure 21, the needle shield (610) is removed from the needle assembly (600) to expose the needle (620) in preparation for injecting the system (100).

[0062] In the step shown in Figure 22, the dual-chamber continuous injection system (100) is positioned with the needle facing upward to move the air bubble (256) toward the distal needle interface (810). In the steps shown in Figures 18 to 24, the perforated separator (900) is in the closed configuration shown in Figure 15A. Subsequently, a distal force is applied to the plunger member (44) and the stopper member (32) attached thereto. The distal force is transmitted to the perforated separator (900) via the incompressible second fluid (254). When the perforated separator (900) is in a closed configuration, the distal force transmitted to the perforated separator (900) causes the perforated separator (900) to move distally along the longitudinal axis of the infusion system body (34), thereby expelling air bubbles (256) from the distal drug chamber (42) and "degassing" the system (100). After the system (100) is degassed, the system (100) is ready for infusion.

[0063] In the steps shown in Figures 23 and 24, the sharp distal end (622) of the needle (620) can be inserted into the target of injection (e.g., the patient). Subsequently, a distal force is further applied to the plunger member (44) and the stopper member (32) attached thereto. The distal force is transmitted to the perforated separator (900) via the incompressible second fluid (254). With the perforated separator (900) in a closed configuration, the distal force transmitted to the perforated separator (900) causes the perforated separator (900) to move distally along the longitudinal axis of the infusion system body (34), and a portion of the first fluid (252) is discharged from the distal drug chamber (42).

[0064] Figure 24 is a detailed side cross-sectional view showing the configuration of the perforated separator (900) in the continuous infusion step shown in Figure 23. During the steps shown in Figures 23 and 24, the pressure in the distal drug chamber (42) (P1) and the pressure in the proximal drug chamber (40) (P2) are equal, and the biasing of the annular flap (958) places the perforated separator (900) in a closed configuration, as shown in Figure 15A and as described above.

[0065] In the steps shown in Figures 25 and 26, a distal force is further applied to the plunger member (44) and the stopper member (32) attached thereto. As the first liquid (252) is largely discharged from the distal drug chamber (42) by the distal movement of the perforated separator (900), the pressure in the proximal drug chamber (40) (P2) rises relative to the pressure in the distal drug chamber (42) (P1). As a result, the perforated separator (900) begins to deform from a closed configuration to an open configuration, as shown in Figure 16A and as described above.

[0066] Figure 26 is a detailed side cross-sectional view showing the configuration of the perforated separator (900) in the continuous infusion step shown in Figure 25. During the steps shown in Figures 25 and 26, the increase in pressure in the proximal drug chamber (40) relative to the distal drug chamber (42) causes the annular flap (958) of the elastic portion (950) to deform distally away from the annular portion (912) of the rigid portion (910) / to become dome-shaped, thereby deforming the perforated separator (900) from a closed configuration to an open configuration. With the perforated separator (900) in the open configuration, the second liquid (254) can flow from the proximal drug chamber (40) to the distal drug chamber (42) through the perforated separator (900), as shown in Figures 16B, 27, and 28, and as described above.

[0067] In the steps shown in Figures 27 and 28, a distal force is further applied to the plunger member (44) and the stopper member (32) attached thereto. While some of the second liquid (254) flows from the proximal drug chamber (40) to the distal drug chamber (42), the pressure (P2) in the proximal drug chamber (40) remains higher than the pressure (P1) in the distal drug chamber (42). Therefore, the perforated separator (900) remains in an open configuration, as shown in Figure 16B and as described above. As the distal force continues to be applied to the plunger member (44) and the stopper member (32) attached thereto, the second liquid (254) is discharged from the distal drug chamber (42) to the needle (620), as shown in Figures 17A and 17B and as described above.

[0068] In the step shown in Figure 29, most of the second liquid (254) is discharged from the distal drug chamber (42). As a result, the pressure (P1) in the distal drug chamber (42) increases, and the pressure (P2) in the proximal drug chamber (40) decreases until the pressure (P2) in the proximal drug chamber (40) becomes lower than the pressure (P1) in the distal drug chamber (42). Consequently, the perforated separator (900) changes from an open configuration to a closed configuration, as shown in Figure 17B and as described above.

