Freeze-drying method, freeze-drying preparation and injection for pharmaceutical, cosmetic or medical beauty products

Abstract

The invention discloses a freeze-drying method of a product for pharmaceutical, cosmetic or medical beauty application, which comprises the following steps of: adding a middle plug into a double-cavity clamping type bottle, filling a product to be freeze-dried, and placing and fixing the double-cavity clamping type bottle on a freeze-drying bracket; the top plug is limited on a bottle opening of the double-cavity clamping bottle; performing freezing, primary drying and secondary drying on the to-be-freeze-dried product respectively; and the top plug is fixed by the top cover and the bottle opening is sealed. According to the freeze-drying method, high-quality freeze-drying parameters and freeze-drying operation can be provided, the top plug and the top cover are used for completing integrated plug pressing and cover sealing of the double-cavity clamping type bottle, the obtained freeze-dried product keeps higher quality, the using effect of the freeze-dried product is improved, and the storage time of the freeze-dried product is prolonged.

Description

Technical Field

[0001] The present application relates to the field of biopharmaceuticals, cosmetics or medical aesthetics, and more specifically, to a freeze-drying method, freeze-dried preparation and injection for pharmaceutical, cosmetic or medical aesthetics products. Background Art

[0002] At present, most of the freeze-dried products on the market use vials as storage containers. Before injection, it is necessary to use a sterile syringe to extract the resolvent from another container containing the resolvent, and then inject the resolvent into the drug container for reconstitution, extraction and administration. The administration accuracy and use compliance are relatively poor, and the double-chamber cartridge packaging material can provide a better choice. The double-chamber cartridge is divided into two chambers by a middle stopper, in which the front chamber is used to hold the freeze-dried drug and the rear chamber is used to hold the resolvent. When in use, the resolvent can be pushed into the front chamber through the bypass by pushing the bottom stopper to reconstitute the freeze-dried drug. After reconstitution, continue to push the bottom stopper to the top to complete the injection process.

[0003] Double-chamber cartridges are used to store freeze-dried products and reconstitution solutions separately. Medical staff can easily reconstitute and administer freeze-dried drugs, and patients can also self-administer drugs, simplifying the operating procedures. For active ingredients in sensitive biomacromolecule drugs, medical device reagents, and cosmetic reagents, double-chamber cartridges can mix or reconstitute the two contents just before administration, helping to maintain the shelf life stability of the active ingredients and reduce degradation or inactivation caused by long-term contact.

[0004] However, conventional freeze-drying processes cannot complete the integrated operation of freeze-drying the freeze-dried liquid and sealing the double-chamber cartridge in the freeze dryer. Therefore, it is necessary to design a freeze-drying method that integrates plugging, freeze-drying and capping to ensure good airtightness of the double-chamber cartridge during the freeze-drying process, so that the freeze-dried product has a good shape and a lower water content.

[0005] Therefore, a new drug freeze-drying method that can solve the above problems is urgently needed to improve the freeze-drying efficiency and quality of drugs, fill the current gap in the field of double-chamber cartridge bottle packaging materials in China, and enhance the core competitiveness of products. Summary of the invention

[0006] The present application aims to provide a solution that can overcome at least one of the above-mentioned defects of the prior art.

[0007] According to one aspect of the present application, there is provided a freeze-drying method for a product for pharmaceutical, cosmetic or medical beauty applications, comprising:

[0008] Add a middle stopper to the double-chamber cartridge bottle, and then fill it with the product to be freeze-dried; assemble the top stopper and the top cover, place them above the bottle mouth of the double-chamber cartridge bottle, and place and fix the double-chamber cartridge bottle on a customized freeze-drying rack; freeze, dry once, and dry twice the product to be freeze-dried respectively; use the top cover to press the top stopper to fit the double-chamber cartridge bottle, so as to seal the double-chamber cartridge bottle and fix the top stopper, and make the top stopper seal the bottle mouth and bottleneck of the double-chamber cartridge bottle.

[0009] The freeze-drying method proposed in the present application simultaneously performs stoppering and capping of the double-chamber cartridge vial after freeze-drying by operating the top cover, thereby sealing the finished freeze-dried preparation in the double-chamber cartridge vial and further sealing the double-chamber cartridge vial. The freeze-dried preparation obtained by the freeze-drying method also has a good frozen powder appearance and low water content, which helps to meet the high-demand freeze-dried product standards and ensure that the preparation product maintains stable quality attributes for a long time.

[0010] In some embodiments of the present application, the freeze-drying rack is a stand-alone freeze-drying rack or a tray-type freeze-drying rack, preferably, the freeze-drying rack is a tray-type freeze-drying rack; and the double-chamber cartridge bottle is placed upright or inverted in the freeze-drying rack, preferably, the double-chamber cartridge bottle is placed upright in the freeze-drying rack.

[0011] In some embodiments of the present application, the temperature range set for freezing the product in the double-chamber cartridge is -60°C to -40°C; the temperature range of the primary drying is -60°C to 0°C, and the temperature range of the secondary drying is 15°C to 40°C; and the pressure range of the primary drying and the secondary drying is 0.02mbar-0.2mbar, preferably, the pressure of the primary drying and the secondary drying is 0.06mbar, respectively.

[0012] In some embodiments of the present application, using the top cover to press the top plug to engage with the double-chamber cartridge vial further comprises: filling the double-chamber cartridge vial with nitrogen before pressing the top plug to maintain a low moisture content in the freeze-dried product.

[0013] In some embodiments of the present application, a lyophilized preparation is also provided, which is prepared according to any of the above lyophilization methods. The lyophilized preparation also has the characteristics of high lyophilization quality and low moisture. For example, when the lyophilized preparation is a medicine, it can be used in various application scenarios such as injection, oral administration, biological experiments, etc., to provide better effects; for another example, when the lyophilized preparation is a reagent or cosmetic for medical beauty, its active ingredients can be retained for a long time, and can also provide users with better effects through rapid reconstitution injection or external use.

[0014] In some embodiments of the present application, an injection is also provided, which may include: a double-chamber cartridge bottle packaging material for injection, a lyophilized preparation, and a resolvent. The injection provided in the present application may include a solution type, an emulsion type, a suspension type, etc., and can be used in a variety of application scenarios such as drug treatment, emergency treatment of critically ill patients, epidemic prevention, and traditional Chinese medicine health care to help improve the health level of the population.

[0015] In some embodiments of the present application, a packaging material for a double-chamber cartridge bottle for injection may include: a double-chamber cartridge bottle and a bottle cap assembly, wherein the double-chamber cartridge bottle is used to hold a drug and a reconstitution solvent; the bottle cap assembly includes a top plug and a top cover; the top plug seals the bottle mouth of the double-chamber cartridge bottle; the top cover is used to press and fix the top plug so that the top plug seals the bottle mouth of the double-chamber cartridge bottle; and a sealed double-chamber cartridge bottle; wherein the process of pressing and fixing the top plug on the top cover so that the top plug seals the bottle mouth of the double-chamber cartridge bottle includes the following steps:

[0016] Pre-assemble the top plug into the top cover; place the top cover equipped with the top plug above the mouth of the double-chamber cartridge bottle, and press the top cover downward. After the top plug is pre-assembled into the top cover, the top plug and the top cover are also integrally formed, and there is no need to introduce a plugging assembly. The top cover can directly achieve plugging and capping by pressing the top plug, so as to improve the sealing efficiency of the double-chamber cartridge bottle in the freeze-drying process and avoid the number of operation failures caused by more operation steps. When the failed operation is difficult to remedy in the conventional way in the freeze-drying process, the self-plugging and capping integrated operation of the top cover is particularly important to ensure the efficiency of the freeze-drying process.

[0017] In some embodiments of the present application, a double-chamber cartridge bottle may include: an inner cavity, a bottle body, a bottleneck and a bottle mouth, wherein a bottle mouth opening connected to the inner cavity is arranged at the center of the bottle mouth, and the inner diameter of the bottle mouth opening is smaller than the inner diameters of the bottle mouth and the bottleneck; and a bypass protrusion is provided on one side outer wall of the bottle body.

[0018] In some embodiments of the present application, the lyophilized preparation is a lyophilized preparation prepared according to any of the above-mentioned lyophilization methods or a lyophilized preparation provided by the present application.

[0019] According to another aspect of the present application, another freeze-drying method for a product for pharmaceutical, cosmetic or medical beauty application is provided, comprising:

[0020] Add a middle stopper to the double-chamber cartridge bottle, and then fill it with the product to be freeze-dried; assemble the top stopper and the top cover, place them above the bottle mouth of the double-chamber cartridge bottle, and place and fix the double-chamber cartridge bottle on a customized freeze-drying rack; freeze, dry once, and dry twice the product to be freeze-dried respectively; use the top cover to press the top stopper to fit the double-chamber cartridge bottle, so as to seal the double-chamber cartridge bottle and fix the top stopper, and make the top stopper seal the bottle mouth of the double-chamber cartridge bottle.

[0021] In some embodiments of the present application, the freeze-drying rack is a stand-alone freeze-drying rack or a tray-type freeze-drying rack, preferably, the freeze-drying rack is a tray-type freeze-drying rack; and the double-chamber cartridge bottle is placed upright or inverted in the freeze-drying rack, preferably, the double-chamber cartridge bottle is placed upright in the freeze-drying rack.

[0022] In some embodiments of the present application, the temperature range set for freezing the product in the double-chamber cartridge is -60°C to -40°C; the temperature range of the primary drying is -60°C to 0°C, and the temperature range of the secondary drying is 15°C to 40°C; and the pressure range of the primary drying and the secondary drying is 0.02mbar-0.2mbar, preferably, the pressure of the primary drying and the secondary drying is 0.06mbar, respectively.

[0023] In some embodiments of the present application, using the top cover to press the top plug to engage with the double-chamber cartridge vial further comprises: filling the double-chamber cartridge vial with nitrogen before pressing the top plug to maintain a low moisture content in the freeze-dried product.

[0024] In some embodiments of the present application, another lyophilized preparation is also included, which is prepared according to any of the above-mentioned another lyophilization methods.

[0025] In some embodiments of the present application, an injection is also included, comprising: a double-chamber cartridge bottle packaging material for injection, a lyophilized preparation, and a reconstitution solvent.

[0026] In some embodiments of the present application, a double-chamber cartridge bottle packaging material for injection includes: a double-chamber cartridge bottle and a bottle cap assembly, wherein the double-chamber cartridge bottle is used to contain a lyophilized preparation and a reconstitution solvent; the bottle cap assembly includes a top plug and a top cover; the top plug seals the bottle mouth of the double-chamber cartridge bottle; the top cover is used to press and fix the top plug so that the top plug seals the bottle mouth of the double-chamber cartridge bottle; and the double-chamber cartridge bottle is sealed;

[0027] The process of pressing and fixing the top plug on the top cover so that the top plug seals the bottle mouth of the double-chamber cartridge bottle includes the following steps: pre-assembling the top plug into the top cover; placing the top cover equipped with the top plug above the bottle mouth of the double-chamber cartridge bottle, and pressing the top cover downward.

[0028] In some embodiments of the present application, a double-chamber cartridge bottle comprises: an inner cavity, a bottle body, a bottleneck and a bottle mouth, wherein a bottle mouth opening connected to the inner cavity is provided at the center of the bottle mouth, and the inner diameter of the bottle mouth opening is smaller than the inner diameters of the bottle mouth and the bottleneck; and a bypass protrusion is provided on one side outer wall of the bottle body.

[0029] In some embodiments of the present application, the lyophilized preparation is a lyophilized preparation prepared according to any one of the above-mentioned another lyophilization methods or another lyophilized preparation provided by the present application.

[0030] Compared with the prior art, the present invention has at least one of the following technical effects:

[0031] 1. The present application provides an integrated sealing method for plugging and capping a double-chamber cartridge vial packaging material for injection during a freeze-drying process.

[0032] 2. The present application provides the optimal freeze-drying parameters and dehydration operation of the freeze-drying process, so that the freeze-dried product obtained by the freeze-drying method of the present application can maintain better quality and be convenient for storage or use.

[0033] 3. The present application provides a high-quality freeze-dried preparation prepared based on a freeze-drying method, which can be a high-purity freeze-dried drug, a medical device reagent, or a cosmetic reagent.

[0034] 4. The present application provides an injection that can contain a lyophilized preparation and a resolvent and stably store them based on a double-chamber cartridge bottle packaging material for injection. When the injection is used, the lyophilized preparation and the resolvent can be quickly mixed and reconstituted to ensure efficient and convenient use of the preparation. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] By describing the embodiments of the present application in more detail in conjunction with the accompanying drawings, the above and other purposes, features and advantages of the present application will become more apparent. The accompanying drawings are used to provide a further understanding of the embodiments of the present application and constitute a part of the specification. Together with the embodiments of the present application, they are used to explain the present application and do not constitute a limitation of the present application. In the accompanying drawings, the same reference numerals generally represent the same components or steps.

[0036] Figure 1 The figure shows a schematic diagram of the freeze-dried scaffold of the present application.

[0037] Figure 2 The figure shows a schematic diagram of the freeze-drying curve of the freeze-dried preparation of the present application.

[0038] Figure 3 The figure shows a schematic diagram of the appearance of the freeze-dried preparation of the present application.

[0039] Figure 4 The figure shows a schematic diagram of the appearance of another freeze-dried preparation of the present application.

[0040] Figure 5 The figure shows a schematic structural diagram of a double-chamber cartridge bottle 1 and a top plug 2 of the present application.

[0041] Fig. 6A The figure shows a schematic structural diagram of the top cover 3 of the present application.

[0042] Figure 6B Another structural schematic diagram of the top cover 3 of the present application is shown in the figure.

[0043] Figure 7 The figure shows another structure of the top plug 2 and yet another structural schematic diagram of the top cover 3 of the present application.

[0044] Fig. 8A The figure shows a schematic structural diagram of the top plug positioning point 303 of the present application.

[0045] Figure 8B Another structural schematic diagram of the top plug positioning point 303 of the present application is shown.

[0046] Fig. 9 The figure shows a schematic structural diagram of the upper end 30 of the present application.

[0047] Fig.10 The figure shows a schematic structural diagram of the maximum length of the protrusion 304 of the present application.

[0048] Fig.11 The figure shows a schematic structural diagram of the upper and lower cut corners of the raised portion 304 of the present application.

[0049] Fig.12 The figure shows a schematic structural diagram of the double-chamber cartridge bottle packaging material assembly of the present application.

[0050] Fig.13 The figure shows a schematic structural diagram of a double-chamber cartridge bottle 1' and a top plug 2' of the present application.

[0051] Fig.14A The figure shows a schematic structural diagram of the top cover 3' of the present application.

[0052] Fig. 14B The figure shows another structural schematic diagram of the top cover 3' of the present application.

[0053] Fig.15 The figure shows another structure of the top plug 2' and yet another structure schematic diagram of the top cover 3' of the present application.

[0054] Fig.16A The figure shows a schematic structural diagram of the top plug positioning point 303' of the present application.

[0055] Fig. 16B Another structural schematic diagram of the top plug positioning point 303 ′ of the present application is shown.

[0056] Fig.17 The figure shows a schematic structural diagram of the upper end 30 ′ of the present application.

[0057] Fig.18 The figure shows a schematic structural diagram of the maximum length, upper cutting angle and lower cutting angle of the protrusion 304 ′ of the present application.

