Membrane-based cannula device

Abstract

The invention relates to a cannula device (2) comprising a base body (4), wherein the base body (4) comprises in its longitudinal direction a hub (6). The hub comprises a first cavity (28) and a second cavity (30) and a membrane (12) arranged transversally within the hub, wherein the first cavity and the second cavity are separated from one another by means of the membrane, wherein the membrane is configured to be convertible between a first position and a second position in response to a reversal of a pressure gradient across the membrane.

Description

[0001] MEMBRANE-BASED CANNULA DEVICE

[0002] DESCRIPTION

[0003] The invention relates to a cannula device comprising a base body, wherein the base body comprises in its longitudinal direction a hub. The hub comprises a first cavity and a second cavity and a membrane arranged transversally within the hub, wherein the first cavity and the second cavity are separated from one another by means of the membrane, wherein the membrane is configured to be convertible between a first position and a second position in response to a reversal of a pressure gradient across the membrane.

[0004] BACKGROUND OF THE INVENTION

[0005] The invention relates to the field of medical devices and healthcare. More specifically, the invention relates to the safe, precise and accurate provision of fluids during medical procedures. In particular, the invention relates to improvements in the provision of fluids during medical procedures where the fluid doses are small.

[0006] To improve vision in individuals with age-related macular degeneration, retinal vein occlusion, or diabetic macular edema, endothelial growth inhibitors (anti-VEGF) are commonly administered through intravitreal injection. Intravitreal injections are one of the most frequent procedures, with approximately 1.5 million treatments per year in Germany and an estimated 20 million worldwide. Patients receive injections of 50 to 100 pl every 4 to 6 weeks. Many clinics employ silicone-oil lubricated, dead space-free syringes in an off-label use, such as BD U-100 insulin syringes. For effective use, the plungers and needles of these syringes need to be lubricated with silicone oil. This results in contamination of the administered medication, reducing the purity tolerances which can be achieved when administering fluids. During intravitreal injection, silicone oil microdroplets which are injected using the devices of the prior art are introduced into the vitreous cavity, where they are not metabolized and can only be removed through vitrectomy. Due to the frequency of this treatment, the likelihood of accumulating clinically relevant amounts of silicone oil microdroplets in the vitreous cavity increases. These microdroplets can be perceived as floaters, causing discomfort, and in rare instances, they may trigger an inflammatory response.

[0007] In addition to the risk of contamination by particles, another critical aspect is precise and accurate dosing in intravitreal injection dosing. Conventionally, a volume of between 50 - 70 pl usually needs to be injected. In current practice, such small volumes are often drawn up and administered with commercially available 1 ml syringes. Using such syringes that are too large compared to the volume to be injected, may easily result in a wrong dose being administered. This is because a 1 ml syringe, for example, is not designed for small volumes in the doubledigit pl range. In addition, such a syringe has to be significantly overfilled in order to set the correct dosage. This practice contributes to the waste of expensive drugs. Overdosing is particularly common with prefilled syringes and can cause significant harm to the patient as intraocular pressure rises significantly due to the excessive volume, which can lead to permanent and irreversible damage.

[0008] In parallel to the challenges faced in ophthalmology, there is a growing concern in the realm of vaccines. Specifically, mRNA vaccines, pivotal in combating numerous diseases, face potential risks during storage. These vaccines can become contaminated with silicone oil, jeopardizing their efficacy. The presence of silicone oil can alter the protein surface and the conformation and stability of the lipid nanoparticles of the mRNA vaccine, which is critical in determining the vaccine's effectiveness. By modifying this protein surface, silicone oil might impede the vaccine's interaction with the immune system, possibly leading to reduced immunogenicity or triggering unintended immune responses.

[0009] The quantity of silicone oil released by various syringes and needles commonly used for intravitreal injections has been investigated. Silicone oil release has been demonstrated and confirmed for all examined syringe-needle combinations. Even in the case of the two tested silicone oil-free syringes (HSW Norm-Ject, Daikyo Crystal Zenith), trace amounts of silicone oil were detected. It is suspected that the needles used may also contribute to this contamination.

[0010] Furthermore, it has been shown that the shaking and snapping typically performed to prepare and prime the injection in clinical practice lead to a significant increase in silicone oil microdroplets. In general, achieving a tight seal between the syringe body and plunger requires a substantial radial sealing force, which generates friction during both insertion and withdrawal. Despite optimal friction pairings and manufacturing tolerances, particle or lubricant abrasion cannot be eliminated in principle, potentially resulting in the contamination of therapeutic products. Even expensive glass-Teflon friction pairings may suffer from this issue.

[0011] In recent years, in clinical practice, silicone oil-reduced tuberculin or insulin syringes, such as the BD Bioscience Tuberculin or BD U-100 Insulin syringe, are sometimes used off-label for intravitreal injections. While these syringes are cost-effective, they do release small quantities of silicone oil. Additionally, they are designed for considerably less expensive therapeutics, resulting in a comparatively high dead space. Given the high costs per injection (e.g. of 50 pl of 10 mg / ml ranibizumab), even a dead space of 3 pl can lead to significant additional expenses. Completely silicone oil-free syringes have not yet become commonplace in general clinical practice, likely due to their higher prices and the increased force required for injection by the administering individuals. There is therefore a need to prevent therapeutic fluids from being contaminated by silicone oil during injection. Furthermore, common syringes as well as silicone oil-free or reduced syringes may cause irritating and damage of sensitive therapeutics or biological fluids due to the friction between the barrel and the plunger. This effect might affect the integrity and stability of proteins, lipid nanoparticles (in case of mRNA vaccines) or cells (CAR cell products) and might hamper the effectiveness of the therapy.

[0012] The use of compressible single-use ampoules to aid in the injection of therapeutic fluids has been considered in the prior art.

[0013] US7011650B2 discloses a syringe comprising within its barrel a pleated compressible container for holding a therapeutic solution. The pleated compressible container serves as an ampoule. The compressible container is provided with a connector which is configured to engage with the plunger of the syringe, such that movement of the plunger directly results in expansion or compression of the compressible container. The direct mechanical connection between the container and the plunger allows the plunger to be used to move the container up and down in the barrel. Further, this is configured to sufficiently crush the compressible container such that a pressure-sensitive seal is burst, allowing ejection of the fluid therein. This configuration is selected such that two different therapeutic fluids may be contained in the syringe - both inside and outside the compressible container - and injected in sequence. Whilst the fluid inside the ampoule is protected from contamination with any silicone oil used to seal the plunger within the barrel, the fluid outside the ampoule may suffer contamination.

[0014] A similar configuration is provided by US2016058946A1. A collapsible syringe is provided inside a pressure jacket. The collapsible syringe serves as a single-use prefilled ampoule and includes a cap member and a compressible or deformable sidewall member, the sidewall being provided with folds analogous to bellows. The folds of ampoule create a large amount of dead space within the collapsible syringe or collapsible chamber which reduces efficiency and prevents precise dosing.

[0015] JP 5854836 B2 discloses a cartridge and needle system, wherein the essential function of the cartridge and needle system is to reduce the dead space in the distal end of the cartridge to reduce the risks of bending the needle, piercing the rubber septum at the end of the cartridge off center, or puncturing the side walls of the closure inside the cartridge. The system features a semi-permeable membrane, which is designed to allow gases to pass through but reduce the transmission of liquids. By advancing the plunger, air trapped in the cartridge can pass through the gas-permeable membrane and escape through the needle, venting the injection system. To allow injection, the needle system is pushed further into the vented housing insert so that the needle tip penetrates the semi-permeable membrane and locks the needle in position. JP 6731943 B2 discloses a rolling diaphragm syringe system comprising an improved syringe with a flexible side wall. This syringe is configured to be selectively filled with liquid, such that the liquid may be precisely dispensed. One aspect of the invention aims to overcome the disadvantages of conventional disposable syringes by creating a more cost-effective and user- friendly syringe design. The rolling diaphragm consists of various sections, including a sidewall. The sidewall of the rolling membrane is flexible and can expand or contract depending on the movement of the plunger. When the plunger moves in the distal direction (to inject), the side wall of the rolling diaphragm is rolled outward. This allows fluid to be drawn into the internal volume of the syringe. When the plunger moves in the proximal direction (withdrawal), the sidewall of the rolling diaphragm is rolled back into itself, dispensing the liquid from the syringe. The rolling diaphragm does not allow for precise dosing and creates a large amount of dead space in the syringe cavity. This reduces the efficiency and increases the cost of supplying the fluid medicament.

[0016] A common feature of the prior art is that the compressible ampoules or the diaphragms are configured for direct connection with the plunger. Further, these ampoules have dimensions similar to those of the interior of the syringe barrel, such that the force used to manually depress the syringe plunger results in the ejection of a large volume of fluid out of the ampoule. Due to the configuration of folds in the ampoule, a significant amount of dead space is created in the syringe barrel. To perform a manual injection, a user must move the plunger over a number of millimeters at the very least due to limitations in manual dexterity. Combined with a wide diameter of several millimeters, this corresponds to fluid amounts at least in the millimeter region. Such devices are thus not suitable for precisely injecting fluids in the microliter region, in particular for eye surgery.

[0017] In addition to the above-mentioned issues, the devices of the prior art are not adapted for a range of uses, including for therapeutic materials which must be stored at very low temperatures. Further, the medical technique required to administer medical fluids using these devices tends to diverge from standard procedures, therefore requiring specialized instruction of medical staff.

