Cellular medicine cryovial and method of making and cellular medicine injection needle

Abstract

The application discloses a cell medicine freezing tube, a manufacturing method thereof and a cell medicine injection needle, wherein the cell medicine freezing tube comprises a freezing tube, a stopper, a bottom cover, a first elastic plug body, a second elastic plug body and a piston rod; the first elastic plug body and the second elastic plug body are arranged in the freezing tube to form a closed diluent cavity and a suspension cavity; when the piston rod pushes the second elastic plug body to move to a preset position, the diluent cavity is communicated with the suspension cavity through a first fluid channel arranged on the freezing tube or a second fluid channel formed on the first elastic plug body. In the cell medicine freezing tube, the manufacturing method thereof and the cell medicine injection needle, the freezing tube is designed as a single tube with double cavities, the diluent and the cell suspension are respectively prearranged in different cavities, and the diluent and the cell suspension are mixed when needed, and further, the stopper of the cell medicine freezing tube is connected with a needle, so that the cell medicine can be prepared and used immediately.

Description

Technical Field

[0001] This invention relates to the field of cell drug production and application technology, specifically to cell drug cryopreservation tubes and their manufacturing methods, and cell drug injection needles. Background Technology

[0002] Cell-based drugs differ from traditional chemical drugs and macromolecular drugs. Often called "living drugs," they exert their therapeutic effects through living cells. Therefore, cell-based drugs require more complex manufacturing processes and higher standards in clinical application. Despite rapid development, cell-based drugs face significant challenges in their pharmaceutical development and production. The pharmaceutical production of cell therapy products signifies a major shift in cell product manufacturing methods. The production and quality control systems for cell products need to be reformed according to GMP (Good Manufacturing Practice) regulations. Key factors in the production process, including the management of personnel, machinery, materials, methods, raw materials, and the environment, as well as each stage of preparation and production, need to be adapted to pharmaceutical requirements. Materials are a crucial element in cell-based drug production, closely related to research and development, production technologies, and the safety, efficacy, and ease of use of cell-based drugs. They are also a key focus of review in market approval processes for cell-based drugs.

[0003] Cell-based drug cryopreservation tubes are one of the key consumable materials for cell-based drugs. Their use spans the entire process of biopharmaceutical production and application, including seed cell cryopreservation, thawing and resuscitation, and final product resuscitation and application. They are commonly used consumables by cell-based drug research and development and manufacturing companies. Cells are living drugs, and cryoprotectants must be added during cryopreservation. However, cryoprotectants are hypertonic solutions and toxic. After thawing, they need to be diluted or removed immediately, otherwise, cell inactivation and death will occur, affecting continued culture and clinical application outcomes. Currently, the cryopreservation tubes used in the cell-based drug field are the same as those used in scientific research, and their structural design and materials cannot effectively meet the requirements of cell-based drug production and application. In existing technologies, cryovials suffer from poor sealing, the inability to pre-fill with thawing diluent, and the inability to quickly and aseptically dilute cells after thawing. Moreover, cell processing operations must be performed in a clean environment (especially in pharmaceutical production, where all materials must be sterilized before being transferred to clean conditions for processing to ensure aseptic operation, using the fastest hydrogen peroxide sterilization method, with each sterilization step taking more than 10 minutes). This not only makes the operation complex and time-consuming, but the toxicity of the cryovial solution during processing can also seriously affect cell viability and function. Summary of the Invention

[0004] The purpose of this invention is to provide a cryopreservation tube for cell drugs, a method for manufacturing the same, and an injection needle for cell drugs, which not only meet the requirements of pharmaceutical packaging but also the process and application characteristics of cell drugs. This invention simplifies the operation steps of cell drug production and application processes, improves production efficiency, and enhances the safety and effectiveness of cell drug applications.

[0005] To solve the above-mentioned technical problems, in a first aspect, the present invention provides a cell drug cryopreservation tube, the cell drug cryopreservation tube comprising: a plug, a cryopreservation tube, a bottom cap, a first elastic plug, a second elastic plug, and a piston rod;

[0006] The cryopreservation tube is a hollow tubular structure with openings at both ends. The sealing device is located at the upper end of the cryopreservation tube and is sealed to the cryopreservation tube. The bottom cap is located at the lower end of the cryopreservation tube for sealing.

[0007] Both the first elastic plug and the second elastic plug are disposed inside the cryopreservation tube and are tightly fitted to the tube wall of the cryopreservation tube, and can slide along the tube wall of the cryopreservation tube. The first elastic plug, together with the occluder and the tube wall of the cryopreservation tube, forms a closed suspension cavity, which is used to store cell suspension. A closed dilution cavity is formed between the first elastic plug and the second elastic plug, which is used to store diluent.

[0008] One end of the piston rod passes through the bottom cover and enters the cryopreservation tube, pushing the second elastic plug to move. When an axial force is applied to the piston rod, the diluent chamber moves towards the suspension chamber under pressure, and pushes the first elastic plug to move along the axial direction of the cryopreservation tube.

[0009] The cryopreservation tube has a first fluid channel on its wall for connecting the suspension chamber and the dilution chamber. When the first elastic plug moves to the position of the first fluid channel, the dilution chamber communicates with the suspension chamber through the first fluid channel; or

[0010] The cryopreservation tube has an annular groove on its wall for accommodating the first elastic plug for elastic recovery. The first elastic plug has a second fluid channel that runs vertically through it. The second fluid channel opens when the first elastic plug recovers its elasticity. The dilution chamber is connected to the suspension chamber through the second fluid channel.

[0011] Preferably, in the cell drug cryopreservation tube, the length of the line connecting the start and end points of the first fluid channel is slightly greater than the thickness of the first elastic plug.

