Lyophilization methods, lyophilized formulations, and injections for pharmaceutical, cosmetic or aesthetic medical products

Abstract

A method for lyophilizing products for pharmaceutical, cosmetic, or medical aesthetic applications is disclosed, comprising: adding a stopper to a dual-chamber cartridge vial; filling it with the product to be lyophilized; placing and fixing the dual-chamber cartridge vial on a lyophilization support; positioning a top stopper on the mouth of the dual-chamber cartridge vial; subjecting the product to be lyophilized to freezing, primary drying, and secondary drying respectively; and fixing the top stopper with a top cap and sealing the mouth of the vial. The lyophilization method provided in this application can offer high-quality lyophilization parameters and operations, utilizing a top stopper and top cap to achieve integrated compression sealing of the dual-chamber cartridge vial, thereby maintaining superior quality of the obtained lyophilized product and improving its effectiveness and shelf life.

Description

Technical Field

[0001] This case involves the fields of biopharmaceuticals, cosmetics, or medical aesthetics, and more specifically, a lyophilization method, lyophilized formulations, and injections for use in pharmaceuticals, cosmetics, or medical aesthetics products. Prior Technology

[0002] Currently, most lyophilized products on the market use vials as storage containers. Before injection, a sterile syringe is used to draw the reconstituted solution from another container, and then the reconstituted solution is injected into the drug container for reconstitution, extraction, and administration. This results in relatively poor dosing accuracy and user compliance. Dual-chamber cartridge vials offer a better alternative. A dual-chamber cartridge vial is divided into two chambers by a stopper. The front chamber contains the lyophilized drug, and the rear chamber contains the reconstituted solution. During use, the reconstituted solution is bypassed and flows into the front chamber to reconstitute the lyophilized drug by pushing the bottom stopper. After reconstitution, pushing the bottom stopper to the top completes the injection process.

[0003] Using dual-chamber cartridges to store lyophilized products and reconstitution solutions separately allows medical staff to easily reconstitute and administer lyophilized drugs, and patients can also self-administer medications, simplifying the operational process. For active ingredients in sensitive biopharmaceuticals, medical device reagents, and cosmetic reagents, dual-chamber cartridges allow the two contents to be mixed or reconstituted just before administration, helping to maintain the shelf-life stability of the active ingredients and reducing degradation or inactivation caused by prolonged contact.

[0004] However, conventional freeze-drying technology cannot integrate the freeze-drying of the liquid to be freeze-dried and the sealing of the double-chamber cartridge bottle within the freeze dryer. Therefore, it is necessary to design a freeze-drying method that integrates stoppering, freeze-drying and capping to ensure good sealing of the double-chamber cartridge bottle during the freeze-drying process, so that the freeze-dried product has a good shape and lower water content.

[0005] Therefore, there is an urgent need for a new drug freeze-drying method that can solve the above problems, so as to improve the freeze-drying efficiency and quality of drugs, fill the current market gap in the field of dual-chamber cartridge packaging materials, and enhance the core competitiveness of products. Summary of the Invention

[0006] This case aims to provide a solution that overcomes at least one of the aforementioned defects of the prior art.

[0007] According to one aspect of this case, a freeze-drying method is provided for a product used in pharmaceutical, cosmetic, or medical aesthetic applications, comprising:

[0008] Add the middle stopper to the double-chamber cartridge bottle, then fill it with the product to be freeze-dried; assemble the top stopper and top cap, place them above the mouth of the double-chamber cartridge bottle, and place and fix the double-chamber cartridge bottle on the custom-made freeze-drying rack; freeze, first-stage dry, and second-stage dry the product to be freeze-dried respectively; use the top cap to press the top stopper into the double-chamber cartridge bottle to seal the double-chamber cartridge bottle and fix the top stopper, so that the top stopper seals the mouth and neck of the double-chamber cartridge bottle.

[0009] The freeze-drying method proposed in this case involves simultaneously capping and sealing the freeze-dried double-chamber cartridge vials by operating the top cap, thereby sealing the finished freeze-dried formulation within the vials and further sealing the double-chamber cartridge vials. The freeze-dried formulation obtained through this method also exhibits a good frozen powder appearance and low water content, which helps meet high-requirement freeze-dried product standards and ensures that the formulation maintains stable quality attributes over a long period.

[0010] In some embodiments of this case, the freeze-drying rack is an independent freeze-drying rack or a tray-type freeze-drying rack, preferably, the freeze-drying rack is a tray-type freeze-drying rack; and the dual-chamber cartridge bottles are placed upright or upside down in the freeze-drying rack, preferably, the dual-chamber cartridge bottles are placed upright in the freeze-drying rack.

[0011] In some embodiments of this case, the temperature range set for freezing the product in the dual-chamber cartridge 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 and secondary drying is 0.02 mbar to 0.2 mbar, preferably, the pressure for primary and secondary drying is 0.06 mbar respectively.

[0012] In some embodiments of this case, the use of a top cap to press the top stopper into the dual-chamber cartridge bottle also includes: purging the dual-chamber cartridge bottle with nitrogen before pressing the top stopper to maintain a low moisture content in the freeze-dried product.

[0013] According to another aspect of this case, a lyophilized formulation is also provided, prepared according to any of the lyophilization methods described above. The lyophilized formulation also features high lyophilization quality and low moisture content. For example, when the lyophilized formulation is a pharmaceutical product, it can be used in various application scenarios such as injection, oral administration, and biological experiments, providing superior effects. Furthermore, when the lyophilized formulation is a reagent or cosmetic used in medical aesthetics, its active ingredients can be preserved for a long time, and through rapid reconstitution for injection or topical application, it can also provide users with superior effects.

[0014] According to another aspect of this case, an injectable preparation is also provided, which may include: a dual-chamber cartridge vial for injection, a lyophilized formulation, and a reconstituted solvent. The injectable preparation provided in this case may include solution, emulsion, and suspension types, and can be used in various application scenarios such as drug therapy, emergency care for critically ill patients, epidemic prevention, and traditional Chinese medicine healthcare to help improve the health of the population.

[0015] In some embodiments of this invention, the packaging material for a dual-chamber cartridge vial for injection may include: a dual-chamber cartridge vial and a cap assembly, wherein the dual-chamber cartridge vial is used to hold a drug and a reconstituted solvent; the cap assembly includes a top stopper and a top cap; the top stopper seals the mouth of the dual-chamber cartridge vial; the top cap is used to press and fix the top stopper, such that the top stopper seals the mouth of the dual-chamber cartridge vial; and the dual-chamber cartridge vial is sealed; wherein the process of pressing and fixing the top stopper with the top cap, such that the top stopper seals the mouth of the dual-chamber cartridge vial, includes the following steps:

[0016] Pre-assemble the top stopper into the top cap; place the top cap with the pre-assembled top stopper above the mouth of the dual-chamber cartridge bottle and press down on the top cap. After the top stopper is pre-assembled into the top cap, the top stopper and the top cap are integrally formed, eliminating the need for a stoppering element. The top cap can directly achieve stoppering and capping by pressing the top stopper, thereby improving the sealing efficiency of dual-chamber cartridge bottles in freeze-drying technology and avoiding the number of operation failures caused by more operational steps. When failed operations are difficult to remedy in the freeze-drying process using conventional methods, the self-stoppering and capping integrated operation of the top cap is particularly important for ensuring the efficiency of freeze-drying technology.

[0017] In some embodiments of this case, a dual-cavity cartridge bottle may include: an inner cavity, a bottle body, a neck, and a bottle mouth. The center of the bottle mouth is provided with a bottle mouth opening connected to the inner cavity, and the inner diameter of the bottle mouth opening is smaller than the inner diameter of the bottle mouth and the neck. One side of the outer wall of the bottle body has a bypass protrusion.

[0018] In some embodiments of this case, the lyophilized formulation is a lyophilized formulation prepared according to any of the above-mentioned lyophilization methods or the lyophilized formulation provided in this case.

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

[0020] 1. This case provides an integrated sealing method for stoppering and capping packaging materials for injection dual-chamber cartridge vials during the freeze-drying process.

[0021] 2. This invention provides optimal freeze-drying parameters and moisture removal procedures for freeze-drying technology, so that freeze-dried products obtained using the freeze-drying method of this invention maintain better quality and are easier to store or use.

[0022] 3. This case provides a high-quality lyophilized formulation prepared by a lyophilization method, which can be a high-purity lyophilized drug, a medical device reagent, or a cosmetic reagent.

[0023] 4. This invention provides an injectable preparation that can be stably stored by holding the lyophilized formulation and the reconstitution solvent in a dual-chamber cartridge vial. When using the injectable preparation, the lyophilized formulation and the reconstitution solvent can be quickly mixed and reconstituted, ensuring the high efficiency and convenience of the preparation. Simple Explanation of the Diagram

[0024] The above and other objects, features, and advantages of this invention will become more apparent through a more detailed description of the embodiments in conjunction with the accompanying drawings. The drawings are provided to offer a further understanding of the embodiments of this invention and form part of the specification. They are used together with the embodiments of this invention to explain the invention and do not constitute a limitation thereof. In the drawings, the same reference numerals generally represent the same components or steps.

[0025] Figure 1 illustrates a schematic diagram of the freeze-drying support in this case. Figure 2 illustrates the freeze-drying curve of the freeze-dried formulation in this case. Figure 3 illustrates the appearance of the lyophilized formulation in this case. Figure 4A illustrates a first schematic diagram of the appearance of another lyophilized formulation in this case. Figure 4B illustrates a second schematic diagram of the appearance of another lyophilized formulation in this case. Figure 5 illustrates the structural diagram of the dual-chamber cartridge bottle 1 and the top stopper 2 in this case. Figure 6A illustrates a structural schematic diagram of the top cover 3 in this case. Figure 6B illustrates another structural schematic diagram of the top cover 3 in this case. Figure 7 illustrates another structure of the top plug 2 and another structural diagram of the top cover 3 in this case. Figure 8A illustrates the structural diagram of the top plug positioning point 303 in this case. Figure 8B illustrates another structural schematic diagram of the top plug positioning point 303 in this case. Figure 9 illustrates the structural diagram of the upper part 30 in this case. Figure 10 illustrates a structural schematic diagram of the maximum length of the protrusion 304 in this case. Figure 11 illustrates the structural diagram of the upper and lower chamfers of the protrusion 304 in this case. Figure 12 illustrates the structural schematic of the dual-chamber cartridge bottle packaging material element in this case. Figure 13 illustrates the structural diagram of the dual-chamber cartridge bottle 1' and the top stopper 2' in this case. Figure 14A illustrates the structural diagram of the top cover 3' in this case. Figure 14B illustrates another structural schematic diagram of the top cover 3' in this case. Figure 14C illustrates another structural schematic diagram of the top cover 3' in this case. Figure 15A illustrates another structure of the top plug 2' and another structural diagram of the top cover 3' in this case. Figure 15B illustrates a structural schematic diagram of the fitting part 306 of the top cover 3' in this case. Figure 16A illustrates the structural diagram of the top plug positioning point 303' in this case. Figure 16B illustrates another structural schematic diagram of the top plug positioning point 303' in this case. Figure 16C shows a top view of the demolding hole 305' in this case. Figure 17 illustrates the structural diagram of the demolding hole 305' in this case. Figure 18 illustrates the structural diagram of the upper 30' of this case. Figure 19 illustrates the structural diagram of the maximum length, upper chamfer, and lower chamfer of the protrusion 304' in this case. Figure 20 illustrates the structural schematic of the dual-chamber cartridge bottle packaging material component in this case. Figure 21A illustrates the structural diagram of the top plug 2” and the pressure plug element in this case. Figure 21B illustrates another structural schematic diagram of the top plug 2” and the pressure plug element in this case. Figure 22 illustrates the structural diagram of the top cover 3” in this case. Implementation

[0026] As described above, the freeze-drying method for products used in pharmaceuticals, cosmetics, or medical aesthetics applications proposed in this case includes: adding a middle stopper to a dual-chamber cartridge bottle 1, and then filling it with the product to be freeze-dried; assembling the top stopper 2 and the top cap 3, and placing them above the bottle opening 10 of the dual-chamber cartridge bottle 1; placing and fixing the dual-chamber cartridge bottle 1 on a custom-made freeze-drying bracket; freezing, primary drying, and secondary drying of the product to be freeze-dried; using the top cap 3 to press the top stopper 2 into the dual-chamber cartridge bottle 1 to seal the dual-chamber cartridge bottle 1 and fix the top stopper 2, so that the top stopper 2 seals the bottle opening 10 of the dual-chamber cartridge bottle 1.

[0027] In this case, the stopper added to the double-chamber cartridge bottle 1 and the product to be freeze-dried can be any double-chamber cartridge bottle stopper and freeze-driable product adapted to the size and structure of the double-chamber cartridge bottle 1. Freezing, primary drying, and secondary drying operations can be carried out in a freeze dryer that can accommodate the freeze-drying support used in the freeze-drying method. During the process of fixing the top stopper 2 with the top cover 3 and sealing the bottle mouth 10 of the double-chamber cartridge bottle 1 through the top stopper 2, the method of driving the top cover 3 to press down can also be any driving method that can be implemented in the freeze dryer, such as mechanical clamping, pneumatic drive, pneumatic clamp drive, or spring pressing.

[0028] In this invention, after adding a stopper to the dual-chamber cartridge vial 1, the product to be lyophilized can be filled in. Specifically, the product to be lyophilized can be a product added to the inner cavity 13 of the dual-chamber cartridge vial 1 for lyophilization and short-term / long-term storage, such as small molecule drugs, peptides, enzymes, antibodies, fusion proteins, antibody-drug complexes, reagents, etc. The user can select any liquid to be lyophilized and fill it into one of the inner cavities 13 of the dual-chamber cartridge vial 1 to perform lyophilization using the lyophilization method of this invention.

[0029] In this case, the freeze-drying support is either a freestanding freeze-drying support or a tray-type freeze-drying support. The type of freeze-drying support used in the freeze-drying method is either a freestanding freeze-drying support or a tray-type freeze-drying support; there are no restrictions on the specific model, size, or operating parameters of the freeze-drying support in the freeze dryer. Preferably, the freeze-drying support is a tray-type freeze-drying support, as a tray-type freeze-drying support facilitates the placement of a larger number of dual-chamber cartridge bottles.

[0030] Specifically, the dual-chamber cartridge bottle 1 is placed upright or upside down in the freeze-drying rack. Preferably, the dual-chamber cartridge bottle 1 is placed upright in the freeze-drying rack to facilitate uniform heat distribution in the dual-chamber cartridge bottle 1, improve solvent sublimation efficiency, and reduce the degree of product sedimentation and aggregation, thus maintaining a uniform and stable product appearance.

[0031] In this case, the temperature range set for freezing the product in the double-chamber cartridge bottle 1 can be a temperature range suitable for freeze-drying the product. Since the raw material to be freeze-dried generally has high freezing efficiency and maintains its quality when the freezing temperature is between -60℃ and -40℃, the freezing temperature can be any value between -60℃ and -40℃. Specifically, the temperature range set for freezing the product in the double-chamber cartridge 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 secondary drying temperature range is -60℃ to 0℃, specifically -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℃, and -3 5℃, -34℃, -33℃, -32℃, -31℃, -30℃, -29℃, -28℃, -27℃, -26℃, -25℃, -24℃, -23℃, -22℃, -21℃, -20℃, -19℃, -18℃, -17℃, -16℃, -15℃, -14℃, -13℃, -12℃, -11℃, -10℃, -9℃, -8℃, -7℃, -6℃, - 5℃, -4℃, -3℃, -2℃, -1℃ or 0℃; the temperature range for secondary drying is 15℃~40℃, namely 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℃.

