Membrane-based sheathing devices

Abstract

The present invention relates to a sleeve device (2) comprising a base (4) wherein the base (4) includes a seat cavity (6) in its longitudinal direction. The seat cavity includes a first cavity (28) and a second cavity (30) and a membrane (12) arranged laterally within the seat cavity, wherein the first cavity and the second cavity are separated from each other by means of the membrane, wherein the membrane is configured to switch between a first position and a second position in response to a reversal of a pressure gradient across the membrane.

Description

[0001] describe The present invention relates to a cannulation device comprising a base, wherein the base includes a cavity in its longitudinal direction. The cavity includes a first cavity and a second cavity, and a membrane arranged laterally within the cavity, wherein the first cavity and the second cavity are separated from each other by means of the membrane, wherein the membrane is configured to switch between a first position and a second position in response to a reversal of a pressure gradient across the membrane. Background Technology

[0002] This disclosure relates to the fields of medical devices and health. More particularly, the present invention relates to the safe, precise, and accurate delivery of fluids during medical procedures. In particular, the present invention relates to improving the delivery of fluids during medical procedures with smaller fluid doses.

[0003] To improve vision in individuals with age-related macular degeneration, retinal vein occlusion, or diabetic macular edema, endothelial growth factor inhibitors (anti-VEGF) are typically administered via intravitreal injection. Intravitreal injection is one of the most common procedures, with approximately 1.5 million treatments performed annually in Germany and an estimated 20 million globally. Patients receive 50 to 100 μl injections every 4 to 6 weeks. Many clinics use silicone-lubricated, dead-cavity-free syringes, such as the BDU-100 insulin syringe, off-label. For effective use, the plunger and needle of these syringes require silicone lubrication. This can lead to contamination of the administered medication and reduce the purity tolerance achievable with fluid administration. During intravitreal injection, silicone oil droplets injected using existing technology are introduced into the vitreous cavity, where they are not metabolized and can only be removed via vitrectomy. Due to the frequency of this treatment, the likelihood of clinically relevant accumulation of silicone oil droplets in the vitreous cavity increases. These droplets may be perceived as floaters, causing discomfort, and in rare cases, may trigger an inflammatory response.

[0004] Besides the risk of particulate contamination, another important aspect is the precision and accuracy of intravitreal injections. Traditionally, volumes of 50-70 µl are typically required. Current practice often uses commercially available 1 ml syringes to draw and administer such small volumes. Using a syringe that is too large compared to the volume to be injected can easily lead to incorrect dosing. For example, this is because 1 ml syringes are not designed for small volumes in the two-digit µl range. Furthermore, to set the correct dose, the syringe must be significantly overfilled. This practice results in the waste of expensive medications. Overdosing is particularly common with prefilled syringes and can cause significant harm to patients because the excess volume leads to a significant increase in intraocular pressure, which can cause permanent and irreversible damage.

[0005] Echoing the challenges facing ophthalmology, the vaccine field is also receiving increasing attention. In particular, mRNA vaccines, crucial in combating a variety of diseases, face potential risks during storage. These vaccines can be contaminated with silicone oil, which can compromise their efficacy. The presence of silicone oil can alter the conformation and stability of the protein surface and lipid nanoparticles of mRNA vaccines, which is important for determining vaccine effectiveness. By modifying the protein surface, silicone oil may hinder the interaction between the vaccine and the immune system, potentially leading to reduced immunogenicity or triggering unintended immune responses.

[0006] The quantification of silicone oil released from various syringes and needles commonly used for intravitreal injections was investigated. Silicone oil release was demonstrated and confirmed in all tested syringe-needle assemblies. Trace amounts of silicone oil were detected even in the two silicone-free syringes tested (HSWNorm-Ject, Daikyo Crystal Zenith). It is speculated that the needles used may also have contributed to this contamination.

[0007] Furthermore, it has been shown that the shaking and bouncing commonly performed in clinical practice for preparing and initiating injections leads to a significant increase in silicone oil droplets. Typically, achieving a tight seal between the syringe body and plunger requires a large radial sealing force, which generates friction during insertion and withdrawal. Even with optimal friction mating and manufacturing tolerances, it is theoretically impossible to eliminate particle or lubricant wear, which can lead to contamination of the therapeutic product. This problem can exist even with expensive glass-Teflon friction mating.

[0008] In recent years, silicone-free tuberculin or insulin injectors (such as the BDBioscience Tuberculin or BD U-100 Insulin injector) have sometimes been used off-label for intravitreal injections in clinical practice. While these injectors are cost-effective, they release a smaller amount of silicone oil. Additionally, these injectors are designed for relatively inexpensive therapeutic agents, resulting in a relatively high dead space. Considering the higher cost per injection (e.g., 50 μl of 10 mg / ml ranibizumab), even a 3 μl dead space can cause significant additional costs. Completely silicone-free injectors have not yet become widespread in clinical practice, likely due to their higher price and the greater force required for individual administration. Therefore, it is necessary to prevent contamination of the therapeutic fluid with silicone oil during injection.

[0009] Furthermore, due to friction between the barrel and plunger, conventional syringes, as well as syringes without silicone oil or with reduced silicone oil, may irritate and damage sensitive therapeutic agents or biofluids. This effect may affect the integrity and stability of proteins, lipid nanoparticles (e.g., mRNA vaccines), or cells (CAR cell products), and may hinder therapeutic efficacy.

[0010] Existing technologies have considered using compressible, disposable ampoules to assist in the injection of therapeutic fluids.

[0011] US7011650B2 discloses a syringe comprising a pleated compressible container within a barrel for containing a therapeutic solution. This pleated compressible container serves as an ampoule. The compressible container is provided with a connector configured to engage with a plunger of the syringe, such that movement of the plunger directly results in the expansion or compression of the compressible container. This direct mechanical connection between the container and the plunger allows the plunger to move the container up and down within the barrel. Furthermore, this direct mechanical connection is configured to sufficiently flatten the compressible container, causing a pressure-sensitive seal to rupture and allowing fluid to escape. This configuration allows the syringe to contain two different therapeutic fluids—on the inside and outside sides of the compressible container—and inject them sequentially. While the fluid inside the ampoule is not contaminated with any silicone oil from the plunger within the barrel, the fluid outside the ampoule may be contaminated.

[0012] US2016058946A1 provides a similar configuration. A retractable syringe is housed within the pressure sheath. This retractable syringe serves as a disposable pre-filled ampoule and includes a cap member and compressible or deformable sidewall members with folds resembling a bellows. These folds in the ampoule create significant dead space within the retractable syringe or retractable chamber, reducing efficiency and hindering accurate drug delivery.

[0013] JP 5854836 B2 discloses a cartridge and needle system whose primary function is to reduce dead space at the distal end of the cartridge, thereby reducing the risk of needle bending, off-center puncture of the rubber spacer at the cartridge end, or puncture of the sidewall of the cartridge's internal closure. The system features a semi-permeable membrane designed to allow gas passage while reducing liquid transport. By advancing the plunger, air trapped within the cartridge can pass through the gas-permeable membrane and be expelled through the needle, thus venting the injection system. To allow injection, the needle system is further pushed into the venting housing insert, causing the needle tip to pierce the semi-permeable membrane and lock the needle in place.

[0014] JP 6731943 B2 discloses a rollable diaphragm injector system comprising an improved injector with flexible sidewalls. The injector is configured to selectively fill with liquid, allowing for precise dispensing of the liquid. One aspect of the invention aims to overcome the drawbacks of conventional disposable injectors by generating a more cost-effective and user-friendly injector design. The rollable diaphragm consists of various segments, including sidewalls. The sidewalls of the rollable diaphragm are flexible and can unfold or retract according to the movement of the plunger. When the plunger moves distally (injection), the sidewalls of the rollable diaphragm roll outwards. This allows fluid to be drawn into the internal volume of the injector. When the plunger moves proximally (withdrawal), the sidewalls of the rollable diaphragm roll back to themselves, dispensing the liquid from the injector. This rollable diaphragm does not allow for precise drug delivery and creates a large amount of dead space within the injector cavity. This reduces the efficiency of fluid drug delivery and increases costs.

[0015] A common feature of existing technologies is that the compressible ampoules or diaphragms are configured to connect directly to the plunger. Furthermore, these ampoules have dimensions similar to those inside syringe barrels, meaning that the force required to manually press the plunger results in the ejection of a large volume of fluid from the ampoule. Due to the folded configuration within the ampoule, a significant amount of dead space is created within the syringe barrel. Due to limitations in hand dexterity, the user must move the plunger at least several millimeters to perform manual injection. Combined with a wide diameter of several millimeters, this corresponds to a fluid volume of at least millimeters. Therefore, such devices are unsuitable for precisely injecting fluids in the microliter range, especially for ocular surgery.

[0016] In addition to the problems mentioned above, existing devices are not suitable for a wide range of applications, including therapeutic materials that must be stored at very low temperatures. Furthermore, the medical techniques required for administering medical fluids using these devices often differ from standard procedures, thus necessitating professional guidance from healthcare personnel.

[0017] Current technology cannot provide a feasible solution for completely eliminating silicone oil from injection solutions while providing precise fluid delivery, especially for small volumes of fluid. Nor can it provide a user-friendly device that medical personnel can use without additional training. Summary of the Invention

[0018] The purpose of this invention is to provide a cannula device that overcomes the shortcomings of existing technologies, enabling precise and accurate drug delivery and injection of medical fluids, avoiding mechanical damage caused by plunger friction and contamination from sealant fluids or abrasive particles, especially avoiding contamination from silicone oil. Another purpose of this invention is to allow the effective use of silicone oil-free needles and cannulas. Yet another purpose of this invention is to provide a cannula device configured for the precise injection of small volumes of therapeutic fluids.