[0058] Fig.19 The figure shows a schematic structural diagram of the double-chamber cartridge bottle packaging material assembly of the present application.

[0059] Description of Reference Numerals

[0060] 1-Dual chamber cartridge 2-Top stopper 3-Top cover 4-Sheath

[0061] 1'-Dual chamber cartridge 2'-Top stopper 3'-Top cover 4'-Sheath

[0062] 10-bottle mouth 11-neck 12-bottle body 13-inner cavity

[0063] 10'-bottle mouth 11'-neck 12'-bottle body 13'-inner cavity

[0064] 20-plug cap 21-plug rod 22-sealing part 20'-plug cap

[0065] 21'- plug 22'- sealing part 30- upper end 31- middle end

[0066] 32-lower end 30'-upper end 31'-chassis 40'-sheath body

[0067] 41'-flange 100-bottle opening 120-bypass protrusion 100'-bottle opening

[0068] 120- bypass protrusion 200- gap 200'- gap 300- top plate

[0069] 301-thread 302-opening 303-top plug positioning point 304-protrusion

[0070] 310- convex ring 320- convex strip 321- first convex opening 300'- top plate

[0071] 301'-thread 302'-opening 303'-top plug positioning point 304'-protrusion

[0072] 321'- first protrusion 400'- second protrusion DETAILED DESCRIPTION

[0073] As described above, the present application proposes a freeze-drying method for products for pharmaceutical, cosmetic or medical beauty applications, which includes: adding a middle stopper to a double-chamber cartridge bottle 1, and then filling the product to be freeze-dried; assembling the top stopper 2 and the top cover 3, placing them above the bottle mouth 10 of the double-chamber cartridge bottle 1, and placing and fixing the double-chamber cartridge bottle 1 on a customized freeze-drying rack; freezing, primary drying and secondary drying the product to be freeze-dried respectively; using the top cover 3 to press the top stopper 2 and the double-chamber cartridge bottle 1 to fit together, so as to seal the double-chamber cartridge bottle 1 and fix the top stopper 2, and make the top stopper 2 seal the bottle mouth 10 of the double-chamber cartridge bottle 1.

[0074] In the present application, the middle plug added to the double-chamber cartridge 1 and the product to be freeze-dried can be any middle plug for double-chamber cartridges and freeze-dried products that are suitable for the size and structure of the double-chamber cartridge 1. The freezing, primary drying and secondary drying operations can be performed in a freeze dryer, and the freeze dryer can accommodate a freeze drying rack used in the freeze drying method; in the process of fixing the top plug 2 with the top cover 3 and sealing the bottle mouth 10 of the double-chamber cartridge 1 through the top plug 2, the method of driving the top cover 3 to press down can also be any driving method that can be implemented in the freeze dryer, such as mechanical compression, pneumatic drive, pneumatic clamp drive or spring pressing.

[0075] In the present application, after adding the middle stopper to the double-chamber cartridge 1, the product to be freeze-dried can be filled in. In particular, the product to be freeze-dried can be a product added to the inner cavity 13 of the double-chamber cartridge 1 for freeze-drying and short-term / long-term storage, such as small molecule drugs, peptides, enzymes, antibodies, fusion proteins, antibody-drug conjugates, etc. The user can select any liquid to be freeze-dried and fill it into one of the inner cavities 13 of the double-chamber cartridge 1 to perform freeze-drying using the freeze-drying method of the present application.

[0076] In the present application, the freeze-drying rack is an independent freeze-drying rack or a tray-type freeze-drying rack. The freeze-drying rack used in the freeze-drying method of the present application is an independent freeze-drying rack or a tray-type freeze-drying rack, and the specific model, size and working parameters of the freeze-drying rack in the freeze dryer are not limited. Preferably, the freeze-drying rack is a tray-type freeze-drying rack, which is easy to place a larger number of double-chamber cartridge bottles 1.

[0077] In particular, the double-chamber cartridge bottle 1 is placed upright or inverted in the freeze-drying rack. Preferably, the double-chamber cartridge bottle 1 is placed upright in the freeze-drying rack to facilitate uniform distribution of heat in the double-chamber cartridge bottle 1 and improve solvent sublimation efficiency. In addition, it can also reduce the degree of sedimentation and aggregation of the product and maintain a uniform and stable appearance of the product.

[0078] In the present application, the temperature range set for freezing the product in the double-chamber cartridge bottle 1 can be a temperature range suitable for freeze-drying the product, and when the freezing temperature is between -60°C and -40°C, the freeze-dried raw material generally has a higher freezing efficiency and maintains its own quality. Therefore, the freezing temperature is any temperature value between -60°C and -40°C. Specifically, the temperature range set for freezing the product in the double-chamber cartridge bottle 1 is -60°C to -40°C, that is, -60°C, -59°C, -58°C, -57°C, -56°C, -55°C, -54°C, -53°C, -52°C, -51°C, -50°C, -49°C, -48°C, -47°C, -46°C, -45°C, -44°C, -43°C, -42°C, -41°C or -40°C; The temperature range of the secondary drying is -60℃~0℃, i.e. -60℃, -59℃, -58℃, -57℃, -56℃, -55℃, -54℃, -53℃, -52℃, -51℃, -50℃, -49℃, -48℃, -47℃, -46℃, -45℃, -44℃, -43℃, -42℃, -41℃, -40℃, -39℃, -38℃, -37℃, -36℃, -3 5℃,-34℃,-33℃,-32℃,-31℃,-30℃,-29℃,-28℃,-27℃,-26℃,-25℃,-24℃,-23℃,-22℃,-21℃,-20℃,-19℃,-18℃,-17℃,-16℃,-15℃,-14℃,-13℃,-12℃,-11℃,-10℃,-9℃,-8℃,-7℃,-6℃,- The temperature range of secondary drying is 15℃~40℃, that is, 15℃, 16℃, 17℃, 18℃, 19℃, 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, 26℃, 27℃, 28℃, 29℃, 30℃, 31℃, 32℃, 33℃, 34℃, 35℃, 36℃, 37℃, 38℃, 39℃ or 40℃.

[0081] Similarly, the temperature of the primary drying and secondary drying of the product can be any temperature value between -60℃ and 0℃ and 15℃ and 40℃, respectively, to increase the sublimation rate of the water content of the drug. In addition, the pressure range of the primary drying and secondary drying can be any value between 0.02mbar and 0.2mbar. When the pressure of the primary drying and secondary drying is preferably 0.06mbar, the drying efficiency can be guaranteed to reach the peak value. Specifically, the pressure range of the primary drying and the secondary drying is 0.02 mbar-0.2 mbar, that is, 0.02 mbar, 0.03 mbar, 0.04 mbar, 0.05 mbar, 0.06 mbar, 0.07 mbar, 0.08 mbar, 0.09 mbar, 0.10 mbar, 0.11 mbar, 0.12 mbar, 0.13 mbar, 0.14 mbar, 0.15 mbar, 0.16 mbar, 0.17 mbar, 0.18 mbar, 0.19 mbar or 0.20 mbar. Preferably, the pressure of the primary drying and the secondary drying is 0.06 mbar, respectively.

[0082] In the present application, the top cover 3 is used to press the top plug 2 to fit with the double-chamber cartridge 1, and the method further includes: before pressing the top plug 2, the double-chamber cartridge 1 is filled with nitrogen to maintain the low moisture content of the freeze-dried product. It can be understood by those skilled in the art that the double-chamber cartridge 1 is filled with nitrogen before the bottle mouth 10 is sealed, and the purpose is to make the nitrogen in the inner cavity 13 reach 1 standard atmosphere. On the one hand, the nitrogen can be used to maintain the low moisture content of the freeze-dried product, and on the other hand, the 1 standard atmosphere nitrogen can also keep the position of the middle plug in the double-chamber cartridge fixed.

[0083] The present application also includes a freeze-dried preparation, which is prepared according to the above freeze-drying method. In particular, since the product to be freeze-dried added to one inner cavity 13 of the double-chamber cartridge bottle 1 in the present application can be one of a plurality of products, when different products to be freeze-dried are filled into the double-chamber cartridge bottle 1, the freeze-dried preparations finally obtained can also be different; in addition, when the freeze-drying parameters implemented in the freeze-drying method of the present application during the freeze-drying of the product, such as the temperature and pressure of the primary drying, are changed, after the same product to be freeze-dried is filled, freeze-dried preparations of different qualities or different properties can be produced through the freeze-drying method, such as preparations with different water contents, different solid forms, etc.

[0084] In the present application, an injection is also included, which includes: a double-chamber cartridge bottle packaging material for injection, a lyophilized preparation and a resolubilizing agent. It should be noted that the lyophilized preparation and the resolubilizing agent can be any lyophilized preparation and resolubilizing agent suitable for the double-chamber cartridge bottle packaging material for injection and the lyophilization process. Specifically, the lyophilized preparation can be any product to be lyophilized that can be filled into the double-chamber cartridge bottle 1 of the present application, and any lyophilized preparation prepared by lyophilization treatment by the lyophilization method of the present application, including the lyophilized preparation provided in the present application.

[0085] In addition, the resolvent can be a resolvent for resolving any of the lyophilized preparations prepared above, such as sterile water for injection (which may contain antibacterial agents such as phenol, m-cresol, benzyl alcohol, etc.), physiological saline, 5% glucose solution, and other buffers, such as phosphate buffer, citric acid buffer, acetate buffer, histidine buffer, succinic acid buffer, tris(hydroxymethyl)aminomethane hydrochloride buffer, etc., which can be used to reconstitute the lyophilized preparations provided in the present application when administered.

[0086] In the present application, the double-chamber cartridge bottle packaging material for injection includes: a double-chamber cartridge bottle 1 and a bottle cap assembly, wherein the double-chamber cartridge bottle 1 is used to contain a lyophilized preparation and a reconstituted solution. The bottle cap assembly includes a top plug 2 and a top cover 3, which are used to seal the double-chamber cartridge bottle 1. The double-chamber cartridge bottle 1 is as follows: Figure 5 As shown, it can be placed in the freeze-drying support used in the existing freeze-drying process, and the double-chamber cartridge bottle packaging material can be fixed and placed upright or inverted in the freeze-drying support and the sheath; the bottle cap assembly can be made of any material suitable for realizing the bottle cap sealing function. The top plug 2 is limited in the top cover 3 and is used to seal the bottle mouth 10 of the double-chamber cartridge bottle 1; the top cover 3 is used to press and fix the top plug 2 so that the top plug 2 seals the bottle mouth 10 of the double-chamber cartridge bottle 1 and seals the double-chamber cartridge bottle 1; wherein, the process of pressing and fixing the top plug 2 on the top cover 3 so that the top plug 2 seals the bottle mouth 10 of the double-chamber cartridge bottle 1 may include the following steps:

[0087] The top plug 2 is preassembled into the top cover 3; and the top cover 3 equipped with the top plug 2 is placed above the bottle mouth 10 of the double-chamber cartridge bottle 1, and the top cover 3 is pressed downward to press the top plug 2. The top cover 3 can be pressed downward by mechanical pressing, pneumatic driving, pneumatic clamp driving, or spring pressing.

[0088] In the present application, the double-chamber cartridge 1 comprises: an inner cavity 13, a bottle body 12, a bottleneck 11 and a bottle mouth 10, wherein a bottle mouth opening 100 connected to the inner cavity 13 is arranged at the center of the bottle mouth 10, and the inner diameter of the bottle mouth opening 100 is smaller than the inner diameters of the bottle mouth 10 and the bottleneck 11; and a bypass protrusion 120 is arranged on one side of the outer wall of the bottle body 12. It can be understood by those skilled in the art that the dimensions of the inner cavity 13, the bottle body 12, the bottleneck 11 and the bottle mouth 10 of the double-chamber cartridge 1 can be adjusted to suit the size range of commonly used freeze-drying racks, such as changing the vertical length of one or more parts of the double-chamber cartridge 1, changing the radial length of one or more parts of the double-chamber cartridge 1, etc., all without departing from the protection scope of the present application.

[0089] In the present application, the top plug 2 includes a plug cap 20 and a plug rod 21. The diameter of the plug rod 21 can be equal to or slightly larger than the inner diameter of the bottle mouth opening 100. After the plug rod 21 is inserted into the bottle mouth opening 100, the lower surface of the plug cap 20 is completely in contact with the upper surface of the bottle mouth 10 to achieve sealing of the bottle mouth 10. In particular, the top plug 2 is made of elastic rubber material, so the diameter of the plug rod 21 can be adjusted within the diameter range of the bottle mouth opening 100 that the plug rod 21 can be inserted into after being pressed by force. The diameter of the plug rod 21 can be slightly larger than the diameter of the bottle mouth opening 100 to ensure the tightness of the seal.

[0090] In this application, the top cover 3 is as shown in FIG. Fig. 6A As shown, it includes an upper end 30, a middle end 31 and a lower end 32; the upper end 30 has a top plate 300, a thread 301 and an opening 302, the middle end 31 has a convex ring 310, and the lower end 32 optionally has a convex strip 320, and the inner wall of the top cover 3 fits with the bottle mouth 20, the bottle neck 21 and at least a part of the bottle body 22; when the top cover 3 faces the bottle mouth 10, the top plate 300 of the upper end 30 presses the top plug 2 to move into the bottle mouth 10, so that the top plug 2 is embedded in the bottle mouth 10. After the bottle mouth 10 of the double-chamber cartridge bottle 1 is capped, the top plate 300 is tightly fitted on the plug cap 20 to press the top plug 2. The opening 302 can discharge the sublimated water in the product, the thread 301 is used to engage with the thread of the sterile injection needle, and the convex ring 310 can match the sheath.

[0091] It should be noted that the shape of the lower end 32 of the top cover 3 can be a cylinder or a prism, such as Figure 6B As shown, its length in the vertical direction is adjustable, so the lower end 32 can fit a small part of the bottle body 12, or can fit most of the bottle body 12 or completely fit the entire bottle body 12, so as to achieve better sealing performance and adapt to the size requirements of the top cover 3 in the freeze-drying process. The convex strip 320 is used to increase the friction between the lower end 32 and the matching sheath to improve the effect of mutual matching and fixing; in particular, the convex strip 320 can also be removed. The shape of the lower end 32 can be cylindrical or multi-prism to prevent the top cover 3 from slipping due to the centrifugal force of rotation or from sliding relative to the double-chamber cartridge bottle 1 to affect the sealing performance.

[0092] In particular, the length of the middle end 31 of the top cover 3 along the direction of the bottleneck 11 and the bottle body 12 can be adjusted, and the convex ring 310 can be adjusted to fit the lower part of the upper end 30 at the highest, so as to meet the sealing requirements of the double-chamber cartridge bottle 1 for different degrees of pressing and fitting of the top cover 3. For example, it is necessary to reduce the length of the top cover 3 along the direction of the bottle body 12 or the volume of the top cover 3 to meet the size requirements of the freeze-drying support for the double-chamber cartridge bottle 1 and the top cover 3 in the freeze-drying process. In particular, the center of the top plate 300 has a top plate opening, and the circumferential lower edge of the top plate opening to its upper edge may have an inclination angle β along the vertical direction, and the circumferential upper edge of the top plate opening has a larger opening length than the circumferential lower edge; the circumferential edge surface of the top plate opening may be a curved surface or a flat surface.