[0012] Preferably, in the cell drug cryopreservation tube, the first fluid channel includes a plurality of strip-shaped grooves formed on the cryopreservation tube, wherein the width of the strip-shaped grooves is wider at the top and narrower at the bottom.

[0013] Preferably, in the cell drug cryopreservation tube, the groove width of the annular groove is adapted to the thickness of the first elastic plug, and the depth range of the annular groove is set according to the linear expansion coefficient of the first elastic plug.

[0014] Preferably, in the cell drug cryopreservation tube, the sidewall of the first elastic plug is a rough surface, and when the first elastic plug moves along the axial direction of the cryopreservation tube, the rough surface slides and rubs against the inner side of the tube wall of the cryopreservation tube.

[0015] Preferably, in the cell drug cryopreservation tube, a microparticle structure is provided on the inner side of the tube wall, and the microparticle structure cooperates with the rough surface of the first elastic plug to define the position of the first elastic plug.

[0016] Preferably, the cell drug cryopreservation tube further includes an identification code, which is disposed at any position among the occluder, the cryopreservation tube, and the bottom cap, and the identification code is any one or any combination of RFID chip, barcode, QR code, and digital code.

[0017] Preferably, in the cell drug cryopreservation tube, the plugging device includes an adapter, the lower end of which is fixedly connected to the cryopreservation tube, and the upper end of which is provided with a needle connection structure.

[0018] Secondly, the present invention also provides a cell-based pharmaceutical injection needle, the cell-based pharmaceutical injection needle comprising:

[0019] Cellular drug cryopreservation tubes as described above;

[0020] The needle is fixedly connected to the cell drug cryopreservation tube via the needle connection structure on the adapter.

[0021] Thirdly, the present invention also provides a method for manufacturing a cell-based drug cryopreservation tube, the method comprising:

[0022] The cryopreservation tube body is prepared by a two-stage melting process to form at least one strip-shaped groove on the tube wall.

[0023] The first elastic plug is inserted into the body of the cryopreservation tube so that it fits tightly against the tube wall.

[0024] Cell suspension is injected from one end of the cryopreservation tube, and a plug is installed on the cryopreservation tube. The plug, together with the first elastic plug and the tube wall of the cryopreservation tube, forms a closed suspension cavity.

[0025] Diluent is injected from the other end of the cryovial, and a second elastic plug is inserted into the body of the cryovial, ensuring it fits tightly against the wall of the cryovial. A sealed diluent chamber is formed between the first and second elastic plugs.

[0026] Install the bottom cover and piston rod in sequence.

[0027] Fourthly, the present invention also provides a method for manufacturing a cell drug cryopreservation tube, the method comprising:

[0028] The body of the cryopreservation tube is prepared by a melting process to form an annular groove on the tube wall for accommodating the first elastic plug for elastic recovery.

[0029] The first elastic plug is inserted into the body of the cryopreservation tube so that it fits tightly against the tube wall. The first elastic plug has a second fluid channel that runs vertically through the tube. The second fluid channel opens only when the first elastic plug recovers its elasticity.

[0030] Cell suspension is injected from one end of the cryopreservation tube, and a plug is installed on the cryopreservation tube. The plug, together with the first elastic plug and the tube wall of the cryopreservation tube, forms a closed suspension cavity.

[0031] Diluent is injected from the other end of the cryopreservation tube, and a second elastic plug is inserted into the tube body, ensuring it fits tightly against the tube wall. A sealed diluent chamber is formed between the first and second elastic plugs.

[0032] Install the bottom cover and piston rod in sequence.

[0033] Compared with the prior art, the present invention has at least the following beneficial effects:

[0034] The cryovial itself is divided into a diluent chamber and a suspension chamber by the first and second elastic plugs, which perfectly isolates the cell suspension and diluent in a closed chamber. Fluid channels are designed on the wall of the cryovial or the first elastic plug to allow the diluent chamber and the suspension chamber to communicate with each other under specific conditions. Thus, the cell suspension and diluent can be aseptically mixed directly inside the cryovial. Attached Figure Description

[0035] Figure 1 This is a schematic diagram of the structure of the cell drug cryopreservation tube according to Embodiment 1 of the present invention;

[0036] Figure 2 This is a partial structural schematic diagram of the cryopreservation tube according to Embodiment 1 of the present invention;

[0037] Figure 3 for Figure 2 A schematic diagram of a half-section structure;

[0038] Figure 4 This is a schematic diagram of the structure of the cryopreservation tube and piston rod in Embodiment 1 of the present invention;

[0039] Figure 5 for Figure 4 A schematic diagram of a half-section structure;

[0040] Figure 6 This is a schematic diagram of the bottom cover structure according to Embodiment 1 of the present invention;

[0041] Figure 7 This is a partial half-section diagram of the cell drug cryopreservation tube according to Embodiment 1 of the present invention;

[0042] Figure 8 This is a schematic diagram of the annular groove in Embodiment 2 of the present invention.

[0043] Note: 1. Occluder; 11. Occluder head; 12. Adapter; 13. Needle connection structure; 14. Third elastic plug; 2. Cryopreservation tube; 21. Strip groove; 22. Identification code; 23. Suspension chamber; 24. Diluent chamber; 25. Annular groove; 3. Bottom cover; 31. Main body; 32. Seal; 33. Piston rod port; 4. First elastic plug; 51. Second elastic plug; 52. Piston rod. Detailed Implementation

[0044] The present invention will now be described in more detail with reference to the accompanying drawings, which illustrate preferred embodiments of the invention. It should be understood that those skilled in the art can modify the invention described herein while still achieving its advantageous effects. Therefore, the following description should be understood as being of general knowledge to those skilled in the art and is not intended to limit the invention.