[0032] Similarly, the temperatures for the primary and secondary drying of the product can be any values ​​within the range of -60℃ to 0℃ and 15℃ to 40℃, respectively, to increase the sublimation rate of the drug's moisture. Furthermore, the pressure range for primary and secondary drying can be any value between 0.02 mbar and 0.2 mbar. When the optimal pressure for both primary and secondary drying is 0.06 mbar, peak drying efficiency can be guaranteed. Specifically, the pressure range for primary and secondary 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. Preferably, the pressure for both primary and secondary drying is 0.06 mbar.

[0033] In this case, the method of using the top cap 3 to press the top stopper 2 into the dual-chamber cartridge bottle 1 also includes: purging the dual-chamber cartridge bottle 1 with nitrogen before pressing the top stopper 2 to maintain the low moisture content of the freeze-dried product. Those skilled in the art will understand that purging the dual-chamber cartridge bottle 1 with nitrogen before sealing the bottle opening 10 aims to bring the nitrogen in the inner chamber 13 to 1 atmosphere. On the one hand, the nitrogen can be used to maintain the low moisture content of the freeze-dried product; on the other hand, 1 atmosphere of nitrogen can also keep the middle stopper fixed in the position of the dual-chamber cartridge bottle.

[0034] In this case, a lyophilized formulation is also included, prepared according to the above-described lyophilization method. In particular, since the product to be lyophilized added to one of the inner cavities 13 of the dual-cavity cartridge bottle 1 can be one of multiple products, the final lyophilized formulation can also be different when different products to be lyophilized are added to the dual-cavity cartridge bottle 1. Furthermore, when the lyophilization parameters implemented during the lyophilization process of the product, such as the temperature and pressure of the primary drying, are changed, different qualities or properties of lyophilized formulations can also be produced by the lyophilization method after adding the same product to be lyophilized, such as formulations with different water contents or different solid forms.

[0035] This application also includes an injectable preparation comprising: a dual-chamber cartridge vial packaging material, a lyophilized formulation, and a rehydrating agent. It should be noted that the lyophilized formulation and rehydrating agent can be any lyophilized formulation and rehydrating agent suitable for the dual-chamber cartridge vial packaging material and lyophilization technology. Specifically, the lyophilized formulation can be any lyophilized formulation prepared by lyophilizing any product to be lyophilized that can be filled into the dual-chamber cartridge vial 1 of this application, including the lyophilized formulation provided in this application.

[0036] In addition, the reconstitution solvent can be any of the lyophilized preparations prepared above, such as sterile water for injection (which may contain antibacterial agents, such as phenol, m-cresol, benzyl alcohol, etc.), physiological saline, 5% glucose solution, and other buffer solutions, such as phosphate buffer, citrate buffer, acetate buffer, histidine buffer, succinate buffer, tris(hydroxymethyl)aminomethane hydrochloride buffer, etc., which can be used to reconstitute the lyophilized preparations provided in this case when administering the medication.

[0037] In this case, the packaging material for the dual-chamber cartridge vial for injection includes: a dual-chamber cartridge vial 1 and a cap assembly, wherein the dual-chamber cartridge vial 1 is used to hold lyophilized formulations and reconstituted solutions. The cap assembly includes a top stopper 2 and a top cap 3 for sealing the dual-chamber cartridge vial 1. As shown in Figure 5, the dual-chamber cartridge vial 1 can be placed in a lyophilization support used in existing lyophilization technology, and the dual-chamber cartridge vial packaging material can be fixed and placed upright or upside down in the lyophilization support and sheath; the cap assembly can be made of any material suitable for achieving the cap sealing function. The top stopper 2 is confined within the top cap 3 for sealing the mouth 10 of the dual-chamber cartridge vial 1; the top cap 3 is used to press and fix the top stopper 2, such that the top stopper 2 seals the mouth 10 of the dual-chamber cartridge vial 1, and seals the dual-chamber cartridge vial 1; wherein the process of pressing and fixing the top stopper 2 with the top cap 3, such that the top stopper 2 seals the mouth 10 of the dual-chamber cartridge vial 1, may include the following steps:

[0038] The top plug 2 is pre-assembled into the top cap 3; and the top cap 3 with the top plug 2 pre-assembled is placed above the bottle mouth 10 of the double-chamber cartridge bottle 1, and the top cap 3 is pressed down to press the top plug 2. The top cap 3 can be pressed down by mechanical clamping, pneumatic drive, pneumatic clamp drive, or spring pressing, etc.

[0039] In this case, the dual-cavity cartridge bottle 1 includes: an inner cavity 13, a bottle body 12, a neck 11, and a bottle mouth 10. The bottle mouth 10 has a centrally located opening 100 connected to the inner cavity 13. The inner diameter of the opening 100 is smaller than the inner diameters of the bottle mouth 10 and the neck 11. One side of the outer wall of the bottle body 12 has a bypass protrusion 120. Those skilled in the art will understand that the dimensions of the inner cavity 13, bottle body 12, neck 11, and bottle mouth 10 of the dual-cavity cartridge bottle 1 can be adjusted to fit the size range of commonly used freeze-drying supports. For example, changing the vertical length of one or more parts of the dual-cavity cartridge bottle 1 or changing the radial length of one or more parts of the dual-cavity cartridge bottle 1 does not depart from the scope of protection of this case.

[0040] In this case, the top stopper 2 includes a stopper cap 20 and a stopper plunger 21. The diameter of the stopper plunger 21 can be equal to or slightly larger than the inner diameter of the bottle opening 100. After the stopper plunger 21 is inserted into the bottle opening 100, the lower surface of the stopper cap 20 completely fits against the upper surface of the bottle opening 10 to achieve a seal on the bottle opening 10. In particular, the top stopper 2 is made of elastic rubber material, so the diameter of the stopper plunger 21 can be adjusted within the range of the diameter of the bottle opening 100 after the stopper plunger 21 is pressed. The diameter of the stopper plunger 21 can be slightly larger than the diameter of the bottle opening 100 to ensure a tight seal.

[0041] In this case, the top cover 3, as shown in Figure 6A, includes an upper end 30, a middle end 31, and a lower end 32. The upper end 30 has a top plate 300, a thread 301, and an opening 302; the middle end 31 has a raised ring 310; and the lower end 32 optionally has a raised strip 320. The inner wall of the top cover 3 fits against the bottle mouth 20, the bottle neck 21, and at least a portion of the bottle body 22. When the top cover 3 faces the bottle mouth 10, the top plate 300 of the upper end 30 presses the top plug 2 into the bottle mouth 10, causing the top plug 2 to embed into the bottle mouth 10. After the bottle mouth 10 of the dual-chamber cartridge bottle 1 is sealed, the top plate 300 fits tightly against the top cap 20 to secure the top plug 2. The opening 302 allows sublimated water in the product to drain, the thread 301 is used for threaded engagement with a sterile injection needle, and the raised ring 310 can be matched with a sheath.

[0042] It should be noted that the lower end 32 of the top cap 3 can be cylindrical or prismatic, as shown in Figure 6B. Its length in the vertical direction is adjustable. Therefore, the lower end 32 can fit a small portion, a large portion, or the entire bottle body 12 to achieve better sealing and to meet the dimensional requirements of the top cap 3 for freeze-drying technology. The raised strip 320 is used to increase the friction between the lower end 32 and the mating sleeve to improve the mutual fixing effect; in particular, the raised strip 320 can also be removed. The shape of the lower end 32 can be cylindrical or prismatic to prevent the top cap 3 from slipping off due to rotational centrifugal force or from sliding relative to the dual-chamber cartridge bottle 1, thus affecting the sealing performance.

[0043] Specifically, the length of the middle end 31 of the top cap 3 along the direction of the neck 11 and the bottle body 12 is adjustable, and the convex ring 310 can be adjusted to fit the lower part of the upper end 30 at its highest point to accommodate the sealing requirements of the double-cavity cartridge bottle 1 for different degrees of sealing of the top cap 3. For example, it may be necessary to reduce the length of the top cap 3 along the direction of the bottle body 12 or the volume of the top cap 3 to meet the size requirements of the freeze-drying support for the double-cavity cartridge bottle 1 and the top cap 3 in freeze-drying technology. Specifically, the top plate 300 has a top plate opening at its center, and the lower edge of the circumferential side of the top plate opening to its upper edge may have an inclination angle β in the vertical direction. The upper edge of the circumferential side of the top plate opening has a larger opening length than the lower edge of the circumferential side. The circumferential edge surface of the top plate opening may be a curved surface or a plane.

[0044] In this case, as shown in Figure 7, the top stopper 2 may further include a sealing portion 22 protruding above the stopper cap 20. The sealing portion 22 can be inserted into the opening of the top plate. When the top stopper 2 is fully embedded in the bottle mouth 10, that is, when the double-cavity cartridge bottle 1 is stopped, its sealing portion 22 is embedded in the opening of the top plate and partially protrudes longitudinally from the opening of the top plate. Those skilled in the art will understand that the size of the sealing portion 22 may be slightly larger than the opening size of the lower periphery of the top plate opening. During the pre-assembly of the top stopper 2 into the top cap 3, the top stopper 2 needs to be fixed by the upper end 30, and the surface of the sealing portion 22 may undergo slight deformation to insert into and embed into the opening of the top plate from the lower periphery of the top plate opening.

[0045] Therefore, during the pre-assembly of the top plug 2 into the top cover 3, the sealing portion 22 can be embedded into the top plate opening, with its edge portion tightly fitting the circumferential outer edge of the top plate opening, and ultimately partially protruding from the upper edge of the top plate opening. By setting the radial length L of the sealing portion to have a longer radial length, the tightness of the fit between its edge portion and the circumferential outer edge of the top plate opening is improved, further preventing the top plug 2 from slipping out of the top plate 300. In addition, by adjusting the size of β, the circumferential lower edge of the top plate opening and the sealing portion 22 can have a tighter fit relative to the circumferential upper edge of the top plate opening, so that the top plate opening tightly surrounds and fixes the sealing portion 22.

[0046] In some embodiments, the radial length L of the sealing portion 22 can be 2.0 mm - 5.0 mm. Specifically, the radial length L of the sealing portion 22 can be 2.0 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3.0 mm, 3.1 mm, 3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4.0 mm, 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 sealing portion 22 can be 3.0 mm - 4.0 mm. Specifically, the radial length L of the sealing portion 22 can preferably be 3.0 mm, 3.1 mm, or 5.0 mm. The diameters are 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 tilt angle β can be 0°, 1°, 2°, 3°, 4°, 5°, 6°, 7°, 8°, 9°, or 10°, etc.

[0047] In some embodiments, the circumferential downward opening length of the top plate opening can be 1.5 mm to 5.0 mm, specifically, the circumferential downward opening length of the top plate 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 downward opening length of the top plate opening can be 2.5 mm to 4.0 mm. Specifically, the circumferential downward opening length of the top plate 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.

[0048] By making the radial length L of the sealing portion 22 slightly larger than the circumferential lower edge opening length of the top plate opening, the sealing portion 22 fits more closely with the circumferential lower edge of the top plate opening, so that the top plate opening as a whole effectively fits and fixes the sealing portion 22. On this basis, the circumferential edge provides further support, so that the top plug 2 as a whole does not slip off. Preferably, setting β to 0°, the top plate opening can provide good fixation for the sealing portion 22 when there is no tilt angle in the vertical direction, while avoiding excessive resistance when the sealing portion 22 is inserted into the top plate opening, making it difficult to insert. In another case, when it is necessary to set a certain tilt angle in the vertical direction of the top plate opening to improve the limiting effect of the top plate 300 on the top plug 2, β can also be set to 5° to improve the fixation of the sealing portion 22, without affecting the insertion and embedding of the sealing portion 22 into the top plate opening. Those skilled in the art can adjust the radial length L, tilt angle β, and circumferential downward opening length of the top plate opening of the sealing part 22 according to the actual application of the bottle cap element, based on the above-mentioned parameter references, so as to adapt the degree of fit and fixation between the sealing part 22 and the top plate 300.

[0049] Specifically, the diameter of the cap 20 of the top stopper 2 can be slightly smaller than the inner diameter of the top cap 3. Due to the fit between the top stopper positioning point 303 and the cap 20, the top stopper 2 can be tightly fixed to the bottle opening 100, achieving a seal. In this case, the diameter of the cap 20 is set slightly smaller than the inner diameter of the top cap 3, leaving a small gap 200 between the surface of the cap 20 and the inner wall of the upper end 30, as shown in Figure 9. In this way, when the top stopper 2 is pressed down by the top cap 3, the pressure volume of the cap 20 extends towards the pre-reserved gap 200 around it, preventing the cap 20 from bulging out towards the top plate opening in the middle due to pressure.

[0050] In some embodiments, the diameter of the cap 20 can range from 5.0 mm to 10.0 mm. Specifically, the diameter of the 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, etc. The diameter of the cap 20 can be 6.0 mm to 8.0 mm, specifically, the diameter of the cap 20 can be 6.0 mm to 8.0 mm, specifically, the diameter of the cap 20 can be 6.0 mm to 8.0 mm, specifically, the diameter of the cap 20 can be 6.0 mm to 8.0 mm, specifically, the diameter of the cap 20 can be 6.0 mm to 8.0 mm, specifically, 6.0 mm to 8.0 mm, specifically, 6.1 mm to 8.0 mm, specifically, 6.2 ...3 mm, 6.4 mm to 8.3 mm, 6.4 mm to 8.5 mm, 6.2 mm to 8.3 mm, 6.4 mm to 8.5 mm, 6.3 mm to 8.4 mm, 6.3 mm to 8.4 mm, 6.3 mm to 8.4 mm, 6.3 mm to 8.4 mm, 6.4 mm to 8.5 mm, 6.6 mm to 8.7 mm, 6.7 mm to 8.8 mm, 7.8 mm to 8.9 mm, or 8.0 mm.

[0051] 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, etc. The diameter of the upper end 30 can be 6.0 mm to 8.0 mm, specifically, the diameter of the upper end 30 can be 6.0 mm to 8.0 mm, specifically, the diameter of the upper end 30 can be 6.0 mm to 8.0 mm, specifically, the diameter of the upper end 30 can be 6.0 mm to 8.0 mm, specifically, the diameter of the upper end 30 can be 6.0 mm to 8.0 mm, specifically, 6.0 mm to 8.0 mm, specifically, 6.1 mm to 8.0 mm, specifically, 6.2 mm to 8.0 mm, specifically, 6.3 mm to 8.4 mm, 6.5 mm to 8.6 mm, 6.7 mm to 6.8 mm, 6.9 mm to 7.0 mm, 7.1 mm to 7.2 mm, 7.3 mm to 7.4 mm, 7.5 mm to 7.6 mm, 7.7 mm to 7.8 mm, 7.9 mm to 8.0 mm.

