Pre-filling needle suitable for low-temperature storage

Abstract

The pre-filling needle suitable for low-temperature preservation comprises a needle tube, a first connector is arranged at the front end of the needle tube, a protruding edge flange is arranged at the tail end of the needle tube, a second connector is connected to the first connector through threads to form a Luer connector, and an exhaust structure communicated with the outside is arranged on the Luer connector. A reinforcing rib protruding towards the outside of the needle tube is arranged on the plane of the tail portion of the protruding edge flange. According to the pre-filling needle, the adaptability, the stability and the sealing performance of the pre-filling needle in the cryopreservation and redissolution process are remarkably improved through the exhaust structure on the Luer taper and the design of the reinforcing ribs on the tail convex edge flange aiming at the structural integrity problem of a pre-filling syringe in a low-temperature environment.

Description

Technical Field

[0001] The present invention relates to the field of medical devices, and in particular to a Luer connector and a prefilled syringe. Background Art

[0002] Cell and gene therapy (CGT) products in clinical applications usually include gene therapy products, vaccines, stem cell gene therapy products, immune cell therapy products, etc. These products are of great value in the treatment of human diseases. This type of drug is extremely sensitive to temperature, and improper storage conditions will cause the drug to fail and reduce efficacy. In the selection of preparation forms for cell therapy products, although fresh cell preparations have their advantages, with the advancement of industry research and technology, the mainstream view is gradually tending to adopt frozen forms. Cryopreserved cell preparations are more in line with the basic characteristics of drug preparations, which is conducive to arranging production, completing the necessary finished product testing and release procedures, supporting multi-dose production and large-scale promotion and application, and are also more in line with the form required for new drug applications (NDA).

[0003] At low temperatures, the expansion of the vial body and rubber stopper, as well as the brittleness of the aluminum cap, affect the sealing effect. Therefore, at low temperatures, the integrity and sealing of the vial packaging face challenges. The development of the low-temperature capping process is difficult and cannot fully meet the CGT industry's demand for low-temperature storage.

[0004] Prefilled syringes (PFS) have the advantages of convenience, dosage accuracy and safety at room temperature, and their front ends are usually equipped with Luer connectors suitable for quick connection. However, during the freezing and reconstitution process of low-temperature storage, the thin wall of the Luer connector may produce uneven stress due to different temperature changes, which may cause cracks in the Luer connector or even direct breakage.

[0005] Furthermore, when the medicine needs to be preserved by low-temperature liquid nitrogen, the filled syringe is directly placed in liquid nitrogen for freezing. At this time, the liquid nitrogen may penetrate into the thread gap of the Luer connector. When it needs to be reconstituted for use, the liquid nitrogen in the aforementioned gap will quickly vaporize, and the excess pressure will have nowhere to be released, which will also cause the Luer connector to rupture.

[0006] Furthermore, the sealing structure at the tail of the prefilled needle is similar to that of the vial in a low-temperature environment. It not only faces the same problem of low-temperature storage, but also needs to withstand the test of rapid temperature changes during reconstitution. Under the combined effect of the stress of the capping, the sealing structure at the tail also has a high risk of rupture. Summary of the invention

[0007] In order to solve the above problems, the present invention provides a prefilled needle suitable for low-temperature storage that meets the requirements of low-temperature storage and can still ensure structural integrity during the freezing and re-dissolving processes.

[0008] In order to achieve the above-mentioned purpose, the present invention is a prefilled needle suitable for low-temperature storage, comprising a needle tube, a first joint is provided at the front end of the needle tube, a convex flange is provided at the rear end of the needle tube, a second joint is threadedly connected to the first joint to form a Luer joint, an exhaust structure connected to the outside is provided on the Luer joint, and a reinforcing rib protruding outward from the needle tube is provided on the rear plane of the convex flange.

[0009] A further solution is that the cross section of the reinforcing rib is small at the top and large at the bottom, and in the profile of the cross section of the reinforcing rib, the slope of the first side close to the inner side of the needle tube is greater than the slope of the second side close to the outer side of the needle tube. The first side is a straight line and is transitionally connected to the straight line where the tail plane is located through the first fillet, and the second side is a curve and is directly transitionally connected to the straight line where the tail plane is located.