[0019] The objective is achieved through the cannula device according to the independent claim, the use of the device, and a kit including the cannula device and at least one disposable syringe and / or needle. The dependent claims represent preferred embodiments of the invention. The invention has applications in various medical facilities where accurate and precise administration of fluids (such as pharmaceuticals or therapeutic substances) is important. The invention addresses problems related to the integrity and sterility of injected substances, making it particularly valuable in ophthalmology, intravitreal injections, and other medical procedures where maintaining the purity, integrity, and stability of injected substances is paramount for patient safety and therapeutic effectiveness.

[0020] In a first aspect, the present invention relates to a cannulation device comprising a base, wherein the base includes a cavity in its longitudinal direction. The cavity includes a first cavity and a second cavity, and a membrane laterally disposed within the cavity, wherein the first cavity and the second cavity are separated from each other by means of the membrane. The membrane is configured to switch between a first position and a second position in response to a reversal of a pressure gradient across the membrane.

[0021] This membrane-based design ensures that the treatment solution remains continuously isolated from the rest of the cannula or the syringe used with the cannula, effectively preventing contamination of the solution by silicone oil, abrasive particles, or other fluids contained in the syringe.

[0022] A significant advantage of the described cannula device is its compatibility with standard syringes, thereby enhancing ease of handling. Healthcare professionals are already familiar with the mechanisms and techniques of conventional syringes. By allowing the cannula device to be used seamlessly with these well-known standard syringes, it eliminates the need for a steep learning curve or additional training. This compatibility facilitates rapid integration with existing medical procedures, simplifies transitions, and ensures uninterrupted patient care. Furthermore, this design choice promotes cost efficiency. Healthcare facilities can continue to use their existing stock of standard syringes without the need to purchase specialized equipment. This factor is crucial, especially in resource-constrained environments. The ease of attaching and detaching the cannula device from these standard syringes also ensures rapid preparation and turnaround times between patient treatments, making it a practical solution for high-volume clinical environments.

[0023] When configured to switch between different locations in response to a pressure gradient, this membrane acts as a reliable barrier, preventing the therapeutic solution from coming into contact with or becoming contaminated by silicone oils or other lubricants or sealants used in other parts of the cannula or syringe. This ensures that the fluid to be injected remains pure and uncontaminated, which is crucial for the safety and efficacy of medical treatments, especially in sensitive areas such as ophthalmology.

[0024] The key advantage of this configuration is that it allows for the complete avoidance of contamination during all stages of the injection process. This is achieved by using an innovative membrane to strictly isolate the injection solution from the friction or lubrication components of the substrate. This membrane ensures that potentially harmful substances (such as silicone oil) from the friction or lubrication components do not enter the fluid to be injected at any time. Avoiding contamination of the injection solution significantly contributes to patient safety. Using this cannula device significantly minimizes the risk of infection or allergic reactions due to contamination. Furthermore, because the medication or solution does not come into contact with potentially harmful substances, the integrity of the administered medication or solution can be maintained. This ensures the effectiveness of the medication, contributes to successful treatment, and also helps maintain stringent quality standards in medical procedures.

[0025] The present invention provides a first chamber with a variable volume, preferably for containing a therapeutic fluid (also referred to herein as an "injection solution" or "medical solution"). The first chamber is preferably sealed by a membrane that separates it from a second chamber. The volume of the first chamber is advantageously variable, eliminating the need for rigid parts to rub against the membrane to change volume, as is the case with prior art mechanically connected plungers. Since there is no risk of friction or poor fit between rigid parts, there is no need to use silicone oil as a sealant in the first chamber. Because the volume of the first chamber is variable depending on the position of the membrane, the pressure within the first chamber can be increased to inject the therapeutic fluid. Alternatively, the pressure within the first chamber can be decreased to create a vacuum and draw fluid into the first chamber.

[0026] A particular advantage of this invention is that the membrane's material and mechanical properties can be adjusted to remain fixed relative to the inner wall of the cavity at its edges, while being movable in its center. Therefore, the membrane does not need to move against the inner wall of the cavity, avoiding friction. This reduces the need for lubricants. Moreover, because it is fixed at its edges, the membrane can be arranged to create a permanent seal between the first and second cavities without the need for additional sealant. For this purpose, the membrane is preferably impermeable, at least for the fluid contained in the cannula. Therefore, silicone oil within the cavity containing the therapeutic fluid can be completely avoided, preventing contamination. This is particularly useful for intravitreal injections, as any silicone oil delivered in this manner cannot be naturally metabolized. Therefore, optical problems caused by eye contamination can be avoided, as can the invasive procedures required to alleviate such optical problems.

[0027] By configuring the membrane to switch between a first and a second position in response to the reversal of the pressure gradient across the membrane, no rigid parts are required to contact and push / pull the membrane to change the volume within the chambers, and thus inject or withdraw the injection fluid. More precisely, a sufficient pressure gradient across the membrane can be generated simply by changing the pressure within one of the multiple chambers. This can be easily achieved by pulling or pushing the plunger of a conventional syringe that can be used with a cannula. By pushing the plunger, the pressure within the second chamber can be increased, causing the pressure on the second side of the membrane to exceed the pressure on the first side. Therefore, the membrane can switch to the first position, reducing the volume of the first chamber, and the therapeutic fluid can be injected through the outlet (preferably through the injection port, especially preferably through a needle). For this purpose, the plunger does not need to contact the membrane at all. By pulling the plunger, the pressure within the second chamber is reduced, instantaneously creating a vacuum, which reverses the pressure gradient and switches the membrane to the second position. In the second position, the volume of the first chamber is preferably increased to reduce the pressure within it. This instantaneous pressure reduction preferably causes fluid to be withdrawn through the outlet (preferably through a needle). Because the membrane seals the syringe to the first chamber, the risk of silicone oil or other contaminants entering the therapeutic fluid from the syringe is eliminated. Contamination-free injection can be achieved in a simple and economical manner.

[0028] Because the membrane can be moved between different positions without excessive mechanical stress, it does not need to be configured to have the same thickness and dimensions as membranes or diaphragms in the prior art. Instead, the membrane can be very thin and compact. Furthermore, since the membrane does not need to move with the syringe plunger, its size and the volume of the first chamber can be separated from the volume of the syringe barrel. For example, the syringe barrel can have a larger volume to allow the user to manually move the plunger in steps of several millimeters. Its diameter can be large enough that the barrel includes clear dosage markings. However, the first chamber defined by the membrane does not need to have a volume substantially corresponding to the volume of the barrel. This is because the volume change of the first chamber is not due to the mechanical load on the plunger, but only to pressure changes in front of and / or behind the membrane. Therefore, the membrane can be positioned at substantially any point in the longitudinal direction along the chamber, and its movement can be limited to a small volume space. Thus, the first chamber can be limited to a small volume, particularly on the order of microliters, while the syringe barrel has the conventionally large volume suitable for good visibility and easy manual operation of the plunger.

[0029] Due to the limited space within the first chamber, overfilling of the medicine and associated waste are advantageously avoided. Furthermore, only precisely defined doses are administered, thereby minimizing the risk of overdose.

[0030] As shown above, the pressure difference across the membrane can be artificially generated or it can be a result of a specific medical procedure using the cannula device. For example, in medical injections, the pressure on the first side of the membrane may be determined by the internal pressure of the body or the pressure within a separate chamber of the device. Conversely, when the membrane transitions from a first position to a second position, the pressure gradient reverses. In this state, the pressure on the first side of the membrane may be higher than the pressure on the second side, causing the membrane to switch its position. The transition of the membrane in response to the reversal of the pressure gradient may involve the membrane flipping. In particular, the side of the membrane with a concave shape may become convex, and vice versa. This design allows the membrane to act as a dynamic barrier, separating or connecting the first and second chambers within the cannula device in response to pressure changes. This mechanism ensures controlled and precise fluid management while maintaining the sterility and purity of the injected material, which is particularly important in medical procedures, as maintaining these parameters is crucial for patient safety and treatment effectiveness.

[0031] The second chamber and the barrel extending up to the syringe plunger are preferably completely filled with fluid, completely filled with gas (such as air), or partially filled with fluid and partially filled with gas (such as air). The gas-filled portion within the second chamber and / or barrel can advantageously act as a pressure buffer. This can potentially result in a surprisingly low reduction in the shear force applied to the therapeutic fluid during injection. Preferably, the peak shear force acting on the fluid is attenuated as injection is performed while overcoming the plunger's initiation force, thus protecting the fluid's integrity. Furthermore, potential tissue damage during the injection process can be minimized.

[0032] As used herein, the term "cannula device" refers to a specialized medical device designed for controlled and precise delivery or extraction of fluids in a medical setting via an outlet with a small diameter (e.g., less than 5 mm, preferably less than 3 mm, more preferably less than 2 mm). The "cannula device" preferably includes an outlet in the shape of a hollow tube or needle extending from a base, the hollow tube or needle having one or more openings at its end. This outlet can be configured as an injection port for attachment to a needle or other fluid channel. Preferably, the end of the hollow tube or needle is configured for insertion into a patient's body, particularly through puncture or incision, to reach a specific anatomical location. The hollow tube or needle is preferably configured for minimally invasive insertion into the patient's body. Therefore, the diameter of the hollow tube or needle is preferably configured to allow absorption or delivery of the relevant fluid while minimizing discomfort and / or scarring. The cannula device can be configured for purposes such as intravenous (IV) administration, aspiration of body fluids, or direct injection of medications into tissues or body cavities.