[0045] The invention is described more specifically by way of example in the following paragraphs with reference to the accompanying drawings. The advantages and features of the invention will become clearer from the following description and claims. It should be noted that the drawings are in a very simplified form and use non-precise proportions, and are only used to facilitate and clarify the illustration of the embodiments of the invention.

[0046] Example 1

[0047] Please refer to Figure 1 This is a schematic diagram of the structure of the cell drug cryopreservation tube according to Embodiment 1 of the present invention. Figure 1As shown, a cell therapy cryopreservation tube includes: a sealing device 1, a cryopreservation tube 2, a bottom cap 3, a first elastic plug 4, a second elastic plug 51, and a piston rod 52. The cryopreservation tube 2 is a hollow tubular structure with openings at both ends. The sealing device 1 is disposed at the upper end of the cryopreservation tube and is sealed to the cryopreservation tube 2. The bottom cap 3 is disposed at the lower end of the cryopreservation tube 2 for sealing. The first elastic plug 4 and the second elastic plug 51 are both disposed inside the cryopreservation tube 2 and are tightly fitted to the tube wall of the cryopreservation tube 2, and can slide along the tube wall of the cryopreservation tube 2. The first elastic plug 4, the sealing device 1, and the tube wall of the cryopreservation tube 2 together form a closed suspension cavity 23, which is used to store cells. A closed dilution chamber 24 is formed between the first elastic plug 4 and the second elastic plug 51 of the cell suspension. The dilution chamber 24 is used to store the dilution. The piston rod 52 passes through the bottom cover 3 and enters the cryopreservation tube 2, pushing the second elastic plug 51 to move. When an axial force is applied to the piston rod 52, the dilution chamber 24 moves towards the suspension chamber 23 under pressure, and pushes the first elastic plug 4 to move along the axial direction of the cryopreservation tube 2. A first fluid channel is opened on the tube wall of the cryopreservation tube 2 to connect the dilution chamber and the suspension chamber. When the dilution chamber 24 moves to the position of the first fluid channel, the dilution chamber is connected to the suspension chamber through the first fluid channel.

[0048] Specifically, the resuscitation diluent can be pre-filled inside the diluent chamber 24, and the cell suspension can be pre-filled inside the suspension chamber 23. The resuscitation diluent is prepared from one or more reagents such as balanced salt solution (clinical use), sodium lactate or compound sodium chloride solution, sodium bicarbonate or isotonic saline solution, research and production use DPBS (Dubor's phosphate buffer), HBSS (Hankes balanced salt solution), human serum albumin, amino acids, and sugars.

[0049] Specifically, the cryopreservation tube 2 can be designed in different specifications according to the needs of the drug users. Different specifications and volumes can be set according to the actual storage volume of cell drugs, such as 1mL, 2mL, 5mL, 10mL, 25mL, 50mL, 100mL, etc., to cover the cryopreservation needs of cell drugs of various specifications.

[0050] Specifically, the first elastic plug 4 and the second elastic plug 51 maintain a certain distance and are both in a compressed (i.e., elastically deformed) state, tightly fitting against the inner wall of the cryopreservation tube 2, thereby forming a dilution chamber 24 and a suspension chamber 23 respectively within the cryopreservation tube 2. When the second elastic plug 51 is pushed, the dilution chamber 24 moves towards the suspension chamber 23 under pressure, while simultaneously pushing the first elastic plug 4 to move in the same direction, that is, both the suspension chamber 23 and the dilution chamber 24 can move along the axial direction of the cryopreservation tube 2.

[0051] In this embodiment, a first fluid channel is provided on the wall of the cryopreservation tube 2, and the length of the first fluid channel is set according to the thickness of the first elastic plug 4. Typically, the length of the line connecting the start and end points of the first fluid channel is slightly greater than the thickness of the first elastic plug 4. Thus, when the first elastic plug 4 moves to the position of the first fluid channel, the dilution chamber 24 is interconnected with the suspension chamber 23 through the first fluid channel, and the fluid can flow smoothly from the start point to the end point of the first fluid channel without the first elastic plug 4 obstructing the fluid flow.

[0052] In some embodiments, the first fluid channel includes a plurality of strip-shaped grooves 21 formed on the cryopreservation tube 2.

[0053] In this embodiment, the strip groove 21 is a straight strip structure. The length direction of the strip groove 21 is parallel to the axis of the cryopreservation tube 2. The length of the strip groove 21 (i.e., the distance between the starting point and the ending point in the first fluid channel) is slightly greater than the thickness of the first elastic plug 4. The width and depth of the strip groove 21 are set according to actual needs, so as to allow the diluent and cell suspension to pass through smoothly.

[0054] like Figure 3 As shown, when the first elastic plug 4 moves to the position of the first fluid channel (i.e., the strip groove 21), the diluent in the diluent chamber 24, blocked by the first elastic plug 4, can only enter the suspension chamber 23 through the strip groove 21 opened on the inner side of the cryopreservation tube 2. Correspondingly, the cell suspension in the suspension chamber 23, blocked by the first elastic plug 4, can only enter the diluent chamber 24 through the strip groove 21.

[0055] Preferably, a plurality of the strip grooves 21 are evenly arranged on the inner side of the wall of the cryopreservation tube 2, and the opening direction of the plurality of strip grooves 21 is all facing the central axis of the cryopreservation tube 2.