[0010] The preferred solution is that the angle between the first side and the diameter of the needle tube is 30 degrees, the second side is an arc line with a radius of 0.8 mm, the first side and the second side are transitioned by an arc line with a radius of 0.1 mm, and the first side and the straight line where the tail plane is located are transitioned by an arc line with a radius of 0.3 mm.

[0011] In order to further enhance the sealing effect, there may be two reinforcing ribs, and the cross-sectional profiles of the two reinforcing ribs are in a mirror image relationship.

[0012] Another solution is that the exhaust structure includes vents, and the vents are arranged in the radial direction of the Luer connector, so that the internal space of the Luer connector can exchange gas with the outside.

[0013] At the same time, the exhaust structure can also include an exhaust groove penetrating the threaded connection structure, wherein the exhaust groove is arranged in the axial direction of the Luer connector, and the bottom of the exhaust groove is lower than the tooth bottom groove of the thread.

[0014] When the second connector is fully connected to the first connector through threads, a gap is directly formed between the end of the second connector and the bottom of the first connector, the vent hole matches the position of the gap, and the central axis of the vent hole is inclined toward the direction of the needle tube.

[0015] The prefilled needle suitable for low-temperature storage provided by the present invention addresses the problem of structural integrity of prefilled syringes in low-temperature environments. By means of the exhaust structure on the Luer connector and the reinforcing rib design of the rear flange, the adaptability, stability and sealing performance of the prefilled needle during freezing and reconstitution are significantly improved.

[0016] The exhaust structure on the Luer connector solves the problem of gas not being able to be discharged smoothly during the freezing and re-dissolving of liquid nitrogen through the design of vent holes and exhaust grooves that run through the threaded connection. The vent holes are set in the radial direction, and combined with the inclined design, the excess pressure generated when the liquid nitrogen is vaporized can be discharged through the vent holes in time; and the exhaust groove runs through the threaded connection structure and the bottom is lower than the bottom groove of the thread teeth. It is designed for liquid nitrogen that penetrates into the threaded structure, so that the exhaust channel is always unobstructed. At the same time, the exhaust groove is set on the relatively weak thread structure of the Luer connector, which also disperses the stress on the Luer connector in the frozen state, making the Luer connector more stable. This design not only effectively avoids the problem of the Luer connector bursting due to the accumulation of air pressure, but also ensures that the sealing effect of the connector is not affected during the gas exchange process, significantly improving the safety and durability of the Luer connector in low temperature environments.

[0017] The convex flange at the tail is designed with reinforcing ribs, which not only effectively enhances the strength of the sealing structure, but also fully considers the compatibility with the gasket. The special cross-sectional shape of the reinforcing rib, through the combination design of the first side and the second side with different slopes, fits tightly with the gasket on the tail plane, while providing stable mechanical support and further improving the sealing performance. The straight line of the first side forms a reliable pressing surface with the gasket plane, ensuring excellent sealing under the combined action of low temperature and mechanical stress; the curve of the second side optimizes the stress distribution and avoids the stress concentration effect in the low temperature environment, thereby enhancing the crack resistance and structural stability of the flange. In addition, the contact between the reinforcing rib and the gasket can also limit the lateral movement caused by the shrinkage or expansion of the gasket due to temperature changes, and also makes a beneficial contribution to the sealing. The double-strip mirror-image rib design further improves the strength of the tail sealing area, enabling the prefilled needle to withstand the high-strength capping process under low temperature conditions, while reducing the risk of damage caused by drastic temperature changes during the re-dissolution process.

[0018] Through the above structural design, the prefilled needle of the present invention can maintain excellent sealing performance and structural integrity under low-temperature freezing conditions. During the reconstitution process, both the pressure release function of the Luer connector and the sealing effect and crack resistance of the tail flange and the sealing gasket significantly improve the safety and reliability of the prefilled needle, thereby meeting the storage requirements of drugs that are extremely sensitive to temperature, such as cell gene therapy. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a cross-sectional view of the overall structure of the prefilling needle in Example 1.

[0020] Figure 2 Embodiment 1 Figure 1 Enlarged view of .

[0021] Figure 3 This is a schematic diagram of the structure in which the second side of the reinforcement rib is a straight line.