[0052] More preferably, the diameter of the stopper cap 20 can be configured to be 7.0 mm, and the inner diameter of the upper end 30 of the mating top cap 3 can be configured to be 7.3 mm. This creates a 0.3 mm gap 200 between the surface of the stopper cap 20 and the inner wall of the upper end 30. During the assembly of the top cap 2 or the insertion of the injection needle, the stopper cap 20 is compressed, increasing in diameter. The gap 200 can accommodate the increased volume of the stopper cap 20, preventing upward pressure. It should be noted that, according to the embodiment of this invention, 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 actual application of the bottle cap component, adapting it to use with the freeze-drying support of the freeze dryer, with the packaging sheath, and / or with the syringe. For example, the stability of the pre-assembly of the top stopper 2 can be adjusted by appropriately adjusting the diameter of the stopper cap 20; a tighter or easier-to-remove capping of the dual-chamber cartridge bottle 1 can be maintained by appropriately adjusting the diameter of the top end 30; and after adjusting the diameter of the stopper cap 20 and the diameter of the top end 30 respectively, in order to properly avoid the influence of pressure on the stopper cap 20 on the assembly and use of the bottle cap component, the size relationship between the diameter of the stopper cap 20 and the diameter of the top end 30 can be appropriately adjusted to provide a suitable gap 200, etc.

[0053] By inserting and fitting the sealing part 22 into the opening of the top plate during the pre-assembly process of the top plug 2, and by using the top plug positioning point 303 to limit the cap 20, the top plug 2 can be stably fixed in the top cover 3. Therefore, mechanical processes implemented on the top cover 3 in the freeze-drying technology, such as vibration and suspension, will not affect the fixation of the top plug 2 in the top cover 3, thereby preventing the top plug 2 from falling out of the top cover 3 before the capping operation, ensuring the capping qualification rate after freeze-drying; the gap part 200 of the cap 20 can also prevent core removal when it is used with an injection needle, thereby ensuring product quality and efficient use.

[0054] In this case, the upper end 30 of the top cover 3 also has a top plug positioning point 303, as shown in Figures 8A and 8B. The top plug positioning point 303 protrudes from the inner wall of the upper end 30 in the direction of the axis of the top cover 3, and is used to fix the top plug 2 that fits into the bottle mouth 10. Specifically, the top plug positioning point 303 extends radially along the upper end 30 and is evenly spaced circumferentially on the inner wall of the top plug positioning point 303. The shape of the top plug positioning point 303 can be cylindrical or prism. In addition, its number and the spacing length / radius between multiple top plug positioning points 303 can be adjusted to maintain optimal fixation of the top plug 2.

[0055] In this case, the number of top stopper positioning points 303 is four or five or more. Specifically, the number of top stopper positioning points 303 can be even to maintain a symmetrical arrangement along the center of the upper end 30, providing a more stable fixing function for the top stopper 2. Preferably, the number of top stopper positioning points 303 is four or eight to provide a more stable fixing function for the top stopper 2; more preferably, the number of top stopper positioning points 303 is eight to provide the most stable fixing function for the top stopper 2. The top stopper positioning points 303 can also be used to position the top stopper 2 before it is pressed into the bottle neck 10. The top stopper 2 is limited by the top stopper positioning points 303 to prevent it from sliding off the bottle neck 10 on its own.

[0056] In this case, the upper end 30 of the top cover 3 is provided with a protrusion 304 protruding in the direction of the axis of the top cover 3 on its inner wall, as shown in Figure 10. The top cover 3 can be limited on the bottle mouth 10 by the protrusion 304 before capping, so that the sublimated water in the inner cavity 13 can be discharged through the opening 302. Therefore, the provision of the protrusion 304 helps to provide gas exchange and sublimated water discharge for the dual-cavity cartridge bottle 1 during the freeze-drying process. Those skilled in the art will understand that the protrusion 304 will not hinder the movement of the top stopper 2 during the process of the top stopper 2 being inserted into the bottle mouth 10. Since the protrusion 304 is evenly distributed on the inner wall of the upper end 30, and the top plate 300 can apply pressure evenly to the entire surface of the cap 20 pre-assembled into the upper end 30 when the top plate is capped, the top stopper 2 can be stably and horizontally inserted into the bottle mouth 10.

[0057] In this case, the number of protrusions 304 is two or three or more; preferably, the maximum length (D) of the protrusions 304 protruding in the direction of the axis of the top cover 3 can be 0.10 mm, 0.11 mm, 0.12 mm, 0.13 mm, 0.14 mm, 0.15 mm, 0.16 mm, 0.17 mm, 0.18 mm, 0.19 mm, 0.20 mm, 0.21 mm, 0.22 mm, 0.23 mm, 0.24 mm, 0.25 mm, 0.26 mm, 0.27 mm, 0.28 mm, 0.29 mm or 0.30 mm. Specifically, D can be 0.15 mm to 0.30 mm; more preferably, D can be 0.20 mm to 0.28 mm, which prevents the top cap 3 from deforming due to excessive pressure during capping, and ensures good sealing performance and prevents slippage after capping; even better, D can be 0.23 mm to 0.28 mm, which can prevent deformation of the top cap 3 due to pressure during capping, and ensure good sealing performance and prevent slippage after capping. It should be noted that the value of D can be adjusted when the material of the protrusion 304 is different, to achieve optimal positioning of the top cap 3 before capping and optimal improvement in the fit between the upper end 30 and the dual-chamber cartridge bottle 1. Preferably, when the outer diameter of the bottle mouth 10 is 7.3 mm, D can be 0.23 mm, 0.25 mm, or 0.28 mm, and the protrusion 304 can provide optimal stability after capping.

[0058] In this case, the shape of the protrusion 304 can be trapezoidal, semi-circular, semi-elliptical, or rectangular. Preferably, the shape of the protrusion 304 is trapezoidal. When the shape of the protrusion 304 is preferably a trapezoid with its short side near the bottle mouth 10, the upper end 30 fits better with the bottle mouth 10, and the top cover 3 can fit very stably on the double-cavity cartridge bottle 1 to maintain good airtightness.

[0059] When the protrusion 304 is trapezoidal in shape, preferably, the upper tangent angle (θ) between the surface of the protrusion 304 facing the axis of the top cap 3 and its side surface can be any angle between 0° and 90°, as shown in Figure 11. More preferably, θ can be 30° to 45°, specifically, θ can be 30°, 31°, 32°, 33°, 34°, 35°, 36°, 37°, 38°, 39°, 40°, 41°, 42°, 43°, 44°, or 45°. It should be noted that when θ is less than 30°, the effect of the protrusion 304 in improving the tightness of the fit between the top cap 3 and the bottle mouth 10 may be significantly weakened; when θ is greater than 45°, the protrusion 304 may significantly hinder the capping process, causing the top cap 3 to deform or even be damaged during the capping process. Therefore, θ can be preferably selected as any angle between 30° and 45°; more preferably, θ can be 30°, so that the protrusion 304 can provide a better fit between the top cap 3 and the bottle mouth 10, without adversely hindering the capping process.

[0060] Furthermore, when the protrusion 304 is trapezoidal, it is further preferable that the downward angle (α) between the surface of the protrusion 304 facing the axis of the top cover 3 and its side surface is any angle between 0° and 90°. Since the pressure during the capping process is mainly affected by the magnitude of θ, when α and θ have the same value, the protrusion 304 can have a stable axisymmetric structure, which is not easily deformed or damaged during the capping or storage process. Therefore, in this case, it is further preferable that α is 30° to improve the efficiency and deformation resistance of the protrusion 304. More preferably, both θ and α of the protrusion 304 are 30°, so that the top cover 3 will not be structurally damaged due to excessive force during the capping process. At the same time, the top cover 3 and the double-cavity cartridge bottle 1 can fit together very tightly, which also improves the efficiency and accuracy of capping the double-cavity cartridge bottle 1.

[0061] This application also provides a packaging material for a dual-chamber cartridge vial for injection, comprising the aforementioned cap element and dual-chamber cartridge vial 1, and a packaging element for a dual-chamber cartridge vial for injection, comprising the packaging material and a sheath 4 for use therewith. It should be noted that the packaging material for a dual-chamber cartridge vial for injection may include any combination of the cap element and dual-chamber cartridge vial 1 that can be formed and / or retained through any of the combinations disclosed in this application.

[0062] The protective sleeve 4 provided in this case is an octagonal prism with an open top, as shown in Figure 12. The inner wall of the protective sleeve 4 has an octagonal shape. After the double-chamber cartridge bottle 1 has completed the freeze-drying process and is sealed by the top cap 3, the double-chamber cartridge bottle 1 can be pressed into the protective sleeve. During this process, the lower end 32 of the top cap 3 fits against the inner wall of the protective sleeve 4 to avoid relative sliding, and the bypass protrusion 120 of the bottle body 12 is fixed at the octagonal vertex of the inner wall of the protective sleeve, which also prevents the double-chamber cartridge bottle 1 from sliding relative to the inner wall of the protective sleeve 4. In this way, the protective sleeve can stably protect the entire packaging material.

[0063] In this case, the lower end 32 is cylindrical or octagonal prism, preferably octagonal prism, and is fixedly assembled with the sleeve 4 used to fix and store the dual-chamber cartridge bottle 1 through an interference fit. Specifically, the upper outer edge of the lower end 32 near the middle end 31 has a first protrusion 321. The top of the sleeve 4 is stretched and confined on the first protrusion 321, and the top cap 3 and the sleeve 4 exert force towards each other and clamp together in the middle. Through this interference fit between the lower end 32 and the sleeve 4, when the dual-chamber cartridge bottle 1 is placed in the sleeve 4, the fixation between the top cap 3 and the top plug 2 therein and the bottle mouth 10 is more tight, effectively preventing air leakage, rotation, and detachment of the packaging material after freeze-drying, so as to ensure high-quality storage of freeze-dried preparations.

[0064] Specifically, in some embodiments, the lyophilized formulation is reconstituted in a dual-chamber cartridge 1 and then subcutaneously injected using an injection needle, such as a microneedle (MFN), for disease treatment or cosmetic applications. The needle hub of the injection needle has a threaded structure. When the MFN is installed onto the top cap 3 to extract the product or removed from the top cap 3, its threaded structure engages or is removed by rotating the threaded structure with the thread 301 of the top cap 3. During this process, the lower end 32 of the top cap 3 is fixed in place by the octagonal inner wall of the sheath 4, preventing rotation. The bypass protrusion 120 of the dual-chamber cartridge 1 is also fixed in place by the apex of the octagonal inner wall of the sheath 4. Therefore, by using the octagonal prism-shaped lower end 32 and engaging with the sheath 4, the dual-chamber cartridge packaging assembly is kept unaffected by rotation during the screwing / removal of the injection needle, avoiding dry spinning of the sterile injection needle during screwing / removal, thus improving the efficiency of using the lyophilized formulation and the ease of operation.

[0065] This case provides a freeze-drying method for products used in pharmaceuticals, cosmetics, or medical aesthetics applications. It can also be used in conjunction with a double-chamber cartridge bottle 1' with a longer neck and corresponding top stopper 2' and top cap 3'. The specific implementation is detailed below.

[0066] Specifically, when using a long-necked double-chamber cartridge bottle 1' and corresponding top stopper 2' and top cap 3', the freeze-drying method includes: adding a middle stopper to the double-chamber cartridge bottle 1', and then filling it with the product to be freeze-dried; assembling the top stopper 2' and the top cap 3', placing them above the bottle mouth 10' of the double-chamber cartridge bottle 1', and placing and fixing the double-chamber cartridge bottle 1' on a custom-made freeze-drying bracket; freezing, primary drying, and secondary drying of the product to be freeze-dried respectively; using the top cap 3 to press the top stopper 2' into the double-chamber cartridge bottle 1' to seal the double-chamber cartridge bottle 1' and fix the top stopper 2', so that the top stopper 2' seals the bottle mouth 10' of the double-chamber cartridge bottle 1'.

[0067] In the freeze-drying method, the stopper added to the double-chamber cartridge bottle 1' and the product to be freeze-dried can be any double-chamber cartridge bottle stopper and a suitable amount of freeze-dryable product added to adapt to the size and structure of the double-chamber cartridge bottle 1'. The freezing, primary drying and secondary drying operations can be carried out in a freeze dryer that can accommodate the freeze-drying support used in the freeze-drying method of this invention; during the process of fixing the top stopper 2' with the top cover 3' and sealing the bottle mouth 10' of the double-chamber cartridge bottle 1' through the top stopper 2', the method of driving the top cover 3' to press down can also be any driving method that can be implemented in the freeze dryer, such as mechanical clamping, pneumatic driving, pneumatic clamp driving or spring pressing.

[0068] In this case, after adding a stopper to the dual-chamber cartridge vial 1', the product to be lyophilized can be filled in. Specifically, the product to be lyophilized can be a product added to the inner cavity 13' of the dual-chamber cartridge vial 1' for lyophilization and short-term / long-term storage, such as small molecule drugs, peptides, enzymes, antibodies, fusion proteins, antibody-drug complexes, reagents, etc. The user can select any liquid to be lyophilized and fill it into one of the inner cavities 13' of the dual-chamber cartridge vial 1' to perform lyophilization using the lyophilization method of this case.

[0069] In this case, the freeze-drying rack is either a freestanding freeze-drying rack or a tray-type freeze-drying rack. The type of freeze-drying rack used in this freeze-drying method is either a freestanding freeze-drying rack or a tray-type freeze-drying rack. Those skilled in the art can select and adjust the specific model, size, and operating parameters of the freeze-drying rack in the freeze dryer according to actual needs. This case only provides a preferred freeze-drying method. Preferably, the freeze-drying rack is a tray-type freeze-drying rack, as a tray-type freeze-drying rack facilitates the placement of a larger number of dual-chamber cartridge bottles 1'.

[0070] Specifically, the dual-chamber cartridge bottle 1' is placed upright or upside down in the freeze-drying rack. Preferably, the dual-chamber cartridge bottle 1' is placed upright in the freeze-drying rack to facilitate uniform heat distribution in the dual-chamber cartridge bottle 1', improve the sublimation efficiency of solvents, such as water, and reduce the sedimentation and aggregation of freeze-dried products, thus maintaining a uniform and stable product appearance.

[0071] In this case, the temperature range set for freezing the product in the double-chamber cartridge bottle 1' can be a temperature range suitable for freeze-drying the product. Since the raw material to be freeze-dried generally has high freezing efficiency and maintains its quality when the freezing temperature is between -60℃ and -40℃, the freezing temperature can be any value between -60℃ and -40℃. Specifically, the temperature range set for freezing the product in the double-chamber cartridge 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 secondary drying temperature range is -60℃ to 0℃, specifically -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℃, and -3 5℃, -34℃, -33℃, -32℃, -31℃, -30℃, -29℃, -28℃, -27℃, -26℃, -25℃, -24℃, -23℃, -22℃, -21℃, -20℃, -19℃, -18℃, -17℃, -16℃, -15℃, -14℃, -13℃, -12℃, -11℃, -10℃, -9℃, -8℃, -7℃, -6℃, - 5℃, -4℃, -3℃, -2℃, -1℃ or 0℃; the temperature range for secondary drying is 15℃~40℃, namely 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℃.

[0072] Similarly, the temperatures for the primary and secondary drying of the product can be any values ​​within the range of -60℃ to 0℃ and 15℃ to 40℃, respectively, to increase the sublimation rate of water in the drug. Furthermore, the pressure range for primary and secondary drying can be any value between 0.02 mbar and 0.2 mbar. When the optimal pressure for both primary and secondary drying is 0.06 mbar, peak drying efficiency can be guaranteed. Specifically, the pressure range for primary and secondary 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. Preferably, the pressure for both primary and secondary drying is 0.06 mbar.