[0056] Preferably, the opening size (i.e., the groove width) of the strip-shaped groove 21 is larger at the top and smaller at the bottom. This ensures that the mixing of the drug solution is relatively slow in the initial stage, meeting the requirements of the dilution process. Figure 1 and Figure 3 As shown, the upper end of the strip-shaped groove 21 is close to the upper end of the cryopreservation tube 2 (i.e., the end relatively far from the bottom cap 3), and the lower end of the strip-shaped groove 21 is close to the lower end of the cryopreservation tube 2 (i.e., the end relatively close to the bottom cap 3). The opening size (i.e., the groove width) of the strip-shaped groove 21 is larger at the top and smaller at the bottom. The groove design of the strip-shaped groove 21, which is larger at the top and smaller at the bottom, can control the initial speed of the diluent flowing into the strip-shaped groove 21, so that the initial mixing rate of the diluent and the cell suspension is not too fast, thus meeting the dilution process requirements.

[0057] In other embodiments, the strip groove 21 can be a spiral, wavy, or other strip structure, or it can be a Z-shaped, X-shaped, mesh, or other structure composed of several straight strip structures extending in different directions. It can also be any combination of straight strip, thread, wavy, Z-shaped, X-shaped, mesh, and other structures.

[0058] In this embodiment, the wall of the cryopreservation tube protrudes beyond the other parts at the location of the strip groove 21, and the wall thickness of the cryopreservation tube at the location of the strip groove 21 is the same as that of the other parts. In other embodiments, the wall of the cryopreservation tube 2 may not protrude beyond the other parts at the location of the strip groove 21, that is, the outer diameter of the cryopreservation tube remains the same, and the wall thickness of the cryopreservation tube 2 at the location of the strip groove 21 is thinner than that of the other parts.

[0059] In some embodiments, the cryovials 2 are made by strictly screening according to the requirements of pharmaceutical packaging materials, taking into account low temperature resistance, stability, safety and biocompatibility. Validated pharmaceutical packaging materials such as EVA ethylene-vinyl acetate copolymer, COP, COC cyclic olefin polymers, etc., can be selected, or glass materials can be selected. These materials enable the cryovials to be used normally at low temperature and room temperature.

[0060] In this embodiment, the cryopreservation tube 2 is made of transparent glass. To ensure the structural integrity of the cryopreservation tube 2 and prevent damage, the depth of the strip groove 21 is required to not exceed 2 / 3 of the wall thickness of the cryopreservation tube 2. Further, the depth of the strip groove 21 does not exceed 1 / 2 of the wall thickness of the cryopreservation tube 2.

[0061] In other embodiments, the cryopreservation tube 2 may be made of transparent plastic or other materials. Compared to cryopreservation tubes made of transparent glass, the depth of the strip groove 21 in a cryopreservation tube 2 made of transparent plastic may be appropriately increased.

[0062] In some embodiments, the sidewall of the first elastic plug 4 is a rough surface. As the first elastic plug 4 moves along the cryopreservation tube 2, its rough surface will rub against the inner side of the tube wall of the cryopreservation tube 2, thereby preventing the first elastic plug 4 from shifting during transportation. This ensures that some cell agents with special requirements cannot be allowed to come into contact with the cell suspension before use.

[0063] like Figure 7 As shown, in some embodiments, the cryopreservation tube 2 is provided with microparticle structures along the moving path of the first elastic plug 4. The semi-circular microparticle structures are integrated with the cryopreservation tube 2 to prevent microparticles from falling off during use, thus affecting practicality and safety. The presence of microparticle structures greatly increases the friction between the cryopreservation tube 2 and the first elastic plug 4.

[0064] Specifically, the combination of microparticle structure and rough surface design increases friction, making the first elastic plug 4 more stable inside the cryopreservation tube 2 and preventing displacement due to external factors. It also avoids leakage of diluent. The combination of rough surface and microparticle structure has a better effect.

[0065] Specifically, the microparticle structure is located on the inner side of the cryopreservation tube 2, excluding the area of ​​the strip groove 21. This ensures that no residue is left when the liquid passes through the first fluid channel, while maintaining a tight seal.

[0066] like Figure 1 As shown, in some embodiments, the piston rod 52 passes through the bottom cover 3 and abuts against the second elastic plug 51. For ease of transportation, the second elastic plug 51 and the piston rod 52 can be easily disassembled and assembled. During transportation, the bottom cover 3 can be installed at the lower end of the cryopreservation tube 2 for sealing. When the medicine inside the cryopreservation tube 2 needs to be used, the bottom cover 3 does not need to be removed. The bottom cover 3 is provided with a piston rod opening 33. The piston rod 52 directly breaks the seal 32 to expose the piston rod opening 33. After the piston rod 52 enters the cryopreservation tube 2, it abuts against the second elastic plug 51. By pushing the piston rod 52, the second elastic plug 51 is pushed, which in turn pushes the entire dilution chamber 24. The dilution chamber 24 pushes the first elastic plug 4, which reaches the first fluid channel 21 and continues to push the second elastic plug 51. The dilution enters the suspension chamber 23 through the first fluid channel 21 and mixes with the cell suspension. When the dilution and cell suspension are completely fused and thoroughly mixed to form a cell drug, the requirements for human injection are met.

[0067] In this embodiment, the cryopreservation tube 2 has an external thread on the outside and an internal thread on the bottom cover 3. The external thread and the internal thread are matched and can be easily tightened by the bottom cover 3 to seal the cryopreservation tube 2 in the dilution chamber 24 direction channel; at the same time, the plug 1 seals the suspension chamber 23 direction channel, thereby completing the sealing of the entire cryopreservation tube.