[0069] Figures 30A to 30D schematically illustrate various steps in a continuous injection method using a dual-chamber continuous injection system (100) according to several embodiments. Figure 30A shows the system (100) in a transport / storage configuration, as shown in Figure 18 and as described above. Figure 30B shows the system (100) after degassing, as shown in Figure 22 and as described above. Figure 30C shows the system (100) after the first liquid (252), which is blue in this embodiment, has been almost completely discharged from the system (100). Figure 30D shows the system (100) after the second liquid (254), which is green in this embodiment, has been almost completely discharged from the system (100).

[0070] As shown in the prefilled dual-chamber continuous injection system (100), the various components of the system (100) and their positions can be modified to adjust the amounts of the first and second liquids (252, 254) to be injected, including portions of the first liquid (252) injected before and after the second liquid (254).

[0071] The magnitude of the force required to deform the perforated separator (900) from a closed configuration to an open configuration can be adjusted to accommodate both system functional requirements and the aesthetic impression given to the user. If the force required for operation is too weak, it will operate, but it may be difficult for the user to apply enough force, potentially causing the perforated separator (900) to open too quickly. On the other hand, if the required force is too strong, the user may perceive the perforated separator (900) as "too stiff" to open. Fortunately, the pre-set force magnitude can be "adjusted" within a range by changing the properties of various components, including, but not limited to, the sizes of the radially inward circumferential surface (962) of the annular flap (958), the groove (918) of the distally extending portion (916), and the distal end radial extension (920) at the distal end of the distally extending portion (916).

[0072] Exemplary Triple Chamber Liquid Mixing and Injection System and Method Figures 31 to 42 show triple-chamber liquid mixing and injection systems (3100) according to several embodiments. The triple-chamber liquid mixing and injection system (3100) is configured to mix three liquids (e.g., drug components) before injecting a mixed liquid (e.g., drug).

[0073] Figure 31 is a side view of a triple-chamber liquid mixing and injection system (3100) according to several embodiments, which is pre-filled with first, second, and third liquids (252, 253, 254) that are first, second, and third drug components for mixing before injection. The triple-chamber liquid mixing and injection system (3100) includes a conventional off-the-shelf injection system body (34) in which a conventional off-the-shelf proximal stopper member (32) is disposed. The triple-chamber liquid mixing and injection system (3100) also includes a separator with an intermediate opening (3110) disposed within the injection system body (34) at a distance of a first distance distal to the stopper member (32). Furthermore, the triple-chamber liquid mixing and injection system (3100) includes a distal stopper member (33) disposed within the injection system body (34) at a distance of a second distance distal to the separator with an intermediate opening (3110). The proximal stopper member (32) and the separator with intermediate opening (3110), together with the infusion system body (34), define the proximal drug chamber (40). The separator with intermediate opening (3110) and the distal stopper member (33), together with the infusion system body (34), define the intermediate drug chamber (41). The distal stopper member (33), together with the infusion system body (34), defines the distal drug chamber (42). The first, second, and third fluids (252, 253, 254) are contained in the distal, intermediate, and proximal drug chambers (42, 41, 40), respectively (see, for example, Figures 31 and 35). The proximal stopper member (32) and the separator with intermediate opening (3110) close the proximal and distal ends of the proximal drug chamber (40), respectively. The separator with an intermediate opening (3110) and the distal stopper member (31) close the proximal and distal ends of the intermediate drug chamber (41), respectively. The distal stopper member (31) closes the proximal end of the distal drug chamber (42).

[0074] The triple-chamber liquid mixing and injection system (3100) also includes a needle (76) having a needle proximal end (50). The triple-chamber liquid mixing and injection system (3100) also includes a plunger member (44), which is coupled to a proximal stopper member (32) and configured to insert the proximal stopper member (32) distally within the injection system body (34).

[0075] The proximal stopper member (32) may be a conventional off-the-shelf stopper member according to some embodiments. The proximal stopper member (32) may be connected to the plunger member (44) using a screw-type connector, as shown in Figures 32 to 34.