[0018] The prior art does not provide feasible solutions for completely eliminating silicone oil from an injection solution whilst providing a precise fluid delivery, in particular for small volumes of fluid. It also does not provide straightforward devices which medical staff may use without further training.

[0019] SUMMARY OF THE INVENTION

[0020] The objective of the invention is to provide a cannula device that addresses the shortcomings of prior art solutions and enables precise and accurate dosing and injection of medical fluids without mechanical damage caused by plunger friction and without contamination by sealant fluids or abrasive particles, in particular without contamination by silicone oil. A further objective of the invention is to allow efficient use of silicone oil-free needles with a cannula. A further objective of the invention is to provide a cannula device configured for the precise injection of small volumes of therapeutic fluids.

[0021] The objectives are achieved by a cannula device, a use of the device and a kit comprising the cannula device and at least one disposable syringe and / or needles according to the independent claims. The dependent claims represent preferred embodiments of the invention. This invention has applications in various medical settings where the accurate and precise administration of fluids, such as medications or therapeutic substances, is critical. It addresses issues related to the integrity and sterility of injected substances, making it particularly relevant in the fields of ophthalmology, intravitreal injections, and other medical procedures where maintaining the purity, integrity and stability of injected substances is essential for patient safety and treatment effectiveness.

[0022] In a first aspect, the invention relates to a cannula device comprising a base body, wherein the base body comprises in its longitudinal direction a hub. The hub comprises a first cavity and a second cavity and a membrane arranged transversally within the hub, wherein the first cavity and the second cavity are separated from one another by means of the membrane. The membrane is configured to be convertible between a first position and a second position in response to a reversal of a pressure gradient across the membrane.

[0023] This membrane-based design ensures a continuous separation of a therapeutic solution from the rest of the cannula device or from a syringe with which the cannula device is used, effectively preventing any contamination of the solution with silicone oil, abrasive particles or with other fluids contained in the syringe.

[0024] A significant advantage of the described cannula device is its compatibility with standard syringes, enhancing the ease of handling. Medical professionals are already familiar with conventional syringe mechanisms and operation techniques. By allowing the cannula device to be used seamlessly with these well-known standard syringes, there is no steep learning curve or additional training required for its adoption. This compatibility promotes rapid integration into existing medical procedures, streamlining the transition and ensuring that patient care is not disrupted. Furthermore, this design choice promotes cost efficiency. Medical institutions can continue to utilize their existing inventory of standard syringes without the need for purchasing specialized equipment. This factor is essential, particularly in environments where resource allocation is critical. The ease of attachment and detachment of the cannula device from these standard syringes also ensures quick preparation and turnaround times between patient treatments, making it a practical solution for high-volume clinical settings. The membrane, when configured to switch between different positions in response to pressure gradients, serves as a reliable barrier, preventing any contact or contamination between the therapeutic solution and any silicone oil or other lubricants or sealants used in other parts of a cannula or a syringe to which it is connected. 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 like ophthalmology.

[0025] A key advantage of this configuration is that it allows complete avoidance of contamination during all phases of the injection process. This is achieved by strictly separating the injection solution from the friction or lubrication components of the base body by means of the innovative membrane. This membrane ensures that potentially harmful substances, like silicon oil from the friction or lubrication components, cannot at any time enter the fluid which is to be injected. Avoiding contamination in the injection solution contributes significantly to patient safety. The use of this cannula device significantly minimizes the risk of infections or allergic reactions due to contamination. In addition, the integrity of the administered medication or solution is maintained, as it does not come into contact with potentially harmful substances. This ensures the effectiveness of the medication and contributes to successful treatment, as well as helping to maintain strict quality standards for medical procedures.

[0026] The inventive solution provides a first cavity with a variable volume, preferably for housing a therapeutic fluid (also referred to herein as “injection solution” or “medical solution”). The first cavity is preferably sealed off by the membrane which separates it from the second cavity. The volume of the first cavity is advantageously variable, without the need for rigid parts to rub against the membrane to vary the volume, as in the case of a mechanically connected plunger of the state of the art. As there is no risk of friction or poor fit between rigid parts, the use of silicone oil as a sealant in the first cavity is not required. As the volume of the first cavity is variable due to the varying position of the membrane, the pressure within the first cavity can be raised to inject the therapeutic fluid. Alternatively, the pressure within the first cavity may be reduced to create a vacuum and draw up a fluid into the first cavity.

[0027] It is a particular advantage of the invention that the membrane may be adjusted in its material and mechanical properties such as to remain fixed at its edges with respect to inner walls of the hub while being movable at its center. The membrane therefore need not move against the inner walls of the hub, avoiding friction. This reduces the need for lubricants. Moreover, due to its ability to be fixed at its edges, the membrane may be arranged to create a fixed seal between the first and second cavities without the need for additional sealants. For this purpose, the membrane is preferably impermeable, at least with respect to fluids held in the canula device. Silicone oil may thus be completely eliminated from the cavity in which the therapeutic fluid is held, avoiding contamination. This is especially useful for delivering intravitreal injections as any silicone oil delivered in this manner cannot be naturally metabolized. Optical problems caused by contamination of the eye can thus be avoided as can the invasive surgeries required to alleviate said optical problems.

[0028] By configuring the membrane to be convertible between a first position and a second position in response to a reversal of a pressure gradient across the membrane, no rigid parts are required to contact and push / pull said membrane in order to change the volumes in the cavities and therefore to inject or draw up an injection fluid. Rather, the pressure in one of the cavities must merely be altered to create a sufficient pressure gradient across the membrane. This is easily achieved by pulling or pushing the plunger of a traditional syringe which may be used in conjunction with the cannula device. By pushing the plunger, the pressure in the second cavity may be increased, causing the pressure on a second side of the membrane to exceed the pressure on a first side of the membrane. The membrane may thus be converted to a first position, reducing the volume of the first cavity and injecting the therapeutic fluid through an outlet, preferably through an injection port, especially preferably through a needle. To do so, the plunger need not contact the membrane at all. By pulling the plunger, the pressure in the second cavity may be decreased, momentarily creating a vacuum which reverses the pressure gradient and converts the membrane to a second position. In the second position, the volume of the first cavity is preferably increased such as to reduce the pressure therein. The momentary reduction in pressure preferably causes a fluid to be drawn up via the outlet, preferably via a needle. As the syringe is sealed from the first cavity by the membrane, the risk of silicone oil or other contaminants from the syringe entering the therapeutic fluid is eliminated. A contamination-free injection is achieved by simple and economic means.

[0029] As the membrane may be converted between different positions without excessive mechanical stress, this does not need to be configured with the same thicknesses and dimensions as the membranes or diaphragms of the prior art. Instead, the membrane may be very thin and compact. Furthermore, as the membrane does not need to move with the plunger of the syringe, its dimensions and the volume of the first cavity may be decoupled from the volume of the syringe barrel. For instance, the syringe barrel may have a large volume to allow for a user to manually move the plunger in steps of several millimeters. Its diameter may be large enough such that the barrel comprises legible dosing markings. The first cavity defined by the membrane however need not have a volume substantially corresponding to that of the barrel. This is because the volume of the first cavity changes not due to it being mechanically carried by the plunger but merely as a result of a pressure change ahead of and / or behind the membrane. Thus, the membrane can be placed at substantially any point along the hub in a longitudinal direction and its movement may be limited to a small volumetric space. The first cavity may thus be limited to a small volume, in particular in the order of microliters, while the barrel of the syringe has a conventional large volume adapted for good visibility and easy manual manipulation of the plunger.

[0030] Due to the limited space in the first cavity, overfilling and the associated waste of medication is advantageously prevented. Additionally, only a precisely defined dose is administered, thereby minimizing the risk of overdosing.

[0031] The pressure differential across the membrane may be created intentionally as illustrated above or may be a result of the specific medical procedure for which the cannula device is used. For example, in a medical injection, the pressure on a first side of the membrane may be determined by the body's internal pressure or the pressure within a separate chamber of the device. Conversely, when the membrane transitions from the first position to the second position, there is a reversal of the pressure gradient. In this state, the pressure on the first side of the membrane may increase above the pressure on the second side, causing the membrane to switch its position. The conversion of the membrane in response to a reversal of the pressure gradient may comprise inversion of said membrane. In particular, a side of the membrane having a concave form may take on a convex form and vice versa. This design allows the membrane to act as a dynamic barrier, responding to changes in pressure to separate or connect the first cavity and the second cavity within the hub of the cannula device. Such a mechanism ensures controlled and precise fluid management while maintaining the sterility and purity of the injected substances, which is particularly important in medical procedures where maintaining these parameters is critical for patient safety and treatment effectiveness.

[0032] The second cavity as well as the barrel up to the syringe plunger may preferably be filled entirely with fluid, or entirely with gas, such as air, or partially with fluid and partially with gas, such as air. A gas filled portion within the second cavity and / or the barrel may advantageously function as a pressure cushion. This may potentially lead to a surprising reduction of shear forces applied to the therapeutic fluid during injection. Preferably when overcoming the break-lose-force of the plunger while injecting, the peak shear force acting on the fluid will be dampened, which consequently may protect its integrity. Additionally, the potential damage to the tissue due to the injection process may be minimized.

