Freeze-drying method for pharmaceuticals, cosmetics or medical beauty products, freeze-dried formulation and injection

Abstract

Disclosed is a freeze-drying method for pharmaceuticals, cosmetics or medical beauty products, comprising: adding a middle plug to a dual-chamber cartridge, filling the dual-chamber cartridge with a product to be freeze-dried, and placing and fixing the dual-chamber cartridge on a freeze-drying holder; limiting a top plug on a bottle opening of the dual-chamber cartridge; respectively performing freezing, primary drying and secondary drying on said product; and fixing the top plug by a top cover and sealing the bottle opening. The freeze-drying method provided by the present application can provide high-quality freeze-drying parameters and freeze-drying operations, integrated plug pressing and cover sealing of the dual-chamber cartridge is implemented by using the top plug and the top cover, such that the obtained freeze-dried product keeps higher quality, thereby improving the use effect of the product and prolonging the storage time of the product.

Description

Freeze-drying method, freeze-dried preparation and injection for pharmaceutical, cosmetic or medical aesthetic products TECHNICAL FIELD

[0001] The present application relates to the biopharmaceutical or cosmetic or medical aesthetic field, and more particularly, to a freeze-drying method, freeze-dried preparation and injection for pharmaceutical, cosmetic or medical aesthetic products. BACKGROUND

[0002] Most of the freeze-dried products on the market currently use a vial as a storage container. Before injection, a sterile syringe is used to extract a reconstituting agent from another container containing the reconstituting agent, and then the reconstituting agent is injected into the drug container for reconstitution, extraction and administration. The precision of administration and the use compliance are relatively poor, and a double-chamber carton bottle package can provide a better choice. The double-chamber carton bottle is divided into two chambers by a middle plug, wherein the front chamber is used to store freeze-dried drugs, and the rear chamber is used to store a reconstituting agent. During use, the reconstituting agent can be pushed through the bypass to flow into the front chamber to reconstitute the freeze-dried drugs, and after reconstitution, the bottom plug is pushed to the top to complete the injection process.

[0003] The use of a double-chamber carton bottle to separately store freeze-dried products and reconstituting agents allows medical personnel to conveniently reconstitute freeze-dried drugs and administer them, and patients can also self-administer, simplifying the operation process. For sensitive biological macromolecular drugs, medical device reagents and active ingredients in cosmetic reagents, the double-chamber carton bottle can mix or reconstitute the two contents before administration, which helps to maintain the stability of the active ingredients, and reduces degradation or inactivation caused by long-term contact.

[0004] However, the conventional freeze-drying process cannot complete the freeze-drying operation of the liquid to be freeze-dried and the integrated operation of sealing the double-chamber carton bottle in the freeze-drying machine, so a freeze-drying method integrating a pressing plug, freeze-drying and capping is needed to meet the good sealing of the double-chamber carton bottle during freeze-drying, so that the freeze-dried product has a good shape and a lower water content.

[0005] Therefore, there is an urgent need for a new drug freeze-drying method to solve the above problems, to improve the freeze-drying efficiency and quality of drugs, to fill the gap in the field of double-chamber carton bottle packaging on the market, and to enhance the core competitiveness of products. SUMMARY

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

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

[0008] The double-cavity carton bottle is filled with the product to be freeze-dried after a middle plug is added to the double-cavity carton bottle; the top plug is assembled with the top cover, and the double-cavity carton bottle is placed and fixed above the bottle opening of the double-cavity carton bottle; the product to be freeze-dried is freeze-dried, primary dried and secondary dried respectively; the top cover is used to press the top plug and embed the top plug with the double-cavity carton bottle, so as to seal the double-cavity carton bottle and fix the top plug, and the top plug seals the bottle opening and the bottle neck of the double-cavity carton bottle.

[0009] The freeze-drying method provided in the present application simultaneously presses the plug and the cover of the double-cavity carton bottle after freeze-drying treatment by operating the top cover, so as to seal the finished freeze-dried preparation in the double-cavity carton bottle and further seal the double-cavity carton bottle. The freeze-dried preparation obtained by the freeze-drying method also has a good freeze-dried powder appearance and a low water content, which helps to meet the high requirement freeze-dried product standard 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 support is a stand-alone freeze-drying support or a tray-type freeze-drying support, preferably, the freeze-drying support is a tray-type freeze-drying support; and the placement mode of the double-cavity carton bottle in the freeze-drying support is upright or inverted, preferably, the placement mode of the double-cavity carton bottle in the freeze-drying support is upright.

[0011] In some embodiments of the present application, the temperature range set for freeze-drying the product in the double-cavity carton bottle is -60℃ to -40℃; the temperature range for primary drying is -60℃ to 0℃, and the temperature range for secondary drying is 15℃ to 40℃; and the pressure range for primary drying and secondary drying is 0.02mbar-0.2mbar, preferably, the pressure for primary drying and secondary drying is 0.06mbar respectively.

[0012] In some embodiments of the present application, the use of the top cover to press the top plug and embed the top plug with the double-cavity carton bottle further comprises: performing a nitrogen filling operation on the double-cavity carton bottle before pressing the top plug, so as to maintain a low moisture content of the freeze-dried product.

[0013] According to another aspect of the present application, a freeze-dried preparation is also provided, which is prepared according to any one of the freeze-drying methods described above. The freeze-dried preparation also has the characteristics of high freeze-drying quality and low moisture, for example, when the freeze-dried preparation is a drug, it can be used in various application scenarios such as injection, oral administration, biological experiments, etc., to provide better effects; for example, when the freeze-dried preparation is a reagent or a cosmetic for medical aesthetics, the active ingredients can be retained for a long time, and through rapid reconstitution injection or external use, better effects can also be provided to the user.

[0014] According to another aspect of the present application, an injection is also provided, which can include a double-cavity carton bottle package for injection, a freeze-dried preparation, and a reconstitution agent. The injection provided by the present application can include a solution type, an emulsion type, a suspension type, etc., and can be used in various application scenarios such as drug treatment, emergency treatment for 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, the double-cavity carton bottle package for injection can include a double-cavity carton bottle and a bottle cap assembly, wherein the double-cavity carton bottle is used to contain a drug and a reconstitution agent; the bottle cap assembly includes a top plug and a top cap; the top plug seals the bottle mouth of the double-cavity carton bottle; the top cap is used to press and fix the top plug so that the top plug seals the bottle mouth of the double-cavity carton bottle; and the double-cavity carton bottle is sealed; wherein the process of pressing and fixing the top plug so that the top plug seals the bottle mouth of the double-cavity carton bottle includes the following steps:

[0016] The top plug is pre-assembled into the top cap; the top cap with the assembled top plug is placed above the bottle mouth of the double-cavity carton bottle, and the top cap is pressed downward. After the top plug is pre-assembled into the top cap, the top plug and the top cap also have the characteristics of being integrally formed, and a plug assembly does not need to be introduced, the top cap can directly realize plug sealing and capping by pressing the top plug, the sealing efficiency of the double-cavity carton bottle in the freeze-drying process is improved, the number of failed operations caused by more operation steps is avoided, and when the failed operation is difficult to remedy in the conventional way in the freeze-drying process, the self-plug and cap integrated operation of the top cap is particularly important to ensure the efficiency of the freeze-drying process.

[0017] In some embodiments of the present application, the double-cavity carton bottle can include an inner cavity, a bottle body, a bottle neck, and a bottle mouth, the center of the bottle mouth is provided with a bottle mouth opening connected with the inner cavity, the inner diameter of the bottle mouth opening is smaller than the inner diameter of the bottle mouth and the bottle neck; and the outer wall of one side of the bottle body has a bypass protrusion.

[0018] In some embodiments of the present application, the freeze-dried preparation is a freeze-dried preparation prepared by the freeze-drying method according to any one of the above or the freeze-dried preparation provided by the present application.

[0019] Compared with the prior art, the present application has at least one of the following technical effects:

[0020] 1. The present application provides an integrated sealing method for plug sealing and cap sealing of the double-cavity carton bottle package for injection in the freeze-drying process.

[0021] 2. The present application provides optimal freeze-drying parameters and water removal operations of the freeze-drying process, so that the freeze-dried product obtained by using the freeze-drying method of the present application maintains better quality and is convenient for storage or use.

[0022] 3. The present application provides a high-quality freeze-dried preparation prepared based on the freeze-drying method, which can be a high-purity freeze-dried drug, a medical instrument reagent, or a cosmetic reagent.

[0023] 4. The application provides a injection, which can be based on double cavity cassette bottle package materials to hold freeze-dried preparation and reconstituted agent and stable storage, and the freeze-dried preparation and reconstituted agent can be quickly mixed and reconstituted when the injection is used, so as to ensure the high efficiency and convenience of the preparation use. BRIEF DESCRIPTION OF DRAWINGS

[0024] The above and other objects, features and advantages of the present application will become more apparent from the following detailed description of embodiments of the present application, when taken in conjunction with the accompanying drawings. The drawings provided in the present application are for the purpose of providing further understanding of the present application and form a part of the specification, and together with the detailed description of the present application, serve to explain the present application. The drawings provided in the present application do not limit the present application, and are merely used to illustrate the embodiments of the present application. In the drawings, the same reference numerals refer to the same components or steps throughout the drawings.

[0025] FIG. 1 illustrates a schematic diagram of a freeze-dried scaffold of the present application.

[0026] FIG. 2 illustrates a freeze-drying curve schematic diagram of a freeze-dried preparation of the present application.

[0027] FIG. 3 illustrates a schematic diagram of the appearance of a freeze-dried preparation of the present application.

[0028] FIG. 4A illustrates a first schematic diagram of the appearance of another freeze-dried preparation of the present application.

[0029] FIG. 4B illustrates a second schematic diagram of the appearance of another freeze-dried preparation of the present application.

[0030] FIG. 5 illustrates a schematic diagram of the structure of a double cavity cassette bottle 1 and a top plug 2 of the present application.

[0031] FIG. 6A illustrates a schematic diagram of the structure of a top cover 3 of the present application.

[0032] FIG. 6B illustrates another schematic diagram of the structure of a top cover 3 of the present application.

[0033] FIG. 7 illustrates another schematic diagram of the structure of a top plug 2 and yet another schematic diagram of the structure of a top cover 3 of the present application.

[0034] FIG. 8A illustrates a schematic diagram of the structure of a top plug positioning point 303 of the present application.

[0035] FIG. 8B illustrates another schematic diagram of the structure of a top plug positioning point 303 of the present application.

[0036] FIG. 9 illustrates a schematic diagram of the structure of an upper end 30 of the present application.

[0037] FIG. 10 illustrates a schematic diagram of the structure of a maximum length of a protruding part 304 of the present application.

[0038] FIG. 11 illustrates a schematic diagram of the structure of an upper cut angle and a lower cut angle of a protruding part 304 of the present application.

[0039] Figure 12 illustrates a structural schematic diagram of the double-cavity carton bottle packaging assembly of the present application.

[0040] Figure 13 illustrates a structural schematic diagram of the double-cavity carton bottle 1' and the top plug 2' of the present application.

[0041] Figure 14A illustrates a structural schematic diagram of the top cover 3' of the present application.

[0042] Figure 14B illustrates another structural schematic diagram of the top cover 3' of the present application.

[0043] Figure 14C illustrates yet another structural schematic diagram of the top cover 3' of the present application.

[0044] Figure 15A illustrates another structural schematic diagram of the top plug 2' and yet another structural schematic diagram of the top cover 3' of the present application.

[0045] Figure 15B illustrates a structural schematic diagram of the fitting portion 306' of the top cover 3' of the present application.

[0046] Figure 16A illustrates a structural schematic diagram of the top plug positioning point 303' of the present application.

[0047] Figure 16B illustrates another structural schematic diagram of the top plug positioning point 303' of the present application.

[0048] Figure 16C illustrates a top view of the demolding hole 305' of the present application.

[0049] Figure 17 illustrates a structural schematic diagram of the demolding hole 305' of the present application.

[0050] Figure 18 illustrates a structural schematic diagram of the upper end 30' of the present application.

[0051] Figure 19 illustrates a structural schematic diagram of the maximum length, upper cutting angle and lower cutting angle of the protruding portion 304' of the present application.

[0052] Figure 20 illustrates a structural schematic diagram of the double-cavity carton bottle packaging assembly of the present application.

[0053] Figure 21A illustrates a structural schematic diagram of the top plug 2" and the pressure plug assembly of the present application.

[0054] Figure 21B illustrates another structural schematic diagram of the top plug 2" and the pressure plug assembly of the present application.

[0055] Figure 22 illustrates a structural schematic diagram of the top cover 3" of the present application.

[0056] Explanation of Reference Marks 1 - Double-chambered Cartridge Bottle 2 - Stopper 3 - Top Cap 4 - Sheath 1' - Double-chambered Cartridge Bottle 2' - Stopper 3' - Top Cap 4' - Sheath 2" - Stopper 3" - Top Cap 10 - Bottle Mouth 11 - Bottle Neck 12 - Bottle Body 13 - Inner Chamber 10' - Bottle Mouth 11' - Bottle Neck 12' - Bottle Body 13' - Inner Chamber 20 - Cap 21 - Plug Column 22 - Sealing Portion 20' - Cap 21' - Plug Column 22' - Sealing Portion 20" - Cap 21" - Plug Column 30 - Upper End 31 - Middle End 32 - Lower End 30' - Upper End 31' - Bottom Disc 40' - Sheath Main Body 41' - Flange 31" - Bottom Disc 50 - Retaining Jig 51 - Press-in Jig 100 - Bottle Mouth Opening 120 - Bypass Protrusion 100' - Bottle Mouth Opening 120 - Bypass Protrusion 200 - Gap Portion 200' - Gap Portion 300 - Top Disc 301 - Thread 302 - Opening 303 - Stopper Positioning Point 304 - Protrusion Portion 310 - Lugs 320 - Protruding Strips 321 - First Lugs 300' - Top Disc 301' - Thread 302' - Opening 303' - Stopper Positioning Point 304' - Protrusion Portion 305' - Demolding Hole 306' - Fitting Portion 310' - Internal Lugs 311' - Lugs Two-side Opening 321' - First Lugs 400' - Second Lugs 300" - Top Disc 301" - Thread 500 - Protrusion Portion 510 - Pressing Column DETAILED DESCRIPTION

[0057] As described above, the freeze-drying method for a product for pharmaceutical, cosmetic or medical aesthetic applications according to the present application includes: adding a stopper into a double-chambered cartridge bottle 1, and then pouring a product to be freeze-dried; assembling a top cap 3 with a stopper 2, and placing the stopper 2 over a bottle mouth 10 of the double-chambered cartridge bottle 1, and placing and fixing the double-chambered cartridge bottle 1 on a customized freeze-drying support; respectively performing freezing, primary drying and secondary drying on the product to be freeze-dried; and pressing the stopper 2 with the top cap 3 to fit the stopper 2 with the double-chambered cartridge bottle 1, to seal the double-chambered cartridge bottle 1 and fix the stopper 2, and to make the stopper 2 seal the bottle mouth 10 of the double-chambered cartridge bottle 1.

