Freeze-drying method, freeze-drying preparation and injection of pharmaceutical, cosmetic or medical beauty product

Abstract

The invention discloses a pharmaceutical, cosmetic or medical beauty product freeze-drying method which comprises the steps that a middle plug is added into a double-cavity clamping type bottle, a product to be freeze-dried is poured into the double-cavity clamping type bottle, and the double-cavity clamping type bottle is placed and fixed to a customized freeze-drying support; the top plug is placed in the plug pressing assembly so as to be fixed to the bottle opening of the double-cavity clamping type bottle; performing freezing, primary drying and secondary drying on the to-be-freeze-dried product respectively; the top plug is fixed by the top cover and the bottle opening is sealed; the plug pressing assembly comprises a pressing-in jig and a maintaining jig, the maintaining jig is attached to the outer wall of the bottle opening, and the top plug is placed in the maintaining jig so that the top plug can be fixed to the bottle opening; the press-in jig presses the top plug to be embedded into the bottle opening, and the plug pressing assembly is removed to complete plug pressing. According to the method disclosed by the invention, high-quality freeze-drying parameters and freeze-drying operation can be provided, so that the top plug and the top cover are utilized to complete plug pressing and cover sealing of the double-cavity cartridge bottle, and the obtained freeze-dried product keeps better appearance and lower moisture.

Description

Technical Field

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

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

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

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

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

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

[0007] One aspect of the present application provides a freeze-drying method for a product for pharmaceutical, cosmetic or medical aesthetic applications, which may include:

[0008] Add a middle stopper to the double-chamber cartridge bottle, then fill it with the product to be freeze-dried, place and fix the double-chamber cartridge bottle on a customized freeze-drying stand; place the top stopper in the stopper assembly to fix the top stopper at the mouth of the double-chamber cartridge bottle; freeze, dry once and dry twice the product to be freeze-dried respectively; fix the top stopper with a top cover, and seal the mouth of the double-chamber cartridge bottle through the top stopper. Placing the top stopper in the stopper assembly to fix the top stopper at the mouth of the double-chamber cartridge bottle includes the following steps:

[0009] The retaining fixture of the plugging assembly is fitted with the outer wall of the bottle mouth of the double-chamber cartridge bottle, and the top plug is placed in the retaining fixture to fix the top plug relative to the bottle mouth of the double-chamber cartridge bottle; the top plug is pressed by the pressing fixture of the plugging assembly to fit into the bottle mouth of the double-chamber cartridge bottle; the pressing fixture and the retaining fixture are removed. The freeze-drying method disclosed in the present application performs plugging on the double-chamber cartridge bottle after freeze-drying by operating the plugging assembly, thereby sealing the finished freeze-dried preparation in the double-chamber cartridge bottle; then the double-chamber cartridge bottle is capped by operating the top cover to further seal the double-chamber cartridge bottle. The freeze-dried preparation obtained by the freeze-drying method has a good frozen powder appearance and low water content, which helps to meet high-demand freeze-dried product standards and maintain the long-term stability and quality characteristics of the preparation.

[0010] In one embodiment of the present application, 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 double-chamber cartridge bottle is placed upright or inverted in the freeze-drying rack, preferably, the double-chamber cartridge bottle is placed upright in the freeze-drying rack. When a tray-type freeze-drying rack is used to carry the double-chamber cartridge bottle, the tray-type freeze-drying rack can hold a larger number of double-chamber cartridge bottles, so that the freeze-drying method of the present application has better freeze-drying efficiency, can be adapted to a variety of freeze-dried raw materials, and select double-chamber cartridge bottles of various sizes.

[0011] In one embodiment of the present application, the temperature range set for freezing the product in the double-chamber cartridge bottle is -60°C to -40°C, which helps to protect the active ingredients of the product while quickly freezing the sample, providing a basis for sample sublimation; the temperature range of the primary drying is -60°C to 0°C, and the temperature range of the secondary drying is 15°C to 40°C, maintaining the product at a suitable sublimation rate without affecting its own quality, and quickly removing moisture from the sample; and the pressure range of the primary drying and the secondary drying is 0.02mbar-0.2mbar, preferably, the pressure of the primary drying and the secondary drying is 0.06mbar, respectively, to improve the sublimation and water removal efficiency of the sample in the primary drying and the secondary drying.

[0012] In one embodiment of the present application, fixing the top plug with the top cover and sealing the mouth of the double-chamber cartridge via the top plug further comprises: filling the double-chamber cartridge with nitrogen before sealing the mouth of the cartridge to maintain a low moisture content of the freeze-dried product. By filling the double-chamber cartridge with nitrogen, oxidation of the sample can be prevented, the quality of the finished freeze-dried preparation can be maintained, and the freeze-drying method can be used to produce a variety of medical, medical beauty or beauty preparations.