[0073] In this case, the use of the top cap 3' to press the top stopper 2' into the dual-chamber cartridge bottle 1' further includes: purging the dual-chamber cartridge bottle 1' with nitrogen before pressing the top stopper 2' to maintain the low moisture content of the lyophilized product, such as a lyophilized formulation. Those skilled in the art will understand that purging the dual-chamber cartridge bottle 1' with nitrogen before sealing the bottle neck 10' aims to bring the nitrogen in the inner chamber 13' to 1 atmosphere. On the one hand, the nitrogen can be used to maintain the low moisture content of the lyophilized product; on the other hand, 1 atmosphere of nitrogen can also keep the stopper in place within the dual-chamber cartridge bottle.

[0074] In this case, a lyophilized formulation is also included, prepared according to the above-described lyophilization method. In particular, since the product to be lyophilized added to one of the inner cavities 13' of the dual-cavity cartridge bottle 1' can be one of multiple products, different products to be lyophilized can be added to the dual-cavity cartridge bottle 1', resulting in different lyophilized formulations. Furthermore, when the lyophilization parameters implemented during the lyophilization process, such as the temperature and pressure of the primary drying, are changed, the same product to be lyophilized can be added, resulting in lyophilized formulations of different qualities or properties, such as lyophilized formulations with different water contents or different solid forms.

[0075] This application also includes an injectable preparation comprising: a dual-chamber cartridge vial packaging material, a lyophilized formulation, and a rehydrating agent. It should be noted that the lyophilized formulation and rehydrating agent can be any lyophilized formulation and rehydrating agent suitable for preparation using the dual-chamber cartridge vial packaging material and lyophilization technology. Specifically, the lyophilized formulation can be any lyophilized formulation prepared by lyophilizing any product to be lyophilized that can be filled into the dual-chamber cartridge vial 1' of this application, or it can be the lyophilized formulation provided in this application.

[0076] In addition, the reconstitution solvent can be any of the lyophilized preparations prepared above, such as sterile water for injection (which may contain antibacterial agents, such as phenol, m-cresol, benzyl alcohol, etc.), physiological saline, 5% glucose solution, and other buffer solutions, such as phosphate buffer, citrate buffer, acetate buffer, histidine buffer, succinate buffer, tris(hydroxymethyl)aminomethane hydrochloride buffer, etc., which can be used to reconstitute the lyophilized preparations provided in this case when administering the medication.

[0077] In this case, the dual-chamber cartridge vial packaging material for injection includes: a dual-chamber cartridge vial 1' and another cap element, wherein the dual-chamber cartridge vial 1' is used to hold lyophilized formulations and reconstituted solutions, as shown in Figure 13. It should be noted that the dual-chamber cartridge vial packaging material for injection can include any combination formed and / or maintained through any of the cap elements and dual-chamber cartridge vials 1' proposed in this case.

[0078] In this case, a corresponding bottle cap element is also proposed, comprising a top stopper 2' and a top cap 3' for sealing a dual-chamber cartridge bottle 1'. The dual-chamber cartridge bottle 1' can be placed within a freeze-drying support and sheath 4' used in existing freeze-drying technologies, and the dual-chamber cartridge bottle packaging can be fixed and positioned upright or upside down within the freeze-drying support; the bottle cap assembly can be made of any material suitable for achieving the bottle cap sealing function. The top stopper 2' is positioned within the top cap 3' for sealing the bottle opening 10' of the dual-chamber cartridge bottle 1'; the top cap 3' is used to press and fix the top stopper 2', thereby sealing the bottle opening 10' of the dual-chamber cartridge bottle 1'; and sealing the dual-chamber cartridge bottle 1'; wherein the process of pressing and fixing the top stopper 2' with the top cap 3', thereby sealing the bottle opening 10' of the dual-chamber cartridge bottle 1', may include the following steps:

[0079] Pre-assemble the top plug 2' into the top cap 3'; and place the top cap 3' with the top plug 2' assembled on top of the bottle mouth 10' of the double-chamber cartridge bottle 1', and press the top cap 3' down. The top cap 3' can be pressed down by mechanical clamping, pneumatic drive, pneumatic clamp drive, or spring pressing, etc.

[0080] In this case, the dual-cavity cartridge bottle 1' includes: an inner cavity 13', a bottle body 12', a neck 11', and a bottle mouth 10'. The bottle mouth 10' has a central opening 100' connected to the inner cavity 13', and the inner diameter of the opening 100' is smaller than the inner diameters of the bottle mouth 10' and the neck 11'. One side of the outer wall of the bottle body 12' has a bypass protrusion 120'. Those skilled in the art will understand that the dimensions of the inner cavity 13', bottle body 12', neck 11', and bottle mouth 10' of the dual-cavity cartridge bottle 1' can be adjusted to fit the size range of commonly used freeze-drying supports. For example, changing the vertical length of one or more parts of the dual-cavity cartridge bottle 1' or changing the radial length of one or more parts of the dual-cavity cartridge bottle 1' does not depart from the scope of protection of this case.

[0081] In this case, the top stopper 2' includes a stopper cap 20' and a stopper plunger 21'. The diameter of the plunger 21' can be equal to or slightly larger than the inner diameter of the bottle opening 100'. After the plunger 21' is inserted into the bottle opening 100', the lower surface of the stopper cap 20' completely fits against the upper surface of the bottle opening 10' to achieve a seal on the bottle opening 10'. In particular, the top stopper 2' is made of elastic rubber material, so the diameter of the plunger 21' can be adjusted within the range of the diameter of the bottle opening 100' after the plunger 21' is pressed down. The diameter of the plunger 21' can be slightly larger than the diameter of the bottle opening 100' to ensure a tight seal.

[0082] In this case, the top cap 3', as shown in Figure 14A, includes an upper end 30' and a base plate 31'. The upper end 30' has a top plate 300', a thread 301', and an opening 302'. The inner wall of the top cap 3' fits against the bottle opening 10'. When the top cap 3' faces the bottle opening 10', the top plate 300' of the upper end 30' presses the top plug 2' into the bottle opening 10', causing the top plug 2' to embed into the bottle opening 10'. After the bottle opening 10' of the dual-chamber cartridge bottle 1' is sealed, the top plate 300' fits tightly against the top plug 20' to secure the top plug 2'. The opening 302' allows sublimated water in the product to drain, and the thread 301' is used for threaded engagement with the injection needle.

[0083] It should be noted that the length of the base 31' in the vertical direction is adjustable. Therefore, the base 31' can fit only the connection between the neck 11' and the bottle body 12', or it can fit at least a portion of the bottle body 12' to achieve better sealing and to adapt to the size requirements of the top cap 3' for freeze-drying technology. The shape of the base 31' can be set as a cylinder or a polygonal prism, as shown in Figure 14B, to prevent the top cap 3' from slipping off due to centrifugal force or from sliding relative to the dual-chamber cartridge bottle 1', thus affecting the sealing performance.

[0084] Specifically, the center of the top plate 300' also has a top plate opening, and the lower edge of the circumferential top plate opening to its upper edge may have an inclination angle β' in the vertical direction. The upper edge of the circumferential top plate opening has a larger opening length than the lower edge. The circumferential edge surface of the top plate opening may be a curved surface or a plane.

[0085] In this case, the top stopper 2' may further include a sealing portion 22' protruding above the stopper cap 20', as shown in Figure 15A. The sealing portion 22' can be inserted into the top plate opening. When the top stopper 2' is fully embedded in the bottle neck 10', that is, when the double-cavity cartridge bottle 1' is stopped, its sealing portion 22' is embedded in the top plate opening and partially protrudes longitudinally from the top plate opening. Those skilled in the art will understand that the size of the sealing portion 22' can be slightly larger than the opening size of the lower circumferential edge of the top plate opening. During the pre-assembly of the top stopper 2' into the top cap 3', the top stopper 2' needs to be fixed by the upper end 30', and the surface of the sealing portion 22' can undergo slight deformation to insert into and embed itself in the top plate opening from the lower circumferential edge of the top plate opening.

[0086] Therefore, during the pre-assembly of the top plug 2' into the top cover 3', the sealing portion 22' can be embedded into the top plate opening, with its edge portion tightly fitting the circumferential outer edge of the top plate opening, and ultimately partially protruding from the upper edge of the top plate opening. Alternatively, by setting the radial length L' of the sealing portion 22' to have a longer radial length, the tightness of the fit between its edge portion and the circumferential outer edge of the top plate opening can be improved, further preventing the top plug 2' from slipping out of the top plate 300'. Furthermore, by adjusting the size of β', the circumferential lower edge of the top plate opening and the sealing portion 22' can have a tighter fit relative to the circumferential upper edge of the top plate opening, so that the top plate opening tightly surrounds and fixes the sealing portion 22'.

[0087] In some embodiments, the radial length L' of the sealing portion 22' can be 2.0 mm - 5.0 mm. Specifically, the radial length L' of the sealing portion 22' can be 2.0 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3.0 mm, 3.1 mm, 3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4.0 mm, 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 sealing portion 22' can be 3.0 mm - 4.0 mm. Specifically, the radial length L' of the sealing portion 22' can preferably be 3.0 mm. The diameters are 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 tilt angle β' can be 0°, 1°, 2°, 3°, 4°, 5°, 6°, 7°, 8°, 9°, or 10°, etc.

[0088] In some embodiments, the circumferential downward opening length of the top plate opening can be 1.5 mm to 5.0 mm, specifically, the circumferential downward opening length of the top plate 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 downward opening length of the top plate opening can be 2.5 mm to 4.0 mm. Specifically, the circumferential downward opening length of the top plate 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.

[0089] By making the radial length L' of the sealing portion 22' slightly larger than the circumferential lower edge opening length of the top plate opening, the sealing portion 22' fits more closely to the circumferential lower edge of the top plate opening. The top plate opening effectively fits and fixes the sealing portion 22', and the circumferential edge provides further support, preventing the top plug 2' from slipping off. Preferably, setting β' to 0° allows the top plate opening to provide good fixation for the sealing portion 22' without any vertical tilt angle, while avoiding excessive resistance when the sealing portion 22' is inserted into the top plate opening, making it difficult to insert. In another case, when a certain tilt angle is required in the vertical direction to improve the limiting effect of the top plate 300' on the top plug 2, β' can also be set to 5° to improve the fixation of the sealing portion 22' without affecting the insertion and embedding of the sealing portion 22' into the top plate opening. Those skilled in the art can adjust the radial length L', tilt angle β', and circumferential downward opening length of the top plate opening of the sealing part 22' appropriately based on the actual application of the cap element in freeze-drying technology, in order to adapt the degree of fit and fixation between the sealing part 22' and the top plate 300'.

[0090] Specifically, the diameter of the cap 20' of the top plug 2' can be slightly smaller than the inner diameter of the top cover 3'. Due to the fit between the top plug positioning point 303' and the cap 20', the top plug 2' can be tightly fixed to the top cover 3', achieving a seal. In this case, the diameter of the cap 20' is designed to be slightly smaller than the inner diameter of the top cover 3', leaving a small gap 200' between the surface of the cap 20' and the inner wall of the upper end 30', as shown in Figure 18. In this way, when the top plug 2' is pressed by the top cover 3', the pressure volume of the cap 20' extends to the gap 200' reserved around it, and the cap 20' will not bulge out of the top plate opening above it due to pressure.

[0091] In some embodiments, the diameter of the cap 20' can range from 5.0 mm to 10.0 mm. Specifically, the diameter of the 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, etc. The diameters of the cap 20' are preferably 6.0 mm to 8.0 mm, and more specifically, the diameters of the cap 20' are preferably 6.0 mm to 8.0 mm, or 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.

[0092] 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, or 9.0 mm. The diameter of the upper end 30' is preferably 6.0 mm to 8.0 mm, specifically, the ...1 mm to 8.0 mm, specifically, the diameter of the upper end 30' is preferably 6.1 mm to 8.0 mm, specifically, the diameter of the upper end 30' is preferably 6.1 mm to 8.0 mm, specifically, the diameter of the upper end 30' is preferably 6.1 mm to 8.2 mm, the diameter of the upper end 30' is preferably 6.1 mm to 8.2 mm, the diameter of the upper end 30' is preferably 6.1 mm to 8.

[0093] More preferably, the diameter of the stopper cap 20' can be configured to be 7.0 mm, and the inner diameter of the upper end 30' of the mating top cap 3' can be configured to be 7.3 mm. This creates a 0.3 mm gap 200' between the surface of the stopper cap 20' and the inner wall of the upper end 30'. During the assembly of the top stopper 2' or the insertion of the injection needle, the stopper cap 20' is compressed, increasing in diameter. The gap 200' can accommodate the increased volume of the stopper cap 20', preventing upward pressure. It should be noted that, according to the embodiment of this invention, 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 actual application of the bottle cap component, to adapt to the use of the bottle cap assembly with the freeze-drying support of the freeze dryer, with the packaging sheath, and / or with the syringe. For example, the stability of the pre-assembly of the top stopper 2' can be adjusted by appropriately adjusting the diameter of the stopper cap 20'; a tighter or easier-to-remove capping of the dual-chamber cartridge bottle 1' can be maintained by appropriately adjusting the diameter of the top end 30'; and after adjusting the diameter of the stopper cap 20' and the diameter of the top end 30' respectively, in order to properly avoid the influence of pressure on the stopper cap 20' on the assembly and use of the bottle cap component, the size relationship between the diameter of the stopper cap 20' and the diameter of the top end 30' can be appropriately adjusted to provide a suitable gap 200', etc.

[0094] By inserting and fitting the sealing part 22' into the opening of the top plate during the pre-assembly process of the top plug 2', and with the top plug positioning point 303' limiting the cap 20', the top plug 2' can be stably limited in the top cover 3'. Therefore, when external forces are applied to the top cover 3' in actual production, such as vibration or suspension, it will not affect the fixation of the top plug 2' in the top cover 3', thereby preventing 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 cap 20' can also prevent core removal when it is used with the injection needle, ensuring the efficient use of the product.

[0095] In this case, the upper end 30' of the top cap 3' also has a top plug positioning point 303', as shown in Figures 16A and 16B. The top plug positioning point 303' protrudes from the inner wall of the upper end 30' in the direction of the axis of the top cap 3', and is used to fix the top plug 2' that fits into the bottle mouth 10'. Specifically, the top plug positioning point 303' extends radially along the upper end 30' and is evenly spaced circumferentially on the inner wall of the top plug positioning point 303'. The shape of the top plug positioning point 303' can be cylindrical or prism. In addition, its number and the interval length / radius between multiple top plug positioning points 303' can be adjusted to maintain optimal fixation of the top plug 2'.

[0096] In this case, the number of top stopper positioning points 303' is four or five or more. Specifically, the number of top stopper positioning points 303' can be even to maintain a symmetrical arrangement along the center of the upper end 30', providing a more stable fixing function for the top stopper 2'. Preferably, the number of top stopper positioning points 303' is four or eight to provide a more stable fixing function for the top stopper 2'; more preferably, the number of top stopper positioning points 303' is eight to provide the most stable fixing function for the top stopper 2'. The top stopper positioning points 303' can also be used to position the top stopper 2' before it is pressed into the bottle neck 10', limiting the top stopper 2' and preventing it from sliding off the bottle neck 10' on its own.