[0093] In this application, if Figure 7 As shown, the top plug 2 may also include: a sealing portion 22 protruding above the plug cap 20, and the sealing portion 22 may be inserted into the top plate opening. When the top plug 2 is completely embedded in the bottle mouth 10, that is, when the double-chamber cartridge bottle 1 is completed, the sealing portion 22 is embedded in the top plate opening and partially protrudes longitudinally from the top plate opening. Those skilled in the art can understand that the size of the sealing portion 22 may be slightly larger than the opening size of the circumferential lower edge of the top plate opening. In the process of pre-assembling the top plug 2 into the top cover 3, the top plug 2 needs to be fixed by the upper end 30, and the surface of the sealing portion 22 may produce a slight deformation to be inserted from the circumferential lower edge of the top plate opening and embedded in the top plate opening.

[0094] Therefore, during the process of pre-assembling the top plug 2 into the top cover 3, the sealing portion 22 can be embedded in the top plate opening, and its edge portion is closely fitted with the circumferential outer edge of the top plate opening, and finally partially protrudes from the upper edge of the top plate opening; by setting the radial length L of the sealing portion, it has a longer radial length to improve the tightness of the fit between its edge portion and the circumferential outer edge of the top plate opening, and further prevent the top plug 2 from slipping off the top plate 300. In addition, by adjusting the size of β, the circumferential lower edge of the top plate opening and the sealing portion 22 can have a closer fit relative to the circumferential upper edge of the top plate opening, so that the top plate opening tightly surrounds the fixed sealing portion 22.

[0095] In some embodiments, the radial length L of the sealing portion 22 can be 2.0 mm-5.0 mm. Specifically, the radial length L of the sealing portion 22 can be 2.0 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3.0 mm, 3.1 mm, 3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4.0 mm m, 4.1mm, 4.2mm, 4.3mm, 4.4mm, 4.5mm, 4.6mm, 4.7mm, 4.8mm, 4.9mm or 5.0mm; preferably, the radial length L of the sealing portion 22 can be 3.0mm-4.0mm, specifically, the radial length L of the sealing portion 22 can be preferably 3.0mm, 3.1mm, 3.2mm, 3.3mm, 3.4mm, 3.5mm, 3.6mm, 3.7mm, 3.8mm, 3.9mm or 4.0mm. The inclination angle β can be 0°, 1°, 2°, 3°, 4°, 5°, 6°, 7°, 8°, 9° or 10°, etc.

[0096] In some embodiments, the circumferential lower edge opening length of the top disk opening can be 1.5mm-5.0mm. Specifically, the circumferential lower edge opening length of the top disk opening can be 1.5mm, 1.6mm, 1.7mm, 1.8mm, 1.9mm, 2.0mm, 2.1mm, 2.2mm, 2.3mm, 2.4mm, 2.5mm, 2.6mm, 2.7mm, 2.8mm, 2.9mm, 3.0mm, 3.1mm, 3.2mm, 3.3mm, 3.4mm, 3.5mm, 3.6mm, 3.7mm, 3.8mm, 3.9mm, 4.0mm m, 4.1mm, 4.2mm, 4.3mm, 4.4mm, 4.5mm, 4.6mm, 4.7mm, 4.8mm, 4.9mm or 5.0mm; preferably, the circumferential lower edge opening length of the top plate opening may be 2.5mm-4.0mm, specifically, the circumferential lower edge opening length of the top plate opening may preferably be 2.5mm, 2.6mm, 2.7mm, 2.8mm, 2.9mm, 3.0mm, 3.1mm, 3.2mm, 3.3mm, 3.4mm, 3.5mm, 3.6mm, 3.7mm, 3.8mm, 3.9mm or 4.0mm.

[0097] By making the radial length L of the sealing portion 22 slightly larger than the opening length of the circumferential lower edge of the top plate opening, the sealing portion 22 fits more closely with the circumferential lower edge of the top plate opening, so that the top plate opening as a whole effectively fits and fixes the sealing portion 22, and the circumferential edge provides further support on this basis, so that the top plug 2 does not slip off as a whole. Preferably, when β is set to 0°, when the top plate opening has no inclination angle in the vertical direction, the sealing portion 22 can be well fixed, and the sealing portion 22 can be prevented from being difficult to insert when being plugged into the top plate opening due to excessive resistance; in another case, when the top plate opening needs to be set to a certain inclination angle in the vertical direction to enhance the limiting effect of the top plate 300 on the top plug 2, β can also be set to 5° to improve the fixing degree of the sealing portion 22, and at the same time, it does not affect the plugging and embedding of the sealing portion 22 into the top plate opening. Those skilled in the art can appropriately adjust the radial length L, the inclination angle β and the circumferential lower edge opening length of the sealing portion 22 based on the above-mentioned parameter standards according to the actual application of the bottle cap assembly, so as to adaptively adjust the degree of fit and fixation between the sealing portion 22 and the top plate 300.

[0098] In particular, the diameter of the plug cap 20 of the top plug 2 can be slightly smaller than the inner diameter of the top cover 3. Due to the cooperation between the top plug positioning point 303 and the plug cap 20, the top plug 2 can be tightly fixed to the bottle mouth opening 100 to achieve sealing. In this case, the diameter of the plug cap 20 is set to be slightly smaller than the inner diameter of the top cover 3, so that a small gap 200 is left between the surface of the plug cap 20 and the inner wall of the upper end 30. Fig. 9 As shown, when the top plug 2 is pressed by the top cover 3, the compressed volume of the plug cap 20 extends toward the gap 200 reserved around it, and the plug cap 20 will not protrude toward the top plate opening in the middle and upper part thereof due to the pressure.

[0099] In some embodiments, the diameter of the plug cap 20 can range from 5.0 mm to 10.0 mm. Specifically, the diameter of the plug cap 20 can range from 5.0 mm to 10.0 mm. Specifically, the diameter of the plug cap 20 can range from 5.0 mm, 5.1 mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7 mm, 5.8 mm, 5.9 mm, 6.0 mm, 6.1 mm, 6.2 mm, 6.3 mm, 6.4 mm, 6.5 mm, 6.6 mm, 6.7 mm, 6.8 mm, 6.9 mm, 7.0 mm, 7.1 mm, 7.2 mm, 7.3 mm, 7.4 mm, 7.5 mm, 7.6 mm, 7.7 mm, 7.8 mm, 7.9 mm, 8.0 mm, 8.1 mm, 8.2 mm, 8.3 mm, 8.4 mm, 8.5 mm m, 8.6mm, 8.7mm, 8.8mm, 8.9mm, 9.0mm, 9.1mm, 9.2mm, 9.3mm, 9.4mm, 9.5mm, 9.6mm, 9.7mm, 9.8mm, 9.9mm or 10.0mm; preferably, the diameter range of the plug cap 20 can be 6.0mm-8.0mm, specifically, the diameter of the plug cap 20 can preferably be 6.0mm, 6.1mm, 6.2mm, 6.3mm, 6.4mm, 6.5mm, 6.6mm, 6.7mm, 6.8mm, 6.9mm, 7.0mm, 7.1mm, 7.2mm, 7.3mm, 7.4mm, 7.5mm, 7.6mm, 7.7mm, 7.8mm, 7.9mm or 8.0mm.

[0100] In some embodiments, the diameter of the upper end 30 of the top cover 3 may range from 5.0 mm to 10.0 mm. Specifically, the diameter of the upper end 30 may range from 5.0 mm, 5.1 mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7 mm, 5.8 mm, 5.9 mm, 6.0 mm, 6.1 mm, 6.2 mm, 6.3 mm, 6.4 mm, 6.5 mm, 6.6 mm, 6.7 mm, 6.8 mm, 6.9 mm, 7.0 mm, 7.1 mm, 7.2 mm, 7.3 mm, 7.4 mm, 7.5 mm, 7.6 mm, 7.7 mm, 7.8 mm, 7.9 mm, 8.0 mm, 8.1 mm, 8.2 mm, 8.3 mm, 8.4 mm, 8.5 mm, 8.6 mm, 8.7 mm, 8.8 mm, 8.9 mm, 9.0 mm, 9.1 mm, 9.2 mm, 9.3 mm, 9.4 mm, 9.5 mm, 9.6 mm, 9.7 mm, 9.8 mm, 9.9 mm, 10.0 mm, 10.1 mm, 10.2 mm, 10.3 mm, 10.4 mm, 10.5 mm 5mm, 8.6mm, 8.7mm, 8.8mm, 8.9mm, 9.0mm, 9.1mm, 9.2mm, 9.3mm, 9.4mm, 9.5mm, 9.6mm, 9.7mm, 9.8mm, 9.9mm or 10.0mm; Preferably, the diameter range of the upper end 30 can be 6.0mm-8.0mm, specifically, the diameter of the upper end 30 can preferably be 6.0mm, 6.1mm, 6.2mm, 6.3mm, 6.4mm, 6.5mm, 6.6mm, 6.7mm, 6.8mm, 6.9mm, 7.0mm, 7.1mm, 7.2mm, 7.3mm, 7.4mm, 7.5mm, 7.6mm, 7.7mm, 7.8mm, 7.9mm or 8.0mm.

[0101] More preferably, the diameter of the plug cap 20 can be configured to be 7.0 mm, and the inner diameter of the upper end 30 of the top cover 3 that matches it can be configured to be 7.3 mm. In this way, a gap portion 200 with a length of 0.3 mm is left between the surface of the plug cap 20 and the inner wall of the upper end 30. The plug cap 20 is squeezed and its diameter increases during the assembly process of the top plug 2 or the insertion process of the injection needle. The gap portion 200 can accommodate the increased volume of the plug cap 20 to avoid the generation of upward pressure. It should be noted that in the bottle cap assembly according to the embodiment of the present application, those skilled in the art can appropriately adjust the diameter of the plug cap 20 and the diameter of the upper end 30 based on the above-mentioned parameter reference according to the actual application of the bottle cap assembly, so as to adapt to the matching of the bottle cap assembly with the freeze-drying support of the freeze dryer, the matching with the packaging material sheath and / or the matching use with the syringe. For example, the stability of the pre-assembly of the top plug 2 can be adjusted by appropriately adjusting the diameter of the plug cap 20; the diameter of the upper end 30 can be appropriately adjusted to maintain a tighter seal or a more easily removable seal on the double-chamber cartridge bottle 1; and after adjusting the diameters of the plug cap 20 and the upper end 30 respectively, in order to appropriately avoid the influence of the pressure on the plug cap 20 on the assembly and use of the bottle cap assembly, a suitable gap portion 200 can be provided by appropriately adjusting the size relationship between the diameter of the plug cap 20 and the diameter of the upper end 30, etc.

[0102] By inserting and fitting the sealing portion 22 into the top plate opening during the pre-assembly process of the top plug 2, and cooperating with the top plug positioning point 303 to limit the plug cap 20, the top plug 2 can be stably fixed in the top cover 3. Therefore, the mechanical processes implemented on the top cover 3 during the freeze-drying process, such as shaking, hanging, etc., will not affect the fixation of the top plug 2 in the top cover 3, thereby preventing the top plug 2 from falling off from the top cover 3 before the capping operation, and ensuring the qualified rate of the capping after the freeze-drying is completed; the configuration of the gap portion 200 of the plug cap 20 can also prevent the core from being removed when it is used with an injection needle, thereby ensuring product quality and efficient use.

[0103] In the present application, the upper end 30 of the top cover 3 also has a top plug positioning point 303, such as Fig. 8A , Figure 8B As shown, the top plug positioning points 303 protrude from the inner wall of the upper end 30 toward the axis direction of the top cover 3, and are used to fix the top plug 2 engaged with the bottle mouth 10. Specifically, the top plug positioning points 303 extend radially along the upper end 30 and are evenly spaced annularly on the inner wall of the top plug positioning points 303. The top plug positioning points 303 may be in the shape of a cylinder or a prism. In addition, the number of the top plug positioning points 303 and the interval length / arc between the multiple top plug positioning points 303 may be adjusted to maintain optimal fixation of the top plug 2.

[0104] In the present application, the number of the top plug positioning points 303 is 4 or 5 or more. In particular, the number of the top plug positioning points 303 can be an even number to maintain their symmetrical arrangement along the center of the upper end 30, so as to provide a more stable fixing function for the top plug 2. Preferably, the number of the top plug positioning points 303 is 4 or 8, so as to provide a relatively stable fixing function for the top plug 2; more preferably, the number of the top plug positioning points 303 is 8, so as to provide the most stable fixing function for the top plug 2. The top plug positioning points 303 can also be used to position the top plug 2 before being pressed into the bottle mouth 10. The top plug 2 is limited by the top plug positioning points 303 to prevent it from sliding toward the bottle mouth 10 on its own.

[0105] In the present application, the upper end 30 of the top cover 3 is also provided with a protrusion 304 protruding toward the axial direction of the top cover 3 on its inner wall. Fig.10 As shown, the top cover 3 can be limited on the bottle mouth 10 by the protrusion 304 before pressing the cap, so that the sublimated water in the inner cavity 13 can be discharged through the opening 302; therefore, the provision of the protrusion 304 helps to provide gas exchange and sublimated water discharge for the double-chamber cartridge bottle 1 during the freeze-drying process. It can be understood by those skilled in the art that the protrusion 304 will not hinder the movement of the top plug 2 during the process of the top plug 2 being inserted into the bottle mouth 10, because the protrusion 304 is evenly distributed on the inner wall of the upper end 30, and the top plate 300 can evenly apply pressure to the entire surface of the plug cap 20 pre-assembled into the upper end 30 during the plug pressing, so the top plug 2 can be stably and horizontally inserted into the bottle mouth 10.

[0106] In the present application, the number of protrusions 304 is 2 or 3 or more; preferably, the maximum length (D) of the protrusion 304 protruding toward the axial direction of the top cover 3 can be 0.10mm, 0.11mm, 0.12mm, 0.13mm, 0.14mm, 0.15mm, 0.16mm, 0.17mm, 0.18mm, 0.19mm, 0.20mm, 0.21mm, 0.22mm, 0.23mm, 0.24mm, 0.25mm, 0.26mm, 0.27mm, 0.28mm, 0.29mm or 0.30mm. Specifically, D can be 0.15mm to 0.30mm; further preferably, D can be 0.20mm to 0.28mm, so that the top cover 3 is not easily deformed by excessive pressure when pressing the cap, and the top cover 3 has a good sealing performance after pressing the cap, and is not easy to slip off; more preferably, D can be 0.23mm to 0.28mm, which can avoid the top cover 3 from being deformed due to pressure when pressing the cap, and the top cover 3 has a good sealing performance after pressing the cap, and is not easy to slip off. It should be noted that when the material of the raised portion 304 is different, the value of D can be adjusted to achieve the optimal limit of the top cover 3 before pressing the cap and the optimal improvement of the fit between the upper end 30 and the double-chamber cartridge bottle 1. Preferably, when the outer diameter of the bottle mouth 10 is 7.3mm, D can be 0.23mm, 0.25mm or 0.28mm, and the raised portion 304 can provide the optimal stability of the top cover 3 after pressing the cap.

[0107] In the present application, the shape of the protrusion 304 can be a trapezoid, a semicircle, a semi-ellipse or a rectangle, and preferably, the shape of the protrusion 304 is a trapezoid. When the shape of the protrusion 304 is preferably a trapezoid whose short side is close to the bottle mouth 10, the upper end 30 and the bottle mouth 10 fit tightly, and the top cover 3 can be highly stably fitted on the double-chamber cartridge bottle 1 to maintain good airtightness.