[0058] In the present application, the middle plug added to the double-chamber carton bottle 1 and the product to be lyophilized can be any middle plug for double-chamber carton bottles and lyophilizable product added to the double-chamber carton bottle 1 according to its size and structure. The freezing, primary drying and secondary drying operations can be carried out in a freeze dryer which can accommodate the freeze-drying rack used in the freeze-drying method. The driving mode of the top cover 3 to press down during the process of fixing the top plug 2 with the top cover 3 and sealing the bottle opening 10 of the double-chamber carton bottle 1 through the top plug 2 can be any driving mode that can be implemented in the freeze dryer, such as mechanical pressing, pneumatic driving, pneumatic clamp driving or spring pressing.

[0059] In the present application, after adding the middle plug to the double-chamber carton bottle 1, the product to be lyophilized can be filled, and in particular, the product to be lyophilized can be a product to be lyophilized and stored for a short / long period in the inner chamber 13 of the double-chamber carton bottle 1, such as a small molecule drug, a polypeptide, an enzyme, an antibody, a fusion protein, an antibody drug conjugate, a reagent, etc. The user can select any liquid to be lyophilized and fill it into one of the inner chambers 13 of the double-chamber carton bottle 1 to lyophilize it using the freeze-drying method of the present application.

[0060] In the present application, the freeze-drying rack is a standalone freeze-drying rack or a tray-type freeze-drying rack. The present application sets the type of freeze-drying rack used in the freeze-drying method to be a standalone freeze-drying rack or a tray-type freeze-drying rack, and neither limits the specific model, size and working parameters of the freeze-drying rack in the freeze dryer. Preferably, the freeze-drying rack is a tray-type freeze-drying rack, which is easy to place a larger number of double-chamber carton bottles 1.

[0061] In particular, the double-chamber carton bottle 1 can be placed in the freeze-drying rack in an upright or inverted manner, and preferably, the double-chamber carton bottle 1 is placed in the freeze-drying rack in an upright manner, which facilitates uniform distribution of heat in the double-chamber carton bottle 1, improves the efficiency of solvent sublimation, and in addition, can reduce the degree of sedimentation and aggregation of the product, maintaining the uniform and stable appearance of the product.

[0062] In the present application, the temperature range for freezing the product in the double-cavity carton bottle 1 can be a temperature range suitable for product freeze-drying, and the freezing temperature is generally -60℃ to -40℃, and the raw material to be freeze-dried generally has a high freezing efficiency and maintains its own quality, so the freezing temperature is any temperature value in the range of -60℃ to -40℃. Specifically, the temperature range for freezing the product in the double-cavity carton bottle 1 is -60℃ to -40℃, i.e. -60℃, -59℃, -58℃, -57℃, -56℃, -55℃, -54℃, -53℃, -52℃, -51℃, -50℃, -49℃, -48℃, -47℃, -46℃, -45℃, -44℃, -43℃, -42℃, -41℃ or -40℃; the temperature range for primary drying is -60℃ to 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℃, -35℃, -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℃, -5℃, -4℃, -3℃, -2℃, -1℃ or 0℃; and the temperature range for secondary drying is 15℃ to 40℃, i.e. 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℃.

[0063] Similarly, the temperature of the first drying and the second drying can be any temperature value in the range of -60°C to 0°C and 15°C to 40°C, respectively, to increase the sublimation rate of the water in the product. In addition, the pressure range of the first drying and the second drying can be any value in the range of 0.02 mbar to 0.2 mbar, and when the pressure of the first drying and the second drying is preferably 0.06 mbar, the drying efficiency can reach a peak. Specifically, the pressure range of the first drying and the second drying is 0.02 mbar to 0.2 mbar, i.e. 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, and preferably, the pressure of the first drying and the second drying is 0.06 mbar, respectively.

[0064] In the present application, the use of the top cover 3 to press the stopper 2 and embed the double-chamber carton bottle 1 also includes the operation of filling nitrogen into the double-chamber carton bottle 1 before pressing the stopper 2 to maintain the low moisture content of the freeze-dried product. Those skilled in the art can understand that the operation of filling nitrogen into the double-chamber carton bottle 1 before closing the bottle opening 10 aims to make the nitrogen in the inner chamber 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 make the position of the stopper in the double-chamber carton bottle fixed.

[0065] In the present application, it also includes a freeze-dried preparation prepared according to the freeze-drying method described above. In particular, since the product to be freeze-dried added to one of the inner chambers 13 of the double-chamber carton bottle 1 in the present application can be one of various products, the freeze-dried preparations obtained finally can also be different when the product to be freeze-dried is poured into the double-chamber carton bottle 1 at different times; in addition, when the freeze-drying parameters, such as the temperature and pressure of the first drying, implemented in the freeze-drying process of the product in the present application are changed, the freeze-dried preparations of the same product to be freeze-dried can also be of different quality or different properties, such as different water content, different solid forms of the preparation, etc.

[0066] In the present application, an injection is also included, which comprises: a double-cavity carton bottle package for injection, a freeze-dried preparation and a reconstituting agent. It should be noted that the freeze-dried preparation and the reconstituting agent can be any freeze-dried preparation and reconstituting agent suitable for the double-cavity carton bottle package for injection and the freeze-drying process. Specifically, the freeze-dried preparation can be any product to be freeze-dried that can be filled into the double-cavity carton bottle 1 of the present application, any freeze-dried preparation prepared by freeze-drying treatment via the freeze-drying method of the present application, including the freeze-dried preparation provided by the present application.

[0067] In addition, the reconstituting agent can be a reconstituting agent for reconstituting any freeze-dried preparation prepared as described above, such as sterile water for injection (which can contain bacteriostatic agents such as phenol, m-cresol, benzyl alcohol, etc.), normal saline, 5% glucose solution, and other buffers such as phosphate buffer, citric acid buffer, acetic acid buffer, histidine buffer, succinic acid buffer, tris-hydroxymethyl aminomethane hydrochloride buffer, etc., which can be used to reconstitute the freeze-dried preparation provided by the present application at the time of administration.

[0068] In the present application, the double-cavity carton bottle package for injection comprises: a double-cavity carton bottle 1 and a bottle cap assembly, wherein the double-cavity carton bottle 1 is used to hold the freeze-dried preparation and the reconstituting agent. The bottle cap assembly comprises a top plug 2 and a top cap 3, which are used to seal the double-cavity carton bottle 1. The double-cavity carton bottle 1, as shown in FIG. 5, can be placed in a freeze-drying support used in the existing freeze-drying process, and the double-cavity carton bottle package can be fixed and placed upright or inverted in the freeze-drying support and sheath; the bottle cap assembly can be made of any material suitable for achieving the sealing function of the bottle cap. The top plug 2 is limited in the top cap 3 and is used to seal the bottle mouth 10 of the double-cavity carton bottle 1; the top cap 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-cavity carton bottle 1 and seals the double-cavity carton bottle 1; wherein the process of pressing and fixing the top plug 2 by the top cap 3 so that the top plug 2 seals the bottle mouth 10 of the double-cavity carton bottle 1 can include the following steps:

[0069] Pre-assembling the top plug 2 into the top cap 3; and placing the top cap 3 with the assembled top plug 2 above the bottle mouth 10 of the double-cavity carton bottle 1 and pressing the top cap 3 downward to press the top plug 2. The driving mode of the top cap 3 downward can be mechanical compression, pneumatic driving, pneumatic clamp driving or spring pressing, etc.

[0070] In the present application, the double-cavity card bottle 1 comprises an inner cavity 13, a bottle body 12, a bottle neck 11 and a bottle mouth 10, the center of the bottle mouth 10 is provided with a bottle mouth opening 100 connected with the inner cavity 13, the inner diameter of the bottle mouth opening 100 is smaller than the inner diameter of the bottle mouth 10 and the bottle neck 11; the outer wall of one side of the bottle body 12 has a bypass protrusion 120. Those skilled in the art can understand that the size of the inner cavity 13, the bottle body 12, the bottle neck 11 and the bottle mouth 10 of the double-cavity card bottle 1 can be adjusted to adapt to the size range of the commonly used lyophilized support, such as changing the vertical length of one or more parts of the double-cavity card bottle 1, changing the radial length of one or more parts of the double-cavity card bottle 1, etc., all of which do not deviate from the protection scope of the present application.

[0071] In the present application, the top plug 2 comprises a plug cap 20 and a plug column 21, the diameter of the plug column 21 can be equal to or slightly larger than the inner diameter of the bottle mouth opening 100, after the plug column 21 is embedded in the bottle mouth opening 100, the lower surface of the plug cap 20 is completely matched with the upper surface of the bottle mouth 10 to realize the sealing of the bottle mouth 10. In particular, the top plug 2 is made of elastic rubber material, so the diameter of the plug column 21 can be adjusted within the diameter range of the bottle mouth opening 100 after the plug column 21 is pressed under force, and the diameter of the plug column 21 can be slightly larger than the diameter of the bottle mouth opening 100 to ensure the tightness of the sealing.

[0072] In the present application, the top cover 3 as shown in FIG. 6A comprises an upper end 30, a middle end 31 and a lower end 32; the upper end 30 has a top disc 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; the inner wall of the top cover 3 is matched with the bottle mouth 20, the bottle neck 21 and at least part of the bottle body 22; when the top cover 3 faces the bottle mouth 10, the top disc 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-cavity card bottle 1 is completed, the top disc 300 is tightly matched above the plug cap 20 to press the top plug 2. The opening 302 can discharge the sublimated moisture in the product, the thread 301 is used for thread engagement with a sterile injection needle, and the convex ring 310 can match a sheath.

[0073] It should be noted that the shape of the lower end 32 of the top cover 3 can be a cylinder or a prism as shown in FIG. 6B, and the length thereof in the vertical direction can be adjusted, so the lower end 32 can be matched with a small part of the bottle body 12, or can be matched with most parts or the entire bottle body 12 to realize better sealing performance of the cover and to adapt to the size requirement of the top cover 3 in the lyophilization process. The convex strip 320 is used to increase the friction between the lower end 32 and the matched sheath to improve the mutual cooperation and fixation effect; in particular, the convex strip 320 can also be removed. The shape of the lower end 32 can be a cylinder or a multi-prism to avoid the top cover 3 from slipping off or relative sliding with the double-cavity card bottle 1 under the rotation centrifugal force, which affects the sealing performance.

[0074] In particular, the length of the middle end 31 of the top cover 3 along the direction of the bottle neck 11 and the bottle body 12 can be adjusted, and the convex ring 310 can be adjusted to the highest part to be attached to the lower part of the upper end 30, so as to adapt to the sealing requirement of the double-cavity carton bottle 1 to the different degrees of pressing cover 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 adapt to the size requirement of the double-cavity carton bottle 1 and the top cover 3 to the freeze-drying support in the freeze-drying process. In particular, the center of the top disc 300 has a top disc opening, and the circumferential lower edge of the top disc opening to the upper edge thereof can have an inclination angle β in the vertical direction, and the circumferential upper edge of the top disc opening has a greater opening length than the circumferential lower edge; the circumferential edge surface of the top disc opening can be curved or flat.

[0075] In the present application, as shown in FIG. 7, the top plug 2 can further include a sealing portion 22 protruding above the plug cap 20, which can be inserted into the top disc opening, and when the top plug 2 is completely embedded in the bottle mouth 10, that is, the double-cavity carton bottle 1 is completed, the sealing portion 22 is embedded in the top disc opening and partially protrudes longitudinally from the top disc 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 disc opening, and 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 be slightly deformed to be inserted into the top disc opening from the circumferential lower edge of the top disc opening.

[0076] Therefore, in the process of pre-assembling the top plug 2 into the top cover 3, the sealing portion 22 can be embedded in the top disc opening, the edge portion thereof closely fits the circumferential outer edge of the top disc opening, and finally partially protrudes from the upper edge of the top disc opening; by setting the radial length L of the sealing portion to have a relatively long radial length, the close fitting of the edge portion thereof to the circumferential outer edge of the top disc opening is improved, and the top plug 2 is further prevented from slipping out of the top disc 300. In addition, by adjusting the size of β, the circumferential lower edge of the top disc opening and the sealing portion 22 can have a closer fit than the circumferential upper edge of the top disc opening, so that the top disc opening closely surrounds and fixes the sealing portion 22.

[0077] In some embodiments, the radial length L of the closure portion 22 can be 2.0 mm - 5.0 mm, in particular, the radial length L of the closure 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, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, or 5.0 mm; preferably, the radial length L of the closure portion 22 can be 3.0 mm - 4.0 mm, in particular, the radial length L of the closure portion 22 can preferably be 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, or 4.0 mm. The inclination angle β can be 0°, 1°, 2°, 3°, 4°, 5°, 6°, 7°, 8°, 9°, or 10°, etc.

[0078] In some embodiments, the circumferential lower edge opening length of the top disc opening can be 1.5 mm - 5.0 mm, in particular, the circumferential lower edge opening length of the top disc opening can be 1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm, 1.9 mm, 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, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, or 5.0 mm; preferably, the circumferential lower edge opening length of the top disc opening can be 2.5 mm - 4.0 mm, in particular, the circumferential lower edge opening length of the top disc opening can preferably be 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, or 4.0 mm.

[0079] By taking the radial length L of the sealing portion 22 slightly larger than the circumferential lower edge opening length of the top disc opening, the sealing portion 22 is more fitted with the circumferential lower edge of the top disc opening, so that the top disc opening as a whole effectively fits and fixes the sealing portion 22, and the circumferential edge provides further support, so that the top plug 2 as a whole does not slip off. Preferably, β is set to 0°, and when the top disc opening has no inclination angle in the vertical direction, the sealing portion 22 can be well fixed, while avoiding excessive resistance when the sealing portion 22 is inserted into the top disc opening. In another case, when the top disc opening needs to have a certain inclination angle in the vertical direction to improve the limiting effect of the top disc 300 on the top plug 2, β can also be set to 5° to improve the fixing degree of the sealing portion 22, while not affecting the insertion and embedding of the sealing portion 22 into the top disc opening. Those skilled in the art can adjust the radial length L of the sealing portion 22, the inclination angle β and the circumferential lower edge opening length of the top disc opening according to the actual application of the bottle cap assembly based on the above parameters, to adaptively adjust the fitting and fixing degree of the sealing portion 22 and the top disc 300.