[0033] The term "cannula device" as used herein refers to a specialized medical instrument designed for the controlled and precise delivery or withdrawal of fluids via an outlet with a small diameter, for example of less than 5 mm, preferably less than 3 mm, more preferably less than 2 mm, within a medical context. A “cannula device” preferably comprises an outlet in the form of a hollow tube or needle which extends from a base body, the hollow tube or needle having one or more openings at its tip. The outlet may be configured as an injection port for fitting with a needle or other fluid channel. Preferably the tip of the hollow tube or needle is configured for insertion into a patient's body, in particular through a puncture or incision, to access a specific anatomical location. The hollow tube or needle is preferably configured for a minimally invasive insertion into the patient’s body. The diameter of said hollow tube or needle is thus preferably configured to allow uptake or delivery of a relevant fluid while causing minimal discomfort and / or scarring. The cannula device may be configured for purposes such as intravenous (IV) administration, the extraction of bodily fluids, or the injection of medications directly into tissues or body cavities.

[0034] The term “base body” in the sense of the invention preferably refers to a rigid structure to which a needle and / or hollow tube may be attached, and which may in turn be attached to a syringe or other pressure-adjusting device. The base body preferably encloses the hub and is configured for manual handling and manipulation, such as for attachment to other devices.

[0035] The term “hub” as used herein refers to a hollow region within the base body of the cannula device, the hollow region at least partially comprising the first cavity, the membrane and the second cavity. This hub is oriented along the length of the device, preferably being coaxial with other parts of the cannula such as the first and second cavities, the outlet and / or a syringe, a needle or hollow tube. The hub encompasses two distinct cavities, referred to as the first cavity and the second cavity, and is equipped with a membrane positioned transversely within it.

[0036] In the sense of the invention, the term “cavity” preferably refers to a hollow region of the cannula device which may hold a fluid. The “cavity” may have a variable volume. The first cavity is preferably defined as the hollow portion of the base body of the cannula device delimited by a first side of the membrane, the hub walls and an outlet of the cannula device. The second cavity is preferably defined as the hollow portion of the base body of the cannula device delimited by a second side of the membrane, the hub walls and a barrier at or connected to a proximal end of the cannula device, wherein the barrier may be the plunger of a syringe. The positions of the plunger and the membrane may thus vary the volumes of the first and second cavities.

[0037] In the sense of the invention, the term “membrane” preferably refers to a pliable sheet of impermeable material which separates the first cavity from the second cavity. The membrane is preferably fixedly connected at its edges to the inner walls of the hub, while a central portion of the membrane is freely movable within a region at least partially spanning a first portion of the hub and a second portion of the hub. For this purpose, the membrane preferably has a first side facing the outlet and a second side facing the plunger of a syringe, a syringe-connection or other connection port. The area of the first and second side of the membrane preferably exceeds the cross-sectional area of the hub at the point where the edges of the membrane are fixed. This larger surface area allows the membrane to protrude either ahead of or behind its edges. The membrane's primary purpose is preferably to separate and isolate the first cavity from the second cavity. Additionally, the membrane is designed to be capable of transitioning between two positions, namely a first position and a second position, in response to changes in pressure gradients acting across it. This hub configuration ensures controlled fluid separation and flow within the cannula device during medical procedures.

[0038] In the sense of the invention, the term “first portion of the hub” preferably refers to a predetermined unchanging volume of the hub adjacent to its outlet. The term “second portion of the hub” preferably refers to a predetermined unchanging volume of the hub adjacent to a syringe, syringe-connection or other connection port. The first portion of the hub preferably falls ahead of the fixed edges of the membrane along a longitudinal axis from the proximal end of the cannula device to the distal end (the outlet or tip) thereof. The second portion of the hub preferably falls behind the fixed edges of the membrane along the longitudinal axis from the proximal end of the cannula device to the distal end (the outlet or tip) thereof. In contrast to the first and second cavities, the first and second portions of the hub may not necessarily be physically separated from one another by the membrane at all times.

[0039] In the sense of the invention, the term “pressure gradient across the membrane” preferably refers to a difference in fluid pressure acting on a first side of the membrane and a second side of the membrane. The fluid pressure may be the pressure of a gas such as air or a liquid such as a therapeutic or inert fluid. Preferably the “pressure gradient across the membrane” does not refer to pressure applied by actively pressing a non-fluid mechanical part such as a plunger onto the membrane or retracting a mechanical part connected to the membrane.

[0040] In a preferred embodiment of the cannula device, in the first position, the membrane extends at least partially into a first portion of the hub and upon drawing up an injection solution with a needle, the membrane is converted to the second position by deforming, in particular by inverting, folding and / or unfolding, the membrane and extending it at least partially into a second portion of the hub, preferably such as to expand the first cavity and to draw the injection solution into the first cavity.

[0041] To draw up an injection solution with a needle, an underpressure is preferably momentarily formed in the second cavity, for example, by withdrawing the plunger of a syringe connected to the base body, wherein the plunger is preferably not connected to the membrane. This preferably creates a fluid pressure gradient across the membrane, such that the fluid pressure in the first cavity is momentarily higher than the fluid pressure in the second cavity. By inverting the membrane such that it extends partially into a second portion of the hub, the second surface of the membrane is preferably made convex, even more preferably such as to substantially conform to a contour of an inner wall of the hub, while the first surface of the membrane takes on a concave form. This increases the volume of the first cavity, momentarily creating a reduced pressure in the first cavity. A fluid thus flows into the first cavity via the outlet, in particular via a needle at the outlet until the pressure across the membrane is balanced.

[0042] The technique of inverting the membrane is particularly advantageous as it maximizes the use of volume within the hub and provides a precise fluid dosing. As the inverted membrane may be free of folds when in the second position, no dead space is created in the second cavity due to the presence of the folds. Rather, the membrane may substantially fully occupy an available volume in the second portion of the hub, such as to maximize the volume of the first cavity and maximize the amount of fluid drawn up. The maximum volume of the first cavity when the membrane is in the second position may be predetermined, resulting in a precise and repeatable uptake of fluid. Moreover, the lack of moving parts in contact with the membrane reduces the risk of membrane puncture, creating a very reliable separation of the first and second cavities.

[0043] It may be preferred for the membrane to be configured to have discrete stable positions. In this manner, the membrane may substantially instantaneously convert between the first and second positions when the pressure gradient across it changes, eliminating the possibility of the membrane resting at an intermediate position. This may be achieved by configuring the membrane to be pliable but substantially non-elastic. For example, the membrane may be configured as a rubber diaphragm having sufficient pliability to convert between two complementary convex forms but being mechanically unstable between those forms. The pliability of the rubber diaphragm may be limited such that this may not be compressed such as to remain within the narrower cross section of the hub at the region where its edges are fixed. Such an embodiment may aid in providing consistent and precise dosing or volumetric fluid uptake, as the first cavity may only convert between being filled or non-filled. The possibility of only partially filling the first cavity is eliminated. This may eliminate errors in medical procedures.

[0044] Alternatively or additionally, the membrane may be configured to be foldable. The membrane may be provided with foldable ribs or scoring such as to control its folding. The membrane may be configured to be folded in an intermediate position between the first and second positions whilst it can be unfolded in either or both directions to bring it to the first and second positions. Alternatively, the membrane may have a folded default configuration in either the first or second position, whereby the membrane is unfolded to bring it to the other of the first or second positions. In contrast to the state of the art, such folding and unfolding of the membrane may occur in response to the change of a pressure gradient across the membrane, in particular to the change of a fluid pressure gradient between the first and second cavity. A rigid mechanical pulling or pushing of the membrane is not required, reducing the dead space and / or risk of puncture. As set out further herein, preferred folding configurations have also been developed to reduce or eliminate any dead space.

[0045] When the syringe is being filled, the membrane undergoes deformation, in particular inversion, folding or unfolding, to bring it into the second position, causing the first cavity of the hub to fill with the injection solution. Upon compression of the syringe, the membrane preferably returns to the first position, displacing the therapeutic fluid through the needle and into the target area for treatment. The delimitation of first and second cavities by the position of the membrane limits the volume of the injection solution that can be administered. This controlled volume delivery is beneficial for precise and accurate dosing during medical procedures, minimizing wastage or over-administration.

[0046] In a further preferred embodiment of the invention, in the second position, the membrane extends at least partially into a second portion of the hub and upon injecting an injection solution with a needle, the membrane is converted to the first position by deforming, in particular inverting, folding up and / or unfolding the membrane and extending it at least partially into a first portion of the hub and displacing the injection solution through the needle. To inject the solution, preferably an overpressure is created in the second cavity, such that the fluid pressure acting on a second surface of the membrane exceeds the fluid pressure acting on the first surface of the membrane. The pressure gradient across the membrane is hereby reversed. The membrane may thus be converted back to the first position.

[0047] The membrane extending at least partially into the first portion of the hub preferably means that at least a portion of the membrane falls ahead of the position at which the edges of the membrane are fixed. Preferably the form of the membrane in the first position substantially conforms to a contour of the inner walls of the first portion of the hub. This eliminates dead space in the hub, improving dosing precision and efficiency. The membrane may preferably be in unbroken contact with the inner walls of the first portion of the hub, with the possible exception of the outlet. In this manner, dead space can be eliminated and the therapeutic fluid can be fully forced out of the cannula device, eliminating waste. The precision of the dosing is hereby further improved.

[0048] In another preferred embodiment of the invention, the cannula device comprises a locking connection. The locking connection is preferably configured for hermetically joining the cannula device to a device for adjusting the pressure in the second cavity, in particular a syringe device. Preferably, the locking connection conforms to a medical or surgical standard, in particular DIN ISO 80369. The locking connection is preferably configured as a snap-fit connection, a plug-in connection, a clamp connection, a threaded connection and / or a Luer-lock fitting, in particular a threaded Luer-lock fitting. The Luer-lock fitting may preferably feature an internal thread adhering to the Luer-Lock standard. The cannula device is particularly preferably attachable to a conventional syringe via a Luer- lock fitting. This makes the cannula device easily combinable with conventional syringes or other medical-grade equipment.