[0033] In the context of this invention, the term "substrate" preferably refers to a rigid structure to which a needle and / or hollow tube may be attached, and which in turn may be attached to a syringe or other pressure regulating device. The substrate preferably includes a seat cavity and is configured for manual handling and operation, such as for attachment to other devices.

[0034] As used herein, the term "hub" refers to a hollow region within the base of the cannula device, which at least partially comprises a first lumen, a membrane, and a second lumen. The hub is oriented along the length of the device and is preferably coaxial with other parts of the cannula, such as the first and second lumen, the outlet, and / or the syringe, needle, or hollow tube. The hub contains two distinct cavities, referred to as the first and second cavities respectively, and is provided with a membrane laterally positioned therein.

[0035] In the context of this invention, the term "cavity" preferably refers to a hollow region of the cannula device that can contain fluid. The "cavity" may have a variable volume. A first cavity is preferably defined as a hollow portion of the cannula device's base defined by a first side of the membrane, a cavity wall, and an outlet of the cannula device. A second cavity is preferably defined as a hollow portion of the cannula device's base defined by a second side of the membrane, a cavity wall, and a barrier located at or connected to a proximal end of the cannula device, wherein the barrier may be a plunger of a syringe. Therefore, the positions of the plunger and the membrane can change the volumes of the first and second cavities.

[0036] In the context of this invention, the term "membrane" preferably refers to a flexible, impermeable sheet of material that separates the first cavity from the second cavity. The membrane is preferably fixed to the inner wall of the cavity at its edges, while the middle portion of the membrane is free to move within a region that at least partially spans the first and second portions of the cavity. For this purpose, the membrane preferably has a first side facing the outlet and a second side facing the plunger, syringe connector, or other connection port of the syringe. The area of ​​the first and second sides of the membrane preferably exceeds the cross-sectional area of ​​the cavity at the point where the edge of the membrane is fixed. This larger surface area allows the membrane to protrude forward or backward at its edges. The primary purpose of the membrane is preferably to separate and isolate the first and second cavities. Furthermore, the membrane is designed to switch between two positions (i.e., the first and second positions) in response to changes in the pressure gradient acting on its sides. This cavity configuration ensures controlled fluid separation and flow within the cannula during medical procedures.

[0037] In the context of this invention, the term "first portion of the cavity" preferably refers to a predetermined, constant volume of the cavity adjacent to its outlet. The term "second portion of the cavity" preferably refers to a predetermined, constant volume of the cavity adjacent to the syringe, syringe connector, or other connection port. The first portion of the cavity preferably falls before the fixed edge of the membrane along a longitudinal axis extending from the proximal end of the cannula to its distal end (i.e., the outlet or end). The second portion of the cavity preferably falls after the fixed edge of the membrane along a longitudinal axis extending from the proximal end of the cannula to its distal end (i.e., the outlet or end). Unlike the first and second cavities, the first and second portions of the cavity are not necessarily always physically separated from each other by the membrane.

[0038] In the context of this invention, the term "pressure gradient across the membrane" preferably refers to the fluid pressure difference acting on a first side and a second side of the membrane. This fluid pressure can be the pressure of a gas (such as air) or a liquid (such as a therapeutic or inert fluid). Preferably, "pressure gradient across the membrane" does not refer to the pressure applied to the membrane by actively pressing a non-fluid mechanical part (such as a plunger) or by retracting a mechanical part connected to the membrane.

[0039] In a preferred embodiment of the cannula device, in a first position, the membrane is at least partially inserted into a first portion of the seat cavity. When the injection solution is drawn with a needle, the membrane is switched to a second position by deforming (particularly by flipping, folding and / or unfolding) the membrane and extending it at least partially into a second portion of the seat cavity, preferably to expand the first cavity and draw the injection solution into the first cavity.

[0040] To draw the injection solution with a needle, a negative pressure is preferably created instantaneously in the second chamber, for example, by withdrawing the plunger of the syringe connected to the substrate, wherein the plunger is preferably not connected to the membrane. This preferably creates a fluid pressure gradient across the membrane, causing the fluid pressure in the first chamber to be instantaneously higher than the fluid pressure in the second chamber. By inverting the membrane so that it partially extends into the second part of the seat cavity, preferably making the second surface of the membrane convex, or even more preferably substantially conforming to the contour of the inner wall of the seat cavity, while the first surface of the membrane is concave. This increases the volume of the first chamber, instantaneously creating a reduced pressure within the first chamber. Therefore, fluid flows into the first chamber through the outlet, particularly through the needle at the outlet, until the pressure across the membrane is equalized.

[0041] Membrane flipping technology offers particular advantages because it maximizes the use of the volume within the chamber and provides precise fluid delivery. Since the flipped membrane can be fold-free in the second position, no dead space is created in the second chamber due to folds. More precisely, the membrane can essentially completely occupy the available volume of the second portion of the chamber to maximize the volume of the first chamber and the amount of fluid extracted. The maximum volume of the first chamber when the membrane is in the second position can be predetermined, enabling precise and repeatable fluid absorption. Furthermore, because the membrane does not contact moving parts, the risk of membrane puncture is reduced, creating a very reliable separation between the first and second chambers.

[0042] The membrane can preferably be configured to have discrete, stable positions. In this way, when the pressure gradient across the membrane changes, the membrane can transition substantially instantaneously between a first position and a second position, eliminating the possibility of the membrane remaining in an intermediate position. This can be achieved by configuring the membrane to be flexible but essentially inelastic. For example, the membrane can be configured as a rubber diaphragm that is flexible enough to transition between two complementary convex shapes, but is mechanically unstable between these two shapes. The flexibility of the rubber diaphragm can be limited so that in the region where its edges are fixed, the diaphragm is not compressed to remain within the narrower cross-section of the cavity. This implementation helps to provide consistent and precise dose or volumetric fluid absorption because the first cavity can only transition between filled and unfilled. This eliminates the possibility of only partially filling the first cavity. This avoids errors in medical procedures.

[0043] Alternatively or additionally, the membrane can be configured to be foldable. The membrane may be provided with foldable ribs or notches to control its folding. The membrane can be configured to fold in an intermediate position between a first position and a second position, while it can unfold in either one or both directions to reach the first and second positions. Alternatively, the membrane may have a default configuration of folding in either the first or second position, which, upon unfolding, leads to another default configuration in either the first or second position. Unlike prior art, this folding and unfolding of the membrane can occur in response to changes in the pressure gradient across the membrane, particularly in response to changes in the fluid pressure gradient between the first and second chambers. No rigid mechanical pulling or pushing of the membrane is required, reducing the risk of dead space and / or puncture. As further explained herein, preferred folding configurations have also been developed to reduce or eliminate any dead space.

[0044] When the syringe is filled, the membrane undergoes deformation, specifically flipping, folding, or unfolding, to reach the second position, causing the first chamber of the syringe to fill with the injection solution. When the syringe is compressed, the membrane preferably returns to the first position, allowing the therapeutic fluid to be delivered through the needle to the target area for treatment. The definition of the first and second chambers by the membrane's position limits the volume of the administerable injection solution. This controlled volume delivery facilitates precise and accurate administration during medical procedures, minimizing waste or over-administration.

[0045] In other preferred embodiments of the invention, in the second position, the membrane is at least partially inserted into the second portion of the cavity. When the injection solution is injected with a needle, the membrane is switched to the first position by deforming the membrane (particularly flipping, folding, and / or unfolding the membrane) and causing it to at least partially extend into the first portion of the cavity, thereby displacing the injection solution through the needle. For injection, it is preferable to generate overpressure in the second cavity such that the fluid pressure acting on the second surface of the membrane exceeds the fluid pressure acting on the first surface of the membrane. This reverses the pressure gradient across the membrane. Therefore, the membrane can be switched back to the first position.

[0046] The membrane extends at least partially into the first portion of the seat cavity, preferably meaning that at least a portion of the membrane lies in front of the location where the edge of the membrane is fixed. Preferably, the shape of the membrane at the first location is substantially conformal to the contour of the inner wall of the first portion of the seat cavity. This eliminates dead space within the seat cavity, improving the accuracy and efficiency of drug delivery. Preferably, the membrane can be in continuous contact with the inner wall of the first portion of the seat cavity, with the exception of the outlet. In this way, dead space can be eliminated, and the therapeutic fluid can be completely expelled from the cannula device, thus avoiding waste. This further improves the accuracy of drug delivery.

[0047] In other preferred embodiments of the invention, the cannula device includes a locking connection. This locking connection is preferably configured to hermetically engage the cannula device with a device for adjusting the pressure within a second cavity (particularly a syringe device). Preferably, the locking connection conforms to medical or surgical standards, particularly DIN ISO 80369. The locking connection is preferably configured as a snap-fit ​​connection, insertion connection, clamping connection, threaded connection, and / or a Luer lock fitting, particularly a threaded Luer lock fitting. The Luer lock fitting may preferably have internal threads conforming to Luer lock standards.

[0048] This cannula device is particularly preferably attachable to a conventional syringe via a Luer lock fitting. This allows the cannula device to be easily combined with conventional syringes or other medical-grade devices.