[0076] The intermediate-opening separator (3110) is an opening separator (3110) for use with a dual-chamber infusion system (3100) according to some embodiments. The intermediate-opening separator (3110) is configured to be located within the infusion system body (34) as described above, and to define the proximal and intermediate drug chambers (40, 41). The intermediate-opening separator (3110) defines an intermediate port (3112). The intermediate-opening separator (3110) also includes a plug (3114) that is removablely located within the intermediate port (3112). Furthermore, the separator with an intermediate opening (3110) also specifies a distally oriented funnel (3116) configured to guide the proximal end of the needle (50) toward the intermediate port (3112) in order to remove the plug (3114) from the intermediate port by distal movement of the separator with an intermediate opening (3110) relative to the needle (76) and the proximal end of the needle (50), as shown in Figure 33.

[0077] The separator with an intermediate opening (3110) has a closed configuration (see Figures 32 and 33), in which the plug (3114) is positioned inside the intermediate port (3112) to block the flow of fluid through the separator with an intermediate opening (3110). The separator with an intermediate opening (3110) also has an open configuration (see Figure 34), in which the plug (3114) is removed from the intermediate port (3112), allowing the fluid to flow from the proximal drug chamber (40) to the intermediate drug chamber (41), and then through the separator with an intermediate opening (3110) to the distal drug chamber (42). The separator with an intermediate opening (3110) is configured to change from a closed configuration to an open configuration by the distal movement of the separator with an intermediate opening (3110) relative to the needle (76) and the proximal end of the needle (50), which causes the plug (3114) to detach from the intermediate port (3112). After the plug (3114) detaches from the intermediate port (3112), the plug is positioned in the proximal drug chamber (40), and after the third liquid (254) is transferred from the proximal drug chamber (40) to the intermediate drug chamber (41), the plug (3114) is positioned between the separator with an intermediate opening (3110) and the proximal stopper member (32), in contact with both of them, and both of them are also in contact with each other.

[0078] The plug (3114) and the intermediate port (3112) can be adjusted to control the magnitude of the proximal force required to remove the plug (3114) from the intermediate port (3112).

[0079] The intermediate-opening separator (3110) includes a proximal gasket (3154) and a distal gasket (3156), as shown in Figures 39 to 42. The proximal and distal gaskets (3154, 3156) are annular bodies extending radially outward from the proximal and distal ends of the intermediate-opening separator (3110), respectively. The proximal and distal gaskets (3154, 3156) are made of an elastic material and are configured to form first and second fluid-tight seals with the inner surface of the injection system body (34). The elastic material can be rubber, thermoplastic elastomer (TPE), butyl rubber, silicone rubber, or polyisoprene elastomer. The intermediate-opening separator (3110) may be coated with PTFE on one or both of the proximal and intermediate drug chambers (40, 41).

[0080] While the separator with intermediate opening (3110) moves longitudinally within the injection system body (34), the separator with intermediate opening (3110) is configured to maintain contact between the inner surface of the injection system body (34) and both the proximal and distal gaskets (3154, 3156). To this end, the proximal and distal gaskets (3154, 3156) are separated by the minimum longitudinal distance. By maintaining contact between the inner surface of the injection system body (34) and both the proximal and distal gaskets (3154, 3156), the separator with intermediate opening (3110) is prevented from twisting or inverting around its diameter, thereby maintaining the respective first and second fluid-tight seals.

[0081] The distal stopper member (33) may, according to some embodiments, be a conventional off-the-shelf stopper member. As shown in Figure 32, the orientation of this conventional distal stopper member (33) is the opposite of the usual orientation, with the uninterrupted surface that normally faces distal facing facing proximal facing. The distal stopper member (33) may include a stopper bush (1110) defining a distally facing funnel (1112) configured to guide the proximal end (50) of the needle to the central portion (33-1) of the distal stopper member (33).