[0049] The term “Luer Lock fitting” as used herein preferably refers to a standardized type of connector used in medical and laboratory settings to secure and seal two components together to ensure a secure and leak-proof connection between the two components. Luer-lock fittings are available in a number of different forms such as Luer tapers, which include such fittings commercially known as Luer-Lok and Luer-slip fittings. Luer tapers may be non-threaded and smooth or ridged to prevent unintentional detachment. Luer-lock fittings are also available in standardized threaded formats. Both tapered and threaded Luer-lock fittings are available in male and female forms and in different dimensions. The threaded male Luer has a cylindrical, tapered or conical tip with external threads. The female Luer has a corresponding cylindrical, tapered or conical cavity with internal threads. To enable a connection using a threaded Luer Lock, the male and female parts are twisted together, causing the threads to engage, and creating a secure, leak-proof seal. This design ensures that medical fluids can be delivered accurately and without leakage. Advantages of this connection further include the provision of venting between the membrane cannula and the syringe through the special screw geometry and pre-filling of the dead space with incompressible solution.

[0050] In another preferred embodiment of the invention, the second cavity of the cannula device is pre-filled with a separated fluid. Consequently, during the process of drawing up an injection solution, the separated fluid is forced into a barrel by inverting, folding or unfolding the membrane. The separated fluid may serve to regulate the pressure in the second cavity, in particular by being substantially incompressible. By forcing the separated fluid into the barrel, the separated fluid in the second cavity need not be compressed when the membrane is brought into the second position but may be at least partially moved to an additional volume.

[0051] The available volume of the barrel is preferably variable, in particular due to the barrel forming part of a pressure-adjusting device, in particular a syringe. This allows the pressure in the second cavity to be reduced by withdrawing a plunger to increase the available volume in the barrel and the pressure to be kept in equilibrium by the movement of the membrane to the second position. The barrel may also be configured to increase the pressure in the second cavity by reducing the available volume in the volume, in particular by compressing the plunger of a syringe. The separated fluid may thus be forced out of the barrel and into the second cavity.

[0052] Preferably, the separated fluid is incompressible. The barrel is preferably transparent. The entry of the separated fluid into the barrel is thus preferably visible to the naked eye and may serve as a visual indication that the membrane has fully reached the second position. In particular, the incompressibility of the separated fluid allows it to fill the barrel to a predetermined level, indicating that the membrane is in the second position and that the first cavity is full. A user may use this as an indication that a step of drawing fluid into the cannula device is complete.

[0053] In a further preferred embodiment of the invention, the barrel volume is between 0.05 - 1 ml. At such a volume, the syringe may be used without requiring high levels of manual dexterity or training. Such a volume is also suitable for the preferred uses of the device, such as for eye injections.

[0054] In a further preferred embodiment of the invention, the ratio of the hub volume to the barrel volume is between 1 :40 and 1 :10, preferably around 1 :20. At such a ratio, the device is especially easy to use, and can be very precisely dosed by hand.

[0055] In a further preferred embodiment of the invention, the barrel has an inner diameter between 1 - 4 mm, preferably around 2 mm. At such diameters, the plunger can be moved over significant distances to vary the volume of the second portion of the hub. Good visibility for manual dosing can also be achieved.

[0056] The barrel is preferably configured to function as a dosing aid, in particular by being equipped with dosing marks, allowing for meticulous control over the administered dosage. This is particularly advantageous when used with a membrane which is mechanically stable not only at the first and second positions but also at intermediate positions therebetween, such that the first cavity may be partially filled to varying degrees. For this purpose a foldable membrane may be especially preferred. The dosing marks on the barrel offer the ability to measure not only the maximum prescribed dosage but also enable precise administration of doses below the maximum limit.

[0057] Surprisingly, due to the pre-filling of the barrel with a separate fluid, this fluid can serve as a dosing aid. This is because the membrane and the cavities already possess a defined filling volume. Preferably, the prefilled separated fluid fills the second cavity fully without reaching the barrel when the membrane is in the first position and no fluid has been drawn up into the first cavity of the cannula device. In particular, the separated fluid fills the second cavity when the plunger of a syringe is fully depressed, leaving no available volume in the barrel. When a volume of fluid is drawn into the first cavity of the hub, this displaces an equal volume of the separated fluid from the second cavity, such that the displaced fluid enters the barrel. The incompressibility of the separated fluid is especially advantageous to achieve said displacement. The dosing marks on the barrel preferably indicate the volume (or another derivable quantity) of the displaced separated fluid. As a result, the exact volume of the injection solution being administered corresponds to the pre-filled separate solution in the barrel. This measurement can be made using the dosing scale, offering significant advantages. By utilizing the dosing scale on the specially designed barrel, precise dosage control is achieved. This improves the accuracy of treatment administration, crucial for ensuring patient safety and treatment efficacy. Further this surprisingly enables the administration of doses that are not only at the maximum prescribed level but also smaller, more tailored dosages. This flexibility is especially crucial in situations such as intravitreal injections, where extremely small, fine and precise dosing is required.

[0058] In a preferred embodiment of the invention, the separated fluid comprises an aqueous solution selected from a group comprising a saline solution, a colored solution and / or a buffered solution. The use of an aqueous solution as the separated 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. Further aqueous solutions are compatible with a wide range of medications and substances, ensuring that they do not interact adversely with the injection solution or compromise its effectiveness. Impermeability of the membrane towards the aqueous solutions can also be achieved by a wide range of medically safe materials.

[0059] In the case of intravitreal injections or other sensitive medical procedures, a colored solution can enhance the visibility of the fluid, aiding in precise placement and reducing the risk of complications. The use of further biocompatible fluids or suspensions can provide enhanced contrast in certain medical imaging applications, aiding in visualization and diagnosis. It is particularly preferred to use a saline solution as the separated fluid. Saline solutions, which are essentially sterile saltwater solutions, offer additional benefits. Saline solutions closely mimic properties of the body's natural fluids, making them physiologically compatible. This reduces the risk of tissue irritation or inflammation.

[0060] Preferably, the separated fluid fulfills the requirements of a medical product, even if not intended to be injected into a living body. The separated fluid is preferably sterile, pyrogen- free, free of suspended particles and preferably has a pH between 5 - 8, more preferably between 7.2 - 7.6, especially preferably around 7.4. This ensures that in the unlikely event that the membrane ruptures, no patient is harmed by injection of an incompatible fluid.

[0061] To enhance the membrane stability, the electrostatic repulsion of the polymer chains is preferably decreased by matching buffer and polymer properties.

[0062] To achieve this, the buffer pH is preferably selected to be close (within a boundary of ±1 in pH) to the point of zero charge of the membrane, which depends on the material composition and any surface treatment. pH ranges for different membrane materials are preferably selected to fall within the following ranges: Polyethylene (PE): 4 to 6

[0063] Polypropylene (PP): 2 to 4

[0064] Polyvinyl Chloride (PVC): 7 to 8

[0065] Polystyrene (PS): 3 to 5

[0066] Polyethylene Terephthalate (PET): 4 to 5

[0067] Polyurethane (Pll): 4 to 6

[0068] Cyclin olefin copolymer (COC): 4 to 7

[0069] Preferably an ionic strength of 100 - 250 mM KCI or NaCI (slightly increased in comparison to physiological ionic strength) is set. This enhances the stability due to a smaller distance of the polymer chains, therefore reducing the repulsive forces between the polymer chains of the membrane material.

[0070] In a preferred embodiment of the invention, the separated fluid comprises a pH buffer. This may serve to keep the pH of the separated fluid close to the normal pH of the relevant tissue or fluid into which the injection is carried out. In some preferred embodiments of the invention, the therapeutic fluid alternatively or additionally comprises a pH buffer.

[0071] The membrane may have various forms which may be adapted for optimizing different properties of the cannula device.

[0072] In a preferred embodiment of the invention, the form of the membrane is configured to complement the form of inner walls of the first and / or second portion of the hub. This may eliminate dead space in the hub, reducing fluid wastage. In particular, the membrane is preferably non-planar and is configured to hold the complementary form by default, e.g., without any pressure gradient acting on it. Such a membrane may be especially adapted to forcing the maximum volume of fluid out of the first cavity and / or may be especially adapted for maximum volumetric fluid uptake into the first cavity. In the preferred embodiment in which the first and second portion of the hub have complementary forms, e.g. by being symmetrical, the membrane may advantageously ensure optimal use of the hub volume and of any fluid therein, At the same time, the membrane provides precise dosing.

[0073] In a preferred embodiment of the invention, the membrane has a planar, truncated conical, untruncated conical or hemispherical shape and / or is configured as a foldable membrane, wherein the foldable membrane is provided by default in a compressed, folded state and is configured to be expanded during filling by unfolding one or more ribs, wherein the ribs are preferably arranged as a vortex. It may also be preferred that the membrane has the shape of a rounded cone.

[0074] A planar membrane may preferably be configured to be elastic, for example by comprising an elastic material such as silicon or latex. Such a planar membrane may by default be arranged stretch across a cross section of the hub while being substantially flat on both sides. The planar membrane may take on a convex / concave form only when forced into the first position or the second position. As such, the elastic membrane may also take on intermediate positions between the first position and the second position, including different degrees of concavity. Such an elastic membrane may be suitable for applications requiring freedom in dosing a therapeutic fluid. This may especially be relevant for larger or repeated doses.