[0049] As used herein, the term "Luer lock fitting" preferably refers to a standardized type of connector used in medical and laboratory environments to securely seal two components together, ensuring a safe and leak-free connection between them. Luer lock fittings are available in a variety of forms, such as Luer cones, including those commercially available as Luer locks and Luer slide fittings. Luer cones can be unthreaded and smooth, or ridged to prevent accidental dislodgement. Luer lock fittings are also available in standardized threaded types. Both conical and threaded Luer lock fittings are available in male and female forms, and in different sizes. Threaded male Luer locks have a cylindrical, conical, or tapered end with external threads. Female Luer locks have a corresponding cylindrical, conical, or tapered cavity with internal threads. To enable a connection using a threaded Luer lock, the male and female parts are screwed together to create a threaded engagement, resulting in a safe and leak-free seal. This design ensures accurate and leak-free delivery of medical fluids. The advantages of this connection also include: providing venting between the cannula and the syringe through a special screw geometry, and pre-filling the dead space with an incompressible solution.

[0050] In other preferred embodiments of the invention, the second cavity of the cannula is pre-filled with a separator fluid. Therefore, during the extraction of the injection solution, the separator fluid is forced into the cylinder by flipping, folding, or unfolding the membrane. The separator fluid can be used to regulate the pressure within the second cavity, particularly in a substantially incompressible manner. By forcing the separator fluid into the cylinder, when the membrane is in the second position, the separator fluid within the second cavity does not need to be compressed but can be at least partially moved into an additional volume.

[0051] The available volume of the cartridge is preferably variable, especially when the cartridge forms part of a pressure regulating device (particularly a syringe). This allows the available volume within the cartridge to be increased by withdrawing the plunger, thereby reducing the pressure in the second chamber, and maintaining pressure balance by moving the membrane to a second position. The cartridge can also be configured to increase the pressure in the second chamber by reducing the available volume within the cartridge, particularly by compressing the plunger of the syringe. Thus, the separating fluid can be forced out of the cartridge and into the second chamber.

[0052] Preferably, the separating fluid is incompressible. Preferably, the cartridge is transparent. Therefore, the entry of the separating fluid into the cartridge is preferably visible to the naked eye and can serve as a visual indication that the membrane has fully reached the second position. In particular, the incompressibility of the separating fluid allows it to fill the cartridge to a predetermined level, indicating that the membrane is in the second position and the first cavity is filled. The user can use this as an indication that the step of drawing fluid into the cannula device has been completed.

[0053] In other preferred embodiments of the invention, the syringe volume is between 0.05 and 1 ml. At this volume, the syringe can be used without requiring a high level of manual dexterity or training. This volume is also suitable for preferred applications of the device, such as ocular injections.

[0054] In other preferred embodiments of the invention, the ratio of the seat cavity volume to the cylinder volume is between 1:40 and 1:10, preferably about 1:20. Below this ratio, the device is particularly easy to use and can deliver medication very accurately by hand.

[0055] In other preferred embodiments of the invention, the inner diameter of the cylinder is between 1 and 4 mm, preferably about 2 mm. With this diameter, the plunger can move a considerable distance to change the volume of the second portion of the seat cavity. Good visibility for manual drug delivery is also achieved.

[0056] The cartridge is preferably configured to serve a dosing aid function, particularly by being equipped with dosing markers to allow for precise control of the administered dose. This is especially advantageous when used with a membrane that is mechanically stable not only in the first and second positions but also in intermediate positions in between, allowing the first cavity to be partially filled to varying degrees. For this purpose, a foldable membrane may be particularly preferred. The dosing markers on the cartridge provide the ability not only to measure the maximum prescribed dose but also to accurately administer doses below the maximum limit.

[0057] Surprisingly, the pre-filled separator fluid in the cartridge can act as a dosing aid. This is because the membrane and the cavity already have a defined filling volume. Preferably, when the membrane is in the first position and no fluid has been drawn into the first cavity of the cannula, the pre-filled separator fluid completely fills the second cavity without reaching the cartridge. Specifically, when the plunger of the syringe is fully depressed, the separator fluid fills the second cavity, leaving no usable volume in the cartridge. When a volume of fluid is drawn into the first cavity of the cartridge, an equal volume of separator fluid is displaced from the second cavity, allowing the displaced fluid to enter the cartridge. The incompressibility of the separator fluid is particularly advantageous for achieving this displacement. The dosing markings on the cartridge preferably indicate the volume of the displaced separator fluid (or other derived quantification). Thus, the exact volume of the injected solution administered corresponds to the pre-filled separator fluid in the cartridge. Measurement can be performed using a dosing scale, which offers significant advantages. Precise dosing control is achieved by utilizing the specially designed dosing scale on the cartridge. This improves the accuracy of treatment administration, which is crucial for ensuring patient safety and therapeutic efficacy. Furthermore, surprisingly, this not only enables administration at the maximum prescribed dose, but also at smaller, more personalized doses. This flexibility is crucial in situations requiring extremely small, precise, and accurate administration, such as intravitreal injections.

[0058] In a preferred embodiment of the invention, the separating fluid comprises an aqueous solution selected from the group consisting of saline solutions, colored solutions, and / or buffer solutions. Using an aqueous solution as the separating fluid offers several advantages. Aqueous solutions are generally biocompatible and safe for medical applications, reducing the risk of adverse reactions when introduced into the human body. Furthermore, aqueous solutions are compatible with a wide range of pharmaceuticals and substances, ensuring that they do not adversely interact with injectable solutions or impair their effectiveness. The membrane's impermeability to aqueous solutions can also be achieved using a wide range of medical-safe materials.

[0059] In intravitreal injections or other sensitive medical procedures, colored solutions can enhance fluid visibility, aiding in precise localization and reducing the risk of complications. In certain medical imaging applications, the use of other biocompatible fluids or suspensions can provide enhanced contrast, thus aiding visualization and diagnosis. Saline solutions are particularly preferred as the separating fluid. Physiological saline solutions, being essentially sterile saline solutions, offer additional benefits. The properties of saline solutions closely resemble those of natural bodily fluids, making them physiologically compatible. This reduces the risk of tissue irritation or inflammation.

[0060] Preferably, the separatory fluid meets the requirements of a medical product, even if it is not intended to be injected into a living organism. The separatory fluid is preferably sterile, pyrogen-free, and free of suspended particles, and preferably has a pH between 5 and 8, more preferably between 7.2 and 7.6, and particularly preferably around 7.4. This ensures that even in the low-probability event of membrane rupture, the patient will not be harmed by the injection of an incompatible fluid.

[0061] To enhance membrane stability, it is preferable to reduce electrostatic repulsion of polymer chains by matching the properties of the buffer solution and the polymer.

[0062] To achieve this, the pH of the buffer solution is preferably selected close to (within ±1) the zero-charge point of the membrane, which depends on the material composition and any surface treatment. The pH range for different membrane materials is preferably selected to fall within the following ranges: Polyethylene (PE): 4 to 6 Polypropylene (PP): 2 to 4 Polyvinyl chloride (PVC): 7 to 8 Polystyrene (PS): 3 to 5 Polyethylene terephthalate (PET): 4 to 5 Polyurethane (PU): 4 to 6 Cyclic protein olefin copolymer (COC): 4 to 7 The ionic strength of KCl or NaCl is preferably 100-250 mM (slightly higher than physiological ionic strength). Due to the smaller distance between polymer chains, this enhances stability and thus reduces the repulsive forces between the polymer chains in the membrane material.

[0063] In a preferred embodiment of the invention, the separation fluid comprises a pH buffer. This allows the pH of the separation fluid to be maintained close to the normal pH of the relevant tissue or fluid being injected. In some preferred embodiments of the invention, the treatment fluid alternatively or additionally comprises a pH buffer.

[0064] The membrane can be in various forms, which can be tailored to optimize different characteristics of the casing device.

[0065] In a preferred embodiment of the invention, the membrane is configured to be complementary in form to the shape of the inner wall of the first and / or second portion of the seat cavity. This eliminates dead space within the seat cavity and reduces fluid waste. In particular, the membrane is preferably non-planar and configured to default to a complementary shape, for example, without any pressure gradient acting upon it. Such a membrane is particularly suitable for expelling the largest volume of fluid from the first cavity and / or particularly suitable for drawing the largest volume of fluid into the first cavity. In a preferred embodiment where the first and second portions of the seat cavity have complementary shapes (e.g., through symmetry), the membrane advantageously ensures optimal administration of the seat cavity volume and any fluid within it. Simultaneously, the membrane provides precise dosing.

[0066] In a preferred embodiment of the invention, the membrane has a planar, truncated conical, non-truncated conical, or hemispherical shape, and / or is configured as a foldable membrane, wherein the foldable membrane is defaulted to a compressed, folded state and is configured to expand during filling by unfolding one or more ribs, wherein the ribs are preferably arranged in vortices.

[0067] Preferably, the membrane has an inverted conical shape.

[0068] The planar membrane is preferably configured to be elastic, for example, comprising an elastic material (such as silicone or latex). This planar membrane is typically arranged to stretch and cover the cross-section of the seat cavity, while its sides are substantially flat. The planar membrane can only present a convex / concave form when forced into a first or second position. Therefore, the elastic membrane can also be presented in an intermediate position between the first and second positions, including varying degrees of concavity. This elastic membrane is suitable for applications requiring free administration of therapeutic fluids. This is particularly relevant to larger or repeated doses.