[0108] When the shape of the protrusion 304 is a trapezoid, the upper cutting angle (θ) between the surface of the protrusion 304 facing the axial direction of the top cover 3 and its side surface can be any angle between 0° and 90°, such as Fig.11As shown. Further preferably, θ can be 30° to 45°, specifically, θ can be 30°, 31°, 32°, 33°, 34°, 35°, 36°, 37°, 38°, 39°, 40°, 41°, 42°, 43°, 44° or 45°. It should be noted that when θ is less than 30°, the effect of the raised portion 304 on improving the tightness of the fit between the top cover 3 and the bottle mouth 10 may be significantly weakened; when θ is greater than 45°, the raised portion 304 may significantly hinder the capping process, causing the top cover 3 to deform or even be damaged during the capping process. Therefore, it can be preferred that θ is any angle between 30° and 45°; more preferably, θ can be 30°, so that the raised portion 304 can provide a better fit between the top cover 3 and the bottle mouth 10, and does not cause adverse obstacles to the capping process.

[0109] In addition, when the shape of the raised portion 304 is a trapezoid, it is further preferred that the lower cut angle (α) between the surface of the raised portion 304 facing the axis direction of the top cover 3 and its side is any angle between 0°-90°. Since the pressure during the capping process is mainly affected by the size of θ, when α and θ have the same value, the raised portion 304 can have a stable axisymmetric structure and is not easily deformed or damaged during the capping process or storage process. Therefore, the present application further prefers that α is 30° to improve the use efficiency and anti-deformation ability of the raised portion 304, and more preferably, θ and α of the raised portion 304 are both 30°, so that the top cover 3 will not be structurally damaged due to a large force during the capping process, and the top cover 3 and the double-chamber cartridge bottle 1 can be highly tightly fitted, which also improves the efficiency and accuracy of capping the double-chamber cartridge bottle 1.

[0110] The present application also provides a dual-chamber cartridge bottle packaging material for injection, which includes the bottle cap assembly and the dual-chamber cartridge bottle 1, and a dual-chamber cartridge bottle packaging material assembly for injection, which includes the dual-chamber cartridge bottle packaging material for injection and a sheath 4 used in conjunction with the dual-chamber cartridge bottle. It should be noted that the dual-chamber cartridge bottle packaging material for injection can include any combination of the bottle cap assembly and the dual-chamber cartridge bottle 1 that can be formed and / or maintained by any combination form disclosed in the present application.

[0111] The sheath 4 provided in the present application is an octagonal prism with an upper opening, and its structure is as follows: Fig.12 As shown, the inner wall of the sheath 4 has an octagonal shape, and after the double-chamber cartridge bottle 1 completes the freeze-drying process and is sealed by the top cover 3, the double-chamber cartridge bottle 1 can be pressed into the sheath and placed. In this process, the lower end 32 of the top cover 3 fits with the inner wall of the sheath 4 to avoid relative sliding, and the bypass protrusion 120 of the bottle body 12 is fixed at the octagonal vertex of the inner wall of the sheath, which also prevents the double-chamber cartridge bottle 1 from sliding relative to the inner wall of the sheath 4, so that the sheath can stably protect the entire packaging material.

[0112] In the present application, the shape of the lower end 32 is a cylinder or an octagonal prism, and can be preferably an octagonal prism, and is fixedly assembled with the sheath 4 for fixing and storing the double-chamber cartridge bottle 1 through interference fit; specifically, the upper outer edge of the lower end 32 close to the middle end 31 has a first protrusion 321, the top end of the sheath 4 is stretched and limited on the first protrusion 321, and the top cover 3 and the sheath 4 apply force to each other and clamp toward the middle. Through the interference fit between the lower end 32 and the sheath 4, when the double-chamber cartridge bottle 1 is placed in the sheath 4, the top cover 3 and the top plug 2 therein are more tightly fixed to the bottle mouth 10, effectively avoiding leakage, rotation, and falling off of the packaging material after freeze-drying, so as to ensure high-quality storage of the freeze-dried preparation.

[0113] Specifically, in some embodiments, the lyophilized preparation is reconstituted in the double-chamber cartridge bottle 1 and then subcutaneously injected through an injection needle, such as a microfine needle (MFN), for skin disease treatment or medical aesthetic applications. The needle seat of the injection needle has a threaded structure. When the MFN is installed on the top cover 3 to extract the product or removed from the top cover 3, its threaded structure is engaged or removed by rotation with the thread 301 of the top cover 3. During this process, the lower end 32 of the top cover 3 is fixed by the octagonal inner wall of the sheath 4 to prevent rotation, and the bypass protrusion 120 of the double-chamber cartridge bottle 1 is also fixed by the vertex of the octagonal inner wall of the sheath 4 to prevent rotation. Therefore, by using the lower end 32 in the shape of an octagonal prism and cooperating with the sheath 4, the double-chamber cartridge bottle packaging material assembly can be kept from being affected by the rotation when the injection needle is screwed / removed, so as to avoid idling when the sterile injection needle is screwed / removed, thereby improving the use efficiency of the lyophilized preparation.

[0114] The present application also provides another freeze-drying method for products used in pharmaceutical, cosmetic or medical beauty applications, which is used in conjunction with a double-chamber cartridge bottle 1' with a longer bottleneck and a corresponding top plug 2' and top cover 3'. Specifically, the other freeze-drying method includes: adding a middle plug to the double-chamber cartridge bottle 1', and then pouring the product to be freeze-dried; assembling the top plug 2' and the top cover 3', placing them above the bottle mouth 10' of the double-chamber cartridge bottle 1', and placing and fixing the double-chamber cartridge bottle 1' on a customized freeze-drying rack; freezing, primary drying and secondary drying the product to be freeze-dried respectively; using the top cover 3 to press the top plug 2' and the double-chamber cartridge bottle 1' to fit together, so as to seal the double-chamber cartridge bottle 1' and fix the top plug 2', and make the top plug 2' seal the bottle mouth 10' of the double-chamber cartridge bottle 1'.

[0115] In the other freeze-drying method, the middle plug added to the double-chamber cartridge 1' and the product to be freeze-dried can also be any middle plug for double-chamber cartridges and a freeze-dryable product of appropriate content that is suitable for the size and structure of the double-chamber cartridge 1'. The freezing, primary drying and secondary drying operations can be performed in a freeze dryer, and the freeze dryer can accommodate the freeze drying rack used in the freeze drying method of the present application; in the process of fixing the top plug 2' with the top cover 3' and sealing the bottle mouth 10' of the double-chamber cartridge 1' through the top plug 2', the method of driving the top cover 3' downward can also be any driving method that can be implemented in the freeze dryer, such as mechanical compression, air pressure drive, pneumatic clamp drive or spring pressing.

[0116] In the present application, after adding the middle stopper to the double-chamber cartridge 1', the product to be freeze-dried can be filled in. In particular, the product to be freeze-dried can be a product added to the inner cavity 13' of the double-chamber cartridge 1' for freeze-drying and short-term / long-term storage, such as small molecule drugs, peptides, enzymes, antibodies, fusion proteins, antibody-drug conjugates, etc. The user can select any liquid to be freeze-dried and fill it into one of the inner cavities 13' of the double-chamber cartridge 1' to perform freeze-drying using the freeze-drying method of the present application.

[0117] In this application, the freeze-drying stand is an independent freeze-drying stand or a tray-type freeze-drying stand. The freeze-drying stand used in the freeze-drying method of this application is an independent freeze-drying stand or a tray-type freeze-drying stand. The technical personnel can select and adjust the specific model, size and working parameters of the freeze-drying stand in the freeze-drying machine according to the actual application. This application only provides a preferred freeze-drying method. Preferably, the freeze-drying stand is a tray-type freeze-drying stand, which is easy to place more double-chamber cartridge bottles 1'.

[0118] In particular, the double-chamber cartridge 1' is placed upright or inverted in the freeze-drying rack. Preferably, the double-chamber cartridge 1' is placed upright in the freeze-drying rack to facilitate uniform heat distribution in the double-chamber cartridge 1' and improve the sublimation efficiency of the solvent, such as water. In addition, it can also reduce the degree of sedimentation and aggregation of the freeze-dried product and maintain the uniform and stable appearance of the product.

[0119] In the present application, the temperature range set for freezing the product in the double-chamber cartridge bottle 1' can be a temperature range suitable for freeze-drying the product, and when the freezing temperature is between -60°C and -40°C, the raw material to be freeze-dried generally has a higher freezing efficiency and maintains its own quality. Therefore, the freezing temperature is any temperature value between -60°C and -40°C. Specifically, the temperature range set for freezing the product in the double-chamber cartridge bottle 1 is -60°C to -40°C, that is, -60°C, -59°C, -58°C, -57°C, -56°C, -55°C, -54°C, -53°C, -52°C, -51°C, -50°C, -49°C, -48°C, -47°C, -46°C, -45°C, -44°C, -43°C, -42°C, -41°C or -40°C; The temperature range of the secondary drying is -60℃~0℃, i.e. -60℃, -59℃, -58℃, -57℃, -56℃, -55℃, -54℃, -53℃, -52℃, -51℃, -50℃, -49℃, -48℃, -47℃, -46℃, -45℃, -44℃, -43℃, -42℃, -41℃, -40℃, -39℃, -38℃, -37℃, -36℃, -3 5℃,-34℃,-33℃,-32℃,-31℃,-30℃,-29℃,-28℃,-27℃,-26℃,-25℃,-24℃,-23℃,-22℃,-21℃,-20℃,-19℃,-18℃,-17℃,-16℃,-15℃,-14℃,-13℃,-12℃,-11℃,-10℃,-9℃,-8℃,-7℃,-6℃,- The temperature range of secondary drying is 15℃~40℃, that is, 15℃, 16℃, 17℃, 18℃, 19℃, 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, 26℃, 27℃, 28℃, 29℃, 30℃, 31℃, 32℃, 33℃, 34℃, 35℃, 36℃, 37℃, 38℃, 39℃ or 40℃.

[0122] Similarly, the temperature of the primary drying and secondary drying of the product can be any temperature value between -60℃ and 0℃ and 15℃ and 40℃, respectively, to increase the sublimation rate of water in the medicine. In addition, the pressure range of the primary drying and secondary drying can be any value between 0.02mbar and 0.2mbar. When the pressure of the primary drying and secondary drying is preferably 0.06mbar, the drying efficiency can be guaranteed to reach the peak value. Specifically, the pressure range of the primary drying and the secondary drying is 0.02 mbar-0.2 mbar, that is, 0.02 mbar, 0.03 mbar, 0.04 mbar, 0.05 mbar, 0.06 mbar, 0.07 mbar, 0.08 mbar, 0.09 mbar, 0.10 mbar, 0.11 mbar, 0.12 mbar, 0.13 mbar, 0.14 mbar, 0.15 mbar, 0.16 mbar, 0.17 mbar, 0.18 mbar, 0.19 mbar or 0.20 mbar. Preferably, the pressure of the primary drying and the secondary drying is 0.06 mbar, respectively.

[0123] In the present application, the top cover 3' is used to press the top plug 2' to fit with the double chamber cartridge 1', and further includes: before pressing the top plug 2', the double chamber cartridge 1' is filled with nitrogen to maintain the low moisture content of the freeze-dried product, such as the freeze-dried preparation. It can be understood by those skilled in the art that the double chamber cartridge 1' is filled with nitrogen before the bottle mouth 10' is sealed, and the purpose is to make the nitrogen in the inner cavity 13' reach 1 standard atmosphere. On the one hand, the nitrogen can be used to maintain the low moisture content of the freeze-dried product, and on the other hand, the 1 standard atmosphere nitrogen can also keep the position of the middle plug in the double chamber cartridge fixed.

[0124] The present application also includes a freeze-dried preparation prepared according to the above freeze-drying method. In particular, since the product to be freeze-dried added to one inner cavity 13' of the double-chamber cartridge bottle 1' in the present application can be one of a plurality of products, when different products to be freeze-dried are filled into the double-chamber cartridge bottle 1', the freeze-dried preparations finally obtained can also be different; in addition, when the freeze-drying parameters implemented in the freeze-drying method of the present application during the freeze-drying of the product, such as the temperature and pressure of the primary drying, are changed, after the same product to be freeze-dried is filled, freeze-dried preparations of different qualities or different properties can be produced through the freeze-drying method, such as freeze-dried preparations with different water contents and different solid forms.

[0125] In the present application, an injection is also included, which includes: a double-chamber cartridge bottle packaging material for injection, a lyophilized preparation and a resolubilizing agent. It should be noted that the lyophilized preparation and the resolubilizing agent can be any lyophilized preparation and resolubilizing agent suitable for the double-chamber cartridge bottle packaging material for injection and the freeze-drying process. Specifically, the lyophilized preparation can be any product to be lyophilized that can be filled into the double-chamber cartridge bottle 1' of the present application, any lyophilized preparation prepared by lyophilization treatment by the freeze-drying method of the present application, and can also be the lyophilized preparation provided in the present application.

[0126] In addition, the resolvent can be a resolvent for resolving any of the lyophilized preparations prepared above, such as sterile water for injection (which may contain antibacterial agents such as phenol, m-cresol, benzyl alcohol, etc.), physiological saline, 5% glucose solution, and other buffers, such as phosphate buffer, citric acid buffer, acetate buffer, histidine buffer, succinic acid buffer, tris(hydroxymethyl)aminomethane hydrochloride buffer, etc., which can be used to reconstitute the lyophilized preparations provided in the present application when administered.

[0127] In the present application, the double-chamber cartridge bottle packaging material for injection includes: a double-chamber cartridge bottle 1' and another bottle cap assembly, wherein the double-chamber cartridge bottle 1' is used to contain a lyophilized preparation and a reconstituted solution, such as Fig.13 It should be noted that the dual-chamber cartridge bottle packaging material for injection may include any combination formed and / or maintained by combining any of the bottle cap components and the dual-chamber cartridge bottle 1 ' proposed in this application.

[0128] In the present application, a bottle cap assembly is also proposed accordingly, wherein the bottle cap assembly includes a top plug 2' and a top cover 3', which are used to seal a double-chamber cartridge bottle 1'. The double-chamber cartridge bottle 1' can be placed in a freeze-drying rack and a sheath 4' used in an existing freeze-drying process, and the packaging material of the double-chamber cartridge bottle can be fixed and placed upright or inverted in the freeze-drying rack; the bottle cap assembly can be made of any material suitable for realizing the bottle cap sealing function. The top plug 2' is limited in the top cover 3', and is used to seal the bottle mouth 10' of the double-chamber cartridge bottle 1'; the top cover 3' is used to press and fix the top plug 2', so that the top plug 2' seals the bottle mouth 10' of the double-chamber cartridge bottle 1'; and to seal the double-chamber cartridge bottle 1'; wherein, the process of pressing and fixing the top plug 2' in the top cover 3' so that the top plug 2' seals the bottle mouth 10' of the double-chamber cartridge bottle 1' may include the following steps:

[0129] The top plug 2' is preassembled into the top cover 3'; and the top cover 3' equipped with the top plug 2' is placed above the bottle mouth 10' of the double-chamber cartridge bottle 1', and the top cover 3' is pressed downward. The top cover 3' can be pressed downward by mechanical pressing, pneumatic driving, pneumatic clamp driving, or spring pressing.