[0068] In another embodiment, the cryopreservation tube 2 and the bottom cover 3 are snap-fitted together, facilitating the assembly and disassembly of the bottom cover 3 and the cryopreservation tube 2. For example... Figure 6As shown, the bottom cover 3 includes a main body 31, a sealing element 32, and a piston rod opening 33. The main body 31 is connected to the male and female slots of the cryopreservation tube 2 to achieve sealing of the cryopreservation tube 2 in the dilution chamber 24. The sealing element 32 is integrated with the main body 31. The main body 31 has a piston rod through hole 43. The sealing element 32 blocks the piston rod opening 33 to achieve pre-sealing of the piston rod opening 33. When pre-dilution is required, the piston rod 52 passes through and compresses the sealing element 32, causing part of the sealing element 32 to separate from the main body 31 and expose the piston rod opening 33. The piston rod 52 passes through the piston rod opening 33 and abuts against the second elastic plug 51. The sealing element 32 is fixed on the main body 31. The sealing element 32 bends or breaks in a preset direction so that the sealing element 32 will not fall into the cryopreservation tube 2, causing inconvenience in use.

[0069] Specifically, the sealing element 32 is a sealing film or sealing sheet, which can be one or more combinations of PE film, aluminum foil, silicone, rubber, plastic and resin.

[0070] like Figure 1 As shown, in some embodiments, an identification code 22 is also included. The identification code 22 is set at any position in the occluder 1, cryopreservation tube 2, and bottom cover 3. The identification code 22 can be any one of RFID chip, barcode, QR code, digital code or any combination thereof. The identification code 22 can efficiently collect information of each cell drug injection needle, making it convenient for medical staff to use.

[0071] like Figure 3 As shown, in some embodiments, the occluder 1 includes an adapter 12, the lower end of which is fixedly connected to the cryopreservation tube 2. The cryopreservation tube 2 is provided with an inverted ring (not shown in the figure), and the adapter 12 has a groove structure (not shown in the figure) that is adapted to it. The adapter 12 and the cryopreservation tube 2 are fixedly connected by a snap-fit ​​method. The upper end of the adapter 12 is provided with a needle connection structure 13. The size of the needle connection structure 13 is the same as the inner diameter of the upper end of the cryopreservation tube 2. The inner diameter of the cryopreservation tube 2 and the size of the needle connection structure 13 are set to the same specification, which can effectively ensure that the fused cell drug is injected without dead corners, reduce the amount of drug residue, and effectively ensure the convenience of cell suspension injection. When the occluder 1 needs to be sealed, the occluder 1 also includes a sealing head 11 connected to the needle connection structure 13. A third elastic plug 14 is installed on the sealing head 11 to achieve sealing on this side of the occluder 1.

[0072] Specifically, the occluder 1 includes an adapter 12, an occluder head 11, and a third elastic plug 14. The adapter 12 is connected to the cryopreservation tube 2 to enable more conversion possibilities. The adapter 12 can be connected to syringes, injection needles, etc., which allows for more usage methods and makes the injection method not limited to one.

[0073] Specifically, one end of the sealing head 11 is tightly connected to the needle connection structure 13, and the other end of the sealing head 11 is provided with an installation groove. The third elastic plug 14 is installed in the installation groove and fits tightly against the groove wall. The third elastic plug 14 and the sealing head 11 form a sealing cap structure to seal the adapter 12. Furthermore, the cell suspension in the suspension chamber 23 can be directly extracted by piercing the third elastic plug 14 with a needle.

[0074] The adapter 12 and the plugging head 11 can be connected by snap-fit, threaded connection, male and female groove connection or other detachable connection methods. The plugging device 1 can more conveniently meet the requirements of different specifications of injection.

[0075] Specifically, the first elastic plug 4, the second elastic plug 51, and the third elastic plug 14 can all be made of butyl rubber or TPE elastomer rubber. The low temperature resistance of butyl rubber is around -80°C, and the low temperature resistance of TPE elastomer rubber is around -190°C. Both butyl rubber and TPE elastomer rubber can meet the current freezing temperature requirements. When the required freezing temperature is above -80°C, butyl rubber can be selected; when the required freezing temperature is above -190°C, TPE elastomer rubber should be selected.

[0076] In some embodiments, in combination with any of the above implementation methods, the plugging head 11 can be replaced with a needle, and the mixture can be directly injected into the human body after completion.

[0077] Specifically, the method of using the cell drug cryopreservation tube is as follows: First, use the sealing device 1 to seal the cell suspension direction of the cryopreservation tube 2. In this case, use the piston rod 52 to break the seal 32 of the bottom cover 3, so that the piston rod 52 passes through the piston rod opening 33 and abuts against the second elastic plug 51. Continue to push the piston rod 52, driving the diluent chamber 24 to move towards the suspension chamber 23, until the first elastic plug 4 moves to the annular groove 25, so that the diluent enters the suspension chamber 23 and mixes with the cell suspension to form cell drug. After that, replace the sealing head 11 on the adapter 12 with a needle, and continue to push the plunger push rod 5. At this time, the cell suspension is pushed to the needle under the pressure of the diluent chamber 24 for human injection.

[0078] The advantage is that the structure of the cryopreservation tube is newly designed according to the safety and convenience of cell cryopreservation and application. It can simultaneously achieve low-temperature cryopreservation, rapid thawing, and pre-dilution. The operation is simple, time-saving and labor-saving when thawing and processing frozen cells.

[0079] Existing cryovials typically employ a single-chamber design. Because pre-filled diluents are not available, rapid aseptic dilution after cell thawing is impossible. The cells must be transferred to cleanroom conditions for further processing (especially in pharmaceutical manufacturing, where all materials must be sterilized before transfer to cleanrooms to ensure aseptic operation; even with the fastest hydrogen peroxide sterilization method, a single sterilization step takes over 10 minutes). This lengthy and complex sterilization process makes it difficult to control the cytotoxicity of the cryovial solution, severely impacting cell viability and function. Furthermore, the drug solution is inevitably exposed to the environment and air during handling, posing a risk of contamination.