[0075] In a preferred embodiment, the membrane is designed with an untruncated conical shape or a truncated conical shape. The untruncated or truncated conical shape of the membrane allows for flexibility and a tight fit of the membrane within the inner cavities of the hub. Preferably the first and second portions of the hub each have complementary truncated or untruncated conical forms to the membrane. The membrane may also be formed such as to correspond to complementary forms of the inner walls of the first and second hub. A perfect fit may be foreseen between the membrane and said inner walls. Such a membrane is preferably non-elastic. This allows it to fully fill the relevant portion of the hub without dead space due to compression or folding. This unique conical design ensures that the membrane is inherently constrained in its expansion by the spatial confines of the hub. It enables the membrane to adjust and conform seamlessly to the varying volumes and pressures encountered within the hub, whilst either forcing substantially all of the therapeutic fluid out of the first cavity in a first position or by taking up 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 exceptionally small or substantially zero. For example, the volume of the first cavity may comprise only the volume of an outlet channel of the base body.

[0076] The truncation of the conical shape allows the membrane to avoid contact with any fittings which may protrude into the hub from its tip, such as the base of a needle or surgical tube. This ensures the integrity of the membrane. Similar advantages are achieved by providing a rounded tip at the end of the conical shape or by using a membrane having a hemispherical or hemi-ellipsoid form.

[0077] The adaptation of the membrane form to the hub is advantageous for accommodating a precise volume of fluid and maintaining a secure seal. The conical shape acts as a physical barrier that efficiently seals off the injection solution from any external substances or contaminants, thus safeguarding the solution's purity. This separation prevents any undesired contamination, including the potential for contamination with silicone oil, ensuring the integrity of the injection solution. Furthermore, this separation extends to maintaining a clear distinction from the pre- filled separate dosing aid solution and ensures that its expansion is inherently limited by the spatial dimensions of the hub. This limitation provides a precise and controlled barrier, further enhancing the device's reliability.

[0078] In another preferred embodiment, the membrane is designed to be a foldable membrane. The membrane may be provided in a compressed, folded state corresponding to either the first or second position, whereby the membrane is unfolded to bring it into the other of the first or second position. It is preferred that the foldability of the membrane is achieved by providing it with side ribs, tabs, scores or otherwise which may be arranged in an accordion-like manner. For simplicity, side ribs will be referred to with reference to preferred features. The skilled person is aware that such features apply equally to any type of folding feature. Said side ribs are preferably non-parallel to a longitudinal axis of the cannula device. It may be preferred for the side ribs to be transversal or to run in an oblique direction having a transversal and longitudinal component.

[0079] The foldable membrane configuration is purposefully engineered to allow for expansion during the filling or injection process by unfolding one or more side ribs. In this preferred embodiment, the folded membrane undergoes expansion and unfolds in response to the applied vacuum or fluid pressure during the filling or injection process. This transformation allows the membrane to effectively accommodate the injection solution. Conversely, upon reversal of the pressure gradient across the membrane, e.g. due to the injection of the solution after filling, the membrane undergoes a folding process, retracting from the second portion of the hub and precisely delivering the injection solution. This design choice offers several advantages, particularly in terms of increasing the volume capacity of the cannula device. The foldable membrane's ability to expand by unfolding side ribs significantly increases the volume it can accommodate and is thus especially advantageous for larger cannula devices or for repeated fluid injections, e.g. steady and frequent application of an anesthetic by a dentist. This expansion capability is also particularly advantageous when dealing with medical procedures that require larger quantities of fluids, such as injections or infusions. By allowing the membrane to be initially compressed, the device can be pre-packaged in a more compact form. The preferred foldable membrane designs minimize dead space within the device. Dead space refers to the unutilized space in a medical device that can trap air or fluid and lead to inaccurate dosing. By unfolding the side ribs and maximizing the membrane's useable volume, the risk of dead space is reduced, ensuring that the administered fluid accurately matches the intended dosage. Unfolding the side ribs allows for precise control over the volume of fluid being administered whilst also accommodating the possibility of intermediate doses.

[0080] In a preferred embodiment of the invention, the folds of the membrane are configured for a stepwise or repeated injection of doses. The folds may for example be configured to “pop” or “click” in or out of place in sequence, for example in a manner analogous to known collapsible cups or expandable silicone funnels. The folds may be arranged such that each expansion step of the membrane corresponds to a single dose or a single medication step. This is especially advantageous for precise dosing where a medication is to be provided in an intermittent manner, such as an anesthetic.

[0081] In especially preferred embodiments of the invention, the side ribs have a curved trajectory, the curved trajectory having a transversal and longitudinal component with respect to the cannula device. It is especially preferred that the side ribs be arranged on the foldable membrane as a vortex (or “helix”). Such side ribs preferably form discrete lines which extend as a curve from an apex, preferably at the center of the membrane, towards its perimeter. This configuration has been found especially space-saving and advantageous for eliminating dead space.

[0082] In another preferred embodiment of the invention the membrane has a wall thickness of 5 pm - 200 pm, preferably around 60 pm. Such a membrane has been found to be especially compact and pliable. Its thickness is low enough such that it occupies only minimal space within the hub. At the same time, the membrane is strong enough to endure being converted from the first to the second position and vice versa multiple times. Furthermore, the membrane could be made strong enough to endure contact with the inner walls of the hub. Advantageously, no rigid mechanical parts must be used to move the membrane, making it possible to achieve very thin thicknesses without risk to the membrane integrity.

[0083] It may also be preferred that the wall thickness of the membrane is uniform or non-uniform. A non-uniform wall thickness of the membrane can be advantageous to control the folding mechanism of the membrane.

[0084] It may also be preferred that the membrane is a multi-layered membrane. A multi-layered membrane could 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 bioinert, non-leaching layer. Further gas-tight membrane layers may be added on the said bioinert, non-leaching membrane layer, on the side facing away from the fluid toward the second cavity.

[0085] In another preferred embodiment of the invention the membrane comprises polypropylene, polystyrene, polyethylene, polyvinylchloride, silicone or a copolymer as a material selected from a group comprising cyclic olefin copolymers and linear olefin copolymers. It is especially preferred that the membrane comprises a cyclic monomer mole fraction of at least 50 %. Such materials have been found to be especially safe and free of contamination, sterilizable, whilst also providing the mechanical properties required for the inversion, folding or unfolding of the membrane.

[0086] It may also be preferred that the membrane comprises polypropylene, polystyrene, polyethylene, polyvinylchloride, polyester, polyether sulfone, silicon or a copolymer.

[0087] In a further preferred embodiment of the invention, the membrane is provided with a surface treatment at least on one side, preferably at least on its first side which delimits the first cavity. The surface treatment is preferably configured to act as a further diffusion barrier and / or to be hydrophilic. The preferred methods of surface treatment include water plasma treatment, oxygen plasma treatment, cold plasma treatment, and microwave plasma surface treatment. Other applicable techniques are corona discharge, acid etching, and reactive gas chemical processes.

[0088] The surface treatment may be based on silicone or glass and may be applied by chemical vapour deposition to form a layer of less than 1 pm thickness. Preferably the surface treatment is free of silicone oil. Such a surface treatment may prevent leakage of fluids from the first cavity into the second cavity and vice versa, in particular where the membrane is thin or stretched. A hydrophilic surface treatment may additionally prevent the formation of bubbles within the first cavity, reducing dead space and unwanted gas injection into the patient.

[0089] In a further preferred embodiment of the invention, an internal surface of the base body, in particular the hub, especially preferably the first portion of the hub, is provided with a hydrophilic surface treatment. This further reduces the risk of air bubble formation, making the device is especially safe and efficient.

[0090] The hydrophilic surface treatment, whether applied to the membrane or other surfaces of the cannula or attached devices, preferably prevents the attachment of lipophilic or hydrophobic particles or contents, e.g. lipid nanoparticles, liposomes and proteins with hydrophobic sites. Such components of a medical fluid may thus be fully ejected from the first cavity in the course of an injection step, without remaining adhered to the device.

[0091] In another preferred embodiment of the invention, the expansion of the membrane is defined by the total volume of a first and second portion of the hub, wherein the total volume of the first and second portion of the hub is from 10 pl - 10000 pl, preferably 50 - 300 pl. Especially preferably the total volume of the first and second portion of the hub is around 200 pl. Preferably the maximum volume of the first cavity corresponds substantially to the total volume of the first and second portion of the hub. Such a cannula device is especially suited to providing therapeutic fluids at high precision, in particular where medical doses are in the pl range such as in the field of ophthalmology. In another preferred embodiment of the invention, the total volume of the first and second portion of the hub ranges from 30 - 70 pl, preferably 40 - 60 pl. Especially preferably the total volume of the first and second portion of the hub is around 50 pl. This design facilitates precise eye treatments that require small yet exact amounts of therapeutic solutions.

[0092] In another preferred embodiment of the invention, the total volume of the first and second portion of the hub is from 0.5 ml - 500 ml, in particular 1 - 50 ml. Such a cannula device may be configured for fluid uptake or delivery on a larger scale such as for example the taking of blood samples, provision of blood transfusion, repeated provision of an anesthetic and the like. The use of a foldable membrane was found especially suited for this purpose, wherein the foldable membrane could also be configured to be sealable and removable from the cannula device and used to store fluids, such as being used as a blood bag.