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

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

[0015] In one embodiment of the present application, a double-chamber cartridge vial packaging material for injection may include: a double-chamber cartridge vial and a bottle cap assembly, wherein the double-chamber cartridge vial is used to contain a lyophilized preparation and a reconstitution solvent; the bottle cap assembly includes a top plug and a top cover; the top plug seals the bottle mouth of the double-chamber cartridge vial; the top plug is pressed by the plug pressing assembly to engage with the double-chamber cartridge vial to achieve sealing of the double-chamber cartridge vial; the top cover is used to fix the top plug and seal the bottle mouth of the double-chamber cartridge vial; wherein the plug pressing assembly includes a pressing jig and a retaining jig.

[0016] In one embodiment of the present application, the process of pressing the top plug through the plug pressing assembly to engage with the double-chamber cartridge bottle to seal the double-chamber cartridge bottle includes the following steps:

[0017] The top plug is placed in the holding jig by fitting the outer wall of the mouth of the double-chamber cartridge bottle with the holding jig, so as to realize the positioning of the top plug relative to the mouth of the double-chamber cartridge bottle; the top plug is pressed by the pressing jig to fit into the mouth of the double-chamber cartridge bottle; the pressing jig and the holding jig are removed. Placing the top plug in the holding jig to realize the positioning of the top plug relative to the mouth of the double-chamber cartridge bottle means that the top plug is supported and positioned by the raised portion of the holding jig and does not slide toward the mouth of the bottle under the influence of gravity, and then the plug column blocks the mouth of the bottle. Therefore, the setting of the raised portion on the inner side of the holding jig helps to provide gas exchange and water sublimation discharge for the double-chamber cartridge bottle.

[0018] In one embodiment of the present application, a double-chamber cartridge bottle may include: an inner cavity, a bottle body, a bottleneck and a bottle mouth, a bottle mouth opening connected to the inner cavity is arranged at the center of the bottle mouth, and the inner diameter of the bottle mouth opening is smaller than the inner diameter of the bottle mouth and the bottleneck; and a bypass is provided on one side of the outer wall of the bottle body. The upper opening of the freeze-drying rack is larger than the bottom opening, and the large upper opening facilitates the insertion of the bypass into the rack, and the small lower opening can properly fix the double-chamber cartridge bottle, so that it is not easy to fall off from the fixed module, so as to avoid the double-chamber cartridge bottle from tilting or falling during the freeze-drying process.

[0019] In one embodiment of the present application, the lyophilized preparation is a lyophilized preparation prepared by any of the above-mentioned lyophilization methods or a lyophilized preparation provided by the present application.

[0020] Compared with the prior art, the present invention has at least one of the following technical effects:

[0021] 1. The present application provides a self-pressing plug and cap sealing method for a double-chamber cartridge bottle packaging material for injection during the product freeze-drying process.

[0022] 2. The present application provides optimal freeze-drying parameters and moisture reduction operations for the freeze-drying process so that the freeze-dried product obtained using the freeze-drying method of the present application maintains better quality.

[0023] 3. The present application provides a high-quality freeze-dried preparation prepared based on a freeze-drying method, which can be a high-purity freeze-dried drug, a medical device reagent, or a cosmetic reagent.

[0024] 4. The present application provides an injection, which can contain a lyophilized preparation and a resolvent based on a double-chamber cartridge bottle packaging material for injection, so as to stably preserve the lyophilized preparation therein before the use of the injection. When the injection is used, the lyophilized preparation and the resolvent are quickly mixed and reconstituted to ensure the accuracy and convenience of the preparation use. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] By describing the embodiments of the present application in more detail in conjunction with the accompanying drawings, the above and other purposes, features and advantages of the present application will become more apparent. The accompanying drawings are used to provide a further understanding of the embodiments of the present application and constitute a part of the specification. Together with the embodiments of the present application, they are used to explain the present application and do not constitute a limitation of the present application. In the accompanying drawings, the same reference numerals generally represent the same components or steps.

[0026] Figure 1 The figure shows a schematic diagram of the freeze-dried scaffold of the present application.

[0027] Figure 2 The figure shows a schematic structural diagram of a double-chamber cartridge bottle 1 of the present application.

[0028] Figure 3 The figure shows a schematic structural diagram of the plug assembly of the present application.

[0029] Figure 4 The figure shows a schematic structural diagram of the top cover 4 of the present application.