[0097] In this case, the upper end 30' of the top cap 3' is also provided with a protrusion 304' protruding in the direction of the axis of the top cap 3' on its inner wall. The top cap 3' can be limited on the bottle mouth 10' through the protrusion 304' before capping, so that the sublimated water in the inner cavity 13' can be discharged through the opening 302'. Therefore, the provision of the protrusion 304' helps to provide gas exchange and water discharge for the dual-cavity cartridge bottle 1'. Those skilled in the art will understand that the protrusion 304' will not hinder the movement of the top stopper 2' during the process of the top stopper 2' being inserted into the bottle mouth 10'. Since the protrusion 304' is evenly distributed on the inner wall of the upper end 30', and the top plate 300' can apply pressure evenly to the entire surface of the cap 20' pre-assembled into the upper end 30' when the top stopper is pressed, the top stopper 2' can be stably and horizontally inserted into the bottle mouth 10'.

[0098] In this case, the number of protrusions 304' is two or three or more; preferably, the maximum length (D') of the protrusions 304' protruding in the direction of the axis of the top cover 3' can be 0.10 mm, 0.11 mm, 0.12 mm, 0.13 mm, 0.14 mm, 0.15 mm, 0.16 mm, 0.17 mm, 0.18 mm, 0.19 mm, 0.20 mm, 0.21 mm, 0.22 mm, 0.23 mm, 0.24 mm, 0.25 mm, 0.26 mm, 0.27 mm, 0.28 mm, 0.29 mm or 0.30 mm. Specifically, D' can be 0.15 mm to 0.30 mm; more preferably, D' can be 0.20 mm to 0.28 mm, which prevents the top cap 3' from deforming due to excessive pressure during capping, and ensures good sealing performance and prevents slippage after capping; even better, D' can be 0.23 mm to 0.28 mm, which can prevent deformation of the top cap 3' due to pressure during capping, and ensure good sealing performance and prevent slippage after capping. It should be noted that the value of D' can be adjusted when the material of the protrusion 304' is different, to achieve optimal positioning of the top cap 3' before capping and optimal improvement in the fit between the upper end 30' and the double-chamber cartridge bottle 1'. When the outer diameter of the bottle mouth 10' is 7.3 mm, D' is preferably 0.23 mm, 0.25 mm, or 0.28 mm, so that the protrusion 304' can provide the most stable fixation for the top cap 3'.

[0099] In this case, the shape of the protrusion 304' can be trapezoidal, semi-circular, semi-elliptical, or rectangular. Preferably, the protrusion 304' is trapezoidal. When the shape of the protrusion 304' is preferably trapezoidal with its short side near the bottle opening 10', the upper end 30' fits more tightly with the bottle opening 10', and the top cap 3' can fit very stably on the double-chamber cartridge bottle 1' to maintain good airtightness.

[0100] When the protrusion 304' is trapezoidal in shape, the upper tangent angle (θ') between the surface of the protrusion 304' facing the axis of the top cap 3' and its side surface can be any angle between 0° and 90°, as shown in Figure 19. Further, θ' can be between 30° and 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' in improving the tightness of the fit between the top cap 3' and the bottle opening 10' may be significantly weakened; when θ' is greater than 45°, the protrusion 304' may significantly hinder the capping process, causing the top cap 3' to deform or even be damaged during the capping process. Therefore, θ' can be preferably selected as any angle between 30° and 45°; more preferably, θ' can be 30°, so that the protrusion 304' can provide a better fit between the top cap 3' and the bottle mouth 10', without adversely hindering the capping process.

[0101] Furthermore, when the protrusion 304' is trapezoidal in shape, the angle (α') between the face of the protrusion 304' facing the axis of the top cover 3' and its side can also be any angle between 0° and 90°. Since the pressure during the capping process is mainly affected by the magnitude of θ', when α' and θ' have the same value, the protrusion 304' can have the most stable axisymmetric structure, and is less prone to deformation or damage during the capping or storage process. Therefore, in this case, α' is further preferably selected as 30° to improve the efficiency and deformation resistance of the protrusion 304'. More preferably, θ' and α' of the protrusion 304' are both 30°, so that the capping process of the top cover 3' will not cause structural damage to the top cover 3' due to excessive pressure, while also maintaining a tight fit between the top cover 3' and the double-chamber cartridge bottle 1', which can improve the capping efficiency and accuracy of the double-chamber cartridge bottle 1' in the freeze-drying process.

[0102] In this case, the upper end 30' of the bottle cap component also has a demolding hole 305', as shown in Figures 16C and 17. The demolding hole 305' is located at the connection between the top plate 300' and the thread 301', and partially connects the two sides of the top plate opening through the demolding hole 305'. In this way, during the manufacturing of the top cap 3', the manufacturing module can be easily opened through the demolding hole 305' for mold closing, thereby facilitating the mass production of the entire top cap 3' and improving the efficiency of the freeze-drying process. The number of demolding holes 305' can be four or five or more, for example, four holes evenly distributed on the outer periphery of the top plate 300' at the upper end 30'. This arrangement of demolding holes 305' does not affect the fit between the sealing part 22' or the top plug positioning point 303' and the surrounding top cap 3' or top plug 2'', and therefore does not affect the airtightness of the top cap 3'.

[0103] In this case, the upper end 30' also has a fitting portion 306', as shown in Figure 15B. This fitting portion 306' is located on the side of the top plate opening of the top plate 300' near the top plug 2', that is, the side that contacts the plug cap 20'. The sealing portion 22' can cooperate with the fitting portion 306' to be inserted into the top plate opening of the top plate 300' of the top cover 3'. Specifically, the fitting portion 306' has a bevel facing the top plug 3'. This bevel smoothly tightens the contact surface between the top plate 300' and the top plug 2' from the side of the top plate opening near the top plug 2' to the other side, that is, a chamfered shape, so that when the sealing portion 22' of the top plug 2' is fitted into the top plate opening, its outer edge can slide along the bevel of the fitting portion 306', reducing the force required for the fitting process, thereby further improving the fitting success rate of the sealing portion 22' and the top plate opening, thereby improving the capping efficiency and enhancing the freeze-drying efficiency.

[0104] In this case, the chassis 31' may also have internal protrusions 310', as shown in Figure 14C. The internal protrusions 310' are located on the inner wall of the chassis 31' away from the upper end 30', i.e., the inner wall of the lowest end of the top cover 3, and protrude towards the top cover 3' along the axial direction. When the top cover 3' seals the double-cavity cartridge bottle 1', due to the presence of the internal protrusions 310', the contact pressure between the bottle body 12' and the chassis 31' at the internal protrusions 310' increases, and the fit is tighter, enhancing the fixing stability of the top cover 3' on the double-cavity cartridge bottle 1', resulting in better airtightness of the entire packaging material. The number of internal protrusions 310' can be an appropriate number, such as 2, 3, 4, 5, or more, and preferably evenly distributed on the radial cross-section of the chassis 31' to form a stable shape, thereby improving the fixing stability of the top cover 3'. In addition, when multiple internal protrusions are evenly distributed on the inner side of the chassis, for example, when four internal protrusions 310' are evenly distributed at 90° on the radial section of the cylindrical chassis 31' on the lower inner edge of the chassis, the stress on the chassis can be effectively dispersed, making the chassis 31' less likely to gradually loosen due to long-term sealed use or temperature changes, thereby further improving the top cover's resistance to loosening.

[0105] Advantageously, openings 311' on both sides of the inner protrusion 310' can be provided along the edge of the base 31' away from the upper end 30', i.e., the lowest edge of the top cover 3'. The number of openings 311' on both sides of the inner protrusion 310' can be matched with the number of inner protrusions 310', so the number can be 4, 6, 8, 10 or more. When the top cover 3' is in contact with the bottle body 12' and the inner protrusion 310' is compressed, the openings 311' on both sides of the inner protrusion 310' can deform and extend to one or both sides, reducing the force required for sealing and improving sealing and freeze-drying efficiency.

[0106] This application also proposes another packaging material for a dual-chamber cartridge vial for injection, comprising the aforementioned alternative cap element and dual-chamber cartridge vial 1', and another packaging material element for a dual-chamber cartridge vial for injection, comprising the aforementioned alternative packaging material for a dual-chamber cartridge vial for injection and a sheath 4' used therewith, as shown in Figure 20. It should be noted that the packaging material for a dual-chamber cartridge vial for injection may include any combination of the cap element and dual-chamber cartridge vial 1' that can be formed and / or retained through any of the combinations proposed in this application.

[0107] The upper outer edge of the base 31' near the upper end 30' has a first protrusion 321'. The top of the inner wall of the sleeve 4' is stretched to create a horizontal protrusion, which is confined to the first protrusion 321' of the base 31'. The top cap 3' and the sleeve 4' are interference-fitted, exerting force in opposite directions and clamping the top plug 2' and the double-chamber cartridge bottle 1' in the middle. In addition, the bypass protrusion 120' of the bottle body 12' is fixed at the octagonal vertex of the inner wall of the sleeve 4' and cannot slide relative to the inner wall of the sleeve 4'. Through the above method, when the double-chamber cartridge bottle packaging is placed in the sleeve 4', the top cap 3' and the top plug 2' therein are more tightly fixed to the bottle mouth 10', effectively preventing air leakage, rotation, and detachment.

[0108] In this case, the base 31' is cylindrical or octagonal, and the sleeve 4' includes the sleeve body 40' and the flange 41'. When the top cap 3' and the sleeve 4' are interference-fitted, the top cap 3' and the double-chamber cartridge bottle 1' are tightly fixed together. Since the bottle mouth 10', neck 11', and bottle body 12' of the double-chamber cartridge bottle 1' are cylindrical, during the process of screwing the injection needle to and / or removing the injection needle from the top cap 3', the top cap 3' may cause the double-chamber cartridge bottle 1' to rotate together due to the force applied. When the base 31' is cylindrical, its smooth outer surface is difficult to be well contained by the inner wall of the sleeve 4'. When using lyophilized formulations, the injection needle needs to be screwed / removed, and the top cap 3' may cause the entire double-chamber cartridge bottle 1' to rotate together, thus causing the injection needle to spin freely and unable to be fixed / removed from the top cap 3'.

[0109] Therefore, the base 31' of the bottle cap component and the sheath body 40' of the packaging material are both octagonal prisms, making the outer wall of the base 31' and the inner wall of the sheath body 40' octagonal, as shown in Figure 20. In this way, the bypass protrusion 120' of the double-chamber cartridge bottle 1' of the packaging material assembly can be limited to the octagonal vertex (B'-B') on the inner wall of the sheath 4'. During the capping process, the bottle body 12' will generate a large frictional force with the inner wall of the base 31'. When the top cap 3' is subjected to external force such as an injection needle, the interference fit between the base 31' and the inner wall of the sheath 4' and their mutual fixation (A'-A') prevents the top cap 3' from slipping off or sliding relative to the double-chamber cartridge bottle 1', further stabilizing the entire packaging material, avoiding affecting the airtightness of the double-chamber cartridge bottle 1', and improving the efficiency of use.

[0110] Specifically, the lower end of the sheath 4' may also have an interference fit structure, and the lower end of the sheath body 40' may be provided with a second protrusion 400', which is pressed and fastened to the flange 41', so that the sheath body 40' and the flange 41' are interference fit and fixed to each other (C'-C'). In this way, the fixing stability of the sheath body 40' can be improved, and the sheath body 40' and the packaging material can be prevented from rotating together.

[0111] Specifically, in some embodiments, the aforementioned lyophilized formulation is reconstituted in a dual-chamber cartridge 1' and then administered subcutaneously via an injection needle for disease treatment or cosmetic purposes. The injection needle's needle hub has a threaded structure. When the injection needle is installed onto the top cap 3' for product injection or removed from the top cap 3', its threaded structure engages or is removed by rotating the threaded structure with the thread 301' of the top cap 3'. During this process, the base 31' of the top cap 3' is fixed in place by the octagonal inner wall of the sheath 4', preventing rotation. The bypass protrusion 120' of the dual-chamber cartridge 1' is also fixed in place by the apex of the inner wall of the sheath 4'. Therefore, by selecting an octagonal prism-shaped base 31' and fitting it with the sheath 4', the dual-chamber cartridge packaging assembly can be kept unaffected by rotation during needle screwing / removal, avoiding dry rotation of the sterile injection needle during screwing / removal, and improving the efficiency and ease of operation of the dual-chamber cartridge packaging component.

[0112] In this case, a bottle cap element is also provided, as shown in Figures 21A, 21B, and 22. This bottle cap assembly includes a top stopper 2” and a top cap 3”, which can seal the mouth of the dual-chamber cartridge bottle 1 or dual-chamber cartridge bottle 1’, particularly the mouth of the dual-chamber cartridge bottle 1’, through cooperation with a stopper element. This bottle cap element can serve as a supplementary or alternative configuration to the aforementioned two bottle cap elements for sealing dual-chamber cartridge bottles in freeze-drying technology. For example, when the requirement for integrated sealing of the top stopper and top cap in freeze-drying technology is not high, the following bottle cap element can be considered.

[0113] Specifically, referring to the examples in Figures 21A-22, as shown in Figure 21A, the top plug 2” of the bottle cap assembly is used to seal the bottle opening 10’ of the double-chamber cartridge bottle 1’. The top plug 2” may include a stopper cap 20” and a stopper post 21”. As shown in Figure 22, the top cover 3” is used to fix the top plug 2” and seal the bottle opening 10’ of the double-chamber cartridge bottle 1’. The top cover 3” may include a body and a base 31”. The body may include a top plate 300” and an annular thread 301”. Continuing to refer to Figure 21A, the stopper element may include a pressing fixture 51 and a retaining fixture 50. The pressing fixture 51 may include a pressing post 510, and the retaining fixture 50 may include a protrusion 500. In the freeze-drying method provided in this case, for the bottle cap element, the top stopper 2” and the top cap 3” are not assembled before freezing. Instead, after the product to be freeze-dried undergoes freezing, primary drying, and secondary drying, the top stopper 2” is first fixed to the bottle mouth 10’ by the stopper assembly, and then the stopper assembly is removed before the top cap 3’ is used to seal the entire bottle mouth. That is, for this bottle cap element, after freeze-drying, the stopper assembly is used to press the top stopper 2” to fit into the double-chamber cartridge bottle 1’, instead of directly using the top cap 3” to press the top stopper 2” as in the two aforementioned bottle cap elements. This sealing process is as follows:

[0114] The process of sealing the double-chamber cartridge bottle 1' by pressing the top stopper 2” with a stopper element to fit it into the bottle neck 10’ includes the following steps: placing the top stopper 2” in the retaining fixture 50 to position the top stopper 2” relative to the bottle neck 10’ of the double-chamber cartridge bottle 1' by fitting the retaining fixture 50 against the outer wall of the bottle neck 10’ of the double-chamber cartridge bottle 1'; pressing the top stopper 2” into the bottle neck 10’ of the double-chamber cartridge bottle 1' by pressing the inserting fixture 51; and removing the inserting fixture 51 and the retaining fixture 50. It should be noted that when the dimensions of some or all of the structures of the double-chamber cartridge bottle 1' change, the dimensions of the top stopper 2”, the inserting fixture 51, and the retaining fixture 50 can also be changed accordingly to adapt to the dimensions of the double-chamber cartridge bottle 1' (especially when its neck 11’ needs further adjustment) to complete the sealing of the bottle neck 10’.

[0115] Furthermore, in another configuration of the bottle cap element shown in Figure 21B, the inner wall of the central recess of the pressing fixture 51 of the stopper element is no longer provided with a pressure post 510. When the top stopper 2” moves toward the bottle mouth 10', the pressing fixture 51 directly abuts against the top stopper 2” by relying on its central recess to press it toward the bottle mouth 10'. In this way, without using a retaining fixture 50 with a long upper protrusion, the pressing fixture 51 can also ensure sufficient stopping length to the top stopper 2” without additional pressure posts 510, so that it can be firmly fitted into the bottle mouth 10'. This simplifies the manufacturing technology of the stopper assembly.