[0093] In another preferred embodiment of the invention, the total volume of the first and second portion of the hub ranges from 200 - 400 pl, preferably 250 - 350 pl. Especially preferably, the total volume of the first and second portion of the hub is around 300 pl. This size is particularly effective for ensuring precise vaccine doses, which can be crucial given the importance of accurate dosing in vaccination procedures.

[0094] In another preferred embodiment of the invention, the total volume of the first and second portion is corresponding to a number of multiple doses to be independently delivered. Especially preferably, the total volume of the first and second portion of the hub is designed to deliver multiple doses, for example 5 doses of 20 pl each, summing up to a total of 100 pl.

[0095] Advantages of this particular embodiment, especially within the context of dental treatments, are manifold. Dental practitioners frequently face situations where they need to administer anesthetics in staggered doses over the course of a single session. This embodiment, with its capability to accurately deliver micro-doses, substantially elevates the precision and predictability of anesthesia dosage. By doing so, it not only minimizes the potential for overdosage but also guarantees that patients receive the appropriate amount of anesthesia, ensuring pain-free procedures.

[0096] Furthermore, by negating the need to refill or switch devices between doses, the workflow in dental procedures is markedly streamlined. This not only saves time but also reduces the potential for errors, thereby ensuring both the efficiency and safety of dental anesthesia administration.

[0097] In another preferred embodiment of the invention the cannula device is manufactured by a process comprising a forming step selected from a group comprising an injection molding process and a blow molding process. These manufacturing processes have been found especially safe, being able to provide smooth surfaces with minimal junctions and / or protrusions. This reduces the risk of friction between parts and therefore improves integrity of the cannula device.

[0098] Injection molding is a precise and versatile manufacturing method employed for crafting various components of the cannula device. This process involves injecting a molten material, typically a plastic or polymer, into meticulously designed molds, replicating the exact specifications of the desired components. Injection molding is particularly suited for producing housing components, connectors, and other non-metallic parts of the cannula device. Its use ensures uniformity, consistency, and high-quality production, meeting the stringent standards required for medical devices.

[0099] In a further preferred embodiment of the device, the base body of the cannula device is formed in two parts. Preferably a first part of the base body corresponds to a first portion of the hub and a second part of the base body corresponds to a second portion of the hub. The membrane is preferably provided between the first and second parts such that its perimeter is fixed with respect to the base body, e.g. by clamping. The use of adhesives and other possible contaminants may hereby be avoided. As an example, the cannula device may be formed by providing two injection molded cup-like parts, providing the membrane therebetween and thermally bonding the two parts to one another such as to fix the perimeter of the membrane in place. A positive or negative pressure may be applied to one of the cavities formed on either side of the membrane such as to thermoform said membrane. In this manner, the membrane may be provided with a form which complements that of the interior of the first and / or second portion of the hub, eliminating dead space.

[0100] In a further preferred embodiment of the invention, the membrane is integrally formed with one of the two parts of the base body. In particular, at least one part of the cannula device base body may be blow-molded, wherein two parts of the base body are initially formed by injection molding. One of the two parts may be formed in a manner similar to a plastic bottle. The part may be provided with a base, which may be formed such as to be so thin that during a blowing process, the base takes on the desired membrane form. Such a production method provides a high degree of integrity and a close fit between the membrane form and the interior of the hub.

[0101] Further preferred manufacturing methods include a deep drawing process. Deep drawing is employed to intricately shape the membrane, transforming it from a flat material into its preferred form, e.g. a truncated conical form. This process allows for precise control over the membrane's geometry, ensuring it conforms perfectly to the cannula device's inner hub and effectively separates the injection solution from external elements, including silicon oil and / or the separate dosing aid solution. The use of deep drawing for the membrane surprisingly achieves the required flexibility and spatial constraint, advantageous for the device's functionality and the preservation of dosage integrity.

[0102] In another preferred embodiment, the cannula device is fixedly, in particular monolithically coupled with the barrel of a syringe. This preferably means that the cannula device and the syringe barrel are manufactured as a single, integrated unit, and they cannot be separated or disassembled. Monolithic coupling ensures that the entire assembly, including the cannula and syringe, is manufactured and packaged under controlled, sterile conditions. This minimizes the risk of contamination during assembly or use, which is critical in medical applications to prevent infections or complications. The integration of the cannula device with the syringe barrel simplifies the production process, as there is no need for separate assembly steps to connect the cannula to the syringe. This can lead to increased manufacturing efficiency and cost savings. Monolithic coupling eliminates the possibility of misalignment or detachment between the cannula and the syringe barrel during medical procedures. This ensures that the device functions as intended, reducing the likelihood of procedural errors or accidents. Since the cannula device is permanently attached to the syringe, its performance characteristics, such as fluid flow rate and precision, remain consistent from one unit to another. Users, such as medical professionals, benefit from the simplicity and convenience of having the cannula device and syringe combined into a single unit. It eliminates the need for additional assembly steps, making it easier to use during medical procedures. While there may be some initial tooling costs for manufacturing monolithically coupled devices, the potential cost savings from increased efficiency, reduced waste, and improved quality control can make this approach more cost-effective in the long run.

[0103] In another preferred embodiment, the cannula device is prefilled with one or more therapeutic products. This preferably means that the cannula device comes preloaded with the required medication or therapeutic substances and / or separated fluid, ready for immediate use in medical procedures.

[0104] Prefilled devices eliminate the need for healthcare professionals to manually draw up and prepare medications before administering them. This can significantly reduce the time required for preparation, allowing for more efficient patient care. Prefilled cannula devices are filled under controlled conditions, ensuring precise dosing and reducing the risk of errors in medication preparation. Since the therapeutic product is preloaded and sealed within the device, it remains in a sterile environment until it is used. This minimizes the risk of contamination and infections associated with traditional medication preparation methods.

[0105] In this preferred embodiment, one of the “one or more therapeutic products" is indeed a separated dosing fluid. The inclusion of a separated dosing fluid ensures accurate and consistent dosing of therapeutic products. The dosing fluid acts as a buffer, helping to measure and deliver the exact amount of medication required for each treatment.

[0106] In a further preferred embodiment of the invention, the prefilled cannula device is storable at a temperature as low as -80 °C. The ability to withstand such low temperatures makes this embodiment particularly suitable for storing vaccines, especially mRNA vaccines. mRNA vaccines have gained prominence for their effectiveness, but one of their challenges is the need for ultra-cold storage to maintain their stability. Thus, having a cannula device that can tolerate these extreme temperatures is advantageous for vaccine distribution and administration.

[0107] The cannula device is thus preferably configured to have sufficient thickness and mechanical properties such as to withstand any expansion or contraction of the therapeutic product or other fluid stored within it when a temperature is lowered to -80 °C and raised to room temperature, patient temperature or higher. Moreover, the material and thickness of the base body are preferably selected to avoid cracking or deformation due to the temperature change. Preferably, leakages after thawing a fluid within the prefilled cannula device are avoided by using a sealed cavity that can endure the predetermined temperature range and the thermal expansion stresses caused by the one or more therapeutic products.

[0108] In a further preferred embodiment of the invention, the cannula device comprises means for venting the cannula device.

[0109] It may be preferred that the venting of the cannula device is initiated by a male luer lock fitting of the cannula device being screwed onto a female luer lock fitting of a syringe. As soon as the cannula device is completely screwed onto the female luer lock fitting of the syringe, the luer lock adapter preferably exerts a slight (direct or indirect) pressure onto the membrane. This pressure leads to a displacement of a small volume of therapeutic fluid, which vents the cannula. This preferably means, that sufficient therapeutic fluid is displaced within the first cavity through the needle, to remove any air from the first cavity and the needle. Because the dimensions of the luer lock adapter are precisely standardized, the remaining volume in the first cavity of the cannula device can be very precisely predetermined. The applied dose is therefore very accurate after venting.

[0110] It may also be preferred, that the venting of the cannula device is initiated by the insertion of a pin into the second cavity of the cannula device. The cannula device preferably is assembled onto a syringe, and a very precise volume of therapeutic fluid is displaced within the first cavity through the needle, by inserting, or pushing a small pin into the second cavity. This preferably means, that sufficient therapeutic fluid is displaced within the first cavity through the needle, to remove any air from the first cavity and the needle. The remaining volume can be predetermined very precisely.

[0111] It may also be preferred that the first cavity is highly transparent and that it comprises a marking, preferably a small marking on the housing. This preferably means that the syringe plunger can be used to eject as much volume as necessary until the membrane is aligned with the marking.

[0112] It is advantageous to provide a reliable mechanism for venting the cannula device in order to allow for removal of air from the device to avoid unintended injection of air while administering the therapeutic fluid, and at the same time still provide a reliable dosage. This is especially relevant for small volumes of therapeutic fluid.

[0113] In another preferred embodiment, the cannula device is provided as part of an injection device, wherein the injection device is provided as one part, preferably one injection molded part comprising cannula device and mechanism for exerting pressure onto the membrane.

[0114] It is particularly preferable that this embodiment may provide a ready to use product with prefilled therapeutic fluid.

[0115] It may be preferred that individual injection devices can be combined to an injection blister pack. This preferably means that the individual injection devices may be connected through perforated links, allowing them to be easily separated.

[0116] It is advantageous that this injection device produces less waste than syringes.