[0082] The distal stopper member (33) has a closed configuration (see Figure 32), in which the central portion (33-1) of the distal stopper member (33) is integral / continuous / unbroken, forming a barrier that prevents fluid flow through the distal stopper member (33). The distal stopper member (33) also has an open configuration (see Figures 33 and 34), in which the central portion (33-1) of the distal stopper member (33) is perforated by the proximal end of the needle (50), allowing fluid to flow from the intermediate drug chamber (41) to the distal drug chamber (42) through this distal stopper member (33). The distal stopper member (33) is configured such that, as the distal stopper member (33) moves distally relative to the needle (76) and the proximal end of the needle (50), the central portion (33-1) of the distal stopper member (33) is perforated, thereby changing from a closed configuration to an open configuration.

[0083] In some embodiments, the distal surface of the proximal stopper member (32), the proximal and distal surfaces of the intermediate-perforated separator (3110), and / or the proximal surface of the distal stopper member (33) are coated with a lubricating polymer coating (e.g., PTFE or ETFE), and the polymer coating on these surfaces, together with the infusion system body (34), defines the proximal, intermediate, and distal drug chambers (40, 41, 42). The lubricating polymer coating also serves to isolate the rubber of the proximal stopper member (32), the intermediate-perforated separator (3110), and the distal stopper member (33) from the first, second, and third liquids (252, 253, 254). In other embodiments, the proximal stopper member (32), the separator with intermediate opening (3110), and / or the distal stopper member (33) may be made of uncoated butyl rubber such as chlorobutyl rubber and / or bromobutyl rubber. Alternatively, the proximal stopper member (32), the separator with intermediate opening (3110), and / or the distal stopper member (33) may be made of other elastomer materials such as TPE, TPU, silicone rubber, or other elastomers.

[0084] The triple-chamber liquid mixing and infusion system (3100) allows for the mixing of the first, second, and third liquids (252, 253, and 254) from the distal drug chamber (42), intermediate drug chamber (41), and proximal drug chamber (40) in the distal drug chamber (42) immediately before infusion. In this way, the triple-chamber liquid mixing and infusion system (3100) enables the infusion of a drug containing three components that rapidly change after mixing.

[0085] Figures 31, 32, and 35-37 show a triple-chamber liquid mixing and injection system (3100) in a storage / transport configuration where the first, second, and third liquids (252, 253, and 254) are stored in the distal drug chamber (42), the intermediate drug chamber (41), and the proximal drug chamber (40), respectively. In the storage / transport configuration, the distal stopper member (33) and the separator with intermediate opening (3110) are in their respective closed configurations, as described above. Thus, the first, second, and third liquids (252, 253, and 254) are isolated from each other, preventing changes due to liquid mixing.

[0086] Figure 33 shows the triple-chamber liquid mixing and injection system (3100) in a first open configuration, in which, as described above, the distal movement of the distal stopper member (33) relative to the needle (76) and the proximal end (50) of the needle causes the proximal end (50) to penetrate the central portion (33-1) of the distal stopper member (33), thereby converting the distal stopper member (33) from a closed configuration to an open configuration. The triple-chamber liquid mixing and injection system (3100) is configured such that a distal force applied to the plunger member (44) is transmitted to the distal stopper member (33) via the proximal stopper member (32), through the third liquid (254) (through its incompressibility), through the intermediate-opening separator (3110), and through the second liquid (253) (through its incompressibility), thereby causing distal movement of the distal stopper member (33) relative to the needle (76) and the needle proximal end (50). When the distal stopper member (33) is in an open configuration, the second liquid (253) flows from the intermediate drug chamber (41) through the distal stopper member (33) along the reduced diameter portion of the needle (76) to the distal drug chamber (42), where it mixes with the first liquid (252) contained in the distal drug chamber (42). The first, second, and third liquids (252, 253, and 254) can be selected such that mixing the first and second liquids (252 and 253) first results in less change than mixing the third liquid (254) with the first and second liquids (252 and 253), in order to minimize changes in the mixed liquid before injection.

[0087] Figure 34 shows the triple-chamber liquid mixing and infusion system (3100) in a second open configuration, in which, as described above, further distal movement of the distal stopper member (33) relative to the needle (76) and the needle proximal end (50) causes the needle proximal end (50) to unplug (3114) from the intermediate port (3112) of the intermediate-open separator (3110), thereby converting the intermediate-open separator (3110) from a closed configuration to an open configuration. With the intermediate-open separator (3110) in the open configuration, the third liquid (254) flows from the proximal drug chamber (40) through the intermediate drug chamber (41) and the distal stopper member (33) to the distal drug chamber (42), where it mixes with the first and second liquids (252, 253) contained within the distal drug chamber (42).