[0069] In a preferred embodiment, the membrane is designed in a non-truncated conical or truncated conical shape. The non-truncated or truncated conical shape of the membrane allows for flexibility and a close fit within the cavity of the seat. Preferably, the first and second portions of the seat cavity each have a truncated conical or non-truncated conical shape complementary to the membrane. The membrane can also be shaped to correspond to the complementary shape of the inner walls of the first and second seats. A perfect fit between the membrane and the inner walls is expected. This membrane is preferably non-elastic. This allows it to completely fill the relevant portion of the seat cavity without creating dead space due to compression or folding. This unique conical design ensures that the membrane is inherently constrained by the spatial limitations of the seat cavity during its expansion. It allows the membrane to seamlessly adjust and conform to changes in volume and pressure encountered within the seat cavity, while expelling almost all therapeutic fluid from the first cavity in the first position or drawing the maximum amount of fluid into the first cavity in the second position. In this case, when the membrane is in the first position, the volume of the first cavity may be extremely small or essentially zero. For example, the volume of the first cavity may only include the volume of the substrate's outlet channel.

[0070] The conical cut-off shape allows the membrane to avoid contact with any fittings (such as the base of a needle or surgical tube) that might protrude from its end into the chamber. This ensures the integrity of the membrane. Similar advantages can be achieved by providing a rounded end at the conical end or by using a membrane with a hemispherical or semi-ellipsoidal shape.

[0071] The fit between the membrane shape and the cavity facilitates the containment of precise fluid volumes while maintaining a secure seal. The conical shape acts as a physical barrier, effectively isolating the injection solution from any external substances or contaminants, thus ensuring solution purity. This separation prevents any unwanted contamination, including the possibility of silicone oil contamination, ensuring the integrity of the injection solution. Furthermore, this separation maintains a clear distinction from the pre-filled divider dose-support solution and ensures its expansion is inherently limited by the cavity's spatial dimensions. This limitation provides precisely controlled barrier properties, further enhancing the device's reliability.

[0072] In other preferred embodiments, the membrane is designed as a foldable membrane. The membrane can be configured in a compressed folded state corresponding to a first or second position, and unfolded to reach another state corresponding to the first or second position. Preferably, the foldability of the membrane is achieved by providing it with side ribs, tabs, notches, or other features that can be arranged in an accordion-like manner. For simplicity, side ribs will be referred to with reference to preferred features. Those skilled in the art will understand that these features are equally applicable to any type of folding feature. The side ribs are preferably not parallel to the longitudinal axis of the sleeve device. Preferably, the side ribs extend laterally or in an oblique direction having both lateral and longitudinal components.

[0073] This foldable membrane configuration is carefully designed to allow expansion during filling or injection by unfolding one or more side ribs. In this preferred embodiment, the folded membrane undergoes expansion and unfolding in response to an applied vacuum or fluid pressure during filling or injection. This transformation allows the membrane to efficiently contain the injection solution. Conversely, when the pressure gradient across the membrane reverses, for example, due to the injection solution after filling, the membrane undergoes a folding process, retracting from a second part of the cannula and precisely delivering the injection solution. This design choice offers several advantages, particularly in increasing the volumetric capacity of the cannula device. The ability of the foldable membrane to expand by unfolding the side ribs significantly increases its accommodating volume, thus being particularly advantageous for larger cannula devices or repetitive fluid injections (e.g., the continuous and frequent administration of anesthetics by a dentist). This expansion capability is also particularly advantageous in medical procedures requiring larger doses of fluid, such as injections or infusions. By allowing initial compression of the membrane, the device can be pre-packaged into a more compact form. The preferred foldable membrane design minimizes dead space within the device. Dead space refers to unused space in a medical device that can trap air or fluid, leading to inaccurate dosing. By deploying the side ribs and maximizing the available volume of the membrane, the risk of dead space is reduced, ensuring that the administered fluid accurately matches the intended dose. Deploying the side ribs allows for precise control of the volume of fluid administered while also accommodating the possibility of intermediate doses.

[0074] In a preferred embodiment of the invention, the membrane folds are configured for stepwise or repeated injection of doses. For example, these folds can be configured to sequentially “pop in” or “click in” or “dislodge” into place, for example, similar to the manner of a known shrinkable cup or expandable silicone funnel. The folds can be arranged such that each expansion step of the membrane corresponds to a single dose or a single administration step. This is particularly advantageous for precise administration of medicines (such as anesthetics) in an intermittent manner.

[0075] In a particularly preferred embodiment of the invention, the side ribs have curved trajectories with lateral and longitudinal components relative to the sleeve assembly. Particularly preferred is that the side ribs are arranged in vortices (or "spirals") on the foldable membrane. These side ribs are preferably formed as discrete lines extending along a curve from the apex (preferably at the center of the membrane) to the periphery of the membrane. This configuration has been found to be particularly space-saving and advantageous in eliminating dead space.

[0076] In other preferred embodiments of the invention, the membrane has a wall thickness of 5 μm to 200 μm, preferably about 60 μm. Such a membrane has been found to be particularly compact and flexible. Its thickness is low enough that it occupies minimal space within the seat cavity. Simultaneously, the membrane is robust enough to withstand multiple transitions from a first position to a second position and vice versa. Furthermore, the membrane can be made robust enough to withstand contact with the inner wall of the seat cavity. Advantageously, rigid mechanical parts are not required to move the membrane, allowing for a very thin thickness to be achieved without risking damage to the membrane's integrity.

[0077] Preferably, the membrane wall thickness can be uniform or non-uniform. Non-uniform membrane wall thickness can facilitate control of the membrane folding mechanism.

[0078] Preferably, the membrane is a multilayer membrane. Multilayer membranes can advantageously enhance the barrier properties of the membrane. The membrane layers are preferably aligned in such a way that the membrane layer in contact with the fluid is a bio-inert, leak-proof layer. On the side facing the second cavity (away from the fluid) of the bio-inert, leak-proof membrane layer, other airtight membrane layers can be added.

[0079] In other preferred embodiments of the invention, the membrane comprises polypropylene, polystyrene, polyethylene, polyvinyl chloride, silicone, or copolymers as materials, wherein the copolymers are selected from the group consisting of cyclic olefin copolymers and linear olefin copolymers. Particularly preferably, the membrane comprises at least 50% cyclic monomers in molar fraction. Such materials have been found to be particularly safe, non-polluting, and capable of sterilization, while also providing the mechanical properties required for the membrane to be flipped, folded, or unfolded.

[0080] Preferably, the membrane may comprise polypropylene, polystyrene, polyethylene, polyvinyl chloride, polyester, polyethersulfone, silicon, or copolymers.

[0081] In other preferred embodiments of the invention, the membrane has a surface treatment on at least one side (preferably at least on the first side defining the first cavity). This surface treatment is preferably configured as a further diffusion barrier and / or has hydrophilic properties. Preferred surface treatment methods include water plasma treatment, oxygen plasma treatment, cold plasma treatment, and microwave plasma surface treatment. Other suitable techniques include corona discharge, acid etching, and reactive gas chemical processes.

[0082] The surface treatment can be based on silicone or glass and can be applied by chemical vapor deposition to form a layer with a thickness of less than 1 μm. Preferably, the surface treatment is silicone oil-free. This surface treatment prevents fluid leakage from the first cavity to the second cavity and vice versa, especially when the membrane is thin or stretched. A hydrophilic surface treatment can further prevent the formation of bubbles in the first cavity, reducing dead space and unwanted gas injection into the patient.

[0083] In other preferred embodiments of the invention, the inner surface of the substrate, particularly the seat cavity, especially the first portion of the seat cavity, is provided with a hydrophilic surface treatment. This further reduces the risk of bubble formation, making the device particularly safe and effective.

[0084] Hydrophilic surface treatments, whether applied to the cannula or the membrane or other surfaces of the attached device, preferably prevent the attachment of lipophilic or hydrophobic particles or contents (e.g., lipid nanoparticles, liposomes, and proteins with hydrophobic sites). Therefore, during the injection step, the components of this medical fluid can be completely drained from the first cavity without leaving any residue adhering to the device.

[0085] In other preferred embodiments of the invention, the expansion of the membrane is defined by the total volume of the first and second portions of the cavity, wherein the total volume of the first and second portions of the cavity is 10 μl to 10,000 μl, preferably 50 to 300 μl. Particularly preferably, the total volume of the first and second portions of the cavity is approximately 200 μl. Preferably, the maximum volume of the first cavity substantially corresponds to the total volume of the first and second portions of the cavity. This cannula device is particularly suitable for providing highly precise therapeutic fluids, especially in cases where medical doses are in the μl range, such as in the ophthalmic field.

[0086] In other preferred embodiments of the invention, the total volume of the first and second portions of the cavity ranges from 30 to 70 μl, preferably 40 to 60 μl. Particularly preferred is that the total volume of the first and second portions of the cavity is approximately 50 μl. This design facilitates precise ocular treatment requiring small but precise amounts of therapeutic solution.

[0087] In other preferred embodiments of the invention, the total volume of the first and second portions of the cannula is 0.5 ml to 500 ml, particularly 1 ml to 50 ml. This cannula device can be configured for the absorption or delivery of large volumes of fluid, such as for collecting blood samples, providing blood transfusions, or repeatedly delivering anesthetics. The use of a foldable membrane has been found particularly suitable for this purpose, wherein the foldable membrane can also be configured to be sealable and removable from the cannula device and used for storing fluids, such as for use as a blood bag.

[0088] In other preferred embodiments of the invention, the total volume of the first and second portions of the cavity ranges from 200 to 400 μl, preferably 250 to 350 μl. Particularly preferred is the total volume of the first and second portions of the cavity being approximately 300 μl. This size is particularly effective in ensuring accurate vaccine dosing, which may be crucial given the importance of accurate dosage in vaccination procedures.