[0030] Description of Reference Numerals

[0031] 1-Double chamber cartridge bottle 3-Top stopper 4-Top cover 10-Bottle mouth

[0032] 11- Bottle neck 12- Bottle body 13- Inner cavity 20- Holding fixture

[0033] 21-press-in fixture 30-plug cap 31-plug 41-chassis

[0034] 100-bottle opening 120-bypass 200-protrusion 210-pressure column

[0035] 400-top plate 401-annular thread DETAILED DESCRIPTION

[0036] The present application discloses a freeze-drying method for products used in pharmaceutical, cosmetic or medical beauty applications, comprising: adding a middle stopper to a double-chamber cartridge bottle 1, then filling the product to be freeze-dried, placing and fixing the double-chamber cartridge bottle 1 on a customized freeze-drying stand; placing a top stopper 3 in a plugging assembly to fix the top stopper 3 at the bottle mouth 10 of the double-chamber cartridge bottle 1; freezing, primary drying and secondary drying the product to be freeze-dried respectively; fixing the top stopper 3 with a top cover 4, and sealing the bottle mouth 10 of the double-chamber cartridge bottle 1 through the top stopper 3. Among them, placing the top stopper 3 in the plugging assembly to fix the top stopper 3 at the bottle mouth 10 of the double-chamber cartridge bottle 1 includes the following steps:

[0037] The retaining fixture 20 of the plug pressing assembly is fitted with the outer wall of the bottle mouth 10 of the double-chamber cartridge 1, and the top plug 3 is placed in the retaining fixture 20 to achieve the fixation of the top plug 3 relative to the bottle mouth 10 of the double-chamber cartridge 1; the top plug 3 is pressed by the pressing fixture 21 of the plug pressing assembly to fit into the bottle mouth 10 of the double-chamber cartridge 1; the pressing fixture 21 and the retaining fixture 20 are removed. In the present application, the middle plug added to the double-chamber cartridge 1 and the product to be freeze-dried can be any middle plug for the double-chamber cartridge and a product that can be freeze-dried that is suitable for the size and structure of the double-chamber cartridge 1. Freezing, primary drying and secondary drying operations can be performed in a freeze dryer, which can accommodate the freeze drying rack used in the freeze drying method of the present application; in the process of fixing the top plug 3 with the top cover 4 and sealing the bottle mouth 10 of the double-chamber cartridge bottle 1 through the top plug 3, the method of driving the pressing fixture 21 of the plug pressing assembly and the top cover 4 to press down can be any driving method that can be implemented in the freeze dryer, such as mechanical compression, pneumatic drive, pneumatic clamp drive or spring pressing.

[0038] In the present application, after adding the middle stopper to the double-chamber cartridge 1, the product to be freeze-dried can be filled in. In particular, the product to be freeze-dried can be a product added to the inner cavity 13 of the double-chamber cartridge 1 for freeze-drying and short-term / long-term storage, such as small molecule drugs, peptides, enzymes, antibodies, fusion proteins, antibody-drug conjugates, etc. The user can select any of the above liquids to be freeze-dried and fill it into one of the inner cavities 13 of the double-chamber cartridge 1 to perform freeze-drying using the freeze-drying method of the present application.

[0039] In the present application, the freeze-dried scaffold is a stand-alone freeze-dried scaffold or a tray-type freeze-dried scaffold, such as Figure 1 As shown. The type of freeze-drying support used in the freeze-drying method of the present application is an independent freeze-drying support or a tray-type freeze-drying support, and the specific model, size and working parameters of the freeze-drying support are not limited; preferably, the freeze-drying support is a tray-type freeze-drying support, and the tray-type freeze-drying support is easy to place more double-chamber cartridge bottles 1 at one time during the freeze-drying process; and the double-chamber cartridge bottle 1 is placed upright or inverted in the freeze-drying support. Preferably, the double-chamber cartridge bottle 1 is placed upright in the freeze-drying support, so as to facilitate the uniform distribution of heat in the double-chamber cartridge bottle 1 and improve the solvent sublimation efficiency. In addition, it can also reduce the sedimentation and aggregation of the product and keep the appearance of the product uniform and stable.