[0022] Figure 4 It is a schematic diagram of the completely symmetrical structure of the first and second sides of the reinforcement.

[0023] Figure 5 It is a structural schematic diagram of a convex flange with two circles of reinforcing ribs.

[0024] Figure 6 This is the finite element analysis diagram of the second side of the reinforcement rib being an arc.

[0025] Figure 7 This is the finite element analysis diagram where the second side of the reinforcement is a straight line.

[0026] Figure 8 It is a finite element analysis diagram showing that the first and second sides of the stiffener are completely symmetrical.

[0027] Fig. 9 It is a stereoscopic view of the exhaust groove provided on the second joint of Example 1.

[0028] Fig.10 This is a cross-sectional view of the exhaust groove provided on the second joint of Example 1. DETAILED DESCRIPTION

[0029] The preferred embodiments of the present invention are described below in conjunction with the accompanying drawings. It should be understood that the preferred embodiments described herein are only used to illustrate and explain the present invention, and are not used to limit the present invention.

[0030] Example 1.

[0031] like Figure 1 The embodiment shown describes a prefilled needle, including a needle tube 1, a plunger (not shown in the figure), a female head, i.e., a first connector 2, is integrally formed at the front end of the needle tube 1, and a guide column 3 is provided at the center of the first connector 2 at the front end of the needle tube 1, and a flow guide hole 4 connected to the inside of the needle tube 1 is provided at the center of the guide column 3. An internal thread is provided on the inner wall of the first connector 2, and the internal thread is used to cooperate with a male head, i.e., a second connector 5, which has an external thread on the outer wall. The second connector 5 is a hollow tubular structure as a whole, and a plug 6 is provided in the hollow tubular structure. At the same time, an inwardly protruding annular collar 7 is provided on the inner wall of the second connector 5, and the plug 6 is limited in the second connector 5 by the cooperation of the annular collar and the annular groove on the plug 6.

[0032] A convex flange 13 is provided at the tail end of the needle tube 1, and a rivet cover (not shown in the figure) is provided on the convex flange 13 to close the tail opening of the needle tube 1, and a sealing gasket 15 is provided between the rivet cover and the tail plane 14 of the convex flange 13, and a reinforcing rib 16 is formed on the tail plane 14 in a ring shape and protruding toward the sealing gasket 15.

[0033] like Figure 2As shown, in the cross section of the reinforcing rib 16, the reinforcing rib 16 is connected to the tail plane 14, and the whole is a triangle. The size of the protruding tail plane 14 is 0.4mm, and its top is a circular chamfer 17 with a radius of 0.1mm, wherein the first edge 18 close to the inner side of the needle tube 1 is a straight line, and the angle α with the diameter of the needle tube 1 is 30°, and the end of the first edge 18 is transitionally connected to the straight line where the tail plane 14 is located through the first fillet 19, and the first fillet 19 is an arc with a radius of 0.3mm.

[0034] In the cross section of the reinforcing rib 16 , the second side 20 close to the outer side of the needle tube 1 is an arc curve with a radius of 0.8 mm, and is directly transitionally connected to the straight line where the tail plane 14 is located.

[0035] It should be noted that, in this embodiment, the slope of the second side 20 is determined by the chord of the arc. Therefore, as long as the arc length meets the requirements, the second side 20 will be flatter than the first side 18 and have a smaller slope than the first side 18.

[0036] At the same time, after the sealing gasket 15 is deformed by the rivet cover, the shape of the sealing gasket 15 is deformed to match the reinforcing rib 16 , that is, the reinforcing rib 16 is squeezed onto a portion of the surface of the sealing gasket 15 , thereby limiting the lateral position of the sealing gasket 15 .

[0037] like Figure 3 As shown, in some applications, the second side 20 of the reinforcing rib 16 is a straight line, and the angle β between the second side 20 and the diameter of the needle tube 1 is 60°. At the same time, the end of the second side 20 is transitionally connected to the straight line where the tail plane 14 is located through a second fillet 21, and the second fillet 21 is an arc with a radius of 0.3 mm.