[0116] In addition, before placing and fixing the dual-chamber cartridge 1' onto the custom-made freeze-drying support, this cap element needs to be pre-assembled with the stopper element and the top stopper 2” to prevent the top stopper 2” from falling into the bottle mouth 10' during the freeze-drying process and affecting the drainage process of the freeze-dried formulation. The specific pre-assembly process is as follows: the top stopper 2” is placed on the upper end of the holding fixture 50, protruding from the protrusion 500 of the holding fixture 50. The protrusion 500 can support the stopper cap 20” to fix the position of the top stopper 2”, prevent it from falling off prematurely, and make the stopper 21” aligned with the bottle mouth opening 100', which is beneficial for the stopper 21” to quickly embed into the bottle mouth opening 100' when it is pressed down by the pressing fixture 51 after freeze-drying.

[0117] Specifically, apart from the two differences mentioned above regarding the freeze-drying process before and after the freeze-drying operation, the process of using this bottle cap element for freeze-drying is unchanged compared to the process of using the two bottle cap elements mentioned above. During the process of sealing the bottle mouth 10' with the top stopper 2” and the top cap 3”, the method of driving the pressing fixture 51 of the stopper assembly to press down and driving the top cap 3” to press down to the bottle mouth 10' can be any driving method that can be deployed and implemented in the freeze dryer, such as mechanical pressing, pneumatic driving, pneumatic clamp driving, or spring pressing.

[0118] In this case, a lyophilized formulation may also be included, prepared by a lyophilization method using a cap element with a stopper element. The selected dual-chamber cartridge can be dual-chamber cartridge 1 or dual-chamber cartridge 1', particularly 1'. In particular, since the product to be lyophilized added to one cavity 13' of the dual-chamber cartridge 1' can be one of multiple products, different products to be lyophilized can result in different lyophilized formulations when different products are added to the dual-chamber cartridge 1'. Furthermore, when the lyophilization parameters implemented during the lyophilization process of this case, such as the temperature and pressure of the primary drying, are changed, different qualities or properties of lyophilized formulations can be produced by the lyophilization method after adding the same product, such as lyophilized formulations with different water contents or different solid forms.

[0119] This application also includes an injectable preparation comprising: a dual-chamber cartridge vial packaging material, a lyophilized formulation, and a rehydrating agent. It should be noted that the lyophilized formulation and rehydrating agent can be any lyophilized formulation and rehydrating agent suitable for use with the dual-chamber cartridge vial packaging material and lyophilization technology. Specifically, the lyophilized formulation can be any product to be lyophilized that can be filled into the dual-chamber cartridge vial 1' of this application, prepared by lyophilization using the lyophilization method implemented in this application with a cap element having a stopper element, or it can be the lyophilized formulation provided in this application.

[0120] In addition, the reconstitution solvent can be any of the lyophilized preparations prepared above, such as sterile water for injection (which may contain antibacterial agents, such as phenol, m-cresol, benzyl alcohol, etc.), physiological saline, 5% glucose solution, and other buffer solutions, such as phosphate buffer, citrate buffer, acetate buffer, histidine buffer, succinate buffer, tris(hydroxymethyl)aminomethane hydrochloride buffer, etc., which can be used to reconstitute the lyophilized preparations provided in this case when administering the medication.

[0121] The two lyophilized formulations provided in this case, as described above, are either any lyophilized formulation prepared according to any of the lyophilization methods provided in this case, or any one of the two lyophilized formulations provided in this case. It is understood that these lyophilized formulations can all serve as raw materials or finished products for pharmaceuticals in the biopharmaceutical field, pharmaceutical reagents in the medical aesthetics field, medical device reagents, and / or cosmetics. The various types of lyophilized formulations obtained through this case also possess the characteristics of high integrity, high purity, and low impurities, thus exhibiting excellent practical application effects.

[0122] Example

[0123] This case provides a general and / or specific description of the materials and experimental methods used in the experiment. Unless otherwise specified, all reagents and instruments used are commercially available standard products.

[0124] Example 1

[0125] A bottle cap element includes a top stopper 2 and a top cap 3 for sealing a dual-chamber cartridge bottle 1. The structure of the top cap 3 is shown in Figure 6A. The top cap 3 achieves a seal between the top stopper 2 and the bottle opening 10 of the dual-chamber cartridge bottle 1, and also seals the bottle opening 10 of the dual-chamber cartridge bottle 1 through the top stopper. Specifically,

[0126] First, the top stopper 2 is positioned inside the top cover 3 through the top stopper positioning point 303, and the top cover 3 is placed on the bottle mouth 10 so that the stopper 21 naturally faces the bottle mouth opening 100 for freeze drying.

[0127] Then, after freeze-drying, the top cap 3 is pressed down to fit the top plug 2 into the mouth 10 of the double-chamber cartridge bottle 1. 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 plate 300 located at its center, a thread 301 located at the edge of the upper end 30 and an opening 302, which is located above the middle end 31. The lower end 32 is located below the middle end 31, and the lower end 32 has an opening below it. After the top plug 2 is initially inserted into the mouth 10, the top cap 3 is pressed down until the upper end 30 is completely fitted onto the mouth 10. During this process, the inner wall of the upper end 30 fits against the mouth 10 and the neck 11, while the inner walls of the middle end 31 and the lower end 32 fit against the bottle body 12.

[0128] The top plate 300 is a hollow cylindrical structure with a shortened middle section. When the top cover 3 is pressed down by external force, the top stopper 2 is pressed to the bottle mouth 10 through the lower surface of the top plate 300, so that the top stopper 2 is further embedded into the bottle mouth 10 until the stopper 21, whose diameter is slightly larger than the inner diameter of the bottle mouth, is completely embedded into the bottle mouth 10 under pressure. The lower surface of the stopper cap 20 is completely in contact with the upper surface of the bottle mouth 10, so that the top stopper 2 can be used to seal the double-chamber cartridge bottle 1. No additional stoppering device is required for sealing, which reduces the additional process and time required to seal the double-chamber cartridge bottle 1, and also avoids the impact of inaccurate sealing on the production efficiency of freeze-drying technology.

[0129] Specifically, when the top cap 3 is configured to press the top plug 2 to fully embed into the bottle mouth 10, the inner wall of the upper surface of the middle end 31 can also fully fit with the upper surface of the bottle body 12; therefore, while the top cap 3 seals the bottle mouth opening 100 with the top plug 2, the top cap 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, thus achieving a complete sealing of the double-cavity cartridge bottle 1.

[0130] The upper end 30 has a diameter of 7.3 mm, leaving a gap 200 between it and the stopper cap 20 with a diameter of 7.0 mm. The upper end 30 also has a top stopper positioning point 303, as shown in Figure 6A. The top stopper positioning point 303 is located below the top plate 300 and protrudes from the inner wall of the upper end 30 in the direction of the axis of the top cover 3. After the top stopper 2 is fully inserted into the bottle mouth 10, the top stopper positioning point 303 fits against the stopper cap 20. The stopper cap 20 is subjected to pressure from the top stopper positioning point 303 in the direction of the axis of the top cover 3, thereby increasing the friction between the stopper cap 20 and the inner wall of the upper end 30, preventing the top stopper 2 from loosening or slipping out of the top cover 3 during the pre-assembly process due to improper fitting. There are 4 top stopper positioning points 303, which are evenly distributed on the inner wall of the upper end 30.

[0131] The upper end 30 also has a protrusion 304, as shown in Figure 10. The protrusion 304 is located below the top stopper 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 stopper 2 is fully embedded in the bottle mouth 10, the protrusion 304 fits against the outer wall of the bottle mouth 10. The bottle mouth 10 is subjected to pressure from the protrusion 304 in the direction of the axis of the top cover 3, thereby increasing the friction between the bottle mouth 10 and the inner wall of the upper end 30. This prevents the top cover 3 from slipping off after sealing due to incomplete fitting, thus improving the sealing performance of the double-cavity cartridge bottle 1. The maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 is set to 0.23 mm. The shape of the protrusion 304 is trapezoidal, and there are two protrusions distributed on both sides of the inner wall of the upper end 30, with an upper tangent angle of 30°.

[0132] The lower end 32 is cylindrical. The protruding ring 310 of the middle end 31 and the protruding strip 320 of the lower end 32 can increase the fit between the top cover 3 and the bottle body 22 after the top cover 3 is attached to the double-cavity cartridge bottle 1, and further improve the stability of the fit between the top cover 3 and the double-cavity cartridge bottle 1.

[0133] The cap components were tested for compression and sealing. It was found that the fit between the top stopper 2 and the top cap 3 was high, and the top stopper 2 did not slip off from the top cap 3. The capping process required a certain amount of pressure, but it did not cause deformation or damage to the top cap 3. The fit between the top cap 3 and the bottle mouth 10 of the double-chamber cartridge bottle 1 was significantly improved, and it was not pulled out after a large force was applied.

[0134] Example 2

[0135] The maximum length of the protrusion 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 in Example 1. A stopper and capping sealing test was performed on the cap element. It was found that the fit between the top stopper 2 and the top cap 3 was high, and the top stopper 2 did not slip off from the top cap 3. After replacing the maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 with 0.25 mm, a certain amount of pressure was required during the capping process, but no deformation or damage was caused to the top cap 3 structure. The fit between the top cap 3 and the bottle mouth 10 of the double-chamber cartridge bottle 1 was also significantly improved, and it was not pulled out after applying a large force.

[0136] Example 3

[0137] The maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 was replaced with 0.28 mm, and other structures and parameters were the same as in Example 1. A stopper and capping sealing test was performed on the cap element. It was found that the fit between the top stopper 2 and the top cap 3 was high, and the top stopper 2 did not slip off from the top cap 3. After replacing the maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 with 0.28 mm, the capping process required greater pressure, but it did not cause deformation or damage to the top cap 3 structure. The fit between the top cap 3 and the bottle mouth 10 of the double-chamber cartridge bottle 1 was significantly improved, and it was not pulled out after applying greater force.

[0138] Example 4

[0139] The drug was lyophilized using a dual-lumen cartridge vial for injection to obtain a lyophilized formulation. Twenty portions of each of the dual-lumen cartridge vials used in Examples 1-3 were selected, and the lyophilization process to obtain the lyophilized formulation is as follows:

[0140] (1) Add a stopper to each double-chamber cartridge 1, and then fill it with the lonapegsomatropin to be lyophilized. There are two types of lonapegsomatropin. The first type contains 22.0 mg hGH / mL lonapegsomatropin, 10 mM succinic acid, 74.0 mg / mL trehalose dihydrate, and an appropriate amount of tris(hydroxymethyl)aminomethane to adjust the pH to 5.0. The second type contains 11.0 mg hGH / mL lonapegsomatropin, 10 mM succinic acid, 83.0 mg / mL trehalose dihydrate, and an appropriate amount of tris(hydroxymethyl)aminomethane to adjust the pH to 5.0. Place and fix the double-chamber cartridge 1 on the lyophilization rack. The lyophilization rack is a tray-type lyophilization rack, as shown in Figure 1. The double-chamber cartridge 1 is placed upright in the lyophilization rack.

[0141] (2) The top stopper 2 and the top cap 3 in Examples 1-3 are pre-assembled and placed at the bottle mouth 10 of the double-cavity cartridge bottle 1. Specifically, the top stopper 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 stopper cap 20 is in contact with the lower end of the top plate 300. The stopper cap 20 is supported by the top stopper positioning point 303 and is limited in the upper end 30. The bottle mouth 10 is aligned with the opening of the lower end 32, and the top stopper 2 is naturally placed at the bottle mouth 10.

[0142] (3) The freeze-drying process of the lyophilized cyclophosphamide, including freezing, primary drying, secondary drying, and laminar flow sealing, is shown in Table 1.

[0143] Table 1. Freeze-drying process and parameter settings for cyclophosphamide to be freeze-dried Technical steps Time (minutes) Temperature (°C) Pressure (mbar) Setting value Warning value Setting value Warning value load As needed +5 ±5 Atm NA freezing 120 +5 ±3 Atm NA 75 -52 ±3 Atm NA 270 -52 ±3 Atm NA 30 -52 ±3 Atm NA One-time drying 30 -52 ±3 Atm NA 180 -52 ±3 0.06 +0.04 / -0.02 120 -15 ±3 0.06 2400 -15 ±3 0.06 Secondary drying 450 +35 ±3 0.06 420 +35 ±3 0.06 Plate-layer plug cap As needed +25 ±5 Atm NA uninstall As needed +25 ±5 Atm NA

[0144] Where Atm is 1 standard atmosphere. In the freeze-drying process, the freeze-drying curve of the drug to be freeze-dried is shown in Figure 2. After unloading and exiting the box, the double-chamber cartridge packaging material for injection has a formed appearance and low water content, and is freeze-dried.

[0145] (4) After the freeze-drying process is completed, the double-chamber cartridge bottle 1 is purged with nitrogen to maintain a low moisture content of the freeze-dried sample, and then simultaneously stoppered and capped for sealing. Specifically,

[0146] After freeze-drying, push the top cap 3 downward to press the top plug 2 into the bottle mouth 10 of the double-chamber cartridge bottle 1. As the top plug 2 is inserted into the bottle mouth 10, the top cap 3 is pressed down until the upper end 30 is completely covered on the bottle mouth 10. During this process, the inner wall of the upper end 30 is in contact with the bottle mouth 10, while the inner walls of the middle end 31 and the lower end 32 are in contact with the bottle body 12, until the stopper 21 is completely inserted into the bottle mouth 10 and the lower surface of the stopper cap 20 is completely in contact with the upper surface of the bottle mouth 10, so as to achieve the sealing of the double-chamber cartridge bottle 1 by using the top plug 2 without the need to introduce an additional stopper assembly.

[0147] (5) Remove the double-chamber cartridge 1 from the freeze dryer to obtain the final freeze-dried formulation.

[0148] The lyophilized formulation prepared by the above lyophilization method in the double-chamber cartridge 1 was subjected to appearance and moisture tests. The test results are shown in Table 2.

[0149] Table 2. Appearance and moisture content test results of the lyophilized formulations. Detection methods Test results Appearance inspection The freeze-dried powder compacts all appear as white, loose powders, intact, and uniform in color, as shown in Figure 3. Moisture testing 0.477%, 0.544%, 0.456%, 0.337%, 0.365%, 0.386%

[0150] As shown in Table 2, the appearance test results of the lyophilized formulation showed that it had a good appearance and the average moisture content of the six tests was low, indicating that the lyophilization effect of the lyophilized formulation was good.

[0151] In addition, the three types of injection dual-chamber cartridge packaging materials in Examples 1-3 were subjected to freeze-drying plate-layer capping operations (without freeze-dried samples added), and the capped packaging materials were tested by CCIT (vacuum decay method). The results showed that the sealing performance of the three packaging materials was good.

[0152] In summary, the above-mentioned freeze-drying technology can be completed using the packaging materials in Examples 1-3, which can meet the requirements of drug freeze-drying technology and sealing. The freeze-dried formulations obtained by the above-mentioned freeze-drying method can meet the requirements of appearance and moisture content of freeze-dried drugs.