[0080] In particular, the diameter of the cap 20 of the top plug 2 can be slightly smaller than the inner diameter of the top cover 3, and since the top plug 2 is fixed with the bottle opening 100 through the cooperation of the top plug positioning point 303 and the cap 20, the sealing is achieved. In this case, the diameter of the cap 20 is set to be slightly smaller than the inner diameter of the top cover 3, so that a small gap part 200 is left between the surface of the cap 20 and the inner wall of the upper end 30, as shown in FIG. 9. In this way, when the top plug 2 is pressed by the top cover 3, the pressed volume of the cap 20 extends to the gap part 200 reserved around it, so that the cap 20 will not protrude upwardly to the top disc opening in the middle due to the pressure.

[0081] In some embodiments, the diameter of the plug cap 20 can range from 5.0 mm to 10.0 mm, in particular, the diameter of the plug cap 20 can be 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, or 10.0 mm; preferably, the diameter of the plug cap 20 can range from 6.0 mm to 8.0 mm, in particular, the diameter of the plug cap 20 can preferably be 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, or 8.0 mm.

[0082] In some embodiments, the diameter of the upper end 30 of the top cover 3 can range from 5.0 mm to 10.0 mm, specifically, the diameter of the upper end 30 can be 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 or 10.0 mm; preferably, the diameter of the upper end 30 can range from 6.0 mm to 8.0 mm, specifically, the diameter of the upper end 30 can preferably be 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 or 8.0 mm.

[0083] More preferably, the diameter of the plug cap 20 can be configured as 7.0 mm, and the inner diameter of the upper end 30 of the top cover 3 that cooperates with the plug cap 20 can be configured as 7.3 mm, so that a gap part 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, and the gap part 200 can accommodate the increased volume of the plug cap 20 when the plug cap 20 is extruded during the assembly of the stopper 2 or the insertion of the injection needle, thereby avoiding the generation of upward pressure. It should be noted that in the bottle cap assembly according to the embodiments 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 benchmarks according to the actual application of the bottle cap assembly, so as to adapt to the cooperation of the bottle cap assembly with the freeze-drying support of the freeze-dryer, the cooperation with the packaging sheath and / or the cooperation with the syringe. For example, the stability of the pre-assembly of the stopper 2 can be adjusted by appropriately adjusting the diameter of the plug cap 20; the more tightly sealed or more easily detached seal of the double-chamber carton bottle 1 can be maintained by appropriately adjusting the diameter of the upper end 30; and after the diameter of the plug cap 20 and the diameter of the upper end 30 are adjusted respectively, in order to appropriately avoid the influence of the extrusion 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 part 200, etc.

[0084] The stopper 2 can be stably fixed in the top cover 3 by inserting and fitting the sealing part 22 into the top disc opening during the pre-assembly of the top plug 2, and limiting the stopper cap 20 by cooperating with the stopper positioning points 303. Therefore, the mechanical processes performed on the top cover 3 during the freeze-drying process, such as shaking and suspension, will not affect the fixation of the top plug 2 in the top cover 3, thereby avoiding the top plug 2 from falling off the top cover 3 before the capping operation, ensuring the capping qualification rate after freeze-drying. The gap part 200 of the stopper cap 20 can also avoid core taking when cooperating with the injection needle, thereby ensuring product quality and efficient use.

[0085] In the present application, the upper end 30 of the top cover 3 also has stopper positioning points 303, as shown in FIGS. 8A and 8B, which protrude from the inner wall of the upper end 30 in the direction of the axis of the top cover 3, and are used to fix the top plug 2 embedded in the bottle mouth 10. Specifically, the stopper positioning points 303 are evenly arranged in the inner wall of the upper end 30 along the radial direction and in a ring shape. The shape of the stopper positioning points 303 can be cylindrical or prismatic, and in addition, the number of stopper positioning points 303 and the spacing length / arc between the plurality of stopper positioning points 303 can be adjusted to maintain optimal fixation of the top plug 2.

[0086] In the present application, the number of stopper positioning points 303 is 4 or 5 or more. In particular, the number of stopper positioning points 303 can be even to maintain a symmetrical arrangement along the center of the upper end 30, thereby providing more stable fixation of the top plug 2. Preferably, the number of stopper positioning points 303 is 4 or 8 to provide relatively stable fixation of the top plug 2; more preferably, the number of stopper positioning points 303 is 8 to provide the most stable fixation of the top plug 2. The stopper positioning points 303 can also be used for positioning the top plug 2 before it is pressed into the bottle mouth 10, and the top plug 2 is limited by the stopper positioning points 303 to avoid it from slipping out of the bottle mouth 10 on its own.

[0087] In the present application, the upper end 30 of the top cover 3 also has protrusions 304 protruding from the inner wall of the upper end 30 in the direction of the axis of the top cover 3, as shown in FIG. 10. The top cover 3 can be limited by the protrusions 304 on the bottle mouth 10 before capping, so that the sublimated water in the inner cavity 13 can be discharged through the opening 302. Therefore, the provision of the protrusions 304 helps to provide gas exchange and sublimated water discharge for the double-cavity cartridge bottle 1 during the freeze-drying process. Those skilled in the art can understand that the protrusions 304 will not hinder the movement of the top plug 2 during the embedding of the top plug 2 into the bottle mouth 10, because the protrusions 304 are evenly distributed on the inner wall of the upper end 30, and the top disc 300 can uniformly apply pressure to the entire surface of the stopper cap 20 pre-assembled into the upper end 30 when capping. Therefore, the top plug 2 can be stably embedded into the bottle mouth 10 horizontally.

[0088] In the present application, the number of protrusions 304 is 2 or more than 3; preferably, the maximum length (D) of the protrusion 304 protruding towards the axis 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-0.30mm; further preferably, D can be 0.20mm-0.28mm, which can make the top cover 3 not easy to deform due to excessive pressure when capping, and the sealing performance of the top cover 3 after capping is good and is not easy to slip off; more preferably, D can be 0.23mm-0.28mm, which can avoid the deformation of the top cover 3 due to pressure during capping, and the sealing performance of the top cover 3 after capping is good and is not easy to slip off. It should be noted that when the material of the protrusion 304 is different, the value of D can be adjusted to achieve the optimal limiting of the top cover 3 before capping and the optimal improvement of the fit between the upper end 30 and the double-cavity carton 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 protrusion 304 can provide optimal stability of the top cover 3 after capping.

[0089] In the present application, the shape of the protrusion 304 can be trapezoidal, semicircular, semi-elliptical or rectangular, preferably the shape of the protrusion 304 is trapezoidal. When the shape of the protrusion 304 is trapezoidal with its short side adjacent to the bottle mouth 10, the fit tightness of the upper end 30 and the bottle mouth 10 is better, and the top cover 3 can be highly stably fitted on the double-cavity carton bottle 1 to maintain good sealing performance.

[0090] When the shape of the protrusion 304 is trapezoidal, preferably, the upper cut angle (θ) of the side surface of the protrusion 304 towards the axis direction of the top cover 3 can be any angle between 0°-90°, as shown in FIG. 11. Further preferably, θ can be 30°-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 protrusion 304 on improving the fit tightness of the top cover 3 and the bottle mouth 10 can be significantly weakened; when θ is greater than 45°, the protrusion 304 can 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 in the range of 30°-45°; more preferably, θ can be 30°, so that the protrusion 304 can provide better fit effect of the top cover 3 and the bottle mouth 10, and also does not adversely hinder the capping process.

[0091] In addition, when the shape of the protruding portion 304 is trapezoidal, it is further preferred that the angle (a) between the face of the protruding portion 304 facing the axis of the cap 3 and the lower cutting angle of the side face is any angle between 0° and 90°. Since the pressure during the capping process is mainly affected by the size of θ, when a and θ have the same value, the protruding portion 304 can have a stable axisymmetric structure and is not prone to deformation or damage during the capping process or storage process. Therefore, it is further preferred that a be 30° in order to improve the efficiency and anti-deformation ability of the protruding portion 304, and more preferably, θ and a of the protruding portion 304 are both 30°, so that the cap 3 will not be structurally damaged due to a large force during the capping process, and the cap 3 can be highly tightly fitted with the double-chamber carton bottle 1, which also improves the efficiency and accuracy of capping the double-chamber carton bottle 1.

[0092] The present application also provides a double-chamber carton bottle package for injection, which comprises the bottle cap assembly and the double-chamber carton bottle 1 described above, and a double-chamber carton bottle package assembly for injection, which comprises the double-chamber carton bottle package for injection and a sheath 4 used in cooperation therewith. It should be noted that the double-chamber carton bottle package for injection can comprise any combination of the bottle cap assembly and the double-chamber carton bottle 1 that can be formed and / or maintained by any combination disclosed in the present application.

[0093] The sheath 4 provided by the present application is an open-top octagonal prism, and its structure is shown in FIG. 12. The inner wall of the sheath 4 has an octagonal shape. After the double-chamber carton bottle 1 completes the freeze-drying process and is sealed by the cap 3, the double-chamber carton bottle 1 can be pressed into the sheath. During this process, the lower end 32 of the cap 3 is fitted with the inner wall of the sheath 4 to avoid relative sliding, and the bypass protrusion 120 of the bottle body 12 is clamped at the octagonal vertex of the inner wall of the sheath, which also prevents the double-chamber carton bottle 1 from sliding relative to the inner wall of the sheath 4. In this way, the sheath can stably protect the entire package.

[0094] In the present application, the lower end 32 is in the shape of a cylinder or an octagonal prism, and can preferably be an octagonal prism, and is fixedly assembled with the sheath 4 used for storing the double-chamber carton bottle 1 through interference fit. Specifically, the lower end 32 has a first notch 321 near the upper outer edge of the middle end 31, the top end of the sheath 4 is stretched and located on the first notch 321, and the cap 3 and the sheath 4 are forced towards each other and clamped in the middle. By this interference fit between the lower end 32 and the sheath 4, when the double-chamber carton bottle 1 is placed in the sheath 4, the cap 3 and the stopper 2 therein are more tightly fixed with the bottle mouth 10, effectively preventing the package after freeze-drying from leaking, rotating, falling off, etc., to ensure the high-quality storage of the freeze-dried preparation.

[0095] Specifically, in some embodiments, the lyophilized preparation is reconstituted in the double-chambered carton bottle 1 and then injected subcutaneously through a needle, such as a microfine needle (MFN), for disease treatment or medical aesthetic application. The needle hub of the injection needle has a threaded structure that is engaged or removed by rotation with the threads 301 of the cap 3 when the MFN is mounted to or removed from the cap 3 for product extraction or removal, during which the lower end 32 of the cap 3 is fixed against rotation by the octagonal inner wall of the sheath 4, and the bypass protrusion 120 of the double-chambered carton bottle 1 is also fixed against rotation by the vertex of the octagonal inner wall of the sheath 4. Thus, by using the lower end 32 in the shape of an octagonal prism and cooperating with the sheath 4, the double-chambered carton bottle packaging assembly can be kept from rotating during screwing / dismounting of the injection needle, thereby avoiding idle rotation during sterile injection needle screwing / dismounting and improving the efficiency of use of the lyophilized preparation and the convenience of operation.

[0096] The present application provides a lyophilization method for a product for pharmaceutical, cosmetic, or medical aesthetic application, which can also be used in cooperation with a double-chambered carton bottle 1' with a longer bottle neck and a corresponding stopper 2' and cap 3'. The specific implementation is described in detail below.

[0097] Specifically, when the double-chambered carton bottle 1' with a longer bottle neck and the corresponding stopper 2' and cap 3' are used, the lyophilization method comprises: adding a middle stopper into the double-chambered carton bottle 1', and then pouring the product to be lyophilized; assembling the stopper 2' and the cap 3', and placing them above the bottle mouth 10' of the double-chambered carton bottle 1'; placing and fixing the double-chambered carton bottle 1' on a customized lyophilization support; freezing, primary drying, and secondary drying the product to be lyophilized, respectively; pressing the stopper 2' and the double-chambered carton bottle 1' using the cap 3' to seal the double-chambered carton bottle 1' and fix the stopper 2', and to make the stopper 2' seal the bottle mouth 10' of the double-chambered carton bottle 1'.

[0098] In the lyophilization method, the middle stopper added into the double-chambered carton bottle 1' and the product to be lyophilized can also be any middle stopper for a double-chambered carton bottle and a product to be lyophilized with a suitable content that are suitable for the size and structure of the double-chambered carton bottle 1'. The freezing, primary drying, and secondary drying operations can be performed in a lyophilization machine that can accommodate the lyophilization support used in the lyophilization method of the present application. During the process of fixing the stopper 2' using the cap 3' and sealing the bottle mouth 10' of the double-chambered carton bottle 1' through the stopper 2', the driving mode of the cap 3' pressing downward can be any driving mode that can be implemented in the lyophilization machine, such as mechanical pressing, pneumatic driving, pneumatic clamp driving, or spring pressing.

[0099] In the present application, the double-cavity carton bottle 1' can be filled with the product to be lyophilized after adding the middle plug, and in particular, the product to be lyophilized can be the product added to the inner cavity 13' of the double-cavity carton bottle 1' for lyophilization and short-term / long-term storage, such as small molecule drugs, polypeptides, enzymes, antibodies, fusion proteins, antibody drug conjugates, reagents, etc. Users can choose any liquid to be lyophilized and fill one of the inner cavities 13' of the double-cavity carton bottle 1' to lyophilize using the lyophilization method of the present application.

[0100] In the present application, the lyophilization support is a stand-alone lyophilization support or a tray-type lyophilization support, and the present application sets the type of lyophilization support used in the lyophilization method as a stand-alone lyophilization support or a tray-type lyophilization support. Skilled persons in the art can select and adjust the specific model, size and working parameters of the lyophilization support in the lyophilization machine according to the actual requirements, and the present application only gives a preferred lyophilization method. Preferably, the lyophilization support is a tray-type lyophilization support, which is easy to place a larger number of double-cavity carton bottles 1'.

[0101] In particular, the double-cavity carton bottle 1' is placed in the lyophilization support in an upright or inverted manner, and preferably, the double-cavity carton bottle 1' is placed in the lyophilization support in an upright manner, which facilitates uniform distribution of heat in the double-cavity carton bottle 1', improves the solvent, such as water sublimation efficiency, and in addition, can also reduce the degree of sedimentation and aggregation of the lyophilized product, and maintain the uniform and stable appearance of the product.