[0088] Figure 38 shows the triple-chamber liquid mixing and injection system (3100) in its post-injection configuration, in which the distal stopper member (33), the separator with intermediate opening (3110), and the proximal stopper member (32) move further distally relative to the needle (76), the proximal end of the needle (50), and the injection system body (34), thereby discharging almost all of the mixed liquid formed by mixing the first, second, and third liquids (252, 253, 254) from the triple-chamber liquid mixing and injection system (3100). When the distal stopper member (33) is advanced so as to be adjacent to the distal end of the injection system body (34), the spring is released, thereby causing the needle (76) to retract until the sharp distal end of the needle (76) is positioned at least inside the injection system body (34) or the needle hub attached to the injection system body (34), making the triple-chamber liquid mixing and injection system (3100) "safe" (i.e., preventing accidental needle stick injuries after injection). In short, additional components of the triple-chamber liquid mixing and injection system (3100) include a needle retraction system, needle holding function, energy storage member (e.g., a spring), energy storage member latch, and needle holder member (e.g., O-ring, needle latch and / or return stopper) inside the plunger member (44).

[0089] In the triple-chamber liquid mixing and injection system (3100) described herein, the intermediate-perforated separator (3110) is positioned between the proximal and distal stopper members (32, 34). Other embodiments of the triple-chamber liquid mixing and injection system may include two perforated separators (intermediate and distal) having a similar structure and function to the intermediate-perforated separator (3110). Similarly, other embodiments of the dual-chamber injection system may include a distal-perforated separator having a similar structure and function to the intermediate-perforated separator (3110) instead of a distal stopper member.

[0090] Some of the embodiments described herein do not include a safe needle retraction system, but those embodiments can be used in conjunction with a multi-chamber safe injection system with a needle retraction function. In short, additional components of a dual-chamber continuous injection system (100) include a needle retraction system inside the plunger member (44), a needle holding function, an energy storage member (e.g., a spring), an energy storage member latch, a needle holder member inside the needle hub (e.g., an O-ring, a needle latch and / or a stopper), and a funnel for guiding the proximal end of the needle during injection and retraction.

[0091] The embodiments described above include dual-chamber and triple-chamber infusion systems, but the claims also include other multi-chamber infusion systems. In the case of a multi-chamber infusion system having two or more chambers, three or more perforated separators or stopper members are inserted into the infusion system body (e.g., syringe body, cartridge body, etc.) to define the corresponding number of chambers.

[0092] This specification describes various exemplary embodiments of the present invention. These examples are used in a non-limiting sense. They are provided to illustrate broader applicable aspects of the present invention. Various modifications can be made to the described invention and replaced with equivalents without departing from the true spirit and scope of the invention. Furthermore, many modifications can be made to adapt specific situations, materials, substance compositions, processes, process operations, or steps to the object, spirit, or scope of the invention. Moreover, as will be understood by those skilled in the art, each of the individual variations described and illustrated herein has separate components and features that can be readily separated from or combined with any of the features of several other embodiments without departing from the scope or spirit of the invention. All such modifications are intended to fall within the scope of the claims relating to this disclosure.

[0093] Any of the devices described for performing the diagnostic or intervention procedure in question 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 commonly employed for such purposes.

[0094] The present invention includes methods that can be performed using the device of interest. These methods may include the act of providing such a suitable device. Such provision may be performed by an end user. That is, the act of “providing” simply requires the end user to take, access, approach, position, set up, start, power on, or perform other actions in order to provide the required device in the method of interest. The methods described herein may perform the described events in any logically possible order, or in the order of the described events.

[0095] 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 are generally known or understandable to those skilled in the art, as well as being understandable in connection with the previously cited patents and publications. For example, those skilled in the art will understand that one or more lubricating coatings (e.g., hydrophilic polymers such as polyvinylpyrrolidone compositions, fluoropolymers such as tetrafluoroethylene, PTFE, ETFE, hydrophilic gels, or silicones) can be used in relation to various parts of a device, such as relatively large interfaces of movably bonded parts, thereby facilitating, for example, low-friction operation or advancement of such objects against other parts of the instrument or nearby tissue structures. The same would apply to embodiments based on the methods of the present invention with respect to additional actions that are generally or logically employed.