[0153] Example 5

[0154] The structure of the top cap 3 of the bottle cap element in Embodiment 1 is adjusted to reduce the volume of the top cap 3, as shown in Figure 6B. Specifically, the length of the portion of the top cap 3 extending along the neck 11 and the bottle body 12 in Embodiment 2 is shortened, thereby shortening the length of the middle end 31. Furthermore, the position of the convex ring 310 relative to the neck 11 and the bottle body 12 is moved upward and fitted to the lower part of the upper end 30. In addition, the convex strip 320 of the lower end 32 is removed, and the non-convex strip portion of the lower end 32 is extended downward along the bottle body 12. The upper part of the lower end 32 near the middle end 31 is shortened radially to form the first convex opening 321.

[0155] It should be noted that in this embodiment, the extended lower end 32 is shaped as an octagonal prism, and its inner wall can still fit at least a portion of the bottle body 12 of the double-cavity cartridge bottle 1. Furthermore, the structure of the adjusted top cap 3, except for the middle end 31 and the lower end 32, is the same as that of the top cap 3 in embodiment 10. The number of top stopper positioning points 303 is 8, evenly distributed on the inner wall of the upper end 30.

[0156] The capping and sealing tests on the capping components revealed that the fit between the top stopper 2 and the top cap 3 was high, and the top stopper 2 did not slip off from the top cap 3. The capping process required a large amount of pressure, but it did not cause deformation or damage to the top cap 3. The fit between the top cap 3 and the bottle mouth 10 of the double-chamber cartridge bottle 1 was significantly improved, and it was not pulled out after a large force was applied.

[0157] Example 6

[0158] The maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 is replaced with 0.25 mm, and the other structures and parameters are the same as in Example 5. A stopper and capping sealing test was performed on the cap element. It was found that the fit between the top stopper 2 and the top cap 3 was high, and the top stopper 2 did not slip off from the top cap 3. The capping process required a large pressure, but it did not cause deformation or damage to the top cap 3. The fit between the top cap 3 and the bottle mouth 10 of the double-chamber cartridge bottle 1 was significantly improved, and it was not pulled out after applying a large force.

[0159] Example 7

[0160] The maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 is replaced with 0.2 mm, and other structures and parameters are the same as in Example 5. A stopper and capping sealing test was performed on the cap element. It was found that the fit between the top stopper 2 and the top cap 3 was high, and the top stopper 2 did not slip off from the top cap 3. The capping process required a large pressure, but it did not cause deformation or damage to the top cap 3. The fit between the top cap 3 and the bottle mouth 10 of the double-chamber cartridge bottle 1 was significantly improved, and it was not pulled out after applying a large force.

[0161] Example 8

[0162] The lyophilization technique for pharmaceuticals using dual-lumen cartridge vials for injection was employed to obtain lyophilized formulations. Twenty-five portions of each of the dual-lumen cartridge vials used in Examples 5-7 were selected, and the steps for lyophilization to obtain lyophilized formulations are as follows:

[0163] (1) Add a stopper to each double-chamber cartridge 1, and then fill it with the lyophilized auxin, which contains: 22.0 mg hGH / mL auxin, 10 mM succinic acid, 74.0 mg / mL trehalose dihydrate, and an appropriate amount of tris(hydroxymethyl)aminomethane to adjust the pH to 5.0. Place and fix the double-chamber cartridge 2 on the lyophilization rack, wherein the lyophilization rack is a tray-type lyophilization rack, as shown in Figure 1, and the double-chamber cartridge 1 is placed upright in the lyophilization rack.

[0164] (2) After pre-assembling the top plug 2 and the top cover 3 in Examples 5-7, place them at the bottle mouth 10 of the double-cavity cartridge bottle 1. The pre-assembly method of the top plug 2 and the top cover 3 is the same as in Example 4.

[0165] (3) The freeze-drying process of freezing, primary drying, secondary drying and plate-sealing of the freeze-dried cyclophosphamide is carried out separately, and the specific operation method is the same as in Example 4.

[0166] (4) After the freeze-drying process is completed, nitrogen gas is purged into the double-chamber cartridge bottle 1 to maintain the low moisture content of the freeze-dried sample, and then the cap is sealed; the capping and sealing method is the same as in Example 4.

[0167] (5) Remove the double-chamber cartridge 4 from the freeze dryer to obtain the final freeze-dried formulation.

[0168] The lyophilized formulation prepared by the above lyophilization method in the double-chamber cartridge 4 was subjected to appearance and moisture tests. The test results are shown in Table 3.

[0169] Table 3. Appearance, moisture content, and CCIT test results of the lyophilized formulations. Detection methods Test results Appearance inspection Freeze-dried powder compacts are all white and porous, with intact compacts and uniform color. Moisture testing 0.584%, 0.706%, 0.572%, 0.401%, 0.748%, 0.872%, 0.803%, 0.688%, 0.668% CCIT Good sealing

[0170] As shown in Table 3, the appearance test results of the lyophilized formulations show that they have good appearance and low average moisture content. In addition, the dual-chamber cartridge packaging materials for injection in Examples 5-7 have good sealing performance in the lyophilization process and can meet the sealing requirements of the formulations.

[0171] Example 9

[0172] A dual-chamber cartridge vial packaging material for injection includes a dual-chamber cartridge vial 1' and a cap assembly. The structure of the dual-chamber cartridge vial 1' is shown in Figure 13, including a bottle neck 10', a bottle body 12', and an inner cavity 13'. The cap assembly includes a top stopper 2' and a top cap 3'. The structure of the top stopper 2' is also shown in Figure 13, and the structure of the top cap 3' is shown in Figure 14A. The top cap 3' uses the top stopper 2' to press and seal the bottle neck 10', and simultaneously caps the bottle neck 10' of the dual-chamber cartridge vial 1' itself.

[0173] The top cap 3' includes an upper end 30' and a base 31'. The upper end 30' has a centrally located top plate 300', a threaded section 301' on the edge, and an opening 302' on the lower outer wall. The base 31' has an opening at the bottom and a cavity extending inward from the opening. After the top plug 2' is pre-assembled into the upper end 30' of the top cap 3', the top cap 3' is pressed down as a whole until the upper end 30' is fitted onto the bottle neck 10'. During this process, the inner wall of the upper end 30' fits against the bottle neck 10', while the inner wall of the base 31' fits against the connection between the bottle neck 11' and the bottle body 12'. The top plate 300' fits against the upper surface of the cap 20' of the pre-assembled top plug 2'. During the overall pressing down of the top cap 3', the top plate 300' simultaneously presses down on the top plug 2', causing the top plug 2' to embed into the bottle neck 10'. Therefore, the top cap 3' can be used to simultaneously perform stopper sealing and capping without the need for additional stoppering elements or to complete the process in multiple steps, reducing the time required for the sealing process of the dual-chamber cartridge bottle 1' and avoiding sealing failure.

[0174] The upper end 30' has eight evenly distributed top stopper positioning points 303', which are located at the lower end of the top plate 300' and protrude from the inner wall of the upper end 30' towards the axis of the top cover 3'. After the top stopper 2' is inserted into the bottle neck 10', the top stopper positioning points 303' fit with the stopper cap 20'. The stopper cap 20' is subjected to pressure from the top stopper positioning points 303' towards the axis of the top cover 3', increasing the frictional resistance between the stopper cap 20' and the inner wall of the upper end 30', preventing the top stopper 2' from slipping out or popping out of the top cover 3', thereby avoiding sealing failure.

[0175] The upper end 30' also has a protrusion 304', which is located below the top stopper positioning point 303' and protrudes from the inner wall of the upper end 30' in the direction of the axis of the top cover 3'. Before the top stopper 2' is inserted into the bottle mouth 10', the protrusion 304' rests on the bottle mouth to ensure that sublimated water can be discharged from the opening 302'; after the top stopper 2' is inserted into the bottle mouth 10', the protrusion 304' fits against the outer wall of the bottle mouth 10', so that the bottle mouth 10' is subjected to the pressure of the protrusion 304' in the direction of the axis of the top cover 3', thereby increasing the friction between the bottle mouth 10' and the inner wall of the upper end 30' and preventing the top cover 3' from slipping off or popping out of the bottle mouth 10'.

[0176] The maximum length of the protrusion 304' protruding from the inner wall of the upper end 30' is 0.23 mm, and the shape of the protrusion 304' is trapezoidal.

[0177] Example 10

[0178] A dual-chamber cartridge packaging material for injection includes a dual-chamber cartridge 1' and a cap element, the cap element including a top stopper 2' and a top cap 3'. The maximum length of the protrusion 304' protruding from the inner wall of the upper end 30' is replaced with 0.25 mm; other structures and parameters are the same as in Embodiment 9.

[0179] Example 11

[0180] A dual-chamber cartridge packaging material for injection includes a dual-chamber cartridge 1' and a cap element, the cap element including a top stopper 2' and a top cap 3'. The maximum length of the protrusion 304' protruding from the inner wall of the upper end 30' is replaced with 0.28 mm; other structures and parameters are the same as in Embodiment 9.

[0181] Example 12

[0182] The drug was lyophilized using a dual-chamber cartridge vial packaging material for injection, and the lyophilized formulation was obtained. Twenty portions of each of the dual-chamber cartridge vial packaging materials from Examples 9-11 were selected, and the steps for lyophilization to obtain the lyophilized formulation are as follows:

[0183] (1) A stopper is added to the double-chamber cartridge 1' of each injection double-chamber cartridge packaging material, and then the drug solution to be lyophilized is filled in. The double-chamber cartridge 1' is placed and fixed on the lyophilization support. The lyophilization support is a tray-type lyophilization support, as shown in Figure 1. The double-chamber cartridge 1' is placed upright in the lyophilization support.

[0184] (2) The top plug 2' is pre-assembled with the top cap 3' in Examples 9-11 and placed at the bottle mouth 10' of the double-cavity cartridge bottle 1' without sealing. Specifically, the top cap 3' is supported by the protrusion 303' and limited to the bottle mouth 10'. The top plug 2' is inserted into the cavity of the upper end 30' from the opening of the base plate 31' until the upper surface of the stopper cap 20' is in contact with the lower end of the top plate 300'. The stopper cap 20' is supported by the top plug positioning point 303' and limited to the cavity inside the upper end 30'.

[0185] In this way, the bottle mouth 10' is aligned with the opening of the base 31', and the top stopper 2' is entirely positioned above the bottle mouth 10'.

[0186] (3) The liquid medicine to be freeze-dried was subjected to freezing, primary drying, secondary drying, and plate-type stoppering and capping. The specific operation process is shown in Table 4.

[0187] Table 4. Freeze-drying process and parameter settings for the drug solution to be freeze-dried Technical steps Time (minutes) Temperature (°C) Pressure (mbar) Setting value Warning value Setting value Warning value load As needed +5 ±5 Atm NA freezing 120 +5 ±3 Atm NA 75 -52 ±3 Atm NA 270 -52 ±3 Atm NA 30 -52 ±3 Atm NA One-time drying 30 -52 ±3 Atm NA 180 -52 ±3 0.06 +0.04 / -0.02 120 -15 ±3 0.06 2400 -15 ±3 0.06 Secondary drying 450 +35 ±3 0.06 420 +35 ±3 0.06 Plate-layer plug cap As needed +25 ±5 Atm NA uninstall As needed +25 ±5 Atm NA Atm refers to one standard atmosphere.

[0188] (4) After the freeze-drying process is completed, the double-chamber cartridge bottle 1' is purged with nitrogen to maintain a low moisture content in the freeze-dried product, and then capped and sealed. Specifically,

[0189] After freeze-drying, push the top cap 3' downwards to press the top stopper 2' into the neck 10' of the double-chamber cartridge bottle 1'. Simultaneously, as the top stopper 2' is inserted into the neck 10', the top cap 3' is pressed down until the upper end 30' is fully fitted over the neck 10'. During this process, the inner wall of the upper end 30' fits against the neck 10' until the stopper 21' is fully embedded in the neck 10', the lower surface of the stopper cap 20' is fully fitted against the upper surface of the neck 10', and the lower surface of the base 31' fits against the connection between the neck 11' and the bottle body 12'. This achieves a seal on the double-chamber cartridge bottle 1' using the top stopper 2', eliminating the need for an additional stopper assembly.

[0190] (5) Remove the double-chamber cartridge bottle 1' and the freeze-drying support from the freeze dryer.

[0191] The lyophilized formulation prepared by the above-described lyophilization method in the double-chamber cartridge 1' was sampled, and its appearance, moisture content, and CCIT (vacuum decay method) were tested. The test results are shown in Table 5.

[0192] Table 5. Results of appearance, moisture content, and CCIT testing of the lyophilized formulations. Detection methods Test results Appearance inspection Freeze-dried powder compacts all appear as white, loose powder, intact, and uniform in color, as shown in Figure 4A. Moisture testing 0.421%, 0.366%, 0.438%, 0.337%, 0.384%, 0.296%, 0.518%, 0.356%, 0.402%, 0.317%, 0.325%, 0.428%, 0.425%, 0.438%, 0.288%, 0.413%, 0.320%, 0.286% CCIT Good sealing

[0193] Figure 4A shows the appearance of the lyophilized product obtained through freeze-drying technology. As can be seen from Table 5 and Figure 4A, the appearance test results of the lyophilized formulation show that its appearance is good and the average moisture content is low. In addition, the injection dual-chamber cartridge packaging material in Examples 9-11 has good sealing performance in the freeze-drying process and can meet the sealing requirements of the formulation.

[0194] Example 13

[0195] A dual-chamber cartridge vial packaging material for injection includes a dual-chamber cartridge vial 1' and a cap assembly. The structure of the dual-chamber cartridge vial 1' is the same as that of the dual-chamber cartridge vial 1 in Example 9. The cap assembly includes a top stopper 2' and a top cap 3'. The structure of the top stopper 2' is the same as that of the top stopper 2' in Example 9. The structure of the top cap 3' is shown in Figure 14B. The base 31' is adjusted to extend downward to additionally fit at least a portion of the vial body 12'. The shape of the downwardly extended portion of the base 31' is set as an octagonal prism. In addition, the maximum length of the protrusion 304' protruding from the inner wall of the upper end 30' is set to 0.25 mm. Other structures and parameters are the same as in Example 9.

[0196] Example 14

[0197] The maximum length of the protrusion 304 protruding from the inner wall of the upper end 30 is replaced with 0.2 mm, and other structures and parameters are the same as in Example 13. A stopper and capping sealing test was performed on the cap element. It was found that the fit between the top stopper 2' and the top cap 3' was high, and the top stopper 2' did not slip off from the top cap 3'. The capping process required a large pressure, but it did not cause deformation or damage to the top cap 3'. The fit between the top cap 3' and the bottle opening 10' of the double-chamber cartridge bottle 1' was significantly improved, and it was not pulled out after applying a large force.

[0198] Example 15

[0199] The drug was lyophilized using a dual-lumen cartridge vial packaging material for injection, and the lyophilized formulation was obtained. Twenty-five portions of the dual-lumen cartridge vial packaging material from Examples 13 and 14 were selected for lyophilization. The steps for obtaining the lyophilized formulation are as follows:

[0200] (1) Add a stopper to each double-chamber cartridge 1', and then fill it with the solution to be lyophilized. The solution is lonpec growth hormone, which contains: 22.0 mg hGH / mL lonpec growth hormone, 10 mM succinic acid, 74.0 mg / mL trehalose dihydrate, and an appropriate amount of tris(hydroxymethyl)aminomethane to adjust the pH of the solution to pH 5.0.