[0117] It is also advantageous that this injection device preferably protects against reuse, because its functionality may be automatically disabled after one use. This can for example be realized by providing a prefilled injection device that does not include a reversible plunger for exerting pressure and injecting the therapeutic fluid, but instead exerts the pressure in a different manner. Pressure for injection of the therapeutic fluid from the first cavity can for example be provided by exerting pressure on a flexible second cavity, which will remain (partially) collapsed after use, thereby preventing refilling and reusing of the device. Partially collapsed may preferably refer to the case where the collapsed volume of the second cavity corresponds to the volume of therapeutic fluid displaced from the first cavity during injection. Therefore, this partial collapsed second cavity reservoir prevents reuse of the injection device.

[0118] In another aspect, the invention relates to the use of the cannula device according to any embodiment described herein for injections, storage and / or transport of liquids, wherein the absence of silicone oil or other abrasives and / or a special purity is required. Preferably, the invention relates to the use of the cannula device where sliding friction is to be avoided due to the potential damage of fragile ingredients, in particular cells, vesicles, lipid nano- or microparticles, liposomes, micelles, nucleic acids (single stranded, double stranded), proteins or antibodies. It was especially surprising that a membrane which changes between a first and second position in response to a reversal of a pressure gradient across it could be used for these applications. It is thought that the lack of moving parts within the first cavity is especially advantageous for avoiding rupture of fine microscopic structures such as cells, vesicles etc.

[0119] The cannula device's design, which prevents contact with silicone oil and maintains the integrity of the injected substances, makes it highly suitable for applications where the absence of silicone oil is imperative. The device's ability to maintain the purity and sterility of the injected substances meets the stringent standards required in certain medical treatments. It ensures that the administered medications or therapeutic products are delivered in a pristine state, free from contaminants. The cannula device's efficiency and precision in delivering controlled doses make it well-suited for situations where recurring or repetitive doses of medications or therapeutic agents are necessary. Its consistent performance helps ensure that each dose is administered accurately and safely.

[0120] In another aspect, the invention encompasses a kit that includes the cannula device, along with at least one additional disposable syringe and / or needles. This kit is designed to provide a comprehensive and versatile solution for various medical scenarios. The kit's core component is the cannula device. This cannula device is designed to maintain the integrity and sterility of the injected substances, 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 up medications or fluids, preparing injections, and facilitating the injection process. Disposable syringes are typically preferred in healthcare settings for their single-use design, reducing the risk of cross-contamination, in addition to syringes, the kit may provide disposable needles. These needles are essential for attaching to the syringes and the cannula device, allowing for the 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, suitable for various medical procedures and treatment protocols.

[0121] Furthermore, as an alternative to the traditional needle and cannula configuration, the kit may also offer an embodiment in the form of a needleless syringe. This needleless syringe design ensures painless injections, thereby enhancing patient comfort. It can be particularly beneficial in scenarios where rapid administration is required, or in settings where patients have a pronounced needle phobia. The needleless syringe can still work in conjunction with the kit's components for drawing up, preparing, and administering medications or fluids.

[0122] Having all the necessary components in one kit streamlines the medical workflow, saving time and effort during procedures. The components of the kit 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.

[0123] In a preferred embodiment of the invention, the kit comprises a device for adjusting the pressure in the second cavity of the cannula device. The cannula device is preferably connectable to the device for adjusting the pressure in the second cavity, for example due to both components comprising complementary plug and socket connections. The device for adjusting the pressure in the second cavity of the cannula may be configured for manual use, such as a traditional syringe. Alternatively, the device may be mechanically and / or electronically controllable, e.g., a mechanical pump.

[0124] Terms such as substantially, approximately, about, etc. preferably describe a tolerance range of less than ± 20%, preferably less than ± 10%, especially preferably less than ± 5%, and especially less than ± 1%, and include the exact value.

[0125] A person skilled in the art understands that technical features and advantages that have been disclosed in regards to the cannula device described herein, equally apply to the method of manufacturing such a device, the use of the device and the kit comprising the device, and vice versa.

[0126] DETAILED DESCRIPTION

[0127] Without intending to be limiting, the invention will be explained in more detail with reference to exemplary embodiments and the following figures:

[0128] Brief description of the figures

[0129] Fig. 1 shows an example of a cannula device according to a preferred embodiment of the invention, wherein the membrane is in the first position.

[0130] Fig. 2 shows the cannula device of Fig. 1 , wherein the membrane is in the second position.

[0131] Figs. 3 and 4 are close-up views of the hubs of the cannula device according to a preferred embodiment of the invention.

[0132] Fig. 5 schematically shows the steps of using the cannula device to draw up a therapeutic solution.

[0133] Fig. 6 schematically shows the steps of injecting the therapeutic solution into a patient.

[0134] Fig. 7 is a perspective view of a cannula device according to a preferred embodiment of the invention, the cannula device being separate from the syringe.

[0135] Fig. 8 shows a perspective view of the cannula device according to a preferred embodiment of the invention connected to a syringe via a Luer-lock. Fig. 9 shows a perspective view of a cannula device according to an alternative preferred embodiment of the invention in which the cannula is integrally formed with the syringe.

[0136] Fig. 10 shows an example of a cannula device according to a preferred embodiment of the invention, wherein the membrane is configured as a foldable membrane.

[0137] Fig. 11 schematically shows the foldable membrane in an expanded unfolded state and in a compressed, folded state.

[0138] Fig. 12 schematically shows an exemplary process of venting the cannula device by means of pressure exerted onto the membrane by screwing the cannula device onto a syringe.

[0139] Fig. 13 schematically shows another exemplary process of venting the cannula device by means of insertion of a small pin.

[0140] Detailed description of the figures

[0141] Fig. 1 shows an example of a cannula device 2 according to a preferred embodiment of the invention, wherein the membrane is in the first position. The cannula device 2 has a base body 4 shown in tight shading. The cannula device 2 is hermetically connected to a syringe 20, shown in loose shading, by means of a male Luer-lock fitting 16 on base body 4 and a female Luer-lock fitting 18 on the syringe. The base body 4 of the of the cannula device 2 comprises a hollow hub 6 (labelled on Fig. 2). The hub comprises a membrane 12, the perimeter of which is clamped in an intermediate position along the hub 6. The central portion of the membrane 12 is however freely movable within the hub. The base body 4 also comprises an outlet channel 14 which extends from the hub. A needle 26 is fixed within the outlet channel 14 and extends therefrom in a longitudinal direction.

[0142] Fig. 1 shows the membrane 12 in a first position. The membrane separates the hollow portion of the base body 4 into two cavities. A first cavity 28 is located between the membrane 12 and the exterior tip of the base body 4. A second cavity 30 is located between the membrane 12 and a depressed plunger 24 of the syringe. In this embodiment, the membrane has a frustoconical form which conforms to the interior of the hub. Due to this close fit, the membrane 12 ensures that the first cavity occupies substantially no volume in the hub, being limited in this case to the volume of the outlet 14. The second cavity 30 occupies substantially all of the hub as well as a transitionary volume which leads to a proximal end of the cannula device. The second cavity 30 is prefilled with a separated solution. The volume of the separated solution 34 fills the second cavity 30 when the plunger 24 is fully depressed. No air bubbles are left in the second cavity such that the separated solution 34 can accurately reflect the volume of fluid entering the cannula device after the membrane 12 has been placed in the first position as shown.

[0143] Fig. 2 shows the cannula device 2 after extending the plunger 24 of the syringe 20 to draw up a therapeutic fluid 32 into the first cavity 28. The extending of the plunger 24 causes a pressure drop in the second cavity 30. The membrane 12 is rapidly inverted as a result of this pressure drop, bringing the membrane 12 to the second position as shown in the figure. Due to the hub having a symmetrical form before and after the membrane 12, the inverted membrane 12 conforms closely to the shape of the lower portion of the hub 6. This causes a portion of the separated fluid 34 to be displaced into a barrel 22 of the syringe 20. At the same time, a pressure drop is created in the first cavity 28 which has expanded to occupy substantially all of the hub 6. Due to the pressure drop, the therapeutic fluid 32 fills the first cavity 28. The volume of therapeutic fluid 32 in the first cavity 28 corresponds to the volume of separated fluid 34 displaced into the barrel 22. The barrel 22 is transparent such that the amount of separated fluid 34 therein is visible. The barrel 22 is also provided with at least one dosing mark indicating that the first cavity 28 has been filled to its maximum capacity. The plunger 24 may then be depressed to inject the fluid, returning the membrane 12 to the first position (shown in Fig. 1). The barrel 22 may be used to verify that all of the fluid has been ejected from the first cavity 28.

[0144] Figs. 3 and 4 provide close-up views of the hub 4, outlet 14 and needle 26 of the cannula device of Figs. 1 and 2. The close-ups show two distinct portions which can be identified within the hub 4. The base body 4 in this embodiment comprises two portions. The two portions are joined together at a cross section of the hub which clamps the perimeter of the membrane 12. A first portion 8 of the hub falls ahead (distally) of the clamped membrane perimeter which a second portion 10 of the hub falls behind (proximally) of the clamped membrane perimeter. The volumes defined by the first and second portions 8 are fixed throughout the use of the cannula device as the perimeter of the membrane 12 is also fixed.

[0145] As can be more closely identified in these figures, the truncated form of the membrane 12 provides a substantially flat tip which rests against the outlet channel 14 in the first position. A needle 26 is positioned within the outlet channel 14 such as to be flush with an interior surface of the hub 6. However, minor errors in the positioning of the needle 26 may cause its base to protrude into the first portion of the hub 8. The flat truncated surface of the membrane 12 prevents puncture of the thin membrane should any minor errors in the positioning of the needle 26 occur.