[0089] In other preferred embodiments of the invention, the total volume of the first and second portions corresponds to multiple doses to be delivered independently. Particularly preferred is that the total volume of the first and second portions of the cavity is designed to deliver multiple doses, for example, 5 doses, each 20 μl, for a total of 100 μl.

[0090] This particular implementation offers several advantages, especially in the context of dental procedures. Dentists often face situations where they need to administer anesthetic in staggered doses throughout a single treatment session. This implementation allows for the precise delivery of micro-dose, significantly improving the accuracy and predictability of anesthetic dosage. This not only minimizes the possibility of overdose but also ensures that the patient receives the appropriate amount of anesthesia, guaranteeing a painless procedure.

[0091] Furthermore, by eliminating the need for refilling or switching devices between doses, the workflow of dental procedures is significantly simplified. This not only saves time but also reduces the possibility of errors, thereby ensuring the efficiency and safety of dental anesthesia administration.

[0092] In other preferred embodiments of the invention, the sleeve device is manufactured by a process including a molding step, selected from the group consisting of injection molding and blow molding. These manufacturing processes have been found to be particularly safe and capable of providing a smooth surface with minimal seams and / or protrusions. This reduces the risk of friction between parts, thus improving the integrity of the sleeve device.

[0093] Injection molding is a precise and versatile manufacturing method used to produce various components for cannulated devices. The process involves injecting molten material (typically plastic or polymer) into a finely designed mold to replicate the exact dimensions of the desired part. Injection molding is particularly suitable for producing housing components, connectors, and other non-metallic parts for cannulated devices. Its use ensures uniform, consistent, and high-quality production that meets the stringent standards required for medical devices.

[0094] In other preferred embodiments of the device, the substrate of the cannula is formed in two parts. Preferably, a first part of the substrate corresponds to a first part of the seat cavity, and a second part of the substrate corresponds to a second part of the seat cavity. The membrane is preferably disposed between the first and second parts, with its periphery fixed relative to the substrate, for example, by clamping. This avoids the use of adhesives and other potential contaminants. For example, the cannula can be formed by providing two injection-molded cup-shaped portions, disposing the membrane between them, and thermally bonding the two portions together to fix the periphery of the membrane in place. Positive or negative pressure can be applied to one of the cavities formed on either side of the membrane to thermoform it. In this way, the membrane can be provided with a shape complementary to the internal shape of the first and / or second parts of the seat cavity, thereby eliminating dead space.

[0095] In other preferred embodiments of the invention, the membrane is integrally formed with one of the two portions of the substrate. Specifically, at least one portion of the sleeve device substrate can be blow-molded, wherein the two portions of the substrate are initially formed by injection molding. One of these portions can be formed in a manner similar to a plastic bottle. This portion can be provided with a base, which can be molded very thin so that during the blow molding process, the base takes on the desired membrane shape. This manufacturing method provides a high degree of integrity and close fit between the membrane shape and the interior of the cavity.

[0096] Other preferred manufacturing methods include deep drawing. Deep drawing is used to precisely shape the membrane, transforming it from a flat material into its preferred shape, such as a frustoconical shape. This process allows for precise control of the membrane's geometry, ensuring a perfect fit to the inner cavity of the cannula device and effectively separating the injection solution from external elements, including silicone oil and / or separated dosing aid solutions. The use of deep drawing on the membrane surprisingly achieves the required flexibility and spatial constraints, which is beneficial for preserving the device's functional and dosing integrity.

[0097] In other preferred embodiments, the cannula device is permanently coupled to the syringe barrel, particularly in an integral manner. This preferably means that the cannula device and syringe barrel are manufactured as a single, integral unit, and they cannot be separated or disassembled. Integral coupling ensures that the entire assembly, including the cannula and syringe, is manufactured and packaged under controlled aseptic conditions. This minimizes the risk of contamination during assembly or use, which is crucial for medical applications to prevent infection or complications. The integration of the cannula device with the syringe barrel simplifies the manufacturing process because no separate assembly step is required to connect the cannula to the syringe. This can lead to increased manufacturing efficiency and cost savings. Integral coupling eliminates the possibility of misalignment or detachment between the cannula and syringe barrel during medical procedures. This ensures the device functions as intended, reducing the likelihood of procedural errors or accidents. Because the cannula device is permanently attached to the syringe, its performance characteristics, such as fluid flow rate and accuracy, remain consistent across different units. Users, such as medical professionals, benefit from the simplicity and convenience of having the cannula device and syringe combined as a single unit. This eliminates the need for additional assembly steps, making it easier to use during medical procedures. While manufacturing an integrated connecting device may require some initial tooling costs, the potential cost savings from increased efficiency, reduced waste, and improved quality control can make the approach more cost-effective in the long run.

[0098] In other preferred embodiments, the cannula is pre-filled with one or more therapeutic products. This preferably means that the cannula is pre-loaded with the desired pharmaceutical or therapeutic substance and / or separation fluid, ready for immediate use in a medical procedure.

[0099] Pre-filled devices eliminate the need for healthcare professionals to manually extract and prepare medications before administration. This significantly reduces the time required for preparation, allowing for more efficient patient care. Pre-filled cannula devices are filled under controlled conditions, ensuring accurate dosing and reducing the risk of errors in medication preparation. Because the therapeutic product is pre-loaded and sealed within the device, it remains sterile until use. This minimizes the risk of contamination and infection associated with traditional medication preparation methods.

[0100] In this preferred embodiment, one of the "one or more therapeutic products" is actually a separated administration fluid. The inclusion of a separated administration fluid ensures accurate and consistent dosage of the therapeutic product. The administration fluid acts as a buffer, facilitating the measurement and delivery of the exact amount of medicine required for each treatment.

[0101] In other preferred embodiments of the invention, the pre-filled cannula device is capable of storage at temperatures as low as -80°C. This ability to withstand such low temperatures makes this embodiment particularly suitable for storing vaccines, especially mRNA vaccines. mRNA vaccines have attracted attention due to their high efficacy, but one of the challenges is the need for ultra-low temperature storage to maintain their stability. Therefore, cannula devices that can withstand these extreme temperatures are beneficial for vaccine dispensing and administration.

[0102] Therefore, the cannula is preferably configured with sufficient thickness and mechanical properties to withstand any expansion or contraction of the therapeutic products or other fluids stored within it as the temperature drops to -80°C and rises to room temperature, patient temperature, or higher. Furthermore, the material and thickness of the substrate are preferably selected to prevent cracking or deformation due to temperature changes. Preferably, leakage of fluid within the pre-filled cannula after thawing is prevented by using a sealed cavity capable of withstanding a predetermined temperature range and the thermal expansion stresses caused by one or more therapeutic products.

[0103] In other preferred embodiments of the invention, the sleeve device includes means for venting the sleeve device.

[0104] Preferably, venting of the cannula is initiated by screwing the male Luer lock fitting of the cannula onto the female Luer lock fitting of the syringe. Once the cannula is fully screwed onto the female Luer lock fitting of the syringe, the Luer lock connector preferably applies slight (direct or indirect) pressure to the membrane. This pressure causes a small volume of therapeutic fluid to displace, thereby venting the cannula. This preferably means that sufficient therapeutic fluid moves through the needle into the first lumen to remove any air from the first lumen and the needle. Because the dimensions of the Luer lock connector are precisely standardized, the remaining volume within the first lumen of the cannula can be precisely predetermined. Therefore, the dose applied after venting is highly accurate.

[0105] Preferably, venting of the cannula can be initiated by inserting a pin into the second chamber of the cannula. The cannula is preferably assembled to a syringe, and by inserting or pushing the pin into the second chamber, a very precise volume of therapeutic fluid is displaced through the needle into the first chamber. This preferably means that sufficient therapeutic fluid is moved through the needle into the first chamber to remove any air from the first chamber and the needle. The remaining volume can be predetermined with very precision.

[0106] Preferably, the first cavity can be highly transparent and includes markings, preferably small markings on the housing. This preferably means that the necessary volume can be ejected using a syringe plunger until the membrane aligns with the markings.

[0107] Advantageously, a reliable mechanism is provided for venting the cannula device, allowing air to be removed from the device to avoid accidental injection of air during the administration of the therapeutic fluid, while still providing a reliable dose. This is particularly relevant for small volumes of therapeutic fluid.

[0108] In other preferred embodiments, the cannula device is provided as part of the injection device, wherein the injection device is provided as a single component, preferably an injection-molded component, including the cannula device and a mechanism for applying pressure to the membrane.

[0109] Particularly preferred, this embodiment may provide a ready-to-use product with pre-filled therapeutic fluid.

[0110] Preferably, individual injection devices can be combined into an injection blister pack. This preferably means that multiple individual injection devices can be connected via perforated connectors, allowing them to be easily separated.

[0111] The advantage of this injection device is that it generates less waste than a syringe.

[0112] Furthermore, the injection device is preferably protected against reuse because its function can automatically fail after a single use. This can be achieved, for example, by providing a pre-filled injection device that does not include a reversible plunger for applying pressure and injecting the therapeutic fluid, but instead applies pressure in a different manner. For example, the pressure for injecting the therapeutic fluid from the first chamber can be provided by applying pressure to a flexible second chamber, which will remain (partially) collapsed after use, thereby preventing refilling and reuse of the device. Partial collapse preferably refers to a situation where the collapsed volume of the second chamber corresponds to the volume of therapeutic fluid displaced from the first chamber during injection. Therefore, such a partially collapsed second chamber reservoir prevents the reuse of the injection device.