[0080] This embodiment employs a single-tube, dual-chamber design, allowing the two substances (i.e., diluent and cell suspension) to be stored separately in the two sealed chambers of a single cryovial 2. They only need to be transferred to a clean environment when filling the diluent and cell suspension. After filling, the cryovial contains pre-filled diluent, allowing for direct dilution as needed. During the process, the diluent and cell suspension remain in a sealed environment, preventing contact with external air and eliminating the risk of contamination. Therefore, there is no need to transfer them to a clean room or perform sterilization. Using the cell drug cryovial provided in this embodiment effectively improves cell viability and production efficiency. Furthermore, the drug solution is not exposed to the external environment during dilution, ensuring the safety and effectiveness of the cell drug application.

[0081]

Example 2

[0082] Please refer to the reference. Figure 1 and Figure 8 This is a schematic diagram of the structure of the cell drug cryopreservation tube of Embodiment 2 of the present invention. Figure 1 and Figure 8As shown, the cell drug cryopreservation tube includes: a sealing device 1, a cryopreservation tube 2, a bottom cap 3, a first elastic plug 4, a second elastic plug 51, and a piston rod 52. The cryopreservation tube 2 is a hollow tubular structure with openings at both ends. The sealing device 1 is located at the upper end of the cryopreservation tube and is sealed to the cryopreservation tube 2. The bottom cap 3 is located at the lower end of the cryopreservation tube 2 for sealing. The first elastic plug 4 and the second elastic plug 51 are both located inside the cryopreservation tube 2 and are tightly fitted to the tube wall of the cryopreservation tube 2, allowing them to slide along the tube wall. The first elastic plug 4, the sealing device 1, and the tube wall of the cryopreservation tube 2 together form a closed suspension cavity 23, which is used to store the cell suspension. A sealed diluent chamber 24 is formed between the plugs 51, which is used to store the diluent. The piston rod 52 passes through the bottom cover 3 and enters the cryopreservation tube 2, pushing the second elastic plug 51 to move. When an axial force is applied to the piston rod 52, the diluent chamber 24 moves towards the suspension chamber 23 under pressure, and pushes the first elastic plug 4 to move along the axial direction of the cryopreservation tube 2. An annular groove 25 is provided on the tube wall of the cryopreservation tube 2 to accommodate the first elastic plug 4 for elastic recovery. The first elastic plug 4 has a second fluid channel that runs vertically through it. The second fluid channel opens when the first elastic plug 4 recovers its elasticity, and the diluent chamber is connected to the suspension chamber through the second fluid channel.

[0083] Specifically, such as Figure 8 As shown, the cryopreservation tube 2 in this embodiment includes an annular groove 25. The annular groove 25 is located in the middle section of the length direction of the cryopreservation tube 2. The specific position can be set according to the configuration ratio of cell suspension and diluent (i.e., the size ratio of cell suspension chamber 23 and diluent chamber 24). The groove width of the annular groove 25 is adapted to the thickness of the first elastic plug 4. The depth of the annular groove 25 is set according to the linear expansion coefficient of the first elastic plug 4. The first elastic plug 4 is compressed into the interior of the cryopreservation tube 2. Its sidewall contacts the inner wall of the cryopreservation tube 2 and is squeezed. The piston rod 52 pushes the diluent chamber 24 and drives the first elastic plug 4 to move towards the annular groove 25. When the first elastic plug 4 reaches the annular groove 25, it can be embedded in the annular groove 25 and achieve elastic recovery. After the first elastic plug 4 recovers its elasticity, its sidewall is still in contact with the inner wall of the cryopreservation tube 2.

[0084] In this embodiment, the formula for calculating the depth of the annular groove 25 is:

[0085] h=(D×K×|T1-T2|)÷2

[0086] Where h is the depth of the annular groove 25, K is the linear expansion coefficient of the first elastic plug 4, D is the outer diameter of the first elastic plug 4 in the free state (at this time, the ambient temperature is the temperature of the first elastic plug 4 during the pre-dilution operation), T1 is the temperature of the first elastic plug 4 during cryopreservation, and T2 is the temperature of the first elastic plug 4 during the pre-dilution operation.

[0087] In other embodiments, the depth of the annular groove 25 can be finely adjusted according to the actual use of the cell drug cryopreservation container.

[0088] In this embodiment, the first elastic plug 4 has at least one second fluid channel. When the first elastic plug 4 is initially prefabricated inside the cryopreservation tube 2, it is in a state of extreme compression. Under these conditions, the second fluid channel is closed due to compression. When the first elastic plug 4 is embedded in the annular groove 25, it deforms and recovers according to its own elasticity. The second fluid channel returns to its original through-hole shape, allowing the diluent to pass through. The diluent in the diluent chamber 24 can enter the suspension chamber 23 through the second fluid channel to mix with the cell suspension.

[0089] Preferably, there are multiple second fluid channels, and the multiple second fluid channels are arranged in an array.

[0090] In this embodiment, the second fluid channel is closed when the first elastic plug 4 is in a compressed state and opens after the first elastic plug 4 recovers its elasticity. Specifically, the first elastic plug 4 is in a compressed state before moving to the annular groove 25, therefore the second fluid channel is also in a closed state, and the suspension chamber 23 and the diluent chamber 24 are not in communication. When the first elastic plug 4 moves to the annular groove 25, it recovers its elasticity, therefore the second fluid channel is in an open state, and the suspension chamber 23 and the diluent chamber 24 are only in communication with each other through the second fluid channel. The diluent in the diluent chamber 24 can only be mixed with the cell suspension in the suspension chamber 23 through the second fluid channel.

[0091] The difference between this embodiment and Embodiment 1 is that the fluid channel is located in the first elastic plug 4, rather than on the wall of the cryopreservation tube 2. The wall of the cryopreservation tube 2 is provided with an annular groove 25 to accommodate the elastic recovery of the first elastic plug 4. When the first elastic plug 4 moves to the annular groove 25, it recovers its elasticity, and the dilution chamber 24 and the suspension chamber 23 can communicate with each other.