[0146] Fig. 5 show schematically a process of drawing up a therapeutic solution into the first cavity therapeutic fluid 32. The needle 26 may pierce a sealed foil at the top of the container. At this stage, the membrane 12 is in the first position.

[0147] The plunger 24 of a syringe 20 connected to the cannula device 2 is then retracted, reversing a pressure difference across the membrane 12. The membrane 12, which is non-elastic, begins to invert as fluid enters the first cavity 28. The first cavity 28 expands and fills with the therapeutic fluid 32.

[0148] The plunger 24 of the syringe 20 is retracted further until the membrane 12 is in the second position. The first cavity 28 expands to occupy substantially all of the hub and is filled with the therapeutic fluid 32. The separated fluid 34 in the transparent barrel 22 of the syringe 20 indicates that the cannula device is full.

[0149] Fig. 6 shows a process of injecting the therapeutic solution into a patient 36. The cannula device 2 has been filled as shown in Fig. 5 and the membrane 12 is in the second position. The plunger 2 of the syringe 22 is depressed, increasing the pressure in the second cavity 30. This reverses a pressure gradient across the membrane 12, causing said membrane 12 to invert again. As the membrane 12 inverts, the first cavity 28 becomes smaller, ejecting the incompressible therapeutic fluid 32 through the needle 26. The membrane 12 returns to the first position in which the first cavity 28 occupies substantially no volume due to the tight fit between the membrane 12 and the inner walls of the first portion of the hub 8. As there is substantially no dead space in the hub 6, all of the therapeutic fluid 32 enters the needle 26. The therapeutic fluid 32 enters the patient in a precise dose and without contamination.

[0150] Fig. 7 shows a cannula device 2 according to a preferred embodiment of the invention, whereby the cannula device 2 is provided separately from the syringe 20. In this view, the injection or blow-molded nature of the cannula can be better observed. The cannula device comprises two halves, proximally and distally of the membrane 12. The two halves are thermally bonded together as can be recognized in the figure. However, the two halves of the cannula device are each smooth and substantially monolithic. The proximal half of the cannula comprises a female threaded connection 18 according to a medical standard. This can be easily attached to a sterile disposable syringe 20 having a complementary male threaded connection as is widely used in the art. A perspective view of the cannula device 2 connected to a disposable syringe 20 is shown in Fig. 8.

[0151] Fig. 9 shows an alternative embodiment in which the syringe 20, in particular the barrel thereof, is integrally formed with the cannula device, for example by injection molding. As can be seen in the figure, the barrel of the syringe 20 and the proximal portion of the base body 4 of the cannula are a single part. The plunger 24 is slidably trapped within the barrel 22. Fig. 10 shows a cannula device 2 according to a preferred embodiment of the invention, wherein the membrane is configured as a foldable membrane. The figure shows the membrane in an unfolded, expanded state 40 during filling, by unfolding one or more ribs 44, wherein the ribs are preferably arranged as a vortex.

[0152] Fig. 11 show schematically the process of folding and unfolding in an intermediate position between the first and second positions. The figure shows the membrane in an unfolded, expanded state 40. The plunger 24 of a syringe 20 connected to the cannula device 2 is depressed, increasing the pressure causing said membrane to fold. During filling the foldable membrane is purposefully engineered to allow for expansion by unfolding one or more side ribs 44. In this state the folded membrane undergoes expansion and unfolds in response to the applied vacuum or fluid pressure during the filling or injection process.

[0153] Fig. 12 shows schematically an exemplary process of venting the cannula device 2. The male luer lock fitting 16 of a cannula device 2 according to a preferred embodiment of the invention is screwed onto a female luer lock fitting 18 of a syringe 20. As soon as the cannula device 2 is completely screwed onto the female luer lock fitting 18 of the syringe 20, the luer lock adapter exerts a slight (direct or indirect) pressure onto the membrane 12. This pressure leads to a displacement of a small volume of therapeutic fluid 32, which vents the cannula. This preferably means, that sufficient therapeutic fluid 32 is displaced within the first cavity 28 through the needle 26, to remove any air 46 from the first cavity 28 and the needle 26. Because the dimensions of the luer lock adapter are precisely standardized, the remaining volume in the first cavity 28 of the cannula device 2 can be very precisely predetermined. The applied dose is therefore very accurate after venting.

[0154] Fig. 13 shows schematically another exemplary process of venting the cannula device 2. The cannula device 2 according to a preferred embodiment of the invention is assembled onto a syringe 20. A very precise volume of therapeutic fluid 32 is displaced within the first cavity 28 through the needle 26, by inserting, or pushing a small pin 48 into the second cavity 30. This preferably means, that sufficient therapeutic fluid 32 is displaced within the first cavity 28 through the needle 26, to remove any air 46 from the first cavity 28 and the needle 26. The remaining volume can be designed very precisely. LIST OF REFERENCE SYMBOLS

[0155] 2 Cannula Device

[0156] 4 Base Body

[0157] 6 Hub

[0158] 8 First portion of Hub

[0159] 10 Second portion of Hub

[0160] 12 Membrane

[0161] 14 Outlet Channel I Injection Port

[0162] 16 Male Luer-lock Fitting

[0163] 18 Female Luer-lock Fitting

[0164] 20 Syringe

[0165] 22 Barrel

[0166] 24 Plunger

[0167] 26 Needle

[0168] 28 First Cavity

[0169] 30 Second Cavity

[0170] 32 Therapeutic Fluid

[0171] 34 Separated Fluid

[0172] 36 Patient

[0173] 38 Vial

[0174] 40 unfolded membrane

[0175] 42 compressed membrane

[0176] 44 side ribs

[0177] 46 air

[0178] 48 pin

Claims

CLAIMS1. A cannula device comprising a base body, wherein the base body comprises in its longitudinal direction a hub, characterized in that the hub comprises a first cavity and a second cavity and a membrane arranged transversally within the hub, wherein the first cavity and the second cavity are separated from one another by means of the membrane, wherein the membrane is configured to be convertible between a first position and a second position in response to a reversal of a pressure gradient across the membrane.

2. A cannula device according to the preceding claim characterized in that in the first position, the membrane extends at least partially into a first portion of the hub and upon drawing up an injection solution with a needle, the membrane is converted to the second position by inverting and / or unfolding the membrane and extending it at least partially into a second portion of the hub, preferably such as to expand the first cavity and to draw the injection solution into the first cavity.

3. A cannula device according to any of the preceding claims characterized in that in the second position, the membrane extends at least partially into a second portion of the hub and upon injecting an injection solution with a needle, the membrane is converted to the first position by inverting and / or folding up the membrane and extending it at least partially into a first portion of the hub and displacing the injection solution through the needle.

4. A cannula device according to any one of the preceding claims characterized in that the cannula device comprises on at least one side a locking connection as a snap-fit connection, a plug-in connection, a clamp connection, a threaded connection and / or a Luer- lock fitting, in particular a threaded Luer-lock fitting.

5. Cannula device according to any of the previous claimscharacterized in that the second cavity of the cannula device is prefilled with a separated fluid, so that during drawing up of an injection solution, the separated fluid is forced into a barrel by inverting, folding or unfolding the membrane, wherein the barrel is preferably configured to serve as a dosing aid, in particular by being provided with dosing marks.

6. Cannula device according to the preceding claim characterized in that the separated fluid comprises an aqueous solution selected from a group comprising a saline solution, a colored solution and / or a buffered solution.

7. Cannula device according to any one of the preceding claims characterized in that the membrane has a planar, truncated conical, untruncated conical, rounded cone or hemispherical shape and / or is configured as a foldable membrane, wherein the foldable membrane is provided by default in a compressed, folded state and is configured to be expanded during filling by unfolding one or more ribs, wherein the ribs are preferably arranged as a vortex.

8. Cannula device according to any one of the preceding claims characterized in that the membrane has a wall thickness of 5 pm - 200 pm, preferably 60 pm.

9. Cannula device according to any one of the preceding claims characterized in that the membrane comprises polypropylene, polystyrene, polyethylene, polyvinylchloride, silicone or a copolymer as a material selected from a group comprising: cyclic olefin copolymers and / or linear olefin copolymers.

10. Cannula device according to any one of the preceding claims characterized in thatthe expansion of the membrane is defined by the total volume of a first and second portion of the hub, wherein the total volume of the first and second portion of the hub is from 10 pl - 10000 pl, preferably about 50 pl - 300 pl.

11. Cannula device according to any one of the preceding claims characterized in that the cannula device is manufactured by a process comprising a forming step selected from a group comprising:- an injection molding process and- a blow molding process.

12. Cannula device according to any one of the preceding claims characterized in that the cannula device is fixedly, in particular monolithically, coupled with a barrel of a syringe.

13. Cannula device according to any one of the preceding claims characterized in that the cannula device is prefilled with one or more therapeutic products, wherein the prefilled device is preferably storable at a temperature as low as -80°C, whereby leakages after thawing up are preferably avoided by using a sealed cavity that can endure a predetermined temperature range and thermal expansion stresses caused by the one or more therapeutic products.

14. Use of the cannula device according to any one of the preceding claims for injections, storage and / or transport of liquids, wherein the absence of silicone oil or other abrasives and / or a special purity is required and / or sliding friction is to be avoided due to potential damage of fragile ingredients, in particular cells, vesicles, lipid nano- or microparticles, liposomes, micelles, nucleic acids (single stranded, double stranded), proteins or antibodies.

15. A kit comprising the cannula device of any one of the preceding claims 1 - 13 and at least one additional disposable syringe and / or needles.

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