[0096] Furthermore, while the present invention has been described with reference to several examples that arbitrarily incorporate various features, the present invention is not limited to those described or disclosed as intended with respect to each variation 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 (whether described herein or not included for brevity). Furthermore, where a range of values ​​is provided, it should be understood that all intermediate values ​​between the upper and lower limits of that range, and other described or intermediate values ​​within the described range, are included within the scope of the present invention.

[0097] Furthermore, any feature of the variations of the present invention described herein is intended to be described and asserted independently or in combination with any one or more features of those described herein. References to singular items include the possibility of multiple instances of the same item. More specifically, in this specification and the accompanying claims, the singular forms “a,” “an,” “said,” and “the” include multiple references unless otherwise specified. In other words, the use of articles, as in the claims accompanying this disclosure, allows for “at least one” of the subject items in the above description. It should be noted that such claims may be drafted to exclude optional elements. For this reason, this statement is intended to serve as a prior reference to use exclusive terms such as “single,” “only,” or “negative” limitations in relation to the enumeration of elements of a claim.

[0098] Without using such exclusive terminology, the term “including” in the claims accompanying this disclosure shall enable the inclusion of any additional elements, regardless of whether a given number of elements are enumerated in such claims or whether the addition of features is deemed to alter the nature of the elements described in such claims. Unless otherwise specifically provided herein, all technical and scientific terms used herein shall be given meanings that are as broadly and generally understood as possible, while maintaining the validity of the claims.

[0099] The scope of the present invention is not limited to the examples and / or subject matter specifications provided, but rather is limited only by the language of the claims accompanying this disclosure.

Claims

1. An injection system, An injection system body having a proximal opening at the proximal end and a distal needle interface at the distal end, A stopper member and a separator with an opening are disposed within the main body of the injection system, wherein a proximal drug chamber is formed between the stopper member and the separator with an opening, and a distal drug chamber is formed between the separator with an opening and the distal end of the main body of the injection system, The system comprises a plunger member configured to be operable for inserting the stopper member into the injection system body, The perforated separator forms an openable and closable barrier between the proximal drug chamber and the distal drug chamber. The system is characterized in that the perforated separator is configured to allow flow from the proximal drug chamber to the distal drug chamber due to an increase in pressure in the proximal drug chamber relative to the distal drug chamber.

2. In the system described in claim 1, The system is characterized in that the perforated separator is configured to move longitudinally within the injection system body.

3. In the system described in claim 1, The system is characterized in that the perforated separator includes proximal and distal gaskets, which are positioned adjacent to the proximal and distal ends of the perforated separator, respectively, and extend radially from the perforated separator.

4. In the system described in claim 3, The system is characterized in that the perforated separator is configured to maintain contact between the inner surface of the injection system body and the proximal gasket, and between the inner surface of the injection system body and the distal gasket, as the separator moves longitudinally within the injection system body.

5. In the system described in claim 4, The system is characterized in that the proximal and distal gaskets are separated by the minimum longitudinal distance.

6. In the system described in claim 3, The system is characterized in that the proximal and distal circumferential gaskets are configured to form first and second fluid-tight seals with the inner surface of the injection system body, respectively.

7. In the system described in claim 3, The system is characterized in that the proximal and distal circumferential gaskets are made of an elastic material.

8. In the system described in claim 7, A system characterized in that the elastic material is rubber, thermoplastic elastomer, butyl rubber, or polyisoprene elastomer.

9. In the system described in claim 1, The system is characterized in that the perforated separator has a port configured to open in response to an increase in pressure in the proximal drug chamber relative to the distal drug chamber.

10. In the system described in claim 1, The system is characterized in that the perforated separator includes a rigid portion and an elastic portion.

11. In the system according to claim 10, A system characterized in that the elastic portion defines a pocket configured to receive the rigid portion.