[0092]

Example 3

[0093] Please continue to refer to this. Figures 1 to 5This embodiment also provides a method for manufacturing a cell drug cryopreservation tube, the method comprising:

[0094] The body of the cryopreservation tube 2 is prepared by a two-stage melting process to form at least one strip-shaped groove 21 on the tube wall of the cryopreservation tube 2;

[0095] The first elastic plug 4 is inserted into the body of the cryopreservation tube 2 so that it fits tightly against the wall of the cryopreservation tube 2.

[0096] Cell suspension is injected from one end of the cryopreservation tube 2, and the plug 1 is installed on the cryopreservation tube 2. The plug 1, the first elastic plug 4, and the tube wall of the cryopreservation tube 2 together form a closed suspension cavity 23.

[0097] Diluent is injected from the other end of cryopreservation tube 2, and a second elastic plug 51 is inserted into the tube body of cryopreservation tube 2, making it tightly fit against the tube wall of cryopreservation tube 2, forming a sealed diluent chamber 24 between the second elastic plugs 51; and

[0098] Install the bottom cover 3 and piston rod 52 in sequence.

[0099] Specifically, due to the complex structure of cryopreservation tubes, especially the small size of the strip groove 21 and the high manufacturing precision, it is not easy to demold and drop the cryopreservation tubes directly by opening the mold. Therefore, this embodiment adopts a two-stage melting process, that is, the cryopreservation tube is divided into two parts and manufactured separately, and then the two parts are melted together to form a complete cryopreservation tube, thereby greatly reducing the manufacturing difficulty of cryopreservation tubes.

[0100] Before injecting the cell suspension and diluent, cryovial 2 is typically assembled with other components and placed in a vacuum sterile bag. In this embodiment, each cryovial 2 is double-layered sealed sterile packaging according to pharmaceutical excipient requirements, ensuring safety and reliability and guaranteeing sterility during transportation and use.

[0101] The first elastic plug 4 is disposed in the cryopreservation tube 2 to separate the diluent chamber 24 and the suspension chamber 23. The plug 1 and the bottom cover 3 are respectively installed at both ends of the cryopreservation tube 2. Since the second elastic plug 51 is detachably connected to the piston rod 52, the second elastic plug 51 can also be pre-placed in the cryopreservation tube 2, and the second elastic plug 51 can be pulled out by the piston rod 52 before the diluent is injected.

[0102] It should be noted that there is no restriction on the order of injection of cell suspension and diluent. The cell suspension can be injected and sealed before or after the diluent.

[0103]

Example 4

[0104] Please continue to refer to this. Figure 1 and Figure 8 This embodiment also provides a method for manufacturing a cell drug cryopreservation tube, the method comprising:

[0105] The body of the cryopreservation tube 2 is prepared by a melting process to form an annular groove 25 on the tube wall of the cryopreservation tube 2 for accommodating the first elastic plug 4 for elastic recovery.

[0106] The first elastic plug 4 is inserted into the body of the cryopreservation tube 2 so that it fits tightly against the tube wall of the cryopreservation tube 2. The first elastic plug 4 has a second fluid channel that runs vertically through the tube. The second fluid channel only opens when the first elastic plug 4 recovers its elasticity.

[0107] Cell suspension is injected from one end of the cryopreservation tube 2, and the plug 1 is installed on the cryopreservation tube 2. The plug 1, together with the first elastic plug 4 and the tube wall of the cryopreservation tube 2, forms a closed suspension cavity 23.

[0108] Diluent is injected from the other end of the cryopreservation tube 2, and a second elastic plug 51 is inserted into the tube body of the cryopreservation tube 2, making it tightly fit against the tube wall of the cryopreservation tube 2. A sealed diluent chamber 24 is formed between the first elastic plug 4 and the second elastic plug 51; and

[0109] Install the bottom cover 3 and piston rod 52 in sequence.

[0110] The difference between this embodiment and Embodiment 3 is that, when preparing the cryopreservation tube 2, an annular groove 25 needs to be formed on the tube wall of the cryopreservation tube 2. The manufacturing precision of the annular groove 25 is relatively low, not as high as that of the strip groove 21, and the preparation of the cryopreservation tube can be completed by a two-stage melting process.

[0111] In summary, the cell drug cryovials, their manufacturing method, and the cell drug injection needle provided in this invention employ a single-tube, double-lumen design, allowing for direct preparation of cell drugs within the cryovial without the need for pipettes or specific aseptic conditions. This design is simple to operate, time-efficient, and effectively avoids leakage and contamination risks. Furthermore, after preparation, the sealing head can be replaced with a needle for injection, eliminating the need to transfer the cell drug to an injection device before use. This simple, time-efficient, and safety-free operation further enhances the benefits.