[0102] In the present application, the temperature range for freezing the product in the double-cavity carton bottle 1' can be the temperature range suitable for the freeze-drying of the product, and when the freezing temperature is -60℃ to -40℃, the raw material to be freeze-dried generally has a high freezing efficiency and maintains its own quality, therefore, the freezing temperature is any temperature value in the range of -60℃ to -40℃. Specifically, the temperature range for freezing the product in the double-cavity carton bottle 1' is -60℃ to -40℃, i.e. -60℃, -59℃, -58℃, -57℃, -56℃, -55℃, -54℃, -53℃, -52℃, -51℃, -50℃, -49℃, -48℃, -47℃, -46℃, -45℃, -44℃, -43℃, -42℃, -41℃ or -40℃; the temperature range for primary drying is -60℃ to 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℃, -35℃, -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℃, -5℃, -4℃, -3℃, -2℃, -1℃ or 0℃; and the temperature range for secondary drying is 15℃ to 40℃, i.e. 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℃.

[0103] Similarly, the temperature of the first drying and the second drying can be any temperature value in the range of -60°C to 0°C and 15°C to 40°C, respectively, to increase the sublimation rate of water in the product. In addition, the pressure range of the first drying and the second drying can be any value in the range of 0.02 mbar to 0.2 mbar, and when the pressure of the first drying and the second drying is preferably 0.06 mbar, the drying efficiency can reach a peak. Specifically, the pressure range of the first drying and the second drying is 0.02 mbar to 0.2 mbar, i.e. 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, and preferably, the pressure of the first drying and the second drying is 0.06 mbar, respectively.

[0104] In the present application, the use of the top cover 3' to press the stopper 2' and embed it in the double-chamber carton bottle 1' also includes: before pressing the stopper 2', the double-chamber carton bottle 1' is subjected to a nitrogen filling operation to maintain the low moisture content of the freeze-dried product, such as a freeze-dried preparation. Those skilled in the art can understand that the double-chamber carton bottle 1' is subjected to a nitrogen filling operation before the bottle opening 10' is closed, and the purpose is to make the nitrogen in the inner chamber 13' reach 1 standard atmosphere. On the one hand, nitrogen can be used to maintain the low moisture content of the freeze-dried product, and on the other hand, 1 standard atmosphere of nitrogen can also make the position of the stopper in the double-chamber carton bottle fixed.

[0105] In the present application, it also includes a freeze-dried preparation prepared according to the freeze-drying method described above. In particular, since the product to be freeze-dried added to one of the inner chambers 13' of the double-chamber carton bottle 1' in the present application can be one of various products, the freeze-dried preparations obtained finally can also be different when the double-chamber carton bottle 1' is filled with different products to be freeze-dried. In addition, when the freeze-drying parameters implemented by the freeze-drying method in the process of freeze-drying the product, such as the temperature and pressure of the first drying, are changed, the freeze-dried preparations obtained by filling the same product to be freeze-dried can also have different qualities or different properties, such as different water contents, different solid forms of freeze-dried preparations, etc.

[0106] In the present application, an injection is also included, which comprises: a double-chamber carton bottle package material for injection, a freeze-dried preparation, and a reconstituting agent. It should be noted that the freeze-dried preparation and the reconstituting agent can be any freeze-dried preparation and reconstituting agent suitable for the double-chamber carton bottle package material for injection and the freeze-drying process. Specifically, the freeze-dried preparation can be any product to be freeze-dried that can be filled into the double-chamber carton bottle 1' of the present application, any freeze-dried preparation prepared by freeze-drying treatment via the freeze-drying method of the present application, or the freeze-dried preparation provided by the present application.

[0107] In addition, the reconstituting agent can be a reconstituting agent for reconstituting any freeze-dried preparation prepared as described above, such as sterile water for injection (which can contain bacteriostatic agents such as phenol, m-cresol, benzyl alcohol, etc.), normal saline, 5% glucose solution, and other buffers such as phosphate buffer, citric acid buffer, acetic acid buffer, histidine buffer, succinic acid buffer, tris-hydroxymethyl aminomethane hydrochloride buffer, etc., which can be used to reconstitute the freeze-dried preparation provided by the present application when administered.

[0108] In the present application, the double-chamber carton bottle package material for injection comprises: a double-chamber carton bottle 1' and another bottle cap assembly, wherein the double-chamber carton bottle 1' is used to hold a freeze-dried preparation and a reconstituting agent, as shown in FIG. 13. It should be noted that the double-chamber carton bottle package material for injection can include any combination formed and / or maintained by the combination of any bottle cap assembly and the double-chamber carton bottle 1' proposed in the present application.

[0109] In the present application, a bottle cap assembly is also proposed accordingly, wherein the bottle cap assembly comprises a top plug 2' and a top cap 3' for sealing the double-chamber carton bottle 1'. The double-chamber carton bottle 1' can be placed in a freeze-drying support and a sheath 4' used in the existing freeze-drying process, and the double-chamber carton bottle package material can be fixed and placed upright or inverted in the freeze-drying support; the bottle cap assembly can be made of any material suitable for achieving the sealing function of the bottle cap. The top plug 2' is limited in the top cap 3' for sealing the bottle mouth 10' of the double-chamber carton bottle 1'; the top cap 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 carton bottle 1'; and the double-chamber carton bottle 1' is sealed; wherein the process of pressing and fixing the top plug 2' in the top cap 3' so that the top plug 2' seals the bottle mouth 10' of the double-chamber carton bottle 1' can include the following steps:

[0110] pre-assembling the top plug 2' into the top cap 3'; and placing the top cap 3' with the assembled top plug 2' above the bottle mouth 10' of the double-chamber carton bottle 1' and pressing the top cap 3' downward. The driving mode of the top cap 3' downward can be mechanical compression, pneumatic driving, pneumatic clamp driving, or spring pressing, etc.

[0111] In the present application, the double-cavity carton bottle 1' comprises an inner cavity 13', a bottle body 12', a bottle neck 11' and a bottle mouth 10', the center of the bottle mouth 10' is provided with a bottle mouth opening 100' connected with the inner cavity 13', the inner diameter of the bottle mouth opening 100' is smaller than the inner diameter of the bottle mouth 10' and the bottle neck 11'; the outer wall of one side of the bottle body 12' has a bypass protrusion 120'. Those skilled in the art can understand that the size of the inner cavity 13', the bottle body 12', the bottle neck 11' and the bottle mouth 10' of the double-cavity carton bottle 1' can be adjusted to adapt to the size range of commonly used lyophilized supports, such as changing the vertical length of one or more parts of the double-cavity carton bottle 1', changing the radial length of one or more parts of the double-cavity carton bottle 1', etc., without departing from the protection scope of the present application.

[0112] In the present application, the top plug 2' comprises a plug cap 20' and a plug column 21', the diameter of the plug column 21' can be equal to or slightly larger than the inner diameter of the bottle mouth opening 100', after the plug column 21' is embedded in the bottle mouth opening 100', the lower surface of the plug cap 20' completely matches 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 column 21' can be adjusted within the diameter range of the bottle mouth opening 100' after the plug column 21' is pressed under force, and the diameter of the plug column 21' can be slightly larger than the diameter of the bottle mouth opening 100' to ensure the tightness of the sealing.

[0113] In the present application, the top cover 3' as shown in FIG. 14A comprises an upper end 30' and a bottom disc 31'; the upper end 30' has a top disc 300', a thread 301' and an opening 302', the inner wall of the top cover 3' matches the bottle mouth 10'; when the top cover 3' faces the bottle mouth 10', the top disc 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-cavity carton bottle 1' is capped, the top disc 300' tightly matches above the plug cap 20' to press the top plug 2'. The opening 302' can discharge the sublimated moisture in the product, and the thread 301' is used for thread engagement with the injection needle.

[0114] It should be noted that the length of the bottom disc 31' in the vertical direction can be adjusted, so the bottom disc 31' can only match the connecting part of the bottle neck 11' and the bottle body 12', or can additionally match at least part of the bottle body 12' to achieve better capping tightness and adapt to the size requirements of the top cover 3' in the lyophilization process. The shape of the bottom disc 31' can be set as a cylinder or a multi-prism, as shown in FIG. 14B, to avoid the top cover 3' from slipping off or relative sliding with the double-cavity carton bottle 1' under the action of rotational centrifugal force, which affects the sealing performance.

[0115] In particular, the center of the top disc 300' also has a top disc opening, the circumferential lower edge of the top disc opening can have an inclination angle β' in the vertical direction to its upper edge, and the circumferential upper edge of the top disc opening has a greater opening length than the circumferential lower edge; the circumferential edge surface of the top disc opening can be a curved surface or a flat surface.

[0116] In the present application, the top plug 2' can further comprise a sealing portion 22' protruding above the plug cap 20', as shown in FIG. 15A, the sealing portion 22' can be inserted into the top disc opening, when the top plug 2' is completely embedded in the bottle mouth 10', i.e. the double-cavity cartridge bottle 1' is completed, the sealing portion 22' of the top plug 2' is embedded in the top disc opening and partially protrudes longitudinally from the top disc 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 disc opening, and 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', the surface of the sealing portion 22' can be slightly deformed to be inserted and embedded in the top disc opening from the circumferential lower edge of the top disc opening.

[0117] Therefore, in the process of pre-assembling the top plug 2' into the top cover 3', the sealing portion 22' can be embedded in the top disc opening, the edge portion thereof closely fits with the circumferential outer edge of the top disc opening, and finally partially protrudes from the upper edge of the top disc opening. The radial length L' of the sealing portion 22' can also be set to have a relatively long radial length, so as to improve the close fitting of the edge portion thereof with the circumferential outer edge of the top disc opening, so as to further prevent the top plug 2' from slipping out of the top disc 300'. In addition, by adjusting the size of β', the circumferential lower edge of the top disc opening and the sealing portion 22' have a closer fit than the circumferential upper edge of the top disc opening, so as to tightly surround the sealing portion 22' and fix it.

[0118] In some embodiments, the radial length L' of the closure portion 22' can be 2.0 mm - 5.0 mm, in particular, the radial length L' of the closure 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, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, or 5.0 mm; preferably, the radial length L' of the closure portion 22' can be 3.0 mm - 4.0 mm, in particular, the radial length L' of the closure portion 22' can preferably be 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, or 4.0 mm. The inclination angle β' can be 0°, 1°, 2°, 3°, 4°, 5°, 6°, 7°, 8°, 9°, or 10°, etc.

[0119] In some embodiments, the circumferential lower edge opening length of the top disc opening can be 1.5 mm - 5.0 mm, in particular, the circumferential lower edge opening length of the top disc opening can be 1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm, 1.9 mm, 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, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, or 5.0 mm; preferably, the circumferential lower edge opening length of the top disc opening can be 2.5 mm - 4.0 mm, in particular, the circumferential lower edge opening length of the top disc opening can preferably be 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, or 4.0 mm.

[0120] By taking the radial length L' of the sealing portion 22' slightly larger than the circumferential lower edge opening length of the top disc opening, the sealing portion 22' is more fitted with the circumferential lower edge of the top disc opening, and the top disc opening is effective to fit and fix the sealing portion 22' as a whole, and the circumferential edge provides further support on this basis, so that the top plug 2' as a whole does not slip off. Preferably, β' is set to 0°, and the top disc opening can provide good fixation to the sealing portion 22' without an inclination angle in the vertical direction, while avoiding excessive resistance when the sealing portion 22' is inserted into the top disc opening; in another case, when the top disc opening needs to be set with a certain size of inclination angle in the vertical direction to improve the limiting effect of the top disc 300' on the top plug 2, β' can also be set to 5° to improve the fixation of the sealing portion 22', while not affecting the insertion and embedding of the sealing portion 22' into the top disc opening. Those skilled in the art can adjust the radial length L' of the sealing portion 22', the inclination angle β' and the circumferential lower edge opening length of the top disc opening according to the actual application of the bottle cap assembly in the freeze-drying process, to adaptively adjust the fitting and fixing degree of the sealing portion 22' and the top disc 300'.

[0121] 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', and since the top plug 2' is fixed with the top cover 3' through the cooperation of the top plug positioning point 303' and the plug cap 20', the top plug 2' can be tightly fixed with the top cover 3' 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 part 200' is left between the surface of the plug cap 20' and the inner wall of the upper end 30', as shown in FIG. 18. In this way, when the top plug 2' is pressed tightly by the top cover 3', the plug cap 20' will not protrude upwards into the top disc opening in the middle due to the expansion of the compressed volume of the plug cap 20' to the gap part 200' reserved around it.

[0122] In some embodiments, the diameter of the plug cap 20' can range from 5.0 mm to 10.0 mm, in particular, the diameter of the plug cap 20' can be 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, or 10.0 mm; preferably, the diameter of the plug cap 20' can range from 6.0 mm to 8.0 mm, in particular, the diameter of the plug cap 20' can preferably be 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, or 8.0 mm.

[0123] In some embodiments, the diameter of the upper end 30' of the top cover 3' can range from 5.0 mm to 10.0 mm, specifically, the diameter of the upper end 30' can be 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 or 10.0 mm; preferably, the diameter of the upper end 30' can range from 6.0 mm to 8.0 mm, specifically, the diameter of the upper end 30' can preferably be 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 or 8.0 mm.

[0124] More preferably, the diameter of the stopper cap 20' can be configured as 7.0 mm, and the inner diameter of the upper end 30' of the top cover 3' that cooperates with the stopper cap 20' can be configured as 7.3 mm, so that a gap part 200' with a length of 0.3 mm is left between the surface of the stopper cap 20' and the inner wall of the upper end 30', and the stopper cap 20' is extruded and the diameter is increased during the assembly of the top plug 2' or the insertion of the injection needle, and the gap part 200' can accommodate the increased volume of the stopper cap 20', thereby avoiding the generation of upward pressure. It should be noted that in the bottle cap assembly according to the embodiments of the present application, those skilled in the art can appropriately adjust the diameter of the stopper cap 20' and the diameter of the upper end 30' based on the above-mentioned parameter benchmarks according to the actual application of the bottle cap assembly, so as to adapt to the cooperation of the bottle cap assembly with the freeze-drying support of the freeze-dryer, the cooperation with the packaging sheath and / or the cooperation 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 stopper cap 20'; the more tightly sealed or more easily removed seal of the double-chamber carton bottle 1' can be maintained by appropriately adjusting the diameter of the upper end 30'; and after adjusting the diameter of the stopper cap 20' and the diameter of the upper end 30' respectively, in order to appropriately avoid the influence of the extrusion of the stopper cap 20' on the assembly and use of the bottle cap assembly, the size relationship between the diameter of the stopper cap 20' and the diameter of the upper end 30' can be appropriately adjusted to provide a suitable gap part 200'.