12. In the system according to claim 10, The system is characterized in that the rigid portion is made from a cyclic olefin copolymer.

13. In the system according to claim 10, The system is characterized in that the elastic portion is made of rubber, thermoplastic elastomer, butyl rubber, or polyisoprene elastomer.

14. In the system according to claim 10, The elastic portion An annular flap configured to be positioned adjacent to the distal surface of the rigid portion, A ring configured to support the aforementioned annular flap, The ring comprises proximal and distal circumferential gaskets extending from the outer circumference of the ring, The system is characterized in that the proximal and distal circumferential gaskets are configured to form first and second fluid-tight seals with the inner surface of the injection system body, respectively.

15. In the system described in claim 14, The rigid portion includes an annular portion, The aforementioned annular portion defines a port through which it passes, The system is characterized in that the port is configured to be closed in a manner that allows it to be opened and closed by the annular flap of the elastic portion.

16. In the system described in claim 15, The annular flap of the elastic portion is The aforementioned port is biased to close in a manner that allows it to be opened and closed. A system characterized in that, due to an increase in pressure in the proximal drug chamber relative to the distal drug chamber, the rigid portion deforms away from the port defined by the annular portion of the rigid portion, thereby opening the port.

17. In the system described in claim 14, The aforementioned annular portion defines multiple ports through which it passes, The system is characterized in that each of the plurality of ports is configured to be closed in a manner that allows it to be opened and closed by the annular flap of the elastic portion.

18. In the system described in claim 17, The annular flap of the elastic portion is Each of the aforementioned multiple ports is biased to close in a manner that allows it to be opened and closed. A system characterized in that, due to an increase in pressure in the proximal drug chamber relative to the distal drug chamber, the rigid portion deforms away from each of the multiple ports defined by the annular portion of the rigid portion, thereby opening each of the multiple ports.

19. In the system according to claim 10, The rigid portion comprises a distally extending portion connected to the annular portion, The system is characterized in that the elastic portion has a radially inward circumferential surface that defines a central port.

20. In the system described in claim 19, A system characterized in that the radially inward circumferential surface of the elastic portion is configured to form a fluid-tight seal around the portion of the rigid portion that extends distally, thereby closing the central port of the elastic portion.

21. In the system described in claim 20, The elastic portion is biased to close the central port by the portion of the rigid portion that extends distally to it. A system characterized in that, due to an increase in pressure in the proximal drug chamber relative to the distal drug chamber, the elastic portion deforms so as to separate from the portion of the rigid portion that extends distally, thereby removing the fluid-tight seal around it and opening the central port of the elastic portion.

22. In the system described in claim 19, A system characterized in that the portion of the rigid portion extending distally defines a circumferential groove configured to receive the radially inward circumferential surface of the elastic portion.

23. In the system according to claim 10, The rigid portion defines the first port, A system characterized in that the elastic portion defines a second port.

24. In the system described in claim 23, The aforementioned separator with openings has a closed configuration and an open configuration. In the closed configuration described above, both the first and second ports are closed. The system is characterized in that, in the open configuration described above, both the first and second ports are open.

25. In the system according to claim 24, In the open configuration described above, the system is characterized in that the flow path fluidly connects the proximal drug chamber and the distal drug chamber via the first and second ports.

26. In the system according to claim 24, The system is characterized in that the elastic portion is biased to close the first and second ports, thereby resulting in the open separator being in the closed configuration.

27. In the system according to claim 24, The system is characterized in that the perforated separator is configured to deform from the closed configuration to the open configuration due to an increase in pressure within the proximal drug chamber relative to the distal drug chamber.