[0130] In the present application, the double-chamber cartridge 1' comprises: an inner cavity 13', a bottle body 12', a bottleneck 11' and a bottle mouth 10', wherein a bottle mouth opening 100' connected to the inner cavity 13' is arranged at the center of the bottle mouth 10', and the inner diameter of the bottle mouth opening 100' is smaller than the inner diameters of the bottle mouth 10' and the bottleneck 11'; and a bypass protrusion 120' is arranged on one side of the outer wall of the bottle body 12'. It can be understood by those skilled in the art that the dimensions of the inner cavity 13', the bottle body 12', the bottleneck 11' and the bottle mouth 10' of the double-chamber cartridge 1' can be adjusted to suit the size range of commonly used freeze-drying racks, such as changing the vertical length of one or more parts of the double-chamber cartridge 1', changing the radial length of one or more parts of the double-chamber cartridge 1', etc., all without departing from the protection scope of the present application.

[0131] In the present application, the top plug 2' includes a plug cap 20' and a plug post 21'. The diameter of the plug post 21' can be equal to or slightly larger than the inner diameter of the bottle mouth opening 100'. After the plug post 21' is inserted into the bottle mouth opening 100', the lower surface of the plug cap 20' is completely in contact with the upper surface of the bottle mouth 10' to achieve sealing of the bottle mouth 10'. In particular, the top plug 2' is made of elastic rubber material, so the diameter of the plug post 21' can be adjusted within the diameter range of the bottle mouth opening 100' after the plug post 21' is pressed by force, and the diameter of the plug post 21' can be slightly larger than the diameter of the bottle mouth opening 100' to ensure the tightness of the seal.

[0132] In this application, the top cover 3 'is as Fig.14A As shown, it includes an upper end 30' and a bottom plate 31'; the upper end 30' has a top plate 300', a thread 301' and an opening 302', and the inner wall of the top cover 3' fits with the bottle mouth 10'; when the top cover 3' faces the bottle mouth 10', the top plate 300' of the upper end 30' presses the top plug 2' to move into the bottle mouth 10', so that the top plug 2' is embedded in the bottle mouth 10'. After the bottle mouth 10' of the double-chamber cartridge bottle 1' is capped, the top plate 300' fits tightly on the plug cap 20' to press the top plug 2'. The opening 302' can discharge the sublimated water in the product, and the thread 301' is used to engage with the injection needle thread.

[0133] It should be noted that the length of the bottom plate 31' in the vertical direction is adjustable, so the bottom plate 31' can only fit the connecting portion between the bottleneck 11' and the bottle body 12', or can additionally fit at least a portion of the bottle body 12', so as to achieve better sealing performance and meet the size requirements of the top cover 3' in the freeze-drying process. The shape of the bottom plate 31' can be set to be a cylinder or a polygonal column, such as Fig. 14B As shown, the top cover 3' is prevented from slipping off due to the centrifugal force of rotation or from sliding relative to the double-chamber cartridge bottle 1', thereby affecting the sealing performance.

[0134] In particular, the center of the top plate 300' also has a top plate opening, and the circumferential lower edge of the top plate opening to its upper edge may have an inclination angle β' along the vertical direction, and the circumferential upper edge of the top plate opening has a larger opening length than the circumferential lower edge; the circumferential edge surface of the top plate opening may be a curved surface or a flat surface.

[0135] In the present application, the top plug 2' may further include: a sealing portion 22' protruding above the plug cap 20', such as Fig.15 As shown, the sealing portion 22' can be inserted into the top plate opening. When the top plug 2' is completely embedded in the bottle mouth 10', that is, when the double-chamber cartridge bottle 1' is completed, the sealing portion 22' is embedded in the top plate opening and partially protrudes longitudinally from the top plate opening. Those skilled in the art can understand that the size of the sealing portion 22' can be slightly larger than the opening size of the circumferential lower edge of the top plate opening. In the process of pre-assembling the top plug 2' into the top cover 3', the top plug 2' needs to be fixed by the upper end 30', and the surface of the sealing portion 22' can produce a slight deformation to be inserted from the circumferential lower edge of the top plate opening and embedded in the top plate opening.

[0136] Therefore, during the process of pre-assembling the top plug 2' into the top cover 3', the sealing portion 22' can be embedded in the top plate opening, and its edge portion is tightly fitted with the circumferential outer edge of the top plate opening, and finally partially protrudes from the upper edge of the top plate opening. The radial length L' of the sealing portion 22' can also be set to have a longer radial length to improve the tightness of the fit between its edge portion and the circumferential outer edge of the top plate opening, so as to further prevent the top plug 2' from slipping out of the top plate 300'. In addition, by adjusting the size of β', the circumferential lower edge of the top plate opening and the sealing portion 22' have a tighter fit relative to the circumferential upper edge of the top plate opening, so that the top plate opening tightly surrounds the fixed sealing portion 22'.

[0137] In some embodiments, the radial length L' of the sealing portion 22' can be 2.0mm-5.0mm. Specifically, the radial length L' of the sealing portion 22' can be 2.0mm, 2.1mm, 2.2mm, 2.3mm, 2.4mm, 2.5mm, 2.6mm, 2.7mm, 2.8mm, 2.9mm, 3.0mm, 3.1mm, 3.2mm, 3.3mm, 3.4mm, 3.5mm, 3.6mm, 3.7mm, 3.8mm, 3.9mm, 4.0mm m, 4.1mm, 4.2mm, 4.3mm, 4.4mm, 4.5mm, 4.6mm, 4.7mm, 4.8mm, 4.9mm or 5.0mm; preferably, the radial length L' of the sealing portion 22' can be 3.0mm-4.0mm, specifically, the radial length L' of the sealing portion 22' can be preferably 3.0mm, 3.1mm, 3.2mm, 3.3mm, 3.4mm, 3.5mm, 3.6mm, 3.7mm, 3.8mm, 3.9mm or 4.0mm. The inclination angle β' can be 0°, 1°, 2°, 3°, 4°, 5°, 6°, 7°, 8°, 9° or 10°, etc.

[0138] In some embodiments, the circumferential lower edge opening length of the top disk opening can be 1.5mm-5.0mm. Specifically, the circumferential lower edge opening length of the top disk opening can be 1.5mm, 1.6mm, 1.7mm, 1.8mm, 1.9mm, 2.0mm, 2.1mm, 2.2mm, 2.3mm, 2.4mm, 2.5mm, 2.6mm, 2.7mm, 2.8mm, 2.9mm, 3.0mm, 3.1mm, 3.2mm, 3.3mm, 3.4mm, 3.5mm, 3.6mm, 3.7mm, 3.8mm, 3.9mm, 4.0mm m, 4.1mm, 4.2mm, 4.3mm, 4.4mm, 4.5mm, 4.6mm, 4.7mm, 4.8mm, 4.9mm or 5.0mm; preferably, the circumferential lower edge opening length of the top plate opening may be 2.5mm-4.0mm, specifically, the circumferential lower edge opening length of the top plate opening may preferably be 2.5mm, 2.6mm, 2.7mm, 2.8mm, 2.9mm, 3.0mm, 3.1mm, 3.2mm, 3.3mm, 3.4mm, 3.5mm, 3.6mm, 3.7mm, 3.8mm, 3.9mm or 4.0mm.

[0139] By making the radial length L' of the sealing portion 22' slightly larger than the opening length of the circumferential lower edge of the top plate opening, the sealing portion 22' fits more closely with the circumferential lower edge of the top plate opening, and the top plate opening is opened so that the top plate opening as a whole effectively fits and fixes the sealing portion 22', and the circumferential edge provides further support on this basis, so that the top plug 2' as a whole does not slip off. Preferably, when β' is set to 0°, when the top plate opening has no inclination angle in the vertical direction, the sealing portion 22' can be well fixed, and the sealing portion 22' is prevented from being difficult to insert when being plugged into the top plate opening due to excessive resistance; in another case, when the top plate opening needs to be set to a certain inclination angle in the vertical direction to enhance the limiting effect of the top plate 300' on the top plug 2, β' can also be set to 5° to improve the fixing degree of the sealing portion 22', and at the same time, it does not affect the plugging and inserting of the sealing portion 22' into the top plate opening. Those skilled in the art can appropriately adjust the radial length L', the inclination angle β' and the circumferential lower edge opening length of the sealing portion 22', the top plate opening and the like based on the above-mentioned parameter references according to the actual application of the bottle cap assembly in the freeze-drying process, so as to adaptively adjust the degree of fit and fixation between the sealing portion 22' and the top plate 300'.

[0140] In particular, the diameter of the plug cap 20' of the top plug 2' can be slightly smaller than the inner diameter of the top cover 3'. Due to the cooperation between the top plug positioning point 303' and the plug cap 20', the top plug 2' and the top cover 3' can be tightly fixed to each other to achieve sealing. In this case, the diameter of the plug cap 20' is designed to be slightly smaller than the inner diameter of the top cover 3', so that a small gap 200' is left between the surface of the plug cap 20' and the inner wall of the upper end 30'. Fig.17 In this way, when the top plug 2' is pressed by the top cover 3', since the compressed volume of the plug cap 20' extends toward the gap 200' reserved around it, the plug cap 20' will not protrude toward the top plate opening in the middle and upper part thereof due to the pressure.

[0141] In some embodiments, the diameter of the plug cap 20' can range from 5.0mm to 10.0mm. Specifically, the diameter of the plug cap 20' can range from 5.0mm to 10.0mm. Specifically, the diameter of the plug cap 20' can range from 5.0mm, 5.1mm, 5.2mm, 5.3mm, 5.4mm, 5.5mm, 5.6mm, 5.7mm, 5.8mm, 5.9mm, 6.0mm, 6.1mm, 6.2mm, 6.3mm, 6.4mm, 6.5mm, 6.6mm, 6.7mm, 6.8mm, 6.9mm, 7.0mm, 7.1mm, 7.2mm, 7.3mm, 7.4mm, 7.5mm, 7.6mm, 7.7mm, 7.8mm, 7.9mm, 8.0mm, 8.1mm, 8.2mm, 8.3mm, 8.4mm, 8.5mm m, 8.6mm, 8.7mm, 8.8mm, 8.9mm, 9.0mm, 9.1mm, 9.2mm, 9.3mm, 9.4mm, 9.5mm, 9.6mm, 9.7mm, 9.8mm, 9.9mm or 10.0mm; preferably, the diameter range of the plug cap 20' can be 6.0mm-8.0mm, specifically, the diameter of the plug cap 20' can preferably be 6.0mm, 6.1mm, 6.2mm, 6.3mm, 6.4mm, 6.5mm, 6.6mm, 6.7mm, 6.8mm, 6.9mm, 7.0mm, 7.1mm, 7.2mm, 7.3mm, 7.4mm, 7.5mm, 7.6mm, 7.7mm, 7.8mm, 7.9mm or 8.0mm.

[0142] In some embodiments, the diameter of the upper end 30' of the top cover 3' may range from 5.0 mm to 10.0 mm. Specifically, the diameter of the upper end 30' may range from 5.0 mm, 5.1 mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7 mm, 5.8 mm, 5.9 mm, 6.0 mm, 6.1 mm, 6.2 mm, 6.3 mm, 6.4 mm, 6.5 mm, 6.6 mm, 6.7 mm, 6.8 mm, 6.9 mm, 7.0 mm, 7.1 mm, 7.2 mm, 7.3 mm, 7.4 mm, 7.5 mm, 7.6 mm, 7.7 mm, 7.8 mm, 7.9 mm, 8.0 mm, 8.1 mm, 8.2 mm, 8.3 mm, 8.4 mm, 8.5 mm, 8.6 mm, 8.7 mm, 8.8 mm, 8.9 mm, 9.0 mm, 9.1 mm, 9.2 mm, 9.3 mm, 9.4 mm, 9.5 mm, 9.6 mm, 9.7 mm, 9.8 mm, 9.9 mm, 10.0 mm, 10.1 mm, 10.2 mm, 10.3 mm, 10.4 mm, 10.5 mm 5mm, 8.6mm, 8.7mm, 8.8mm, 8.9mm, 9.0mm, 9.1mm, 9.2mm, 9.3mm, 9.4mm, 9.5mm, 9.6mm, 9.7mm, 9.8mm, 9.9mm or 10.0mm; preferably, the diameter range of the upper end 30' can be 6.0mm-8.0mm, specifically, the diameter of the upper end 30' can preferably be 6.0mm, 6.1mm, 6.2mm, 6.3mm, 6.4mm, 6.5mm, 6.6mm, 6.7mm, 6.8mm, 6.9mm, 7.0mm, 7.1mm, 7.2mm, 7.3mm, 7.4mm, 7.5mm, 7.6mm, 7.7mm, 7.8mm, 7.9mm or 8.0mm.

[0143] More preferably, the diameter of the plug cap 20' can be configured to be 7.0 mm, and the inner diameter of the upper end 30' of the top cover 3' that matches it can be configured to be 7.3 mm, so that a gap portion 200' with a length of 0.3 mm is left between the surface of the plug cap 20' and the inner wall of the upper end 30'. The plug cap 20' is squeezed and its diameter increases during the assembly process of the top plug 2' or the insertion process of the injection needle. The gap portion 200' can accommodate the increased volume of the plug cap 20' to avoid the generation of upward pressure. It should be noted that in the bottle cap assembly according to the implementation scheme of the present application, those skilled in the art can appropriately adjust the diameter of the plug cap 20' and the diameter of the upper end 30' based on the above-mentioned parameter reference according to the actual application of the bottle cap assembly, so as to adapt to the matching of the bottle cap assembly with the freeze-drying support of the freeze dryer, the matching with the packaging material sheath and / or the matching use with the syringe. For example, the stability of the pre-assembly of the top plug 2' can be adjusted by appropriately adjusting the diameter of the plug cap 20'; the diameter of the upper end 30' can be appropriately adjusted to maintain a tighter seal or a more easily removable seal on the double-chamber cartridge bottle 1'; and after adjusting the diameters of the plug cap 20' and the upper end 30' respectively, in order to appropriately avoid the influence of the pressure of the plug cap 20' on the assembly and use of the bottle cap assembly, the size relationship between the diameter of the plug cap 20' and the diameter of the upper end 30' can be appropriately adjusted to provide a suitable gap portion 200', etc.

[0144] By inserting and fitting the sealing portion 22' into the top plate opening during the pre-assembly process of the top plug 2', and cooperating with the top plug positioning point 303' to limit the plug cap 20', the top plug 2' can be stably limited in the top cover 3'. Therefore, when external forces are applied to the top cover 3' in actual production, such as vibration, suspension, etc., it will not affect the fixation of the top plug 2' in the top cover 3', thereby preventing the top plug 2' from falling off from the top cover 3' before the capping operation, and ensuring the qualified rate of the capping after the freeze-drying is completed; in addition, the configuration of the gap portion 200' of the plug cap 20' can also prevent the core from being taken out when it is used with an injection needle, ensuring the efficient use of the product.

[0145] In the present application, the upper end 30' of the top cover 3' further has a top plug positioning point 303', such as Fig.16A , Fig. 16B As shown, the top plug positioning point 303' protrudes from the inner wall of the upper end 30' toward the axis direction of the top cover 3', and is used to fix the top plug 2' engaged with the bottle mouth 10'. Specifically, the top plug positioning points 303' extend radially along the upper end 30' and are evenly spaced annularly on the inner wall of the top plug positioning points 303'. The top plug positioning points 303' can be in the shape of a cylinder or a prism. In addition, the number of the top plug positioning points 303' and the interval length / radian between the multiple top plug positioning points 303' can be adjusted to maintain the optimal fixation of the top plug 2'.