[0125] By inserting and fitting the sealing part 22' into the top disc opening during the pre-assembly of the top plug 2', and limiting the plug cap 20' with the top plug positioning point 303', the top plug 2' can be stably positioned in the top cover 3'. Therefore, when the top cover 3' is subjected to external forces in actual production, such as shaking, hanging, etc., the fixation of the top plug 2' in the top cover 3' will not be affected, thereby avoiding the top plug 2' from falling out of the top cover 3' before the capping operation, ensuring the capping qualification rate after freeze-drying; in addition, the gap part 200' of the plug cap 20' can also avoid core taking when used with a syringe, ensuring efficient use of the product.

[0126] In the present application, the upper end 30' of the top cover 3' also has a top plug positioning point 303', as shown in FIGS. 16A and 16B, the top plug positioning point 303' protrudes from the inner wall of the upper end 30' towards the axis direction of the top cover 3', for fixing the top plug 2' embedded with the bottle mouth 10'. Specifically, the top plug positioning point 303' is uniformly arranged along the radial direction of the upper end 30' and is arranged in a ring shape, the shape of the top plug positioning point 303' can be cylindrical or prismatic, in addition, the number of top plug positioning points 303' and the interval length / arc between the plurality of top plug positioning points 303' can be adjusted to maintain optimal fixation of the top plug 2'.

[0127] In the present application, the number of top plug positioning points 303' is 4 or 5 or more. In particular, the number of top plug positioning points 303' can be an even number to maintain its symmetrical arrangement along the center of the upper end 30' to provide more stable fixation function for the top plug 2'. Preferably, the number of top plug positioning points 303' is 4 or 8 to provide a relatively stable fixation function for the top plug 2'; more preferably, the number of top plug positioning points 303' is 8 to provide the most stable fixation function for the top plug 2'. The top plug positioning point 303' can also be used for positioning the top plug 2' before being pressed into the bottle mouth 10', the top plug 2' is limited by the top plug positioning point 303' to avoid its independent slipping out of the bottle mouth 10'.

[0128] In the present application, the upper end 30' of the top cover 3' is further provided with a protruding part 304' protruding towards the axis direction of the top cover 3' on the inner wall thereof, and the top cover 3' can be limited by the protruding part 304' on the bottle mouth 10' before pressing, so that the sublimation moisture in the inner cavity 13' is discharged through the opening 302'; therefore, the provision of the protruding part 304' helps to provide gas exchange and moisture discharge for the double-cavity carton bottle 1'. Those skilled in the art can understand that the protruding part 304' will not hinder the movement of the top plug 2' during the process of embedding the top plug 2' into the bottle mouth 10', because the protruding part 304' is uniformly distributed on the inner wall of the upper end 30', and the top disc 300' can uniformly apply pressure to the entire surface of the plug cap 20' pre-assembled into the upper end 30' when pressing, so that the top plug 2' can be stably embedded horizontally into the bottle mouth 10'.

[0129] In the present application, the number of protruding parts 304' is 2 or more than 3; preferably, the maximum length (D') of the protruding part 304' protruding towards the axis 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-0.30mm; further preferably, D' can be 0.20mm-0.28mm, which can prevent the top cover 3' from deforming due to excessive pressure when pressing, and the top cover 3' has good sealing performance after pressing and is not easy to slip off; more preferably, D' can be 0.23mm-0.28mm, which can avoid the top cover 3' from deforming due to pressure when pressing, and the top cover 3' has good sealing performance after pressing and is not easy to slip off. It should be noted that when the material of the protruding part 304' is different, the value of D' can be adjusted to achieve the optimal limitation of the top cover 3' before pressing and the optimal improvement of the adhesion between the upper end 30' and the double-cavity carton 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 protruding part 304' can provide the most stable fixation for the top cover 3'.

[0130] In the present application, the shape of the protruding part 304' can be trapezoidal, semicircular, semi-elliptical or rectangular, preferably the shape of the protruding part 304' is trapezoidal. When the shape of the protruding part 304' is trapezoidal with the short side adjacent to the bottle mouth 10', the adhesion tightness of the upper end 30' to the bottle mouth 10' is relatively optimal, and the top cover 3' can be highly stably adhered to the double-cavity carton bottle 1' to maintain good sealing performance.

[0131] When the shape of the protrusion 304' is trapezoidal, the upper cutting angle (θ') of the side surface of the face of the protrusion 304' towards the axis direction of the top cover 3' can be any angle between 0° and 90°, as shown in FIG. 19. Further, θ' can be 30°-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 protrusion 304' on improving the close-fitting of the top cover 3' and the bottle mouth 10' can be significantly weakened; when θ' is greater than 45°, the protrusion 304' can 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' be any angle in the range of 30°-45°; more preferably, θ' can be 30°, so that the protrusion 304' can provide a better close-fitting effect of the top cover 3' and the bottle mouth 10' and not adversely hinder the capping process.

[0132] In addition, when the shape of the protrusion 304' is trapezoidal, it is further preferred that the lower cutting angle (α') of the side surface of the face of the protrusion 304' towards the axis direction of the top cover 3' can also be any angle between 0° and 90°. Since the pressure of the capping process is mainly affected by the size of θ', when α' and θ' have the same value, the protrusion 304' can have the most stable axisymmetric structure and is not prone to deformation or damage during the capping process or storage process. Therefore, it is further preferred that α' can be 30° to improve the use efficiency and deformation resistance of the protrusion 304'. More preferably, θ' and α' of the protrusion 304' are both 30°, which will not cause structural damage to the top cover 3' due to excessive capping force, while also maintaining a high close-fitting of the top cover 3' and the double-chamber carton bottle 1', which can improve the capping efficiency and accuracy of the double-chamber carton bottle 1' in the freeze-drying process.

[0133] In the present application, the upper end 30' of the bottle cap assembly also has a demolding hole 305', as shown in FIGS. 16C and 17, the demolding hole 305' is located at the connection between the top disc 300' and the thread 301', and the demolding hole 305' partially connects the two sides of the top disc opening, so that the top cover 3' can be easily opened and closed during manufacturing by the demolding hole 305', thereby facilitating the batch manufacturing of the entire top cover 3' and improving the efficiency of the freeze-drying process. The number of demolding holes 305' can be 4 or 5 or more, for example, 4 holes evenly distributed on the outer periphery of the top disc 300' of the upper end 30'. This arrangement of demolding holes 305' does not affect the cooperation of the sealing part 22' or the top plug positioning point 303' with the surrounding top cover 3' or top plug 2'' of the top cover 3', and therefore does not affect the air tightness of the top cover 3'.

[0134] In the present application, the upper end 30' also has a fitting portion 306', as shown in FIG. 15B, which is located on the side of the top disc opening of the top disc 300' close to the top plug 2', i.e. the side in contact with the plug cap 20'. The sealing portion 22' can be fitted in the top disc opening of the top disc 300' of the top cover 3' to adapt to the insertion. Specifically, the fitting portion 306' has a slope towards the top plug 3', which is smoothly tightened from the side of the top disc opening close to the top plug 2' to the other side of the top disc 300' to chamfer the contact surface of the top plug 2', i.e. the chamfer shape, so that when the sealing portion 22' of the top plug 2' is fitted into the top disc opening, the outer edge thereof can slide along the slope of the fitting portion 306', reducing the force required for fitting, further improving the success rate of fitting the sealing portion 22' into the top disc opening, improving the sealing efficiency, and improving the freeze-drying efficiency.

[0135] In the present application, the bottom disc 31' can also have an internal protrusion 310', as shown in FIG. 14C, which is located on the inner wall of the bottom disc 31' away from the upper end 30', i.e. the inner wall of the lowermost end of the top cover 3', and protrudes in the axial direction of the top cover 3'. When the top cover 3' is sealed to the double-chamber carton bottle 1', due to the presence of the internal protrusion 310', the contact pressure between the bottle body 12' and the bottom disc 31' at the internal protrusion 310' is increased, and the fit is tighter, enhancing the fixation stability of the top cover 3' on the double-chamber carton bottle 1', making the entire packaging material have better air tightness. The number of internal protrusions 310' can be an appropriate number, for example, 2 or 3 or 4 or 5 or more, and preferably evenly distributed on the radial section of the bottom disc 31' to form a stable shape, thereby improving the fixation stability of the top cover 3'. In addition, when multiple internal protrusions are evenly distributed on the inner side of the bottom disc, for example, 4 internal protrusions 310' are evenly distributed at 90° on the inner side of the lower edge of the cylindrical bottom disc 31', the stress on the bottom disc can be effectively dispersed, making the bottom disc 31' less likely to gradually loosen due to long-term sealing use or temperature changes, thereby further improving the anti-loosening ability of the top cover.

[0136] Advantageously, the bottom disc 31' can also have protrusion side openings 311' on both sides of the internal protrusion 310' along the edge of the bottom disc 31' away from the upper end 30', i.e. the edge of the lowermost end of the top cover 3'. The number of protrusion side openings 311' can be matched with the number of internal protrusions 310', so the number thereof can be 4 or 6 or 8 or 10 or more. When the top cover 3' is fitted with the bottle body 12' and the internal protrusion 310' is pressed, the protrusion side openings 311' on one side / two sides can be deformed and extended, reducing the force required for sealing, thereby improving the sealing and freeze-drying efficiency.

[0137] The present application also proposes another injection dual-chamber carton bottle packaging material, which comprises the above-mentioned another bottle cap assembly and a dual-chamber carton bottle 1', and another injection dual-chamber carton bottle packaging material assembly, which comprises the above-mentioned another injection dual-chamber carton bottle packaging material and a sheath 4' used in cooperation therewith, as shown in FIG. 20. It should be noted that the injection dual-chamber carton bottle packaging material can comprise any combination of the bottle cap assembly and the dual-chamber carton bottle 1' capable of being formed and / or maintained by any combination proposed in the present application.

[0138] The bottom disc 31' has a first protrusion 321' near the upper outer edge of the upper end 30'. The top end of the inner wall of the sheath 4' is stretched to form a protrusion in the horizontal direction and is limited to the first protrusion 321' of the bottom disc 31'. The top cap 3' and the sheath 4' achieve an interference fit, and the top plug 2' and the dual-chamber carton bottle 1' are clamped in the middle. In addition, the bypass protrusion 120' of the bottle body 12' is clamped 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 dual-chamber carton bottle packaging material is placed in the sheath 4', the top cap 3' and the top plug 2' therein are more tightly fixed with the bottle mouth 10', effectively avoiding air leakage, rotation, falling off, and the like.

[0139] In the present application, the bottom disc 31' is in the shape of a cylinder or an octagonal prism, and the sheath 4' comprises a sheath body 40' and a flange 41'. When the top cap 3' and the sheath 4' are in interference fit, the top cap 3' and the dual-chamber carton bottle 1' are tightly fixed with each other. Since the bottle mouth 10', the bottle neck 11', and the bottle body 12' of the dual-chamber carton bottle 1' are in the shape of a cylinder, during the process of screwing and / or detaching the injection needle with / from the top cap 3', the top cap 3' is driven to rotate together with the dual-chamber carton bottle 1' due to force. When the bottom disc 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 a lyophilized preparation is used, the injection needle needs to be screwed / detached, and the top cap 3' may drive the entire dual-chamber carton bottle 1' to rotate together, so that the injection needle is idle and cannot be fixed / unfixed with / from the top cap 3'.

[0140] Therefore, the bottom disc 31' of the bottle cap assembly of 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 disc 31' and the inner wall of the sheath body 40' are both octagonal, as shown in FIG. 20. In this way, the bypass protrusion 120' of the dual-chamber carton 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 disc 31' during capping; when the top cap 3' is subjected to external force from, for example, an injection needle, the interference fit between the bottom disc 31' and the inner wall of the sheath 4' and the mutual fixation (A'-A') therebetween prevent the top cap 3' from slipping or relatively sliding with the dual-chamber carton bottle 1', further stabilize the entire packaging material, avoid the airtightness of the dual-chamber carton bottle 1' from being affected, and improve the use efficiency.

[0141] In particular, the lower end of the sheath 4' can also have an interference fit structure, and the lower end of the sheath body 40' can be provided with a second protrusion 400' which is clamped on the flange 41' by pressing, so that the sheath body 40' and the flange 41' are interference fitted 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' can be prevented from rotating with the packaging material.

[0142] Specifically, in some embodiments, the other lyophilized preparation described above is subcutaneously injected by an injection needle after reconstitution in the double-chamber carton bottle 1', and is used for disease treatment or medical aesthetics. The hub of the injection needle has a threaded structure, and when the injection needle is installed on the top cover 3' for product injection or removed from the top cover 3', the threaded structure is engaged or removed with the threads 301' of the top cover 3' by rotating, and in this process, the bottom disc 31' of the top cover 3' is fixed and prevented from rotating by the octagonal inner wall of the sheath 4', and the bypass protrusion 120' of the double-chamber carton bottle 1' is also fixed and prevented from rotating by the vertex of the inner wall of the sheath 4'. Therefore, by selecting an octagonal bottom disc 31' and cooperating with the sheath 4', the double-chamber carton bottle packaging assembly can be prevented from rotating when the injection needle is screwed on / dismounted, so as to avoid idling when the sterile injection needle is screwed on / dismounted, and improve the use efficiency and operation convenience of the double-chamber carton bottle packaging assembly.

[0143] In the present application, a bottle cap assembly is also provided, as shown in FIGS. 21A, 21B and 22, which includes a top plug 2" and a top cover 3", and can be used in cooperation with the pressure plug assembly to seal the bottle opening of the double-chamber carton bottle 1 or the double-chamber carton bottle 1', in particular the bottle opening of the double-chamber carton bottle 1'. The bottle cap assembly can be used as a supplementary or alternative configuration of the two aforementioned bottle cap assemblies for sealing the double-chamber carton bottle in the lyophilization process, for example, when the lyophilization process does not require high integration of the top plug and the top cover.