[0113] In other respects, the present invention relates to the use of a cannula device according to any embodiment described herein for the injection, storage, and / or transport of liquids, wherein the absence of silicone oil or other abrasives and / or the requirement of special purity are required. Preferably, the present invention relates to the use of such a cannula device in which sliding friction is avoided to prevent potential damage to fragile components, particularly cells, vesicles, lipid nanoparticles or microparticles, liposomes, micelles, nucleic acids (single-stranded, double-stranded), proteins, or antibodies. Particularly surprising is the use of membranes that change between a first and a second position in response to the reversal of the pressure gradient across the membrane in these applications. It is believed that the absence of moving parts within the first cavity is particularly advantageous for preventing the rupture of delicate microstructures such as cells, vesicles, etc.

[0114] The cannula is designed to prevent contact with silicone oil and maintain the integrity of the injected substance, making it highly suitable for applications where silicone oil is critically absent. Its ability to maintain the purity and sterility of the injected substance meets stringent standards for certain medical procedures. It ensures that the administered medicine or therapeutic product is delivered in its original, uncontaminated state. The cannula's efficiency and accuracy in delivering controlled doses make it ideal for situations requiring repeated or repetitive administration of medicines or therapeutic agents. Its stable performance helps ensure that every dose is accurate and safe.

[0115] In other respects, the invention includes a kit comprising a cannula device and at least one additional disposable syringe and / or needle. The kit is designed to provide a comprehensive and versatile solution for a variety of medical scenarios. The core component of the kit is the cannula device. This cannula device is designed to maintain the integrity and sterility of the injected substance, ensuring precise and controlled delivery. The kit may include one or more disposable syringes. These syringes can be used in conjunction with the cannula device for drawing medications or fluids, preparing injection solutions, and assisting in injection procedures. Disposable syringes are generally preferred in healthcare settings due to their single-use design, reducing the risk of cross-contamination. In addition to the syringes, the kit may also provide disposable needles. These needles are essential for attachment to the syringes and cannula device, allowing for safe and precise administration of medications or fluids. Like the syringes, disposable needles contribute to infection control and safety. The inclusion of additional syringes and needles makes the kit versatile and suitable for a variety of medical procedures and treatments.

[0116] Furthermore, as an alternative to traditional needle and cannula configurations, this kit also provides an implementation of a needle-free injector. This needle-free injector design ensures painless injection, thereby enhancing patient comfort. It can be particularly beneficial in scenarios requiring rapid drug administration or in patients with severe needle phobia. The needle-free injector can still be used with components of the kit for drawing, preparing, and administering medications or fluids.

[0117] Combining all necessary components into a single kit streamlines medical workflows, saving time and effort during procedures. Kit components are typically organized and packaged in a sterile and convenient manner. Proper packaging helps maintain the sterility of the contents until they are ready for use.

[0118] In a preferred embodiment of the invention, the kit includes means for adjusting the pressure within a second cavity of the cannula. The cannula is preferably connectable to the means for adjusting the pressure within the second cavity, for example, thanks to both components including complementary plug-in connections. The means for adjusting the pressure within the second cavity of the cannula can be configured for manual use, such as a conventional syringe. Alternatively, the means can be mechanically and / or electronically controlled, such as a mechanical pump.

[0119] Terms such as basic, about, and approximately preferably describe tolerance ranges of less than ±20%, more preferably less than ±10%, especially preferably less than ±5%, especially less than ±1%, and include exact values.

[0120] Those skilled in the art will understand that the technical features and advantages of the sleeve device described herein also apply to the method of manufacturing the device, the use of the device, and kits that include the device, and vice versa.

[0121] Specific implementation methods Without being intended to limit, the invention will be explained in more detail with reference to exemplary embodiments and the following figures: Attached Figure Description Figure 1 An example of a sleeve device according to a preferred embodiment of the present invention is shown, wherein the membrane is in a first position.

[0122] Figure 2 It shows Figure 1 The sleeve device, wherein the membrane is in the second position.

[0123] Figure 3 and Figure 4 This is a close-up view of the seat cavity of the sleeve device according to a preferred embodiment of the present invention.

[0124] Figure 5 The steps for drawing up a treatment solution using a cannula device are illustrated schematically.

[0125] Figure 6 The steps for injecting the treatment solution into the patient are illustrated schematically.

[0126] Figure 7 This is a perspective view of a cannula device according to a preferred embodiment of the present invention, which is detachable from the syringe.

[0127] Figure 8 A perspective view of a cannula device according to a preferred embodiment of the present invention is shown, the cannula device being connected to a syringe via a Luer lock.

[0128] Figure 9 A perspective view of a cannula device according to an alternative preferred embodiment of the invention is shown, wherein the cannula is integrally formed with the syringe.

[0129] Figure 10 An example of a sleeve device according to a preferred embodiment of the present invention is shown, wherein the membrane is configured as a foldable membrane.

[0130] Figure 11 The diagram schematically illustrates a foldable membrane in both an expanded and compressed folded state.

[0131] Figure 12 An exemplary process is illustrated in which the cannula is vented by applying pressure to the membrane through screwing the cannula onto the syringe.

[0132] Figure 13 Other exemplary processes for venting the bushing assembly by means of inserting a small pin are illustrated schematically.

[0133] Detailed description of the attached figures Figure 1 An example of a cannula device 2 according to a preferred embodiment of the present invention is shown, wherein the membrane is in a first position. The cannula device 2 has a base 4 (shown in close shadow). The cannula device 2 is hermetically connected to the syringe 20 by means of a male Luer lock fitting 16 on the base 4 and a female Luer lock fitting 18 on the syringe 20 (shown in loose shadow). The base 4 of the cannula device 2 includes a hollow seat cavity 6 ( Figure 2 (As indicated in the diagram). The seat cavity includes a membrane 12, the periphery of which is clamped in the middle position along the seat cavity 6. However, the middle portion of the membrane 12 is free to move within the seat cavity. The substrate 4 also includes an outlet channel 14 extending from the seat cavity. The needle 26 is fixed within the outlet channel 14 and extends longitudinally from the outlet channel.

[0134] Figure 1The membrane 12 in its first position is shown. This membrane divides the hollow portion of the substrate 4 into two cavities. The first cavity 28 is located between the membrane 12 and the outer end of the substrate 4. The second cavity 30 is located between the membrane 12 and the plunger 24 of the syringe. In this embodiment, the membrane has a truncated conical shape that conforms to the internal shape of the seat cavity. Due to this close fit, the membrane 12 ensures that the first cavity occupies virtually no volume within the seat cavity, in this case limited only to the volume of the outlet 14. The second cavity 30 substantially occupies the entire seat cavity plus the transition volume leading to the proximal end of the cannula. The second cavity 30 is pre-filled with a separating solution. When the plunger 24 is fully depressed, the volume of the separating solution 34 fills the second cavity 30. No residual air bubbles remain in the second cavity, allowing the separating solution 34 to accurately reflect the fluid volume entering the cannula after the membrane 12 is placed in the first position shown.

[0135] Figure 2 The cannula 2 is shown after the plunger 24 of the syringe 20 is pulled to draw therapeutic fluid 32 into the first chamber 28. The pulling of the plunger 24 causes a pressure drop within the second chamber 30. Due to this pressure drop, the membrane 12 rapidly flips, bringing it to the second position shown in the figure. Because the seat cavity has a symmetrical shape before and after the membrane 12, the flipped membrane 12 fits tightly against the shape of the lower portion of the seat cavity 6. This causes a portion of the separating fluid 34 to be moved into the barrel 22 of the syringe 20. Simultaneously, a pressure drop is generated within the first chamber 28, which expands and substantially occupies the entire seat cavity 6. Due to this pressure drop, the therapeutic fluid 32 fills the first chamber 28. The volume of the therapeutic fluid 32 in the first chamber 28 corresponds to the volume of the separating fluid 34 moved into the barrel 22. The barrel 22 is transparent, allowing the amount of separating fluid 34 to be visible within it. The barrel 22 is also provided with at least one dosage mark indicating that the first chamber 28 has been filled to its maximum capacity. Then the plunger 24 can be pressed to inject fluid, causing the membrane 12 to return to the first position (e.g., Figure 1 (As shown). Cylinder 22 can be used to verify whether all fluid has been discharged from the first chamber 28.

[0136] Figure 3 and Figure 4 Provided Figure 1 and Figure 2 A close-up view of the cannula assembly's seat cavity 4, outlet 14, and needle 26. This close-up shows two distinct identifiable portions within the seat cavity 4. In this embodiment, the base 4 comprises two portions. These two portions join together at a cross-section of the seat cavity that clamps the periphery of the membrane 12. The first portion 8 of the seat cavity is located in front of (distal) the clamped membrane periphery, while the second portion 10 of the seat cavity is located behind (proximal) the clamped membrane periphery. Since the periphery of the membrane 12 is also fixed, the volume defined by the first and second portions 8 remains constant during use of the cannula assembly.

[0137] As can be more closely identified in these figures, the truncated shape of the membrane 12 provides a substantially flat end that fits snugly against the outlet channel 14 in the first position. The needle 26 is located within the outlet channel 14, flush with the inner surface of the seat cavity 6. However, minor errors in the positioning of the needle 26 may cause its base to protrude into the first portion 8 of the seat cavity. The flat, truncated surface of the membrane 12 prevents the thin membrane from puncturing in the event of any minor errors in the positioning of the needle 26.