[0038] like Figure 4 As shown, in some applications, the second side 20 of the reinforcing rib 16 is a straight line, and the angle α between the second side 20 and the diameter of the needle tube 1 is 30°. At the same time, the end of the second side 20 is transitionally connected to the straight line where the tail plane 14 is located through the first fillet 19, and the first fillet 19 is an arc with a radius of 0.3 mm. That is, the first side 18 and the second side 20 of the reinforcing rib 16 and the curves where they transition to the tail plane 14 are completely symmetrical.

[0039] Finite element analysis is performed on the above three applications. The needle tube 1, i.e., the flange 13, is set to be a rigid material, the sealing gasket 15 is set to be 45A rubber, and the Neo-Hookean model is used. The contact type between the flange 13 and the sealing gasket 15 is rough (no penetration, separable, no slip), and the analysis type is: direct solver, large deformation open; the boundary conditions are: the flange 13 does not displace in the Y direction, the sealing gasket 15 displaces in the Y direction +2mm, corresponding to a 1mm compression of the 3mm thick rubber gasket. The analysis conditions of the three reinforcement ribs are the same. After simulation analysis, the results are as follows: Figure 6-Figure 8 .

[0040] Figure 8 In the results, under the pressure of simulating the rivet cover pressing, the sealing gasket 15 and the convex flange 13 fit well, however, there is a relatively obvious gap on the left side of the sealing gasket 15, but the sealing gasket 15 and the tail plane 14 outside the gap fit well.

[0041] Figure 7 In the results, under the pressure of simulating the pressing of the rivet cover, the sealing gasket 15 and the convex flange 13 fit well, but there is an extremely small gap on the right side of the sealing gasket 15, which is almost invisible and can be ignored, while other parts fit well and the sealing effect is better.

[0042] Figure 6 In the results, under the pressure of simulating the rivet cover pressing, the sealing gasket 15 fits perfectly with the convex flange 13 without any gap, and from the overall shape, the width of the tail platform occupied by the sealing gasket 15 is less than Figure 7 Therefore, under the condition of achieving the same effect, it uses less material and is also conducive to obtaining the ejection area of ​​the mold during production, which is the optimal solution for the shape of the reinforcement rib.

[0043] In some applications, such as Figure 5 As shown, there are two circles of reinforcing ribs 16 on the tail plane 14 of the convex flange 13. The cross-sectional profiles of the two reinforcing ribs 16 are completely mirrored. The two mirrored reinforcing ribs 16 can form obstacles to the lateral movement of the sealing gasket 15 from two directions, thereby better fixing the position of the sealing gasket 15. At the same time, the two circles of reinforcing ribs 16 also form a certain maze effect, which improves the sealing effect to a certain extent.

[0044] like Fig. 9 , Fig.10As shown, the second connector 5 is screwed into the first connector 2 by threaded connection. When entering the innermost limit position, a gap, or an annular space 8, is formed between the end of the second connector 5 and the bottom of the first connector 2. A vent 9 is provided at the corresponding part, that is, the transition between the first connector 2 and the needle tube 1. The vent 9 provided on the side wall of the first connector 2 is generally in the radial direction, but is not required to be completely parallel to the radial section of the needle tube 1, and can be appropriately tilted in the direction of the needle tube 1. This structural design, that is, the vent 9 is provided at the transition between the first connector 2 and the needle tube 1, and the central axis of the vent 9 is tilted in the direction of the needle tube 1, is a special design for the reconstitution use scenario. During the reconstitution process, the user holds the end of the needle tube 1 and inserts it into the warm water, that is, the front end of the needle tube 1 is inserted downward into the warm water. The vent 9 provided at the connection between the first connector 2 and the needle tube 1 and tilted toward the needle tube 1 is located above the Luer connector and tilted upward, so it is easier to discharge gas, thereby making the pressure relief smoother.

[0045] Meanwhile, in some embodiments, the number of the vent hole 9 may be one, or may be a plurality of vent holes 9 evenly distributed in a ring shape.

[0046] The outer wall of the second joint 5 is provided with an external thread, and the end of the external thread is a circle of annular retaining ring 10, which is used to cooperate with the front end of the first joint 2 to limit the relative positions of the two joints.