[0146] In the present application, the number of the top plug positioning points 303' is 4 or 5 or more. In particular, the number of the top plug positioning points 303' can be an even number to maintain their symmetrical arrangement along the center of the upper end 30', so as to provide a more stable fixing function for the top plug 2'. Preferably, the number of the top plug positioning points 303' is 4 or 8, so as to provide a relatively stable fixing function for the top plug 2'; more preferably, the number of the top plug positioning points 303' is 8, so as to provide the most stable fixing function for the top plug 2'. The top plug positioning points 303' can also be used to position the top plug 2' before being pressed into the bottle mouth 10'. The top plug 2' is limited by the top plug positioning points 303' to prevent it from slipping off to the bottle mouth 10' on its own.

[0147] In the present application, the upper end 30' of the top cover 3' is also provided with a protrusion 304' protruding toward the axial direction of the top cover 3' on its inner wall. The top cover 3' can be limited on the bottle mouth 10' by the protrusion 304' before pressing the cap, so that the sublimated water in the inner cavity 13' can be discharged through the opening 302'; therefore, the provision of the protrusion 304' helps to provide gas exchange and water discharge for the double-chamber cartridge bottle 1'. Those skilled in the art can understand that the protrusion 304' will not hinder the movement of the top plug 2' during the process of the top plug 2' being inserted into the bottle mouth 10'. Since the protrusion 304' is evenly distributed on the inner wall of the upper end 30', and the top plate 300' can evenly apply pressure to the entire surface of the plug cap 20' preassembled into the upper end 30' during the pressing, the top plug 2' can be stably and horizontally inserted into the bottle mouth 10'.

[0148] In the present application, the number of protrusions 304' is 2 or 3 or more; preferably, the maximum length (D') of the protrusion 304' protruding toward the axial direction of the top cover 3' can be 0.10mm, 0.11mm, 0.12mm, 0.13mm, 0.14mm, 0.15mm, 0.16mm, 0.17mm, 0.18mm, 0.19mm, 0.20mm, 0.21mm, 0.22mm, 0.23mm, 0.24mm, 0.25mm, 0.26mm, 0.27mm, 0.28mm, 0.29mm or 0.30mm. Specifically, D' can be 0.15mm to 0.30mm; further preferably, D' can be 0.20mm to 0.28mm, so that the top cover 3' is not easily deformed by excessive pressure when pressing the cap, and the top cover 3' has a good sealing performance after pressing the cap, and it is not easy to slip off; more preferably, D' can be 0.23mm to 0.28mm, which can avoid the top cover 3' from being deformed due to pressure when pressing the cap, and the top cover 3' has a good sealing performance after pressing the cap, and it is not easy to slip off. It should be noted that when the material of the raised portion 304' is different, the value of D' can be adjusted to achieve the optimal limit of the top cover 3' before pressing the cap and the optimal improvement of the fit between the upper end 30' and the double-chamber cartridge bottle 1'. When the outer diameter of the bottle mouth 10' is 7.3mm, D' is preferably 0.23mm, 0.25mm or 0.28mm, so that the raised portion 304' can provide the most stable fixation for the top cover 3'.

[0149] In the present application, the shape of the protrusion 304' can be a trapezoid, a semicircle, a semi-ellipse or a rectangle. Preferably, the shape of the protrusion 304' is a trapezoid. When the shape of the protrusion 304' is preferably a trapezoid with the short side close to the bottle mouth 10', the upper end 30' and the bottle mouth 10' fit tightly, and the top cover 3' can be highly stably fitted on the double-chamber cartridge bottle 1' to maintain good airtightness.

[0150] When the shape of the protrusion 304' is a trapezoid, the upper cutting angle (θ') between the surface of the protrusion 304' facing the axis direction of the top cover 3' and its side surface can be any angle between 0° and 90°, such as Fig.18 As shown. Further, θ' can be 30° to 45°, specifically, θ' can be 30°, 31°, 32°, 33°, 34°, 35°, 36°, 37°, 38°, 39°, 40°, 41°, 42°, 43°, 44° or 45°. It should be noted that when θ' is less than 30°, the effect of the raised portion 304' on improving the tightness of the fit between the top cover 3' and the bottle mouth 10' may be significantly weakened; when θ' is greater than 45°, the raised portion 304' may significantly hinder the capping process, causing the top cover 3' to deform or even be damaged during the capping process. Therefore, it is preferred that θ' is any angle between 30° and 45°; more preferably, θ' can be 30°, so that the raised portion 304' can provide a better fit between the top cover 3' and the bottle mouth 10', and does not cause adverse obstacles to the capping process.

[0151] In addition, when the shape of the raised portion 304' is a trapezoid, it is further preferred that the lower cut angle (α') of the surface of the raised portion 304' facing the axis direction of the top cover 3' and its side surface can also be any angle between 0°-90°. Since the pressure during the capping process is mainly affected by the size of θ', when α' and θ' have the same value, the raised portion 304' can have the most stable axisymmetric structure, which is not easy to deform or damage during the capping process or storage process. Therefore, the present application further prefers that α' can be 30° to improve the use efficiency and anti-deformation ability of the raised portion 304'. More preferably, θ' and α' of the raised portion 304' are both 30°, and the capping process of the top cover 3' will not cause structural damage to the top cover 3' due to excessive capping force, and at the same time, the top cover 3' can be kept in close contact with the height of the double-chamber cartridge bottle 1', which can improve the capping efficiency and accuracy of the double-chamber cartridge bottle 1' in the freeze-drying process.

[0152] The present application also proposes another double-chamber cartridge bottle packaging material for injection, which includes the above-mentioned another bottle cap assembly and a double-chamber cartridge bottle 1', and another double-chamber cartridge bottle packaging material assembly for injection, which includes the above-mentioned another double-chamber cartridge bottle packaging material for injection and a sheath 4' used in conjunction with the same, such as Fig.19 It should be noted that the dual-chamber cartridge bottle packaging material for injection may include any combination of the bottle cap assembly and the dual-chamber cartridge bottle 1 ' that can be formed and / or maintained by any combination form proposed in this application.

[0153] The upper outer edge of the bottom plate 31' near the upper end 30' has a first protrusion 321', and the top end of the inner wall of the sheath 4' is stretched to produce a protrusion in the horizontal direction, and is limited on the first protrusion 321' of the bottom plate 31'. The top cover 3' and the sheath 4' achieve an interference fit, apply forces in opposite directions, and clamp the top plug 2' and the double-chamber cartridge bottle 1' in the middle. In addition, the bypass protrusion 120' of the bottle body 12' is fixed at the octagonal vertex of the inner wall of the sheath 4', and cannot slide relative to the inner wall of the sheath 4'. In the above manner, when the double-chamber cartridge bottle packaging material is placed in the sheath 4', the top cover 3' and the top plug 2' therein are more tightly fixed to the bottle mouth 10', effectively avoiding leakage, rotation, falling off, etc.

[0154] In the present application, the bottom plate 31' is in the shape of a cylinder or an octagonal prism, and the sheath 4' includes a sheath body 40' and a flange 41'. When the top cover 3' and the sheath 4' are interference fit, the top cover 3' and the double-chamber cartridge bottle 1' are tightly fixed to each other. Since the bottle mouth 10', the bottleneck 11' and the bottle body 12' of the double-chamber cartridge bottle 1' are cylindrical, during the process of the injection needle being screwed to the top cover 3' and / or being removed from the top cover 3', the top cover 3' is subjected to force and drives the double-chamber cartridge bottle 1' to produce a co-rotation tendency. When the bottom plate 31' is in the shape of a cylinder, its smooth outer surface is difficult to be well limited by the inner wall of the sheath 4'. When the freeze-dried preparation is used, the injection needle needs to be screwed / removed, and the top cover 3' may drive the entire double-chamber cartridge bottle 1' to rotate together, so that the injection needle rotates idly and cannot be fixed / released with the top cover 3'.

[0155] Therefore, the bottom plate 31' of the bottle cap assembly configured with the packaging material assembly is in the shape of an octagonal prism, and the sheath body 40' is in the shape of an octagonal prism, so that the outer wall of the bottom plate 31' and the inner wall of the sheath body 40' are both octagonal. Fig.19 As shown. In this way, the bypass protrusion 120' of the double-chamber cartridge bottle 1' of the packaging material assembly can be limited to the octagonal vertex (B'-B') of the inner wall of the sheath 4', and the bottle body 12' will generate a large friction force with the inner wall of the bottom plate 31' during the capping process; when the top cover 3' is subjected to external force such as an injection needle, the bottom plate 31' and the inner wall of the sheath 4' are interference-fitted and fixed to each other (A'-A'), so that the top cover 3' will not slip off or slide relative to the double-chamber cartridge bottle 1', further making the overall packaging material stable and motionless, avoiding the airtightness of the double-chamber cartridge bottle 1' from being affected, and improving the use efficiency.

[0156] In particular, the lower end of the sheath 4' may also have an interference fit structure, and the lower end of the sheath body 40' may be provided with a second protrusion 400', which is pressed and buckled on the flange 41', so that the sheath body 40' and the flange 41' are interference fit and fixed to each other (C'-C'). In this way, the fixing stability of the sheath body 40' can be improved, and the sheath body 40' and the packaging material can be prevented from rotating together.

[0157] Specifically, in some embodiments, the above-mentioned another lyophilized preparation is reconstituted in the double-chamber cartridge bottle 1' and then subcutaneously injected through an injection needle for skin disease treatment or medical beauty. The needle seat of the injection needle has a threaded structure. When the injection needle is installed on the top cover 3' for product injection or removed from the top cover 3', its threaded structure is engaged or removed by rotation with the thread 301' of the top cover 3'. During this process, the bottom plate 31' of the top cover 3' is fixed by the octagonal inner wall of the sheath 4' to prevent rotation, and the bypass protrusion 120' of the double-chamber cartridge bottle 1' is also fixed by the vertex of the inner wall of the sheath 4' to prevent rotation. Therefore, by selecting the bottom plate 31' in the shape of an octagonal prism and cooperating with the sheath 4', the double-chamber cartridge bottle packaging material assembly can be kept from being affected by the rotation when the injection needle is screwed / removed, so as to avoid idling when the sterile injection needle is screwed / removed, and improve the use efficiency of the double-chamber cartridge bottle packaging material assembly.

[0158] The two lyophilized preparations as described above provided in the present application are any lyophilized preparations prepared according to any lyophilization method provided in the present application or any lyophilized preparations in the two lyophilized preparations provided in the present application. It is understood that these lyophilized preparations can all be raw material reagents or finished products of pharmaceutical reagents, medical device reagents and / or cosmetics in the field of biomedicine, medical cosmetology. The various types of lyophilized preparations obtained by the present application also have the characteristics of high integrity, high purity and low impurities, so they also have excellent practical application effects.

[0159] Example

[0160] This application provides a general and / or specific description of the materials and test methods used in the test. The reagents or instruments used without indicating the manufacturer are all conventional reagent products that can be obtained through commercial purchase.

[0161] Example 1

[0162] A bottle cap assembly, comprising a top plug 2 and a top cover 3, is used to seal a double-chamber cartridge bottle 1. The structure of the top cover 3 is as follows: Fig. 6A The double-chamber cartridge bottle 1 uses the top cover 3 to seal the top plug 2 to the bottle mouth, and seals the bottle mouth 10 of the double-chamber cartridge bottle 1 through the top plug. Specifically,

[0163] First, the top plug 2 is positioned inside the top cover 3 through the top plug positioning point 303, and the top cover 3 is placed on the bottle mouth 10 so that the plug 21 naturally faces the bottle mouth opening 100 for freeze drying.

[0164] Then, after the freeze-drying is completed, the top plug 2 is pressed through the top cover 3 to be embedded in the bottle mouth 10 of the double-chamber cartridge bottle 1. The top cover 3 includes an upper end 30, a middle end 31 and a lower end 32. The upper end 30 has a top plate 300 located at its center, a thread 301 and an opening 302 located at the edge of the upper end 30, which is arranged above the middle end 31, and the lower end 32 is located below the middle end 31. The lower end 32 is an opening; after the top plug 2 is initially embedded in the bottle mouth 10, the top cover 3 is pressed downward until the upper end 30 is completely covered on the bottle mouth 10. During this process, the inner wall of the upper end 30 is in contact with the bottle mouth 10 and the bottleneck 11, while the inner walls of the middle end 31 and the lower end 32 are in contact with the bottle body 12.

[0165] The top plate 300 is a hollow cylindrical structure shortened in the middle. When the top cover 3 is pressed downward by external force, the top plug 2 is pressed to the bottle mouth 10 through the lower surface of the top plate 300, so that the top plug 2 is further embedded in the bottle mouth 10 until the plug column 21 with a diameter slightly larger than the inner diameter of the bottle mouth is completely embedded in the bottle mouth 10 under the action of pressure, and the lower surface of the plug cap 20 is completely in contact with the upper surface of the bottle mouth 10, so that the double-chamber cartridge bottle 1 is sealed with the top plug 2, and no additional plugging device is required to participate in the sealing, which reduces the additional process and time required for sealing the double-chamber cartridge bottle 1, and avoids the influence of inaccurate sealing on the production efficiency of the freeze-drying process.

[0166] In particular, the top cover 3 is configured so that when the top plug 2 is pressed to be completely embedded in the bottle mouth 10, the inner wall of the upper surface of the middle end 31 can also be completely fitted with the upper surface of the bottle body 12; therefore, while the top cover 3 uses the top plug 2 to seal the bottle mouth opening 100, the top cover 3 also seals the top plug 2 embedded in the bottle mouth, and seals the bottle mouth 10, the bottleneck 11 and at least a portion of the bottle body 12 through the top plug 2, thereby achieving a sealed cap for the entire double-chamber cartridge bottle 1.

[0167] The diameter of the upper end 30 is 7.3 mm, and a gap 200 is left between the plug cap 20 with a diameter of 7.0 mm; the upper end 30 also has a top plug positioning point 303, such as Fig. 6A and Figure 5 As shown in the figure, the top plug positioning point 303 is located below the top plate 300 and protrudes from the inner wall of the upper end 30 in the direction of the axis of the top cover 3. After the top plug 2 is completely embedded in the bottle mouth 10, the top plug positioning point 303 fits with the plug cap 20, and the plug cap 20 is pressed by the top plug positioning point 303 in the direction of the axis of the top cover 3, thereby increasing the friction between the plug cap 20 and the inner wall of the upper end 30, preventing the top plug 2 from loosening or slipping off the top cover 3 during the pre-assembly process due to loose fitting. The number of top plug positioning points 303 is 4, evenly distributed on the inner wall of the upper end 30.

[0168] The upper end 30 also has a protrusion 304, as shown in FIG6 , the protrusion 304 is arranged below the top plug positioning point 303, and protrudes from the inner wall of the upper end 30 in the direction of the axis of the top cover 3. After the top plug 2 is completely embedded in the bottle mouth 10, the protrusion 304 fits against the outer wall of the bottle mouth 10, and the bottle mouth 10 is subjected to the pressure of the protrusion 304 in the direction of the axis of the top cover 3, thereby increasing the friction between the bottle mouth 10 and the inner wall of the upper end 30, preventing the top cover 3 from slipping off after sealing due to loose fitting, and improving the sealing performance of the double-chamber cartridge bottle 1. The maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 is set to 0.23 mm, and the shape of the protrusion 304 is set to be trapezoidal, the number is 2, and it is distributed on both sides of the inner wall of the upper end 30, and its upper cutting angle is 30°.