28. A method of injection, A step of providing a prefilled injection system, wherein the injection system is An injection system body having a proximal opening at the proximal end and a distal needle interface at the distal end, A stopper member and a separator with an opening are disposed within the main body of the injection system, wherein a proximal drug chamber is formed between the stopper member and the separator with an opening, and a distal drug chamber is formed between the separator with an opening and the distal end of the main body of the injection system, The first drug and air bubbles are arranged in the distal drug chamber, The second drug placed in the proximal drug chamber, A step comprising a plunger member coupled to the stopper member, The steps include stirring the pre-filled injection system to mix the first agent, The steps include attaching a needle assembly having a needle to the distal needle interface located at the distal end of the injection system body, The steps include: positioning the injection system body so that the needle faces upward; With the needle facing upward, the plunger and the stopper member coupled thereto are moved distally within the injection system body, thereby removing at least a portion of the air bubbles from the distal drug chamber. The plunger and the stopper member connected thereto are moved further distally within the injection system body, thereby, At least a portion of the first drug is discharged from the distal drug chamber through the needle. The steps include moving the perforated separator longitudinally toward the distal end of the injection system body, The steps include moving the plunger and the stopper member coupled thereto further distally within the injection system body, thereby opening the perforated separator and transferring at least a portion of the second drug from the proximal drug chamber to the distal drug chamber, A method characterized by comprising the step of moving the plunger and the stopper member coupled thereto further distally within the injection system body, thereby discharging at least a portion of the second drug from the distal drug chamber via a needle.

29. In the method of claim 28, A method characterized in that, after at least a portion of the first drug has been discharged from the distal drug chamber via the needle, the plunger and the stopper member coupled thereto are moved further distally within the injection system body, thereby increasing the pressure in the proximal drug chamber relative to the distal drug chamber, and thereby opening the perforated separator.

30. In the method of claim 28, The steps include moving the perforated separator so that it comes into contact with the distal end of the injection system body, A method further comprising the step of moving the stopper member so as to contact the perforated separator, thereby completing the injection.

31. An injection system, An injection system body having a proximal opening at the proximal end and a distal needle interface at the distal end, A proximal stopper member, a member with an intermediate opening, and a distal stopper member are arranged within the injection system body, wherein the proximal stopper member, the member with an intermediate opening, the distal stopper member, and the injection system body are A proximal drug chamber is formed between the proximal stopper member and the separator with an intermediate opening. An intermediate drug chamber is formed between the separator with the intermediate opening and the distal stopper member. A distal drug chamber is formed between the distal stopper member and the distal end of the injection system body, comprising a proximal stopper member, a member with an intermediate opening, and a distal stopper member, The system comprises a plunger member configured to be operable for inserting the proximal stopper member into the injection system body, The perforated separator forms an openable and closable barrier between the proximal drug chamber and the intermediate drug chamber. The system is characterized in that the perforated separator is configured to selectively allow flow from the proximal drug chamber to the intermediate drug chamber.

32. In the system described in claim 31, The system is characterized in that the separator with the intermediate opening is configured to move longitudinally within the injection system body.

33. In the system described in claim 31, The system is characterized in that the separator with an intermediate opening includes proximal and distal gaskets, the proximal and distal gaskets are arranged adjacent to the proximal and distal ends of the separator with an intermediate opening, respectively, and extend radially from the separator with an intermediate opening.

34. In the system described in claim 33, The system is characterized in that the separator with the intermediate opening is configured to maintain contact between the inner surface of the injection system body and the proximal gasket, and between the inner surface of the injection system body and the distal gasket, as the separator moves longitudinally within the injection system body.

35. In the system described in claim 34, The system is characterized in that the proximal and distal gaskets are separated by the minimum longitudinal distance.

36. In the system described in claim 33, The system is characterized in that the proximal and distal circumferential gaskets are configured to form first and second fluid-tight seals with the inner surface of the injection system body, respectively.

37. In the system described in claim 33, The system is characterized in that the proximal and distal circumferential gaskets are made of an elastic material.

38. In the system described in claim 37, A system characterized in that the elastic material is rubber, thermoplastic elastomer, butyl rubber, or polyisoprene elastomer.

39. In the system described in claim 31, The separator with intermediate opening defines an intermediate port, The system is characterized in that the separator with the intermediate opening is provided with a plug configured to be removably placed in the intermediate port and to seal the intermediate port.

40. In the system described in claim 39, The injection system further comprises a needle having a proximal end, The system is characterized in that the plug is configured to detach from the intermediate port by the proximal end of the needle.

41. In the system described in claim 40, The system is characterized in that the separator with an intermediate opening defines a distally oriented funnel configured to guide the proximal end of the needle to the plug in the intermediate port.

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