[0138] Figure 5 The process of drawing a treatment solution into the first chamber 28 of the cannula device 2 is illustrated schematically. First, a needle 26 is inserted into a sealed container holding the treatment fluid 32. The needle 26 can pierce the sealing foil at the top of the container. At this point, the membrane 12 is in the first position.

[0139] The plunger 24 of the syringe 20, connected to the cannula assembly 2, is then pulled back, thereby reversing the pressure difference across the membrane 12. The membrane 12 is inelastic, and when fluid enters the first chamber 28, the membrane 12 begins to flip. The first chamber 28 expands and fills with the therapeutic fluid 32.

[0140] The plunger 24 of syringe 20 is pulled back further until the membrane 12 is in the second position. The first chamber 28 expands to substantially occupy the entire seat chamber and is filled with therapeutic fluid 32. The septal fluid 34 in the transparent tube 22 of syringe 20 indicates that the cannula is full.

[0141] Figure 6 The procedure for injecting the treatment solution into patient 36 is shown. Figure 5 As shown, the cannula device 2 is filled, and the membrane 12 is in the second position. Pressing the plunger 2 of the syringe 22 increases the pressure within the second chamber 30. This reverses the pressure gradient across the membrane 12, causing the membrane 12 to flip again. As the membrane 12 flips, the first chamber 28 shrinks, expelling the incompressible therapeutic fluid 32 through the needle 26. The membrane 12 returns to the first position, where the first chamber 28 occupies virtually no volume due to the tight fit between the membrane 12 and the inner wall of the first portion of the seat cavity 8. Since there is virtually no dead space within the seat cavity 6, all the therapeutic fluid 32 enters the needle 26. The therapeutic fluid 32 is delivered to the patient in a precise, uncontaminated dose.

[0142] Figure 7A cannula device 2 according to a preferred embodiment of the present invention is shown, wherein the cannula device 2 is disposed separately from the syringe 20. The injection-molding or blow-molding characteristics of the cannula can be better observed in this view. The cannula device comprises two halves, proximal and distal, of the membrane 12. As can be seen in the figure, these two halves are thermally bonded together. However, both halves of the cannula device are smooth and substantially monolithic. The proximal half of the cannula includes a medical-standard internal threaded connection 18. This allows for easy attachment to a sterile disposable syringe 20 with a complementary external threaded connection, which is widely used in the art. Figure 8 A perspective view of the cannula device 2 connected to the disposable syringe 20 is shown.

[0143] Figure 9 An alternative embodiment is shown in which the syringe 20 (particularly its barrel) is integrally formed with the cannula assembly, for example by injection molding. As can be seen, the barrel of the syringe 20 and the proximal portion of the base 4 of the cannula are a single part. The plunger 24 is slidably confined within the barrel 22.

[0144] Figure 10 A sleeve device 2 according to a preferred embodiment of the present invention is shown, wherein the membrane is configured as a foldable membrane. The figure shows that during filling, the membrane is in an expanded, extended state 40 by unfolding one or more ribs 44, wherein the ribs are preferably arranged in a vortex shape.

[0145] Figure 11 The folding and unfolding process is schematically illustrated in an intermediate position between the first and second positions. The membrane is shown in its unfolded, expanded state 40. The plunger 24 of the syringe 20, connected to the cannula assembly 2, is pressed, increasing the pressure and causing the membrane to fold. The foldable membrane is intentionally modified to allow expansion during filling by unfolding one or more side ribs 44. In this state, the folded membrane undergoes expansion and unfolding in response to applied vacuum or fluid pressure during the filling or injection process.

[0146] Figure 12An exemplary process for venting the cannula device 2 is illustrated schematically. The male Luer lock fitting 16 of the cannula device 2, according to a preferred embodiment of the invention, is screwed onto the female Luer lock fitting 18 of the syringe 20. Once the cannula device 2 is fully screwed onto the female Luer lock fitting 18 of the syringe 20, the Luer lock connector applies slight (direct or indirect) pressure to the membrane 12. This pressure causes a small volume of therapeutic fluid 32 to displace, thereby venting the cannula. Preferably, this means that sufficient therapeutic fluid 32 is displaced within the first chamber 28 via the needle 26 to remove any air 46 from the first chamber 28 and the needle 26. Because the dimensions of the Luer lock connector are precisely standardized, the remaining volume in the first chamber 28 of the cannula device 2 can be precisely predetermined. Therefore, the dose applied after venting is highly accurate.

[0147] Figure 13 Other exemplary processes for venting the cannula device 2 are illustrated schematically. The cannula device 2, according to a preferred embodiment of the invention, is assembled onto the syringe 20. A very precise volume of therapeutic fluid 32 is displaced through the needle 26 within the first chamber 28 by inserting or pushing the pin 48 into the second chamber 30. Preferably, this means that sufficient therapeutic fluid 32 is displaced within the first chamber 28 by the needle 26 to remove any air 46 from the first chamber 28 and the needle 26. The remaining volume can be designed very precisely.

[0148] List of symbols in the attached diagram 2-tube assembly 4 matrix 6-seat chamber The first part of the 8-seat cavity The second part of the 10-seat cavity 12 membranes 14 Outlet Channels / Injection Ports 16mm Luer lock accessories 18-pin Luer lock accessories 20 syringes 22 tubes 24 plungers 26 needles 28 First Cavity 30 Second cavity 32 therapeutic fluids 34 Separated Fluids 36 patients 38 small bottles 40 unfolded membrane 42 compressed membrane 44 lateral ribs 46 air 48 sales.

Claims

1. A cannulation device, comprising a base, wherein the base includes a seat cavity in its longitudinal direction. Its features are, The seat cavity includes a first cavity and a second cavity, and a membrane arranged laterally within the seat cavity, wherein the first cavity and the second cavity are separated from each other by means of the membrane, and wherein the membrane is configured to switch between a first position and a second position in response to a reversal of the pressure gradient across the membrane.

2. The sleeve device according to the preceding claims, Its features are, In the first position, the membrane extends at least partially into a first portion of the seat cavity, and when the injection solution is drawn with a needle, the membrane is switched to a second position by flipping and / or unfolding the membrane and extending it at least partially into a second portion of the seat cavity, preferably such that the first cavity is expanded and the injection solution is drawn into the first cavity.

3. The sleeve device according to any one of the preceding claims, Its features are, In the second position, the membrane extends at least partially into the second part of the seat cavity, and when the injection solution is injected with a needle, the membrane is switched to the first position by flipping and / or folding the membrane and extending it at least partially into the first part of the seat cavity, and by displacing the injection solution with the needle.

4. The sleeve device according to any one of the preceding claims, Its features are, The sleeve device includes a locking connection on at least one side, which serves as a snap-fit ​​connector, an insertion connector, a clamping connector, a threaded connector, and / or a Luer lock fitting, particularly a threaded Luer lock fitting.

5. The sleeve device according to any one of the preceding claims, Its features are, The second cavity of the cannula is pre-filled with a separating fluid, such that during the extraction of the injection solution, the separating fluid is forced into the cylinder by flipping, folding or unfolding the membrane, wherein the cylinder is preferably configured to act as a dose aid, particularly by being provided with dose markings.

6. The sleeve device according to the preceding claims, Its features are, The separating fluid includes an aqueous solution selected from the group consisting of salt solutions, colored solutions, and / or buffer solutions.

7. The sleeve device according to any one of the preceding claims, Its features are, The membrane has a planar, truncated conical, non-truncated conical, rounded conical or hemispherical shape, and / or is configured as a foldable membrane, wherein the foldable membrane is defaulted to being in a compressed, folded state, and is configured to expand during filling by unfolding one or more ribs, wherein the ribs are preferably arranged in a vortex shape.

8. The sleeve device according to any one of the preceding claims, Its features are, The membrane has a wall thickness of 5 μm to 200 μm, preferably 60 μm.

9. The sleeve device according to any one of the preceding claims, Its features are, The membrane comprises polypropylene, polystyrene, polyethylene, polyvinyl chloride, silicone, or copolymers, wherein the copolymers are materials selected from the group consisting of cyclic olefin copolymers and / or linear olefin copolymers.

10. The sleeve device according to any one of the preceding claims, Its features are, The expansion of the membrane is defined by the total volume of the first and second portions of the seat cavity, wherein the total volume of the first and second portions of the seat cavity is 10 μl - 10000 μl, preferably about 50 μl - 300 μl.

11. The sleeve device according to any one of the preceding claims, Its features are, The sleeve device is manufactured by a process including molding steps selected from the group consisting of: - Injection molding process and - Blow molding process.

12. The sleeve device according to any one of the preceding claims, Its features are, The cannula device is fixedly connected to the syringe barrel, particularly in an integral connection.

13. The sleeve device according to any one of the preceding claims, Its features are, The cannula is prefilled with one or more therapeutic products, wherein the prefilled device is preferably capable of being stored at temperatures as low as -80°C, thereby preferably preventing leakage after thawing by using a sealed cavity capable of withstanding a predetermined temperature range and the thermal expansion stress caused by the one or more therapeutic products.

14. Use of the cannula device according to any one of the preceding claims for injecting, storing and / or transporting liquids, wherein, The absence of silicone oil or other abrasives is required and / or special purity is required, and / or sliding friction will be avoided to prevent potential damage to fragile components, especially cells, vesicles, lipid nanoparticles or microparticles, liposomes, micelles, nucleic acids (single-stranded, double-stranded), proteins or antibodies.

15. A kit comprising a cannula device according to any one of claims 1-13 and at least one additional disposable syringe and / or needle.

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