[0144] In particular, referring to the examples of FIGS. 21A-22, as shown in FIG. 21A, the top plug 2" of the bottle cap assembly is used to seal the bottle mouth 10' of the double- cavity carton bottle 1', and the top plug 2" can include a plug cap 20" and a plug column 21". As shown in FIG. 22, the top cover 3" is used to fix the top plug 2" and seal the bottle mouth 10' of the double-cavity carton bottle 1'; the top cover 3" can include a main body and a bottom disc 31", and the main body can include a top disc 300" and an annular thread 301". With continued reference to FIG. 21A, the press plug assembly can include a press-in jig 51 and a holding jig 50, the press-in jig 51 can include a press column 510, and the holding jig 50 can include a protrusion 500. In the freeze-drying method provided in the present application, for the bottle cap assembly, the top plug 2" is not assembled with the top cover 3" before freezing, but is first fixed to the bottle mouth 10' by the press plug assembly after the product to be freeze-dried is frozen, primary dried, and secondary dried, and then the press plug assembly is removed and the entire bottle mouth 10' is sealed by the top cover 3". That is, for the present bottle cap assembly, after freeze-drying is completed, the press plug assembly is used to press the top plug 2" to fit with the double-cavity carton bottle 1', rather than directly using the top cover 3" to press the top plug 2" as in the two previous bottle cap assemblies, and the sealing process is as follows:

[0145] The process of using the press plug assembly to press the top plug 2" to fit with the double-cavity carton bottle 1' to achieve sealing of the double-cavity carton bottle 1' includes the following steps: placing the top plug 2" in the holding jig 50 by fitting the holding jig 50 with the outer wall of the bottle mouth 10' of the double-cavity carton bottle 1' to achieve positioning of the top plug 2" relative to the bottle mouth 10' of the double-cavity carton bottle 1'; pressing the top plug 2" by the press-in jig 51 to fit into the bottle mouth 10' of the double-cavity carton bottle 1'; and removing the press-in jig 51 and the holding jig 50. It should be noted that when the size of part or all of the structure of the double-cavity carton bottle 1' changes, the size of the top plug 2", the press-in jig 51, and the holding jig 50 can also change to adapt to the size of the double-cavity carton bottle 1' (especially when the bottle neck 11' needs to be further adjusted) to complete the sealing of the bottle mouth 10'.

[0146] In addition, in another configuration of the bottle cap assembly shown in FIG. 21B, the inner wall of the central recess of the press-in jig 51 of the press plug assembly is no longer provided with the press column 510, and when the top plug 2" moves towards the bottle mouth 10', the press-in jig 51 directly abuts against the top plug 2" in the central recess to press it to move towards the bottle mouth 10'. In this way, without using the holding jig 50 with a long protruding length at the upper end, the press-in jig 51 can also provide sufficient press plug length to the top plug 2" without additionally providing multiple press columns 510 to ensure that the top plug 2" is firmly fitted in the bottle mouth 10'. This simplifies the manufacturing process of the press plug assembly.

[0147] In addition, before the double-chambered carton bottle 1' is placed and fixed on the customized freeze-drying support, the bottle cap assembly needs to be pre-assembled with the compression plug assembly and the top plug 2" to avoid the top plug 2" from falling into the bottle mouth 10' during the freeze-drying process and affecting the drainage process of the freeze-dried preparation. The specific pre-assembly process is as follows: the top plug 2" is placed on the upper end of the holding jig 50, protruding from the protruding part 500 of the holding jig 50, the protruding part 500 can hold the plug cap 20" to fix the position of the top plug 2", prevent it from falling prematurely, and make the plug column 21" align with the bottle mouth opening 100', which is beneficial to the plug column 21" quickly embedded in the bottle mouth opening 100' when it is pressed down by the compression jig 51 after the freeze-drying is completed.

[0148] In particular, in addition to the two points of before and after the freeze-drying operation described above, the process of the freeze-drying process using the bottle cap assembly does not change compared with the process of the freeze-drying process using the two bottle cap assemblies described above. During the process of successively sealing the bottle mouth 10' with the top plug 2" and the top cap 3", the driving mode of the compression jig 51 of the compression plug assembly and the driving mode of the top cap 3" pressed down to the bottle mouth 10' can be any driving mode that can be implemented inside the freeze-drying machine, such as mechanical compression, air pressure driving, pneumatic clamp driving or spring pressing.

[0149] In the present application, a freeze-dried preparation can also be included, which is prepared according to the freeze-drying method implemented by using the bottle cap assembly with a compression plug assembly, and the double-chambered carton bottle selected can be the double-chambered carton bottle 1 or the double-chambered carton bottle 1', especially 1'. In particular, since the product to be freeze-dried added to one of the inner chambers 13' of the double-chambered carton bottle 1' in the present application can be one of a variety of products, the final freeze-dried preparation obtained can also be different when the double-chambered carton bottle 1' is filled with different products to be freeze-dried; in addition, when the freeze-drying parameters implemented by the freeze-drying method in the process of freeze-drying the product, such as the temperature and pressure of the first drying, are changed, the freeze-dried preparation obtained after filling the same product to be freeze-dried can also be of different quality or different properties, such as freeze-dried preparations with different water contents, different solid forms, etc.

[0150] In the present application, an injection also includes a double-chambered carton bottle package, a freeze-dried preparation and a reconstitution agent. It should be noted that the freeze-dried preparation and the reconstitution agent can be any freeze-dried preparation and reconstitution agent suitable for the double-chambered carton bottle package and the freeze-drying process. In particular, the freeze-dried preparation can be any product to be freeze-dried that can be filled into the double-chambered carton bottle 1' of the present application, any freeze-dried preparation prepared by the freeze-drying method implemented by using the bottle cap assembly with a compression plug assembly of the present application, or the freeze-dried preparation provided by the present application.

[0151] In addition, the reconstituting agent can be a reconstituting agent for reconstituting any one of the freeze-dried preparations prepared above, such as sterile water for injection (which can contain bacteriostatic agents such as phenol, m-cresol, benzyl alcohol, etc.), normal saline, 5% glucose solution, and other buffers such as phosphate buffer, citric acid buffer, acetic acid buffer, histidine buffer, succinic acid buffer, tris-hydroxymethyl aminomethane hydrochloride buffer, etc., which can be used to reconstitute the freeze-dried preparations provided herein before administration.

[0152] The two freeze-dried preparations provided herein as described above are any one of the freeze-dried preparations prepared according to any one of the freeze-drying methods provided herein above or any one of the two freeze-dried preparations provided herein. It can be understood that these freeze-dried preparations can all be raw material reagents or finished products of drugs, medical and cosmetic reagents, medical device reagents, and / or cosmetics in the field of biological medicine. The various types of freeze-dried preparations obtained by the present application also have the characteristics of high integrity, high purity and low impurities, and therefore have excellent practical application effects.

[0153] EMBODIMENT

[0154] The materials used in the experiments and the experimental methods are generally and / or specifically described herein. The reagents or instruments used are not specified by the manufacturer, and are all conventional reagent products that can be obtained commercially.

[0155] EMBODIMENT 1

[0156] A bottle cap assembly includes a top plug 2 and a top cap 3 for sealing a double-cavity card bottle 1. The structure of the top cap 3 is shown in FIG. 6A. The double-cavity card bottle 1 is sealed by the top plug 2 through the top cap 3, and the bottle opening 10 of the double-cavity card bottle 1 is closed by the top plug. Specifically,

[0157] First, the top plug 2 is positioned inside the top cap 3 by the top plug positioning point 303, and the top cap 3 is placed on the bottle opening 10 so that the plug column 21 naturally faces the bottle opening 100 for freeze-drying.

[0158] Then, after freeze-drying is completed, the top plug 2 is pressed into the bottle opening 10 of the double-cavity card bottle 1 by the top cap 3, and the top cap 3 includes an upper end 30, a middle end 31, and a lower end 32. The upper end 30 has a top disc 300 in the center, a thread 301 and an opening 302 at the edge of the upper end 30, and the lower end 32 is located below the middle end 31, and the lower end 32 is open below. After the top plug 2 is initially inserted into the bottle opening 10, the top cap 3 is pressed downward until the upper end 30 is completely fitted on the bottle opening 10. In this process, the inner wall of the upper end 30 is fitted with the bottle opening 10 and the bottle neck 11, and the inner walls of the middle end 31 and the lower end 32 are fitted with the bottle body 12.

[0159] The top disc 300 is a hollow cylindrical structure with a middle shortened part. During the process of pressing the top cover 3 downward by external force, the top plug 2 is pressed to the bottle mouth 10 by the lower surface of the top disc 300, so that the top plug 2 is further embedded into 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 into the bottle mouth 10 under the pressure, and the lower surface of the plug cap 20 completely fits the upper surface of the bottle mouth 10, so as to seal the double-cavity carton bottle 1 by the top plug 2, without the participation of additional plug pressing device, thereby reducing the additional process and time required for sealing the double-cavity carton bottle 1, and avoiding the influence of inaccurate sealing on the production efficiency of the freeze-drying process.

[0160] In particular, when the top cover 3 is pressed to completely embed the top plug 2 into the bottle mouth 10, the inner wall of the upper surface of the middle end 31 can also completely fit the upper surface of the bottle body 12; therefore, while the top cover 3 seals the bottle mouth opening 100 by the top plug 2, the top cover 3 also seals the top plug 2 embedded in the bottle mouth, and seals the bottle mouth 10, the bottle neck 11 and at least a part of the bottle body 12 through the top plug 2, so as to realize the overall sealing of the double-cavity carton bottle 1.

[0161] The upper end 30 has a gap part 200 with a diameter of 7.3 mm and the plug cap 20 with a diameter of 7.0 mm; the upper end 30 also has a top plug positioning point 303, as shown in FIG. 6A, which is located below the top disc 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 into the bottle mouth 10, the top plug positioning point 303 fits 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, so as to increase the friction between the plug cap 20 and the inner wall of the upper end 30, thereby preventing the top plug 2 from loosening or slipping out of the top cover 3 during the pre-assembly process due to loose fitting. The number of top plug positioning points 303 is four, which are evenly distributed on the inner wall of the upper end 30.

[0162] The upper end 30 also has a protruding part 304, as shown in FIG. 10, 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. After the top plug 2 is completely embedded into the bottle mouth 10, the protruding part 304 fits the outer wall of the bottle mouth 10, and the bottle mouth 10 is pressed by the protruding part 304 in the direction of the axis of the top cover 3, so as to increase the friction between the bottle mouth 10 and the inner wall of the upper end 30, thereby preventing the top cover 3 from slipping out after sealing due to loose fitting, and improving the sealing performance of the double-cavity carton bottle 1. The maximum length of the protruding part 304 protruding from the inner wall of the upper end 30 is set to 0.23 mm, and the shape of the protruding part 304 is set to trapezoidal with a number of two, which are distributed on both sides of the inner wall of the upper end 30, and the upper cutting angle is 30°.

[0163] 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 of the top cover 3 and the bottle body 22 after the top cover 3 is attached to the double-cavity carton bottle 1, and further improve the stability of the fit of the top cover 3 and the double-cavity carton bottle 1.

[0164] The compression plug and compression cover sealing test of the bottle cap assembly shows that the fit of the top plug 2 and the top cover 3 is high, and the top plug 2 does not slip out of the top cover 3; a certain pressure needs to be applied during the compression cover process, but it does not cause deformation and damage to part of the structure of the top cover 3; the fit of the top cover 3 and the mouth 10 of the double-cavity carton bottle 1 is obviously improved and is not pulled out after a larger force is applied.

[0165] Example 2

[0166] The maximum length of the convex part 304 protruding from the inner wall of the upper end 30 is replaced with 0.25 mm, and other structures and parameters are the same as in Example 1. The compression plug and compression cover sealing test of the bottle cap assembly shows that the fit of the top plug 2 and the top cover 3 is high, and the top plug 2 does not slip out of the top cover 3; after the maximum length of the convex part 304 protruding from the inner wall of the upper end 30 is replaced with 0.25 mm, a certain pressure needs to be applied during the compression cover process, but it does not cause deformation and damage to part of the structure of the top cover 3; the fit of the top cover 3 and the mouth 10 of the double-cavity carton bottle 1 is also obviously improved and is not pulled out after a larger force is applied.

[0167] Example 3

[0168] The maximum length of the convex part 304 protruding from the inner wall of the upper end 30 is replaced with 0.28 mm, and other structures and parameters are the same as in Example 1. The compression plug and compression cover sealing test of the bottle cap assembly shows that the fit of the top plug 2 and the top cover 3 is high, and the top plug 2 does not slip out of the top cover 3; after the maximum length of the convex part 304 protruding from the inner wall of the upper end 30 is replaced with 0.28 mm, a larger pressure needs to be applied during the compression cover process, but it does not cause deformation and damage to part of the structure of the top cover 3; the fit of the top cover 3 and the mouth 10 of the double-cavity carton bottle 1 is obviously improved and is not pulled out after a larger force is applied.

[0169] Example 4

[0170] The injection double-cavity carton bottle packaging material is used for the freeze-drying process of a drug, and a freeze-dried preparation is obtained. The injection double-cavity carton packaging material in Examples 1-3 is selected for 20 parts each to perform the freeze-drying process and obtain the freeze-dried preparation, and the steps are as follows:

[0171] (1) Add a middle plug to each double-chamber carton bottle 1, and then fill the to-be-lyophilized lonapegsomatropin. The lonapegsomatropin includes two types, wherein the first type of lonapegsomatropin comprises: 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 comprises: 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 carton bottle 1 on the lyophilization support, wherein the lyophilization support is selected from a tray type lyophilization support, as shown in FIG. 1, and the double-chamber carton bottle 1 is placed in the lyophilization support in an upright manner.

[0172] (2) Pre-assemble the top plug 2 and the top cover 3 in Example 1-Example 3, and place them at the bottle opening 10 of the double-chamber carton 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 is in contact with the lower end of the top disc 300, and the plug cap 20 is limited in the upper end 30 by the support of the top plug positioning point 303; align the bottle opening 10 with the opening of the lower end 32, and place the top plug 2 naturally at the bottle opening 10.

[0173] (3) Perform the lyophilization process of freezing, primary drying, secondary drying, and plate lamination plug and cover pressing on the to-be-lyophilized lonapegsomatropin, respectively, and the specific operation process is shown in Table 1:

[0174] Table 1 Lyophilization process and parameter settings of to-be-lyophilized lonapegsomatropin

[0175] wherein Atm is 1 standard atmosphere. In the lyophilization process, the lyophilization curve of the to-be-lyophilized drug is shown in FIG. 2, and the injection double-chamber carton bottle package material after unloading from the box has a low water content and a low water content.

[0176] (4) After the lyophilization process is completed, nitrogen charging operation is performed on the double-chamber carton bottle 1 to maintain the low moisture content of the lyophilized sample, and then the plug pressing and cover pressing sealing are simultaneously performed. Specifically,

[0177] After the freeze-drying is completed, the top cover 3 is pushed down to press the top plug 2 to fit into the bottle mouth 10 of the double-cavity carton bottle 1. In the process of embedding the top plug 2 into the bottle mouth 10, the top cover 3 is pressed down until the upper end 30 is completely sleeved on the bottle mouth 10. In this process, the inner wall of the upper end 30 is attached to the bottle mouth 10, and the inner walls of the middle end 31 and the lower end 32 are attached to the bottle body 12 until the plug column 21 is completely embedded into the bottle mouth 10, and the lower surface of the plug cap 20 is completely attached to the upper surface of the bottle mouth 10 to achieve the sealing of the double-cavity carton bottle 1 by the top plug 2, without the need to introduce an additional plug assembly.