[0112] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A cell pharmaceutical cryo tube, characterized in that, The application relates to a cryopreservation device. The device comprises a stopper (1), a cryopreservation tube (2), a bottom cover (3), a first elastic plug body (4), a second elastic plug body (51) and a piston rod (52). The cryopreservation tube (2) is a tubular structure with hollow interiors at both ends, the stopper (1) is arranged at the upper end of the cryopreservation tube (2) and is in sealed connection with the cryopreservation tube (2), and the bottom cover (3) is arranged at the lower end of the cryopreservation tube (2) for sealing. The first elastic plug body (4) and the second elastic plug body (51) are arranged in the cryopreservation tube (2) and are tightly attached to the tube wall of the cryopreservation tube (2), can slide along the tube wall of the cryopreservation tube (2), the first elastic plug body (4) and the tube wall of the cryopreservation tube (2) and the stopper (1) jointly form a closed suspension cavity (23), the suspension cavity (23) is used for storing cell suspension, a closed diluent cavity (24) is formed between the first elastic plug body (4) and the second elastic plug body (51), and the diluent cavity (24) is used for storing diluent. One end of the piston rod (52) penetrates through the bottom cover (3) into the cryopreservation tube (2) and pushes the second elastic plug body (51) to move, when an axial force is applied to the piston rod (52), the diluent cavity (24) moves to the direction of the suspension cavity (23) under the action of pressure and pushes the first elastic plug body (4) to move along the axial direction of the cryopreservation tube (2). A first fluid channel is arranged on the tube wall of the cryopreservation tube (2) and is used for connecting the suspension cavity (23) and the diluent cavity (24), when the first elastic plug body (4) moves to the position of the first fluid channel, the diluent cavity (24) is in communication with the suspension cavity (23) through the first fluid channel, the first fluid channel comprises a plurality of strip-shaped grooves (21) arranged on the cryopreservation tube (2), the groove width of the strip-shaped grooves (21) is large at the upper end and small at the lower end, or a ring-shaped groove (25) is arranged on the tube wall of the cryopreservation tube (2) and is used for accommodating the first elastic plug body (4) to recover elasticity, the first elastic plug body (4) has a second fluid channel penetrating through the upper and lower ends, the second fluid channel is opened when the first elastic plug body (4) recovers elasticity, and the diluent cavity (24) is in communication with the suspension cavity (23) through the second fluid channel; the groove width of the ring-shaped groove (25) is matched with the thickness of the first elastic plug body (4), and the depth range of the ring-shaped groove (25) is set according to the linear expansion coefficient of the first elastic plug body (4), the temperature during cryopreservation and the temperature during dilution.

2. The cell pharmaceutical cryovial of claim 1, wherein, The length of the line connecting the starting point and the ending point of the first fluid channel is slightly larger than the thickness of the first elastic plug body (4).

3. The cell pharmaceutical cryovial of claim 1, wherein, The side wall of the first elastic plug body (4) is a rough surface, and the rough surface slides and rubs the inner side of the tube wall of the cryopreservation tube (2) when the first elastic plug body (4) moves along the axial direction of the cryopreservation tube (2). The inner side of the tube wall of the cryogenic tube (2) is provided with a microstructure which cooperates with the rough surface of the first elastic plug body (4) to define the position of the first elastic plug body (4).

4. The cell pharmaceutical cryovial of claim 1, wherein, Also included are: An identification code (22) is arranged in any position of the stopper (1), the cryogenic tube (2), and the bottom cover (3), and the identification code (22) is any one or any combination of an RFID chip, a bar code, a two-dimensional code, and a digital code.

5. The cell pharmaceutical cryovial of claim 1, wherein, The stopper (1) comprises an adapter (12), the lower end of the adapter (12) is fixedly connected with the cryogenic tube (2), and the upper end of the adapter (12) is provided with a needle connection structure (13).

6. A cell-pharmaceutical injection needle, characterized in that Included are: The cell pharmaceutical cryogenic tube according to any one of claims 1 to 5; A needle (6) is fixedly connected with the cell pharmaceutical cryogenic tube through the needle connection structure (13) on the adapter (12).

7. A method for manufacturing a cell pharmaceutical cryo tube, characterized by, For preparing the cell pharmaceutical cryogenic tube according to any one of claims 1 to 5; The manufacturing method comprises the following steps: The tube body of the cryogenic tube (2) is prepared by a twice-melting process to form at least one strip-shaped groove (21) on the tube wall of the cryogenic tube (2); The first elastic plug body (4) is inserted into the tube body of the cryogenic tube (2) to tightly fit with the tube wall of the cryogenic tube (2); Cell suspension is injected from one end of the cryogenic tube (2), and the stopper (1) is installed on the cryogenic tube (2), the stopper (1), the first elastic plug body (4), and the tube wall of the cryogenic tube (2) together form a closed suspension cavity (23); Diluent is injected from the other end of the cryogenic tube (2), and the second elastic plug body (51) is inserted into the tube body of the cryogenic tube (2) to tightly fit with the tube wall of the cryogenic tube (2), a closed diluent cavity (24) is formed between the first elastic plug body (4) and the second elastic plug body (51); and The bottom cover (3) and the piston rod (52) are sequentially installed.

8. A method for manufacturing a cell pharmaceutical cryo tube, characterized by, For preparing the cell pharmaceutical cryogenic tube according to any one of claims 1 to 5; The manufacturing method comprises the following steps: The tube body of the cryogenic tube (2) is prepared by a melting process to form an annular groove (25) on the tube wall of the cryogenic tube (2) for accommodating the first elastic plug body (4) to recover elasticity; The first elastic plug body (4) is inserted into the tube body of the cryogenic tube (2) to tightly fit with the tube wall of the cryogenic tube (2), the first elastic plug body (4) has a second fluid passage which penetrates through the upper and lower parts and is only opened when the first elastic plug body (4) recovers elasticity; Cell suspension is injected from one end of the cryogenic tube (2), and the stopper (1) is installed on the cryogenic tube (2), the stopper (1), the first elastic plug body (4), and the tube wall of the cryogenic tube (2) together form a closed suspension cavity (23); A diluent is injected from the other end of the cryopreservation tube (2), and a second elastic plug (51) is inserted into the tube body of the cryopreservation tube (2) to tightly adhere to the tube wall of the cryopreservation tube (2), so that a closed diluent cavity (24) is formed between the first elastic plug (4) and the second elastic plug (51); and The bottom cover (3) and the piston rod (52) are sequentially installed.

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