[0201] The dual-chamber cartridge bottle 1' is placed and fixed on the freeze-drying rack. The freeze-drying rack is a tray-type freeze-drying rack, and the dual-chamber cartridge bottle 1' is placed upright in the freeze-drying rack.

[0202] (2) After pre-assembling the top stopper 2' and the top cap 3' in Examples 13-14, place them at the bottle mouth 10' of the double-cavity cartridge bottle 1'. The pre-assembly method of the top stopper 2' and the top cap 3' is the same as in Example 12.

[0203] (3) The liquid medicine to be freeze-dried was subjected to freezing, primary drying, secondary drying and plate-type sealing, and the specific operation method was the same as in Example 12.

[0204] (4) After the freeze-drying process is completed, the double-chamber cartridge bottle 1' is purged with nitrogen to maintain the low moisture content of the freeze-dried product, and then capped and sealed. The capping and sealing method is the same as in Example 12.

[0205] (5) Remove the double-chamber cartridge 1' from the freeze dryer to obtain the freeze-dried formulation therein.

[0206] The lyophilized formulation prepared by the above-described lyophilization method in the double-chamber cartridge 1' was sampled, and its appearance, moisture content, and CCIT were tested. The test results are shown in Table 6.

[0207] Table 6. Appearance, moisture content, and CCIT test results of the lyophilized formulations. Detection methods Test results Appearance inspection Freeze-dried powder compacts are all white and porous, with intact compacts and uniform color. Moisture testing 0.369%, 0.492%, 0.448%, 0.389%, 0.524%, 0.662% CCIT Good sealing

[0208] As shown in Table 6, the appearance test results of the lyophilized formulations show that they have good appearance and low average moisture content. In addition, the dual-chamber cartridge packaging materials for injection in Examples 13 and 14 have good sealing performance in the lyophilization process and can meet the sealing requirements of the formulations.

[0209] Example 16

[0210] A dual-chamber cartridge vial packaging material for injection includes a dual-chamber cartridge vial 1' and a cap element, the cap element including a top stopper 2' and a top cap 3'. A fitting portion 306' is provided on the side of the top plate opening of the top plate 300' near the top stopper 2', and it uniformly tapers inward in the opposite direction to the top plate opening along the direction near the top stopper 2'. Furthermore, four internal protrusions 310' are equidistantly arranged on the inner wall of the base plate 31' on the side away from the upper end 30', each internal protrusion 310' having an opening 311' on each of its left and right sides, as shown in Figures 14C and 15B. Other structures and parameters are the same as in Embodiment 13.

[0211] Example 17

[0212] The drug was lyophilized using a dual-lumen cartridge vial packaging material for injection, and the lyophilized formulation was obtained. Ten portions of the dual-lumen cartridge vial packaging material from Example 16 were selected. The steps for lyophilizing the drug and obtaining the lyophilized formulation are as follows:

[0213] (1) Add a stopper to each double-chamber cartridge 1', and then fill it with the solution to be lyophilized. The solution is lonpec growth hormone, which contains: 22.0 mg hGH / mL lonpec growth hormone, 10 mM succinic acid, 74.0 mg / mL trehalose dihydrate, and an appropriate amount of tris(hydroxymethyl)aminomethane to adjust the pH of the solution to pH 5.0.

[0214] The dual-chamber cartridge bottle 1' is placed and fixed on the freeze-drying rack. The freeze-drying rack is a tray-type freeze-drying rack, and the dual-chamber cartridge bottle 1' is placed upright in the freeze-drying rack.

[0215] (2) After pre-assembling the top stopper 2' and the top cap 3' in Example 16, place them at the bottle mouth 10' of the double-cavity cartridge bottle 1'. The pre-assembly method of the top stopper 2' and the top cap 3' is the same as in Example 12.

[0216] (3) The liquid medicine to be freeze-dried was subjected to freezing, primary drying, secondary drying and plate-type sealing, and the specific operation method was the same as in Example 12.

[0217] (4) After the freeze-drying process is completed, the double-chamber cartridge bottle 1' is purged with nitrogen to maintain the low moisture content of the freeze-dried product, and then capped and sealed. The capping and sealing method is the same as in Example 12.

[0218] (5) Remove the double-chamber cartridge 1' from the freeze dryer to obtain the freeze-dried formulation therein.

[0219] The lyophilized formulation prepared by the above-described lyophilization method in the double-chamber cartridge 1' was sampled, and its appearance, moisture content, and CCIT were tested. The test results are shown in Table 7.

[0220] Table 7. Appearance, moisture content, and CCIT test results of the lyophilized formulations. Detection methods Test results Appearance inspection The freeze-dried powder compacts all appear as white, loose powders, intact, and uniform in color, as shown in Figure 4B. Moisture testing 0.758%, 0.618%, 0.248% CCIT Good sealing

[0221] Figure 4B shows the appearance of the lyophilized product obtained through freeze-drying technology. As can be seen from Table 7 and Figure 4B, the appearance test results of the lyophilized formulation show that its appearance is good and the average moisture content is low. In addition, the dual-chamber cartridge packaging material for injection in Example 16 has good sealing performance in the freeze-drying process and can meet the sealing requirements of the formulation.

[0222] Example 18

[0223] A dual-chamber cartridge vial packaging material for injection includes a dual-chamber cartridge vial 1' and a cap element. The cap element includes a top stopper 2" and a top cap 3" for sealing the dual-chamber cartridge vial 1'. The top stopper 2" is used to seal the mouth 10' of the dual-chamber cartridge vial 1'. The dual-chamber cartridge vial 1' achieves the seal of the mouth 10' by the top stopper 2" through a stoppering element. The stoppering assembly includes a pressing fixture 51 and a retaining fixture 50, the structure of which is shown in Figure 21A. The top stopper has a stopper cap 20" and a stopper plunger 21" which needs to be fully embedded into the mouth opening 100' at the center of the mouth 10', and the lower surface of the stopper cap 20" needs to be fully fitted with the upper surface of the mouth 10' to achieve a seal on the mouth 10'.

[0224] For this cap element, when an airtight lyophilized formulation is required after lyophilization, a stopper element can be used to seal the top stopper 2” to the bottle mouth 10”, and a top cap 3” can be added after fixing the top stopper 2” to further improve the airtightness of the double-chamber cartridge bottle 1’. Specifically:

[0225] (1) Top plug seal

[0226] First, the retaining fixture 50 of the stopper assembly has openings at both the top and bottom. The inner wall of the retaining fixture 50 is pressed against the outer surface of the bottle neck 10' and the bottle body 12' until it is completely in contact with the upper end of the bottle body 12'. Because the retaining fixture 50 is tightly fitted with the bottle neck 10' and the bottle body 12', it has a large frictional force, so the retaining fixture 50 is not easy to fall off the double-chamber cartridge bottle 1'. In addition, the upper end of the retaining fixture 50 protrudes from the bottle neck 10'.

[0227] Next, the top plug 2” is placed in the retaining fixture 50. Specifically, the top plug 2” is placed on the upper end of the retaining fixture 50, protruding from the protrusion 500 of the retaining fixture 50. The protrusion 500 can support the stopper cap 20” to fix the position of the top plug 2”, so that the stopper 21” is aligned with the bottle opening 100’, so as to facilitate the insertion of the stopper 21” into the bottle opening 100’ when it moves down. In particular, there are two protrusions 500, which are respectively provided on both sides of the upper end of the retaining fixture 50.

[0228] Next, the inner wall of the pressing fixture 51 of the stopper element is attached to the outer wall of the holding fixture 50 and slid downward. The lower end of the pressing fixture 51 is open, the upper surface is closed and the center is concave downward. A pressing post 510 protruding along the axis of the pressing fixture 51 is provided on one side of the inner wall of the concave part. During the downward sliding of the pressing fixture 51, the pressing post 510 can contact and apply downward pressure to the stopper cap 20”, so as to press the top stopper 2” to move towards the bottle mouth 10’ until the stopper post 21” is completely embedded in the bottle mouth 10’. After the stopper post 21” is completely embedded in the bottle mouth 10’, the stopper cap 20” can be just locked at the lower end of the protrusion 500. Therefore, the protrusion 500 can further lock the top stopper 2” to prevent it from falling off.

[0229] It is important to note that before the stopper 21” is fully embedded in the bottle neck 10’, the height of the retaining fixture 50 protruding from the bottle neck 10’ is less than the height of the outer side of the upper surface of the pressing fixture 51 protruding from the bottle neck 10’. Therefore, before the stopper 21” is fully embedded in the bottle neck 10’, the pressing fixture 51 will not be obstructed by the retaining fixture 50 and will not be able to move downward, thus avoiding incomplete engagement between the top stopper 2” and the bottle neck 10’. In particular, there are two pressing rods 510, which are respectively set on both sides of the inner wall of the recess on the upper surface of the pressing fixture 51 to apply a uniform downward pressure to the top stopper 2”.

[0230] Finally, remove the pressing fixture 51 and the retaining fixture 50. The stopper assembly is only used to control the top stopper 2” to seal the bottle mouth 10’, so it needs to be removed after sealing so that the cap can be sealed later.

[0231] (2) The top cover is sealed.

[0232] The top cap 3” is used to fix the top plug 2” and seal the mouth 10’ of the double-chamber cartridge bottle 1’ through the top plug 2”. The structure of the top cap 3” is shown in Figure 21B, including a body and a base 31”. The body has a top plate 300” located at the upper center of the top end of the top cap 3” and a thread 301” located at the upper edge of the top end of the top cap 3”, which is set above the base 31”. The bottom of the base 31” is open. After the top plug 2” is fully inserted into the mouth 10’, the top cap 3” is pressed down and put on the mouth 10’. During this process, the inner wall of the body and the base 31” fits against the mouth 10’ and the neck 11’. Therefore, after the top cap 3” is pressed until the base 31” is fully fitted with the upper surface of the bottle body 12’, there is a large friction between the top cap 3” and the double-chamber cartridge bottle 1’, which can prevent itself from falling off and improve the sealing performance of the double-chamber cartridge bottle 1’.

[0233] In addition, the top plate 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 hollow cylinder. After the bottom plate 31” is completely attached to the upper surface of the bottle body 12’, the top plate 300” can support the top plug 2” embedded in the bottle mouth 10’ through the lower cylinder, so as to prevent the top plug 2” from falling out of the bottle mouth 10’, which can improve the airtightness of the double-cavity cartridge bottle 1’.

[0234] In summary, the lyophilized formulation prepared using the provided lyophilization method for pharmaceutical, cosmetic, or medical aesthetic applications, combined with a dual-chamber cartridge vial packaging material, exhibits regular lyophilization curve parameters, good appearance, low moisture content, and high storage stability. The lyophilized packaging material provides excellent sealing, offering a high-purity and sterile storage environment. Therefore, the lyophilized formulation obtained using the lyophilization method described in the above embodiments possesses a higher core market competitiveness.

[0235] 1: Double-chamber cartridge bottle 2: Top plug 3: Top cover 4: Sheath 1': Double-chamber cartridge bottle 2': Top plug 3': Top cover 4': Sheath 2”: Top plug 3”: Top cover 10: Bottle opening 11: Bottleneck 12: Bottle body 13: Inner cavity 10': Bottle neck 11': Bottleneck 12': Bottle body 13': Inner cavity 20: Hat 21: plug 22: Sealing section 20': Cap 21': plug 22': Sealing section 20”: Hat 21”: plug 30: Top 31: Mid-range 32: Lower end 30': Top 31': Chassis 40': Sheath body 41': Flange 31”: Chassis 50: Keep the fixture 51: Press-in jig 100: Bottle opening 120: Bypass protrusion 100': Bottle neck opening 120: Bypass protrusion 200: Gap section 200': Gap section 300: Top Plate 301: Thread 302: Opening 303: Top plug positioning point 304: Protrusion 310:Protruding ring 320: convex strip 321: First protrusion 300': Top plate 301': Thread 302': Opening 303': Top plug positioning point 304': Protrusion 305': Demolding hole 306': Chimeric part 310': Internal bump 311': Openings on both sides of the protrusion 321': First protrusion 400': Second protrusion 300”: Top plate 301”: Thread 500: Protrusion 510: Pressure Column

Claims

1. A method for freeze-drying a product for pharmaceutical, cosmetic, or medical aesthetic applications, comprising: Add a stopper to a double-chamber cartridge bottle, then fill it with the product to be freeze-dried; pre-assemble the top stopper into the top cap to assemble the top stopper and the top cap, then place the top cap with the top stopper assembled above the bottle opening of the double-chamber cartridge bottle, and place and fix the double-chamber cartridge bottle on a custom-made freeze-drying rack; freeze, perform primary drying and secondary drying on the product to be freeze-dried respectively; and press down on the top cap, using the top cap to press the top stopper into the double-chamber cartridge bottle to seal the double-chamber cartridge bottle and fix the top stopper, so that the top stopper seals the bottle opening of the double-chamber cartridge bottle.

2. The freeze-drying method as described in claim 1, wherein, The freeze-drying rack is either an independent freeze-drying rack or a tray-type freeze-drying rack; and the dual-chamber cartridge bottle is placed upright or upside down in the freeze-drying rack.

3. The freeze-drying method as described in claim 2, wherein, The freeze-drying rack is a tray-type freeze-drying rack; and the dual-chamber cartridge bottle is placed upright in the freeze-drying rack.

4. The freeze-drying method as described in claim 1, wherein, The temperature range set for freezing the product in the dual-chamber cartridge is -60℃ to -40℃; the temperature range for primary drying is -60℃ to 0℃, the temperature range for secondary drying is 15℃ to 40℃; and the pressure range for primary and secondary drying is 0.02 mbar to 0.2 mbar.

5. The freeze-drying method as described in claim 4, wherein, The pressures for primary and secondary drying were 0.06 mbar, respectively.

6. The freeze-drying method as described in claim 1, wherein pressing down the top cap and using the top cap to press the top stopper into the dual-chamber cartridge bottle further comprises: Nitrogen gas is purged into the dual-chamber cartridge before pressing the top stopper to maintain a low moisture content in the freeze-dried product.

7. A lyophilized formulation prepared according to any one of claims 1 to 6.

8. An injectable preparation comprising: A dual-chamber cartridge vial packaging material for injection, a lyophilized formulation, and a reconstituter; wherein the dual-chamber cartridge vial packaging material includes: a dual-chamber cartridge vial and a cap element, wherein the dual-chamber cartridge vial is used to hold the lyophilized formulation and the reconstituter; the cap element includes a stopper and a cap; the stopper seals the mouth of the dual-chamber cartridge vial; the cap is used to press and fix the stopper, such that the stopper seals the mouth of the dual-chamber cartridge vial; and to seal the dual-chamber cartridge vial; wherein the process of pressing and fixing the stopper with the cap, such that the stopper seals the mouth of the dual-chamber cartridge vial, includes the following steps: pre-assembling the stopper into the cap; placing the cap with the stopper pre-assembly above the mouth of the dual-chamber cartridge vial, and pressing the cap downward.

9. The injectable preparation as claimed in claim 8, wherein, The dual-cavity cartridge includes: an inner cavity, a bottle body, a neck, and a bottle mouth, wherein the center of the bottle mouth is provided with a bottle mouth opening connected to the inner cavity, and the inner diameter of the bottle mouth opening is smaller than the inner diameter of the bottle mouth and the neck; one side of the outer wall of the bottle body has a bypass protrusion.

10. The injectable preparation as claimed in claim 8, wherein, The lyophilized formulation is the lyophilized formulation as described in claim 7.

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