[0178] (5) The double-cavity carton bottle 1 is taken out of the freeze-drying machine to obtain the final freeze-dried preparation therein.

[0179] The freeze-dried preparation prepared in the double-cavity carton bottle 1 by the freeze-drying method described above is subjected to appearance detection and moisture detection, and the detection results are shown in Table 2:

[0180] Table 2: Appearance detection and moisture detection results of freeze-dried preparation

[0181] As can be seen from Table 2, the appearance detection result of the freeze-dried preparation shows that its appearance is good, and the average moisture detection result of 6 detections is low, indicating that the freeze-drying effect of the freeze-dried preparation is good.

[0182] In addition, the freeze-drying machine plate layer pressing cover operation (without adding freeze-dried samples) is performed on the three injection double-cavity carton bottle packaging materials in Example 1-Example 3, and the CCIT (vacuum decay method) detection is performed on the packaging materials after pressing. The results show that the sealing properties of the three packaging materials are good.

[0183] In summary, the freeze-drying process described above can be completed by using the packaging materials in Example 1-Example 3, which can meet the requirements of drug freeze-drying process and sealing property. The freeze-dried preparation obtained by the freeze-drying method described above can meet the requirements of freeze-dried drug appearance and moisture.

[0184] Example 5

[0185] 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, as shown in FIG. 6B. Specifically, the length of the top cover 3 extending along the neck 11 and the bottle body 12 in Example 2 is shortened, the length of the middle end 31 is shortened, the position of the convex ring 310 relative to the neck 11 and the bottle body 12 is further moved upward, and the lower part of the upper end 30 is attached. In addition, the convex strip 320 of the lower end 32 is removed, and the non-convex strip part of the lower end 32 is extended downward along the bottle body 12, the lower end 32 near the upper part of the middle end 31 is shortened in the radial direction to form a first notch 321.

[0186] It should be noted that the shape of the extended lower end 32 in this embodiment is set as an octagonal prism, the inner wall of which can still fit at least part of the bottle body 12 of the double-chamber carton 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 that of the top cover 3 in Embodiment 10. The number of top plug positioning points 303 is 8, which are evenly distributed in the inner wall of the upper end 30.

[0187] The bottle cap assembly was subjected to plug pressing and cap sealing test, and it was found that the fit degree of the top plug 2 and the top cover 3 was high, and the top plug 2 did not slip out of the top cover 3; a large pressure was required during the cap pressing process, but no deformation and damage of part of the structure of the top cover 3 occurred; the fit degree of the top cover 3 and the bottle mouth 10 of the double-chamber carton bottle 1 was obviously improved, and the top cover 3 was not pulled out after a large force was applied.

[0188] Embodiment 6

[0189] The maximum length of the protruding part 304 protruding from the inner wall of the upper end 30 was replaced with 0.25 mm, and the other structures and parameters were the same as those of Embodiment 5. The bottle cap assembly was subjected to plug pressing and cap sealing test, and it was found that the fit degree of the top plug 2 and the top cover 3 was high, and the top plug 2 did not slip out of the top cover 3; a large pressure was required during the cap pressing process, but no deformation and damage of part of the structure of the top cover 3 occurred; the fit degree of the top cover 3 and the bottle mouth 10 of the double-chamber carton bottle 1 was obviously improved, and the top cover 3 was not pulled out after a large force was applied.

[0190] Embodiment 7

[0191] The maximum length of the protruding part 304 protruding from the inner wall of the upper end 30 was replaced with 0.2 mm, and the other structures and parameters were the same as those of Embodiment 5. The bottle cap assembly was subjected to plug pressing and cap sealing test, and it was found that the fit degree of the top plug 2 and the top cover 3 was high, and the top plug 2 did not slip out of the top cover 3; a large pressure was required during the cap pressing process, but no deformation and damage of part of the structure of the top cover 3 occurred; the fit degree of the top cover 3 and the bottle mouth 10 of the double-chamber carton bottle 1 was obviously improved, and the top cover 3 was not pulled out after a large force was applied.

[0192] Embodiment 8

[0193] The double-chamber carton bottle packaging material for injection was used for lyophilization process of drugs, and lyophilized preparations were obtained. The double-chamber carton bottle packaging material for injection in Embodiments 5-7 was selected for 25 parts, respectively, to perform the steps of lyophilization process and obtain lyophilized preparations as follows:

[0194] (1) Add a middle plug to each double-chamber vial 1, then fill the vial with a growth hormone to be lyophilized, which comprises 22.0 mg hGH / mL growth hormone, 10 mM succinic acid, 74.0 mg / mL trehalose dihydrate, and an appropriate amount of tromethamine to adjust the pH to pH 5.0. Place and fix double-chamber vial 2 on a lyophilization support, wherein the lyophilization support is selected from a tray-type lyophilization support, as shown in FIG. 1, and the double-chamber vial 1 is placed in the lyophilization support in an upright position.

[0195] (2) After pre-assembling the top plug 2 and the cap 3 in Examples 5-7, place the pre-assembled combination of the top plug 2 and the cap 3 at the mouth 10 of the double-chamber vial 1, and the pre-assembled combination of the top plug 2 and the cap 3 is in the same manner as in Example 4.

[0196] (3) Perform the lyophilization process of freezing, primary drying, secondary drying, and plate lamination plug pressure covering on the growth hormone to be lyophilized, respectively, and the specific operation method is the same as in Example 4.

[0197] (4) After the lyophilization process is completed, perform nitrogen filling operation on the double-chamber vial 1 to maintain the low moisture content of the lyophilized sample, and then perform pressure covering sealing; the pressure covering sealing method is the same as in Example 4.

[0198] (5) Take out the double-chamber vial 4 from the lyophilization machine to obtain the final lyophilized preparation therein.

[0199] Perform appearance detection and moisture detection on the lyophilized preparation prepared in the double-chamber vial 4 through the above lyophilization method, and the detection results are shown in Table 3:

[0200] Table 3 Appearance detection, moisture detection, and CCIT detection results of the lyophilized preparation

[0201] As can be seen from Table 3, the appearance detection result of the lyophilized preparation shows that the appearance is good, and the average moisture detection result is low; in addition, the injection double-chamber vial package material in Examples 5-7 has good sealing performance in the lyophilization process, which can meet the sealing performance requirements of the preparation.

[0202] Example 9

[0203] An injection double-chamber vial package material comprises a double-chamber vial 1' and a cap assembly. The structure of the double-chamber vial 1' is shown in FIG. 13, which comprises a mouth 10', a neck 11', a body 12', and an inner cavity 13'. The cap assembly comprises a top plug 2' and a cap 3'. The structure of the top plug 2' is also shown in FIG. 13, and the structure of the cap 3' is shown in FIG. 14A. The cap 3' seals the mouth 10' of the double-chamber vial 1' by using the top plug 2' to press the plug, and simultaneously covers the mouth 10' of the double-chamber vial 1'.

[0204] The top cover 3' includes an upper end 30' and a bottom disc 31'. The upper end 30' has a central top disc 300', an edge screw thread 301', and an opening 302' of the lower outer wall. The bottom disc 31' is open at the bottom, and a cavity is arranged inward from the opening. After the top plug 2' is pre-assembled into the upper end 30' of the top cover 3', the top cover 3' is pressed downward as a whole until the upper end 30' is sleeved on the bottle mouth 10'. In this process, the inner wall of the upper end 30' is attached to the bottle mouth 10', and the inner wall of the bottom disc 31' is attached to the joint of the bottle neck 11' and the bottle body 12'. The top disc 300' is attached to the upper surface of the plug cap 20' of the pre-assembled top plug 2'. During the process of pressing the top cover 3' as a whole, the top disc 300' simultaneously presses 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 simultaneously perform plug sealing and capping, without the participation of an additional plug pressing assembly or in multiple steps, thereby reducing the time required for the sealing process of the double-cavity carton bottle 1' and avoiding sealing failure.

[0205] The upper end 30' has eight evenly distributed plug positioning points 303'. The plug positioning points 303' are located at the lower end of the top disc 300' and protrude from the inner wall of the upper end 30' toward the axis of the top cover 3'. After the top plug 2' is embedded in the bottle mouth 10', the plug positioning points 303' are attached to the plug cap 20'. The plug cap 20' is subjected to the pressure of the plug positioning points 303' toward the axis of the top cover 3', and the frictional resistance between the plug cap 20' and the inner wall of the upper end 30' is increased, thereby preventing the top plug 2' from slipping out of or popping out of the top cover 3' and avoiding sealing failure.

[0206] The upper end 30' also has a protruding part 304'. The protruding part 304' is arranged below the plug positioning points 303' and protrudes from the inner wall of the upper end 30' toward the axis of the top cover 3'. Before the top plug 2' is embedded in the bottle mouth 10', the protruding part 304' is placed on the bottle mouth to ensure that the sublimated moisture can be discharged from the opening 302'. After the top plug 2' is embedded in the bottle mouth 10', the protruding part 304' is attached to the outer wall of the bottle mouth 10', so that the bottle mouth 10' is subjected to the pressure of the protruding part 304' toward the axis of the top cover 3', thereby increasing the frictional force between the bottle mouth 10' and the inner wall of the upper end 30' and preventing the top cover 3' from slipping out of or popping out of the bottle mouth 10'.

[0207] The maximum length of the protruding part 304' protruding from the inner wall of the upper end 30' is 0.23 mm. The shape of the protruding part 304' is trapezoidal.

[0208] Example 10

[0209] A double-cavity carton bottle packaging material for injection includes a double-cavity carton bottle 1' and a bottle cap assembly. The bottle cap assembly includes a top plug 2' and a top cover 3'. The maximum length of the protruding part 304' protruding from the inner wall of the upper end 30' is replaced by 0.25 mm, and the other structures and parameters are the same as those of Example 9.

[0210] Example 11

[0211] A double-cavity carton bottle package for injection, comprising a double-cavity carton bottle 1' and a bottle cap assembly, the bottle cap assembly comprising a top plug 2' and a top cap 3'. Wherein the maximum length of the protruding part 304' protruding from the inner wall of the upper end 30' is replaced by 0.28 mm, and the other structures and parameters are the same as those of Example 9.

[0212] Example 12

[0213] The double-cavity carton bottle package for injection is used for the freeze-drying process of a drug, and a freeze-dried preparation is obtained. The double-cavity carton bottle package for injection in Examples 9-11 is selected for 20 parts respectively, and the steps of the freeze-drying process and the freeze-dried preparation are as follows:

[0214] (1) Add a middle plug to each double-cavity carton bottle 1' of the double-cavity carton bottle package for injection, then fill the drug solution to be freeze-dried, and place and fix the double-cavity carton bottle 1' on a freeze-drying support. Wherein the freeze-drying support is selected to be a tray type freeze-drying support, as shown in FIG. 1, and the double-cavity carton bottle 1' is placed in the freeze-drying support in an upright manner.

[0215] (2) The top plug 2' is pre-assembled with the top cap 3' in Examples 9-11 respectively, and is placed at the bottle mouth 10' of the double-cavity carton bottle 1'. Specifically, the top cap 3' is limited in the bottle mouth 10' by the support of the protruding part 303', the top plug 2' is inserted into the cavity of the upper end 30' from the opening of the bottom disc 31' until the upper surface of the plug cap 20' is in contact with the lower end of the top disc 300', and the plug cap 20' is limited in the internal cavity of the upper end 30' by the support of the top plug positioning point 303'.

[0216] In this way, the bottle mouth 10' is aligned with the opening of the bottom disc 31', and the top plug 2' is limited above the bottle mouth 10' as a whole.

[0217] (3) The drug solution to be freeze-dried is subjected to freezing, primary drying, secondary drying and plate layering and plug capping respectively, and the specific operation process is shown in Table 4:

[0218] Table 4 Freeze-drying process flow and parameter setting of drug solution to be freeze-dried

[0219] Wherein, Atm refers to 1 standard atmosphere.

[0220] (4) After the freeze-drying process is completed, nitrogen charging operation is performed on the double-cavity carton bottle 1' to maintain the low moisture content of the freeze-dried product, and then the cap is sealed. Specifically,

[0221] After the freeze-drying process is completed, the top cover 3' is pushed down to press the stopper 2' so that the stopper 2' is fitted into the bottle mouth 10' of the dual-chamber carton bottle 1'. At the same time that the stopper 2' is fitted into the bottle mouth 10', the top cover 3' is pressed down until the upper end 30' is completely fitted on the bottle mouth 10'. In this process, the inner wall of the upper end 30' is fitted with the bottle mouth 10' until the stopper column 21' is completely fitted into the bottle mouth 10', the lower surface of the stopper cap 20' is completely fitted with the upper surface of the bottle mouth 10', and the lower surface of the bottom disc 31' is fitted with the joint between the bottle neck 11' and the bottle body 12'. In this way, the sealing of the dual-chamber carton bottle 1' by the stopper 2' is achieved, and no additional stopper assembly needs to be introduced.

[0222] (5) The dual-chamber carton bottle 1' and the freeze-drying support are taken out of the freeze-drying machine.

[0223] The freeze-dried preparation prepared in the dual-chamber carton bottle 1' by the freeze-drying method described above is sampled, appearance detected, moisture detected, and CCIT (vacuum decay method) detected, and the detection results are shown in Table 5:

[0224] Table 5 Appearance detection, moisture detection, and CCIT detection results of freeze-dried preparations

[0225] FIG. 4A is an appearance diagram of a freeze-dried product obtained by a freeze-drying process. As can be seen from Table 5 and FIG. 4A, the appearance detection results of the freeze-dried preparations show that the appearance is good, and the average moisture detection results are low; in addition, the sealing of the dual-chamber carton bottle packaging material for injection in Examples 9-11 in the freeze-drying process is good, and can meet the sealing requirement of the preparation.

[0226] Example 13

[0227] A dual-chamber carton bottle packaging material for injection, comprising a dual-chamber carton bottle 1' and a bottle cap assembly, the structure of the dual-chamber carton bottle 1' is the same as that of the dual-chamber carton bottle 1 in Example 9. The bottle cap assembly comprises a stopper 2' and a top cover 3', the structure of the stopper 2' is the same as that of the stopper 2' in Example 9, and the structure of the top cover 3' is shown in FIG. 14B, the bottom disc 31' is adjusted to extend downward to additionally fit at least a part of the bottle body 12'; the shape of the downward extending part of the bottom disc 31' is set as an octagonal prism. In addition, the maximum length of the protruding part 304' protruding from the inner wall of the upper end 30' is set as 0.25 mm, and other structures and parameters are the same as those in Example 9.