[0169] The lower end 32 is in the shape of a cylinder. The convex ring 310 of the middle end 31 and the convex strip 320 of the lower end 32 can increase the fit between the top cover 3 and the bottle body 22 after the top cover 3 is attached to the double-chamber cartridge bottle 1, and further improve the stability of the attachment between the top cover 3 and the double-chamber cartridge bottle 1.

[0170] The bottle cap assembly was subjected to plugging and capping sealing tests, and it was found that the top plug 2 had a high degree of fit with the top cover 3, and the top plug 2 did not slip off the top cover 3; a certain amount of pressure needed to be applied during the capping process, but it did not cause deformation or damage to the partial structure of the top cover 3; the fit between the top cover 3 and the bottle mouth 10 of the double-chamber cartridge bottle 1 was significantly improved, and it was not pulled out after a large force was applied.

[0171] Example 2

[0172] The maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 is replaced with 0.25 mm, and the other structures and parameters are the same as those in Example 1. The bottle cap assembly is subjected to plugging and capping sealing tests, and it is found that the top plug 2 and the top cover 3 have a high degree of fit, and the top plug 2 does not slip off from the top cover 3; after the maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 is replaced with 0.25 mm, a certain amount of pressure needs to be applied during the capping process, but no deformation or damage is caused to the structure of the top cover 3; the fit between the top cover 3 and the bottle mouth 10 of the double-chamber cartridge bottle 1 is also significantly improved, and it is not pulled out after applying a large force.

[0173] Example 3

[0174] The maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 is replaced with 0.28 mm, and the other structures and parameters are the same as those in Example 1. The bottle cap assembly is subjected to plugging and capping sealing tests, and it is found that the top plug 2 and the top cover 3 have a high degree of fit, and the top plug 2 does not slip off from the top cover 3; after the maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 is replaced with 0.28 mm, the capping process needs to apply a large pressure, but does not cause deformation and damage to the structure of the top cover 3; the fit between the top cover 3 and the bottle mouth 10 of the double-chamber cartridge bottle 1 is significantly improved, and it is not pulled out after applying a large force.

[0175] Example 4

[0176] The freeze-drying process of the drug is carried out using the double-chamber cartridge packaging material for injection, and the freeze-dried preparation is obtained. The double-chamber cartridge packaging material for injection is selected from 20 portions of the double-chamber cartridge packaging material for injection in Example 1 to Example 3, respectively, and the freeze-drying process is carried out to obtain the freeze-dried preparation in the following steps:

[0177] (1) Add a middle stopper to each double-chamber cartridge bottle 1, and then fill it with the lonapegsomatropin to be freeze-dried. There are two types of lonapegsomatropin, wherein the first type of lonapegsomatropin contains: 22.0 mg hGH / mL lonapegsomatropin, 10 mM succinic acid, 74.0 mg / mL trehalose dihydrate, and an appropriate amount of tromethamine to adjust the pH value to pH 5.0; wherein the second type of lonapegsomatropin contains: 11.0 mg hGH / mL lonapegsomatropin, 10 mM succinic acid, 83.0 mg / mL trehalose dihydrate, and an appropriate amount of tromethamine to adjust the pH value to pH 5.0. Place and fix the double-chamber cartridge bottle 1 on a freeze-drying rack, wherein the freeze-drying rack is a tray-type freeze-drying rack, such as Figure 1 As shown, the dual-chamber cartridge bottle 1 is placed upright in the freeze-drying rack.

[0178] (2) The top plug 2 and the top cover 3 in Examples 1 to 3 are preassembled and placed at the mouth 10 of the double-chamber cartridge bottle 1. Specifically, the top plug 2 is inserted into the cavity of the upper end 30 from the opening of the lower end 32 until the upper surface of the plug cap 20 fits with the lower end of the top plate 300, and the plug cap 20 is supported by the top plug positioning point 303 and is limited in the upper end 30; the mouth 10 of the bottle is aligned with the opening of the lower end 32, and the top plug 2 is naturally placed at the mouth 10 of the bottle.

[0179] (3) The freeze-drying process of freezing, primary drying, secondary drying and plate layer plugging and capping of the lyophilized lompein is respectively performed. The specific operation process is shown in Table 1:

[0180] Table 1 Freeze-drying process flow and parameter settings of the lyophilized longpei somatotropin

[0181]

[0182] Where Atm is 1 standard atmosphere. In the freeze-drying process, the freeze-drying curve of the freeze-dried drug is as follows: Figure 2 As shown, after unloading from the box, the double-chamber cartridge bottle packaging material for injection already has a freeze-dried sample with a formed appearance and low water content.

[0183] (4) After the freeze-drying process is completed, the double-chamber cartridge bottle 1 is filled with nitrogen to maintain the low moisture content of the freeze-dried sample, and then the plugging and capping are performed simultaneously. Specifically,

[0184] After freeze-drying is completed, push the top cover 3 downward to press the top plug 2 to fit into the bottle mouth 10 of the double-chamber cartridge bottle 1. While the top plug 2 is embedded in the bottle mouth 10, the top cover 3 is pressed down until the upper end 30 is completely covered on the bottle mouth 10. During this process, the inner wall of the upper end 30 fits with the bottle mouth 10, and the inner walls of the middle end 31 and the lower end 32 fit with the bottle body 12, until the plug 21 is completely embedded in the bottle mouth 10, and the lower surface of the plug cap 20 is completely in contact with the upper surface of the bottle mouth 10, so as to achieve the sealing of the double-chamber cartridge bottle 1 by using the top plug 2, without the need to introduce an additional plug pressing component.

[0185] (5) The double chamber cartridge 1 is taken out from the freeze dryer to obtain the final freeze-dried preparation.

[0186] The freeze-dried preparation prepared by the freeze-drying method in the double-chamber cartridge 1 was subjected to appearance inspection and moisture inspection. The inspection results are shown in Table 2:

[0187] Table 2 Appearance test and moisture test results of freeze-dried preparations

[0188]

[0189] As shown in Table 2, the appearance test results of the freeze-dried preparation showed that it had a good appearance, the average moisture test results of the 6 tests were all low, and the freeze-drying effect of the freeze-dried preparation was better.

[0190] In addition, the three double-chamber cartridge bottle packaging materials for injection in Examples 1 to 3 were subjected to freeze-drying machine plate layer capping operation (without adding freeze-dried samples), and the packaging materials after capping were subjected to CCIT (vacuum decay method) testing. The results showed that the sealing properties of the three packaging materials were good.

[0191] In summary, the freeze-drying process described above using the packaging materials in Examples 1 to 3 can meet the freeze-drying process requirements and sealing requirements for drugs, and the freeze-dried preparations obtained using the freeze-drying method described above can meet the requirements for the appearance and moisture content of freeze-dried drugs.

[0192] Example 5

[0193] The structure of the top cover 3 of the bottle cap assembly in Example 1 is adjusted to reduce the volume of the top cover 3, such as Figure 6BSpecifically, the length of the portion of the top cover 3 extending along the bottleneck 11 and the bottle body 12 in Example 2 is shortened, so that the length of the middle end 31 is shortened, and the position of the convex ring 310 relative to the bottleneck 11 and the bottle body 12 is further moved upward and fits with the lower part of the upper end 30. In addition, the convex strip 320 of the lower end 32 is removed, and the non-convex strip portion of the lower end 32 is extended downward along the bottle body 12, and the upper part of the lower end 32 close to the middle end 31 is shortened in the radial direction to form a first convex opening 321.

[0194] It should be noted that the shape of the extended lower end 32 in this embodiment is set to be an octagonal prism, and its inner wall can still fit at least a portion of the bottle body 12 of the double-chamber cartridge bottle 1, and the structure of the adjusted top cover 3 except the middle end 31 and the lower end 32 is the same as the top cover 3 in Example 10. The number of the top plug positioning points 303 is 8, which are evenly distributed on the inner wall of the upper end 30.

[0195] The bottle cap assembly was subjected to plugging and capping sealing tests, and it was found that the top plug 2 had a high degree of fit with the top cover 3, and the top plug 2 did not slip off the top cover 3; the capping process required a large pressure to be applied, but did not cause deformation or damage to the partial structure of the top cover 3; the fit between the top cover 3 and the bottle mouth 10 of the double-chamber cartridge bottle 1 was significantly improved, and it was not pulled out after applying a large force.

[0196] Example 6

[0197] The maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 is replaced to 0.25 mm, and the other structures and parameters are the same as those of Example 5. The bottle cap assembly is subjected to plugging and capping sealing tests, and it is found that the top plug 2 and the top cover 3 have a high degree of fit, and the top plug 2 does not slip off from the top cover 3; the capping process requires a large pressure to be applied, but does not cause deformation and damage to the structure of the top cover 3; the fit between the top cover 3 and the bottle mouth 10 of the double-chamber cartridge bottle 1 is significantly improved, and it is not pulled out after applying a large force.

[0198] Example 7

[0199] The maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 is replaced to 0.28 mm, and the other structures and parameters are the same as those of Example 5. The bottle cap assembly is subjected to plugging and capping sealing tests, and it is found that the top plug 2 and the top cover 3 have a high degree of fit, and the top plug 2 does not slip off from the top cover 3; the capping process requires a large pressure to be applied, but does not cause deformation and damage to the structure of the top cover 3; the fit between the top cover 3 and the bottle mouth 10 of the double-chamber cartridge bottle 1 is significantly improved, and it is not pulled out after applying a large force.

[0200] Example 8

[0201] The freeze-drying process of the drug is carried out using the double-chamber cartridge bottle packaging material for injection, and the freeze-dried preparation is obtained. The double-chamber cartridge packaging material for injection is selected from 25 portions of the double-chamber cartridge packaging material for injection in Example 5 to Example 7, respectively, and the freeze-drying process is carried out to obtain the freeze-dried preparation in the following steps:

[0202] (1) Add a middle stopper to each double-chamber cartridge bottle 1, and then fill it with the lyophilized lompe somatotropin, which contains: 22.0 mg hGH / mL lompe somatotropin, 10 mM succinic acid, 74.0 mg / mL trehalose dihydrate, and an appropriate amount of tromethamine to adjust the pH value to pH 5.0. Place and fix the double-chamber cartridge bottle 2 on a lyophilization rack, wherein the lyophilization rack is a tray-type lyophilization rack, such as Figure 1 As shown, the dual-chamber cartridge bottle 1 is placed upright in the freeze-drying rack.

[0203] (2) After the top plug 2 and the top cover 3 in Examples 5 to 8 are pre-assembled, they are placed at the bottle mouth 10 of the double-chamber cartridge bottle 1. The pre-assembly method of the top plug 2 and the top cover 3 is the same as that of Example 4.

[0204] (3) The freeze-drying process of freezing, primary drying, secondary drying and plate layer plugging and capping the lyophilized lompexin is respectively carried out, and the specific operation method is the same as that in Example 4.

[0205] (4) After the freeze-drying process is completed, the double-chamber cartridge bottle 1 is filled with nitrogen to maintain a low moisture content of the freeze-dried sample, and then the cap is sealed; the cap sealing method is the same as that in Example 4.

[0206] (5) The double-chamber cartridge 4 is taken out from the freeze dryer to obtain the final freeze-dried preparation.

[0207] The freeze-dried preparation prepared by the freeze-drying method in the double-chamber cartridge 4 was subjected to appearance inspection and moisture inspection. The inspection results are shown in Table 3:

[0208] Table 3 Appearance test, moisture test and CCIT test results of freeze-dried preparations

[0209]

[0210] As can be seen from Table 3, the appearance test results of the freeze-dried preparations show that they have good appearance and the average moisture test results are low; in addition, the double-chamber cartridge bottle packaging materials for injection in Examples 5 to 7 have good sealing properties during the freeze-drying process and can meet the sealing requirements of the preparations.

[0211] Example 9

[0212] A double-chamber cartridge bottle packaging material for injection includes a double-chamber cartridge bottle 1' and a bottle cap assembly. The double-chamber cartridge bottle 1' has a structure as shown in Fig.13As shown, it includes a bottle mouth 10', a bottle neck 11', a bottle body 12' and an inner cavity 13'. The bottle cap assembly includes a top plug 2' and a top cover 3', wherein the structure of the top plug 2' is as shown in FIG. Fig. 9 As shown, the structure of the top cover 3' is as follows Fig.14A The top cover 3' utilizes the top plug 2' to press-seal the bottle mouth 10', and at the same time, it seals the bottle mouth 10' of the double-chamber cartridge bottle 1'.

[0213] The top cover 3' includes an upper end 30' and a bottom plate 31'. The upper end 30' has a top plate 300' located in the center, a thread 301' located at the edge, and an opening 302' on the lower outer wall. The bottom of the bottom plate 31' is an opening, and a cavity is provided inward from the opening to the bottom plate 31'. After the top plug 2' is preassembled into the upper end 30' of the top cover 3', the top cover 3' is pressed down as a whole until the upper end 30' is sleeved on the bottle mouth 10'. During this process, the inner wall of the upper end 30' fits with the bottle mouth 10', and the inner wall of the bottom plate 31' fits with the connection between the bottleneck 11' and the bottle body 12'. The top plate 300' fits with the upper surface of the plug cap 20' of the preassembled top plug 2'. During the process of pressing down the top cover 3' as a whole, the top plate 300' simultaneously presses down the top plug 2', so that the top plug 2' is embedded in the bottle mouth 10'. Therefore, the top cover 3' can also be used to perform plugging and capping at the same time, without the need for additional plugging components or multiple steps, thereby reducing the time required for the sealing process of the dual-chamber cartridge 1' and avoiding sealing failure.

[0214] The upper end 30' has 8 evenly distributed top plug positioning points 303', which are located at the lower end of the top plate 300' and protrude from the inner wall of the upper end 30' toward the axis direction of the top cover 3'. After the top plug 2' is inserted into the bottle mouth 10', the top plug positioning points 303' fit with the plug cap 20', and the plug cap 20' is pressed by the top plug positioning points 303' toward the axis direction of the top cover 3', and the friction resistance between the plug cap 20' and the inner wall of the upper end 30' increases, preventing the top plug 2' from slipping off or popping out of the top cover 3', thereby avoiding sealing failure.

[0215] The upper end 30' also has a protrusion 304', which is arranged below the top plug positioning point 303' and protrudes from the inner wall of the upper end 30' in the direction of the axis of the top cover 3'. Before the top plug 2' is inserted into the bottle mouth 10', the protrusion 304' rests on the bottle mouth to ensure that the sublimated water can be discharged from the opening 302'; after the top plug 2' is inserted into the bottle mouth 10', the protrusion 304' fits against the outer wall of the bottle mouth 10', so that the bottle mouth 10' is subjected to the pressure of the protrusion 304' in the direction of the axis of the top cover 3', thereby increasing the friction between the bottle mouth 10' and the inner wall of the upper end 30', and preventing the top cover 3' from slipping off or popping out of the bottle mouth 10'.