[0047] like Figure 4 , Figure 5 As shown, the threaded section of the second joint 5 is provided with an exhaust groove 11 that penetrates all the threads. The depth of the exhaust groove 11 formed on the outer wall of the second joint 5 is deeper than the tooth bottom groove 12 of the thread, so as to avoid that when the threads are engaged, the threads completely block the exhaust groove 11, thereby reducing the exhaust effect. In some embodiments, the number and position of the exhaust grooves 11 on the circumference are opposite to the vent holes 9.

[0048] In this embodiment, the first joint 2 is provided with an internal thread, and the second joint 5 is provided with an external thread. However, in some embodiments, the opposite may be true, that is, the internal thread is provided on the second joint 5, and the external thread is provided on the first joint 2. At the same time, the position of the exhaust groove 11 is also flexible and variable, and can be provided on the first joint 2 or the second joint 5, or on the internal thread or the external thread. These do not affect the function of the exhaust groove 11.

[0049] Although this embodiment describes a prefilled needle, the technical solution of this application is not limited to the field of prefilled needles, and all scenarios involving injection use can use the Luer connector described in this application and the corresponding syringes equipped with the Luer connector. As mentioned above, the exhaust structure at the front end of the Luer connector only connects the inside of the Luer connector with the outside. In the entire structure, the plug and the guide column are responsible for sealing. The function of the threaded connection is to connect the first connector supported by the plug with the guide column on the second connector, and then press the plug against the guide column to provide a sealing effect.

[0050] In the description of the present invention, it should be noted that the terms "vertical", "up", "down", "horizontal", etc. indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.

[0051] In the description of the present invention, it is also necessary to explain that, unless otherwise clearly specified and limited, the terms "set", "install", "connect", and "connect" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0052] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A prefilled needle suitable for low-temperature storage, comprising a needle tube, a first connector is provided at the front end of the needle tube, and a flange is provided at the rear end of the needle tube, wherein: The first connector is threadedly connected to the second connector to form a Luer connector. The Luer connector is provided with an exhaust structure connected to the outside. The tail plane of the convex flange is provided with a reinforcing rib protruding outward from the needle tube.

2. The prefilled needle suitable for low-temperature storage according to claim 1 is characterized in that the cross-section of the reinforcing rib is small at the top and large at the bottom, and in the contour of the cross-section of the reinforcing rib, the slope of the first side close to the inside of the needle tube is greater than the slope of the second side close to the outside of the needle tube.

3. The prefilled needle suitable for low-temperature storage according to claim 2 is characterized in that in the profile of the cross section of the reinforcing rib, the first side is a straight line and is transitionally connected to the straight line where the tail plane is located through a first fillet, and the second side is a curve that is directly transitionally connected to the straight line where the tail plane is located.

4. The prefilled needle suitable for low-temperature storage according to claim 3 is characterized in that in the profile of the cross section of the reinforcing rib, the angle between the first side and the diameter of the needle tube is 30 degrees, and the second side is an arc line with a radius of 0.8 mm.

5. The prefilled needle suitable for low-temperature storage according to claim 4, characterized in that The first side and the second side are transitioned by an arc line with a radius of 0.1 mm, and the straight line between the first side and the tail plane is transitioned by an arc line with a radius of 0.3 mm.

6. The prefilled needle suitable for low-temperature storage according to claim 5, characterized in that There are two reinforcing ribs, and the cross-sectional profiles of the two reinforcing ribs are in a mirror image relationship.

7. The prefilled needle suitable for cryopreservation according to any one of claims 1 to 6, characterized in that The exhaust structure comprises vent holes, and the vent holes are arranged in the radial direction of the Luer connector so that the internal space of the Luer connector can exchange gas with the outside.

8. The prefilled needle suitable for cryopreservation according to claim 7, characterized in that The exhaust structure comprises an exhaust groove penetrating the threaded connection structure, and the exhaust groove is arranged in the axial direction of the Luer connector.

9. The prefilled needle suitable for cryopreservation according to claim 8, characterized in that The bottom of the exhaust groove is lower than the tooth bottom groove of the thread.

10. The prefilled needle suitable for cryopreservation according to claim 9, characterized in that When the second connector is fully connected to the first connector through threads, a gap is directly formed between the end of the second connector and the bottom of the first connector, the vent hole matches the position of the gap, and the central axis of the vent hole is inclined toward the direction of the needle tube.

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