[0228] Example 14

[0229] The maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 is replaced by 0.2 mm, and the other structures and parameters are the same as those of Example 13. The compression plug and capping sealing test is performed on the bottle cap assembly, and it is found that the fit degree of the top plug 2' and the top cap 3' is high, and the top plug 2' is not slipped off from the top cap 3'; a larger pressure needs to be applied during the capping process, but it does not cause deformation and damage to part of the structure of the top cap 3'; and the fit degree of the top cap 3' and the bottle mouth 10' of the double-cavity carton bottle 1' is obviously improved and is not pulled out after a larger force is applied.

[0230] Example 15

[0231] The double-cavity carton bottle packaging material for injection is used for the freeze-drying process of a drug, and a freeze-dried preparation is obtained. The steps of using 25 parts of the double-cavity carton bottle packaging material for injection in Examples 13 and 14 to perform the freeze-drying process and obtain the freeze-dried preparation are as follows:

[0232] (1) Add a middle plug into each double-cavity carton bottle 1', and then fill the drug solution to be freeze-dried. The drug solution is long-acting growth hormone, which contains 22.0 mg hGH / mL long-acting growth hormone, 10 mM succinic acid, 74.0 mg / mL trehalose dihydrate, and an appropriate amount of tromethamine to adjust the pH value of the solution to pH 5.0.

[0233] Place and fix the double-cavity carton bottle 1' on the freeze-drying support. The freeze-drying support is a tray-type freeze-drying support, and the double-cavity carton bottle 1' is placed in the freeze-drying support in an upright manner.

[0234] (2) After the top plug 2' and the top cap 3' in Examples 13-14 are pre-assembled and combined, they are placed at the bottle mouth 10' of the double-cavity carton bottle 1', and the pre-assembled and combined manner of the top plug 2' and the top cap 3' is the same as that in Example 12.

[0235] (3) The drug solution to be freeze-dried is respectively subjected to freezing, primary drying, secondary drying, and plate layer plug capping, and the specific operation method is the same as that in Example 12.

[0236] (4) After the freeze-drying process is completed, nitrogen charging operation is performed on the double-cavity carton bottle 1' to maintain the low moisture content of the freeze-dried product, and then capping sealing is performed. The capping sealing method is the same as that in Example 12.

[0237] (5) The double-cavity carton bottle 1' is taken out of the freeze-drying machine, and the freeze-dried preparation in the double-cavity carton bottle 1' is obtained.

[0238] The freeze-dried preparation prepared in the double-cavity carton bottle 1' by the above freeze-drying method is sampled, appearance detected, moisture detected, and CCIT detected, and the detection results are shown in Table 6:

[0239] Table 6 Appearance detection, moisture detection, and CCIT detection results of the freeze-dried preparation

[0240] As shown in Table 6, the appearance test results of the freeze-dried preparations show that the appearance is good, and the average moisture test results are low; in addition, the sealing performance of the dual-chamber carton bottle package material in Example 13 and Example 14 in the freeze-drying process is good, which can meet the sealing requirements of the preparation.

[0241] Example 16

[0242] A dual-chamber carton bottle package material for injection, comprising a dual-chamber carton bottle 1' and a bottle cap assembly, the bottle cap assembly comprising a top plug 2' and a top cap 3'. Wherein, a fitting part 306' is arranged on one side of the top disc opening of the top disc 300' close to the top plug 2', which uniformly recedes in the direction away from the top disc opening close to the top plug 2'; in addition, four internal protrusions 310' are equidistantly arranged on the inner wall of the bottom disc 31' away from the upper end 30', and each internal protrusion 310' has a protrusion two-side opening 311' on the left and right sides, as shown in FIGS. 14C and 15B, and other structures and parameters are the same as those of Example 13.

[0243] Example 17

[0244] A drug freeze-drying process is carried out using the dual-chamber carton bottle package material for injection, and a freeze-dried preparation is obtained. The dual-chamber carton bottle package material for injection is selected as 10 parts of the dual-chamber carton bottle package material for injection in Example 16, and the steps of carrying out the freeze-drying process and obtaining the freeze-dried preparation are as follows:

[0245] (1) Add a middle plug into each dual-chamber carton bottle 1', and then fill the drug solution to be freeze-dried. The drug solution is long-acting growth hormone, which contains 22.0 mg hGH / mL long-acting growth hormone, 10 mM succinic acid, 74.0 mg / mL trehalose dihydrate, and an appropriate amount of tromethamine to adjust the pH value of the solution to pH 5.0.

[0246] Place and fix the dual-chamber carton bottle 1' on the freeze-drying support. Wherein, the freeze-drying support is selected as a tray-type freeze-drying support, and the placement mode of the dual-chamber carton bottle 1' in the freeze-drying support is upright.

[0247] (2) After pre-assembling the top plug 2' and the top cap 3' in Example 16, place them at the bottle opening 10' of the dual-chamber carton bottle 1', and the pre-assembling mode of the top plug 2' and the top cap 3' is the same as that of Example 12.

[0248] (3) Freeze, primary drying, secondary drying, and plate layering and plug capping are carried out on the drug solution to be freeze-dried, respectively, and the specific operation method is the same as that of Example 12.

[0249] (4) After the freeze-drying process is completed, nitrogen charging operation is carried out on the dual-chamber carton bottle 1' to maintain the low moisture content of the freeze-dried product, and then the cap is sealed. The capping and sealing method is the same as that of Example 12.

[0250] (5) The double chamber carton bottle 1' is taken out from the freeze dryer to obtain the freeze-dried preparation therein.

[0251] The freeze-dried preparation prepared in the double chamber carton bottle 1' via the freeze-drying method described above is sampled, appearance tested, moisture tested, and CCIT tested, and the test results are shown in Table 7:

[0252] Table 7 Appearance test, moisture test, and CCIT test results of freeze-dried preparation

[0253] FIG. 4B is an appearance diagram of a freeze-dried product obtained by a freeze-drying process. As can be seen from Table 7 and FIG. 4B, the appearance test results of the freeze-dried preparation show that the appearance is good, and the average moisture test results are low; in addition, the injection double chamber carton bottle packaging material in Example 16 has good sealing performance in the freeze-drying process, and can meet the sealing performance requirements of the preparation.

[0254] Example 18

[0255] An injection double chamber carton bottle packaging material includes a double chamber carton bottle 1' and a bottle cap assembly including a top plug 2" and a top cap 3" for sealing the double chamber carton bottle 1'. The top plug 2" is used to seal the bottle mouth 10' of the double chamber carton bottle 1'. The double chamber carton bottle 1' is sealed by a plug pressing assembly, wherein the plug pressing assembly includes a pressing jig 51 and a holding jig 50, and the structure is shown in FIG. 21A. The top plug has a plug cap 20" and a plug column 21", and the plug column 21" needs to be completely embedded in the bottle mouth opening 100' in the center of the bottle mouth 10', and the lower surface of the plug cap 20" needs to be completely attached to the upper surface of the bottle mouth 10' to achieve sealing of the bottle mouth 10'.

[0256] For this bottle cap assembly, when the freeze-drying is completed and the freeze-dried preparation needs to be airtight, the plug pressing assembly can be used to complete the sealing of the bottle mouth 10' by the top plug 2", and the top cap 3" is installed after the top plug 2" is fixed to further improve the airtightness of the double chamber carton bottle 1', specifically:

[0257] (1) Top plug sealing

[0258] First, the upper and lower ends of the holding jig 50 of the plug pressing assembly are both open, the inner wall of the holding jig 50 is attached to the outer surface of the bottle mouth 10' and the bottle body 12', and the holding jig 50 is pressed until it is completely attached to the upper end of the bottle body 12'. Since the holding jig 50 is closely attached to the bottle mouth 10' and the bottle body 12', it has a large friction force, so the holding jig 50 is not easy to fall off from the double chamber carton bottle 1'; in addition, the upper end of the holding jig 50 protrudes from the bottle mouth 10'.

[0259] Next, the top plug 2" is placed in the holding fixture 50, specifically, the top plug 2" is placed on the upper end of the holding fixture 50 protruding on the protruding part 500 of the holding fixture 50, the protruding part 500 can hold the plug cap 20" to fix the position of the top plug 2", so that the plug column 21" is aligned with the bottle opening 100', facilitating the plug column 21" to embed in the bottle opening 100' when moving down. In particular, the number of protruding parts 500 is two, which are respectively arranged on both sides of the upper end of the holding fixture 50.

[0260] Then, the inner wall of the pressing-in fixture 51 of the pressing plug assembly is attached to the outer wall of the holding fixture 50 and slides downward, the lower end of the pressing-in fixture 51 is open, the upper surface is closed and the center is concave downward, the inner wall of the concave part is provided with a pressing column 510 protruding along the axis direction of the pressing-in fixture 51, during the downward sliding of the pressing-in fixture 51, the pressing column 510 can contact and apply downward pressure on the plug cap 20", so as to realize the movement of the whole top plug 2" to the bottle opening 10' by pressing, until the plug column 21" is completely embedded in the bottle opening 10'; after the plug column 21" is completely embedded in the bottle opening 10', the plug cap 20" can be just clamped under the protruding part 500, so the protruding part 500 can further clamp the top plug 2" to avoid its falling off.

[0261] It should be noted that before the plug column 21" is completely embedded in the bottle opening 10', the height of the holding fixture 50 protruding from the bottle opening 10' is less than the height of the upper surface of the pressing-in fixture 51 protruding from the bottle opening 10'; therefore, before the plug column 21" is completely embedded in the bottle opening 10', the pressing-in fixture 51 cannot move downward due to the obstruction of the holding fixture 50, avoiding the incomplete embedding of the top plug 2" and the bottle opening 10'. In particular, the number of pressing columns 510 is two, which are respectively arranged on both sides of the inner wall of the concave part on the upper surface of the pressing-in fixture 51, so as to apply uniform downward pressure on the top plug 2".

[0262] Finally, the pressing-in fixture 51 and the holding fixture 50 are removed, the pressing plug assembly is only used to control the sealing of the top plug 2" to the bottle opening 10', therefore, it needs to be removed after the sealing is completed, so as to facilitate the subsequent capping.

[0263] (2) Top cover sealing

[0264] The top cover 3" is used to fix the top plug 2" and seal the bottle mouth 10' of the double-chamber carton bottle 1' through the top plug 2". The structure of the top cover 3" is shown in FIG. 21B, which includes a main body and a bottom disc 31", the main body has a top disc 300" at the center of the upper end of the top cover 3" and a thread 301" at the edge of the upper end of the top cover 3", the bottom disc 31" is arranged above the main body, and the bottom disc 31" is open below; after the top plug 2" is completely embedded in the bottle mouth 10', the top cover 3" is pressed downward and sleeved on the bottle mouth 10', in this process, the inner walls of the main body and the bottom disc 31" are attached to the bottle mouth 10' and the bottle neck 11'; therefore, after the top cover 3" is pressed until the bottom disc 31" is completely attached to the upper surface of the bottle body 12', the top cover 3" has a large friction with the double-chamber carton bottle 1', which can avoid itself from falling off to improve the sealing performance of the double-chamber carton bottle 1'.

[0265] In addition, the top disc 300" has a double-layer structure, the upper layer is a hollow cylinder, and the lower layer is a cylinder with an inner diameter equal to the inner diameter of the hollow part of the upper layer, after the bottom disc 31" is completely attached to the upper surface of the bottle body 12', the top disc 300" can hold the top plug 2" embedded in the bottle mouth 10' through the lower layer cylinder, to prevent the top plug 2" from falling out of the bottle mouth 10', which can improve the sealing performance of the double-chamber carton bottle 1'.

[0266] In summary, the freeze-drying method provided by the present application is used to prepare freeze-dried preparations of products for pharmaceutical, cosmetic or medical beauty applications with double-chamber carton bottles, which have regular freeze-drying curve parameters, good appearance and low moisture content, high stability in storage; after freeze-drying, the packaging material has good sealing performance, providing a high-purity and sterile storage environment. Therefore, the freeze-dried preparations obtained by the freeze-drying method of the above-mentioned embodiments of the present application have higher market core competitiveness.

Claims

1. A freeze-drying method for a product used in pharmaceutical, cosmetic or medical aesthetic applications, comprising: adding a middle plug into a double-chambered vial, and then filling the double-chambered vial with a product to be freeze-dried; assembling a top plug with a top cap, and placing the top cap above a bottle opening of the double-chambered vial, and placing and fixing the double-chambered vial on a customized freeze-drying support; freezing, primary drying and secondary drying the product to be freeze-dried, respectively; pressing the top plug into the double-chambered vial using the top cap to seal the double-chambered vial and fix the top plug, and to make the top plug seal the bottle opening of the double-chambered vial.

2. The freeze-drying method according to claim 1, wherein: the freeze-drying support is a stand-alone freeze-drying support or a tray-type freeze-drying support, preferably, the freeze-drying support is a tray-type freeze-drying support; and the double-chambered vial is placed in the freeze-drying support in an upright position or an inverted position, preferably, the double-chambered vial is placed in the freeze-drying support in an upright position.

3. The freeze-drying method according to claim 1, wherein: a temperature range for freezing the product in the double-chambered vial is -60℃ to -40℃; a temperature range for primary drying is -60℃ to 0℃, and a temperature range for secondary drying is 15℃ to 40℃; and a pressure range for primary drying and secondary drying is 0.02mbar to 0.2mbar, preferably, the pressure for primary drying and secondary drying is 0.06mbar, respectively.

4. The freeze-drying method according to claim 1, wherein: pressing the top plug into the double-chambered vial using the top cap further comprises: performing a nitrogen filling operation on the double-chambered vial before pressing the top plug to maintain a low moisture content of the freeze-dried product.

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

6. A syringe comprising: A double-chambered vial package for injection, a freeze-dried preparation and a reconstitution agent.

7. The injection according to claim 6, wherein: the double-chambered vial package for injection comprises a double-chambered vial and a cap assembly, wherein: the double-chambered vial is used to contain the freeze-dried preparation and the reconstitution agent; the cap assembly comprises the top plug and the top cap; the top plug seals the bottle opening of the double-chambered vial; the top cap is used to press and fix the top plug so that the top plug seals the bottle opening of the double-chambered vial; and to seal the double-chambered vial; wherein the process of pressing and fixing the top plug using the top cap so that the top plug seals the bottle opening of the double-chambered vial comprises the following steps: pre-assembling the top plug into the top cap; placing the top cap with the assembled top plug above the bottle opening of the double-chambered vial, and pressing the top cap downward.

8. The injection according to claim 7, wherein: the double-chambered vial comprises an inner chamber, a bottle body, a bottle neck and a bottle opening, wherein a center of the bottle opening is provided with a bottle opening opening connected with the inner chamber, and an inner diameter of the bottle opening opening is smaller than an inner diameter of the bottle opening and the bottle neck; a side outer wall of the bottle body has a bypass protrusion.

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

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