[0216] The maximum length of the protrusion 304' protruding from the inner wall of the upper end 30' is set to 0.23 mm, and the shape of the protrusion 304' is trapezoidal.

[0217] Example 10

[0218] A double-chamber cartridge bottle packaging material for injection includes a double-chamber cartridge bottle 1' and a bottle cap assembly, wherein the bottle cap assembly includes a top plug 2' and a top cover 3'. The maximum length of the protrusion 304' protruding from the inner wall of the upper end 30' is replaced with 0.25mm, and other structures and parameters are the same as those of Example 9.

[0219] Embodiment 11

[0220] A double-chamber cartridge bottle packaging material for injection includes a double-chamber cartridge bottle 1' and a bottle cap assembly, wherein the bottle cap assembly includes a top plug 2' and a top cover 3'. The maximum length of the protrusion 304' protruding from the inner wall of the upper end 30' is replaced with 0.28mm, and other structures and parameters are the same as those of Example 9.

[0221] Example 12

[0222] The freeze-drying process of the drug is carried out using the double-chamber cartridge bottle packaging material for injection, and the freeze-dried preparation is obtained. The double-chamber cartridge bottle packaging material for injection is selected from 20 portions of the double-chamber cartridge bottle packaging material for injection in Example 9 to Example 11, respectively, and the freeze-drying process is carried out to obtain the freeze-dried preparation in the following steps:

[0223] (1) A middle stopper is added to each double-chamber cartridge bottle 1' of the double-chamber cartridge bottle packaging material for injection, and then the liquid medicine to be lyophilized is filled, and the double-chamber cartridge bottle 1' is placed and fixed on a lyophilization rack. The lyophilization rack is a tray-type lyophilization rack, such as Figure 1 As shown, the dual chamber cartridge vial 1' is placed upright in the freeze drying rack.

[0224] (2) The top plug 2' is preassembled with the top cover 3' in Examples 9 to 11, and placed at the bottle mouth 10' of the double-chamber cartridge bottle 1' without sealing. Specifically, the top cover 3' is supported by the protrusion 303' and is limited at the bottle mouth 10', and the top plug 2' is inserted into the cavity of the upper end 30' from the opening of the bottom plate 31' until the upper surface of the plug cap 20' is in contact with the lower end of the top plate 300', and the plug cap 20' is supported by the top plug positioning point 303' and is limited in the internal cavity of the upper end 30'.

[0225] In this way, the bottle mouth 10' is aligned with the opening of the bottom plate 31', and the top plug 2' is entirely located above the bottle mouth 10'.

[0226] (3) The drug solution to be lyophilized is subjected to freezing, primary drying, secondary drying, and plate layer plugging and capping, respectively. The specific operation process is shown in Table 1:

[0227] Table 4 Freeze-drying process flow and parameter settings of the freeze-dried drug solution

[0228]

[0229]

[0230] Here, Atm refers to 1 standard atmosphere.

[0231] (4) After the freeze-drying process is completed, the double-chamber cartridge bottle 1' is filled with nitrogen to maintain a low moisture content of the freeze-dried product, and then the cap is sealed. Specifically,

[0232] After freeze drying is completed, push the top cover 3' downward to press the top plug 2' so that the top plug 2' fits into the bottle mouth 10' of the double-chamber cartridge bottle 1'. While the top plug 2' is inserted into the bottle mouth 10', the top cover 3' is pressed down until the upper end 30' is completely covered on the bottle mouth 10'. In this process, the inner wall of the upper end 30' fits with the bottle mouth 10' until the plug 21' is completely inserted into the bottle mouth 10', the lower surface of the plug cap 20' is completely fitted with the upper surface of the bottle mouth 10', and the lower surface of the bottom plate 31' fits with the connection between the bottleneck 11' and the bottle body 12'. In this way, the double-chamber cartridge bottle 1' is sealed by the top plug 2' without introducing an additional plug pressing component.

[0233] (5) Take the double chamber cartridge 1' and the freeze drying rack out of the freeze dryer.

[0234] The freeze-dried preparation prepared by the freeze-drying method in the double-chamber cartridge 1' was sampled, tested for appearance, moisture and CCIT (vacuum decay method), and the test results are shown in Table 2:

[0235] Table 5 Appearance test, moisture test and CCIT test results of freeze-dried preparations

[0236]

[0237]

[0238] Figure 4 This is the appearance of the freeze-dried product obtained through the freeze-drying process. Figure 4 It can be seen that the appearance test results of the freeze-dried preparations show that they have good appearance and the average moisture test results are low; in addition, the double-chamber cartridge bottle packaging materials for injection in Examples 9 to 11 have good sealing properties during the freeze-drying process and can meet the sealing requirements of the preparations.

[0239] Embodiment 13

[0240] A double-chamber cartridge bottle packaging material for injection includes a double-chamber cartridge bottle 1' and a bottle cap assembly. The double-chamber cartridge bottle 1' has the same structure as the double-chamber cartridge bottle 1 of Example 9. The bottle cap assembly includes a top plug 2' and a top cover 3'. The top plug 2' has the same structure as the top plug 2' of Example 9. The top cover 3' has a structure as shown in FIG. Fig. 14BAs shown, the bottom plate 31' is adjusted to extend downward to fit at least a portion of the bottle body 12'; the shape of the downwardly extending portion of the bottom plate 31' is set to be an octagonal prism. In addition, the maximum length of the protrusion 304' protruding from the inner wall of the upper end 30' is set to 0.25mm, and other structures and parameters are the same as those of Example 9.

[0241] Embodiment 14

[0242] The freeze-drying process of the drug is carried out using the double-chamber cartridge packaging material for injection, and the freeze-dried preparation is obtained. The double-chamber cartridge packaging material for injection uses 25 portions of the double-chamber cartridge packaging material for injection in Example 13, and the freeze-drying process is carried out to obtain the freeze-dried preparation in the following steps:

[0243] (1) Add a middle stopper to each double chamber cartridge bottle 1', and then fill it with the drug solution to be lyophilized. The drug solution is lompezotropin, which contains: 22.0 mg hGH / mL lompezotropin, 10 mM succinic acid, 74.0 mg / mL trehalose dihydrate, and an appropriate amount of tromethamine to adjust the solution pH to pH 5.0.

[0244] The double-chamber cartridge bottle 1' is placed and fixed on a freeze-drying rack, wherein the freeze-drying rack is a tray-type freeze-drying rack, and the double-chamber cartridge bottle 1' is placed upright in the freeze-drying rack.

[0245] (2) The top plug 2' and the top cover 3' of Example 13 are preassembled and placed at the bottle mouth 10' of the double-chamber cartridge bottle 1'. The preassembly method of the top plug 2' and the top cover 3' is the same as that of Example 12.

[0246] (3) The liquid medicine to be freeze-dried is subjected to freezing, primary drying, secondary drying and plate layer plugging and capping respectively, and the specific operation method is the same as that of Example 12.

[0247] (4) After the freeze-drying process is completed, the double-chamber cartridge bottle 1' is filled with nitrogen to maintain a low moisture content of the freeze-dried product, and then the bottle is capped and sealed. The capping and sealing method is the same as in Example 12.

[0248] (5) The double-chamber cartridge 1' is taken out of the freeze dryer to obtain the freeze-dried preparation therein.

[0249] The freeze-dried preparation prepared by the freeze-drying method in the double-chamber cartridge 1' was sampled, tested for appearance, moisture and CCIT, and the test results are shown in Table 3:

[0250] Table 6 Appearance test, moisture test and CCIT test results of freeze-dried preparations

[0251]

[0252] As can be seen from Table 6, the appearance test results of the freeze-dried preparations show that they have good appearance and the average moisture test results are low; in addition, the double-chamber cartridge bottle packaging material for injection in Example 13 has good sealing properties during the freeze-drying process and can meet the sealing requirements of the preparations.

Claims

1. A freeze-drying method for a product for pharmaceutical, cosmetic or medical aesthetic applications, comprising: Adding a middle stopper to a double chamber cartridge (1) and then filling it with the product to be freeze-dried; After assembling the top plug (2) and the top cover (3), place them above the mouth (10) of the double-chamber cartridge bottle (1), and place and fix the double-chamber cartridge bottle (1) on a customized freeze-drying stand; Respectively performing freezing, primary drying and secondary drying on the product to be freeze-dried; The top cover (3) is used to press the top plug (2) to engage with the double-chamber cartridge bottle (1), so as to seal the double-chamber cartridge bottle (1) and fix the top plug (2), and the top plug (2) seals the bottle mouth (10) of the double-chamber cartridge bottle (1).

2. The freeze-drying method according to claim 1, wherein The freeze-drying scaffold is an independent freeze-drying scaffold or a tray-type freeze-drying scaffold. Preferably, the freeze-drying scaffold is a tray-type freeze-drying scaffold; and The dual-chamber cartridge bottle (1) is placed in the freeze-drying rack in an upright position or an inverted position. Preferably, the dual-chamber cartridge bottle (1) is placed in the freeze-drying rack in an upright position.

3. The freeze-drying method according to claim 1, wherein The temperature range set for freezing the product in the double-chamber cartridge bottle (1) is -60°C to -40°C; The temperature range of primary drying is -60℃~0℃, and the temperature range of secondary drying is 15℃~40℃; and The pressure range of the primary drying and the secondary drying is 0.02 mbar-0.2 mbar. Preferably, the pressure of the primary drying and the secondary drying is 0.06 mbar respectively.

4. The freeze-drying method according to claim 1, wherein The top cover (3) is used to press the top plug (2) to engage with the double-chamber cartridge bottle (1), and further comprises: The double chamber cartridge (1) is filled with nitrogen before pressing the top stopper (2) to maintain a low moisture content of the freeze-dried product.

5. A freeze-dried preparation prepared according to the freeze-drying method according to any one of claims 1 to 4.

6. An injection, comprising: Double chamber cartridge packaging materials for injection, lyophilized preparations and reconstitution solutions.

7. The injection according to claim 6, wherein The double-chamber cartridge bottle packaging material for injection comprises: a double-chamber cartridge bottle (1) and a bottle cap assembly, wherein: The double-chamber cartridge (1) is used to contain the lyophilized preparation and the reconstitution solution; The bottle cap assembly comprises the top plug (2) and the top cover (3); The top plug (2) seals the bottle mouth (10) of the double-chamber cartridge bottle (1); The top cover (3) is used to press and fix the top plug (2) so that the top plug (2) seals the bottle mouth (10) of the double-chamber cartridge bottle (1); and to seal the double-chamber cartridge bottle (1); The process of pressing and fixing the top plug (2) on the top cover (3) so that the top plug (2) seals the bottle mouth (10) of the double-chamber cartridge bottle (1) comprises the following steps: Pre-assembling the top plug (2) into the top cover (3); The top cover (3) equipped with the top plug (2) is placed above the bottle mouth (10) of the double-chamber cartridge bottle (1), and the top cover (3) is pressed downward.

8. The injection according to claim 7, wherein The double-chamber cartridge bottle (1) comprises: an inner cavity (13), a bottle body (12), the bottle neck (11) and the bottle mouth (10), wherein a bottle mouth opening (100) connected to the inner cavity (13) is arranged at the center of the bottle mouth (10), and the inner diameter of the bottle mouth opening (100) is smaller than the inner diameters of the bottle mouth (10) and the bottle neck (11); One side outer wall of the bottle body (12) is provided with a bypass protrusion (120).

9. The injection according to claim 6, wherein The lyophilized preparation is a lyophilized preparation prepared by the lyophilization method according to any one of claims 1 to 4 or the lyophilized preparation according to claim 5.

10. A freeze-drying method for a product for pharmaceutical, cosmetic or medical aesthetic applications, comprising: Adding a middle stopper to a double chamber cartridge (1') and then filling it with the product to be freeze-dried; After assembling the top plug (2') and the top cover (3'), place them above the mouth (10') of the double-chamber cartridge bottle (1'), and place and fix the double-chamber cartridge bottle (1') on a customized freeze-drying stand; Respectively freezing, primary drying and secondary drying the product to be freeze-dried; The top cover (3') is used to press the top plug (2') to engage with the double-chamber cartridge bottle (1'), so as to seal the double-chamber cartridge bottle (1') and fix the top plug (2'), and make the top plug (2') seal the bottle mouth (10') of the double-chamber cartridge bottle (1').

11. The freeze-drying method according to claim 10, wherein: The freeze-drying scaffold is an independent freeze-drying scaffold or a tray-type freeze-drying scaffold. Preferably, the freeze-drying scaffold is a tray-type freeze-drying scaffold; and The dual-chamber cartridge bottle (1') is placed in the freeze-drying rack in an upright position or an inverted position. Preferably, the dual-chamber cartridge bottle (1') is placed in the freeze-drying rack in an upright position.

12. The freeze-drying method according to claim 10, wherein: The temperature range set for freezing the product in the double-chamber cartridge bottle (1') is -60°C to -40°C; The temperature range of primary drying is -60℃~0℃, and the temperature range of secondary drying is 15℃~40℃; and The pressure range of the primary drying and the secondary drying is 0.02 mbar-0.2 mbar. Preferably, the pressure of the primary drying and the secondary drying is 0.06 mbar respectively.

13. The freeze-drying method according to claim 10, wherein: The top cover (3') is used to press the top plug (2') to engage with the double-chamber cartridge bottle (1'), and further comprises: The double chamber cartridge (1') is filled with nitrogen before pressing the top stopper (2') to maintain a low moisture content of the freeze-dried product.

14. A freeze-dried preparation prepared according to the freeze-drying method according to any one of claims 10 to 13.

15. An injection, comprising: Double chamber cartridge packaging materials for injection, lyophilized preparations and reconstitution solutions.

16. The injection according to claim 15, wherein The double-chamber cartridge bottle packaging material for injection comprises: a double-chamber cartridge bottle (1') and a bottle cap assembly, wherein: The double-chamber cartridge bottle (1') is used to contain the lyophilized preparation and the reconstitution solvent; The bottle cap assembly comprises the top plug (2') and the top cover (3'); The top plug (2') seals the bottle mouth (10') of the double-chamber cartridge bottle (1'); The top cover (3') is used to press and fix the top plug (2') so that the top plug (2') seals the bottle mouth (10') of the double-chamber cartridge bottle (1'); and to seal the double-chamber cartridge bottle (1'); The process of pressing and fixing the top plug (2') on the top cover (3') so that the top plug (2') seals the bottle mouth (10') of the double-chamber cartridge bottle (1') comprises the following steps: Pre-assembling the top plug (2') into the top cover (3'); The top cover (3') equipped with the top plug (2') is placed above the bottle mouth (10') of the double-chamber cartridge bottle (1'), and the top cover (3') is pressed downward.

17. The injection according to claim 16, wherein The double-chamber cartridge bottle (1') comprises: an inner cavity (13'), a bottle body (12'), the bottle neck (11') and the bottle mouth (10'), wherein a bottle mouth opening (100') connected to the inner cavity (13') is arranged at the center of the bottle mouth (10'), and the inner diameter of the bottle mouth opening (100') is smaller than the inner diameters of the bottle mouth (10') and the bottle neck (11'); One side outer wall of the bottle body (12') is provided with a bypass protrusion (120').

18. The injection according to claim 15, wherein The lyophilized preparation is a lyophilized preparation prepared by the lyophilization method according to any one of claims 10 to 13 or the lyophilized preparation according to claim 14.

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