[0040] In the present application, the temperature range set for freezing the product in the double-chamber cartridge bottle 1 can be a temperature range suitable for freeze-drying the product, and when the freezing temperature is between -60°C and -40°C, the freeze-dried raw material generally has a higher freezing efficiency and maintains its own quality. Therefore, the freezing temperature is a temperature value between -60°C and -40°C. Specifically, the temperature range set for freezing the product in the double-chamber cartridge bottle 1 is -60°C to -40°C, that is, -60°C, -59°C, -58°C, -57°C, -56°C, -55°C, -54°C, -53°C, -52°C, -51°C, -50°C, -49°C, -48°C, -47°C, -46°C, -45°C, -44°C, -43°C, -42°C, -41°C or -40°C; The temperature range of the secondary drying is -60℃~0℃, i.e. -60℃, -59℃, -58℃, -57℃, -56℃, -55℃, -54℃, -53℃, -52℃, -51℃, -50℃, -49℃, -48℃, -47℃, -46℃, -45℃, -44℃, -43℃, -42℃, -41℃, -40℃, -39℃, -38℃, -37℃, -36℃, -3 5℃,-34℃,-33℃,-32℃,-31℃,-30℃,-29℃,-28℃,-27℃,-26℃,-25℃,-24℃,-23℃,-22℃,-21℃,-20℃,-19℃,-18℃,-17℃,-16℃,-15℃,-14℃,-13℃,-12℃,-11℃,-10℃,-9℃,-8℃,-7℃,-6℃,- The temperature range of secondary drying is 15℃~40℃, that is, 15℃, 16℃, 17℃, 18℃, 19℃, 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, 26℃, 27℃, 28℃, 29℃, 30℃, 31℃, 32℃, 33℃, 34℃, 35℃, 36℃, 37℃, 38℃, 39℃ or 40℃.

[0043] Similarly, the temperature of the primary drying and secondary drying of the product can be any temperature value between -60℃ and 0℃ and 15℃ and 40℃, respectively, to increase the sublimation rate of the water content of the drug. In addition, the pressure range of the primary drying and secondary drying can be any value between 0.02mbar and 0.2mbar. When the pressure of the primary drying and secondary drying is preferably 0.06mbar, the drying efficiency can be guaranteed to reach the peak value. Specifically, the pressure range of the primary drying and the secondary drying is 0.02 mbar-0.2 mbar, that is, 0.02 mbar, 0.03 mbar, 0.04 mbar, 0.05 mbar, 0.06 mbar, 0.07 mbar, 0.08 mbar, 0.09 mbar, 0.10 mbar, 0.11 mbar, 0.12 mbar, 0.13 mbar, 0.14 mbar, 0.15 mbar, 0.16 mbar, 0.17 mbar, 0.18 mbar, 0.19 mbar or 0.20 mbar. Preferably, the pressure of the primary drying and the secondary drying is 0.06 mbar, respectively.

[0044] In the present application, fixing the top plug 3 with the top cover 4 and sealing the mouth 10 of the double-chamber cartridge 1 through the top plug 3 also includes: filling the double-chamber cartridge 1 with nitrogen before sealing the mouth 10 to maintain the low moisture content of the freeze-dried product. It can be understood by those skilled in the art that the purpose of filling the double-chamber cartridge 1 with nitrogen before sealing the mouth 10 is to make the nitrogen in the inner cavity 13 reach 1 standard atmospheric pressure. On the one hand, the nitrogen can be used to maintain the low moisture content of the freeze-dried product, and on the other hand, the nitrogen at 1 standard atmospheric pressure can also keep the position of the middle plug in the double-chamber cartridge 1 fixed.

[0045] The present application also includes a freeze-dried preparation, which is prepared according to the above freeze-drying method. In particular, since the product to be freeze-dried added to one inner cavity 13 of the double-chamber cartridge bottle 1 in the present application can be one of a plurality of products, when different products to be freeze-dried are filled into the double-chamber cartridge bottle 1, the freeze-dried preparations finally obtained can also be different; in addition, when the freeze-drying parameters implemented in the freeze-drying method of the present application during the freeze-drying of the product, such as the temperature and pressure of the primary drying, are changed, after the same product to be freeze-dried is filled, freeze-dried preparations of different qualities or different properties can be produced through the freeze-drying method, such as preparations with different water contents and different solid forms.

[0046] In the present application, an injection is also included, which includes: a double-chamber cartridge bottle packaging material for injection, a lyophilized preparation and a resolubilizing agent. It should be noted that the lyophilized preparation and the resolubilizing agent can be any lyophilized preparation and resolubilizing agent suitable for the double-chamber cartridge bottle packaging material for injection and the lyophilization process. Specifically, the lyophilized preparation can be any product to be lyophilized that can be filled into the double-chamber cartridge bottle 1 of the present application, and any lyophilized preparation prepared by lyophilization treatment by the lyophilization method of the present application, including the lyophilized preparation disclosed in the present application. In addition, the resolubilizing agent can be a resolubilizing agent for re-dissolving any of the lyophilized preparations prepared above, such as sterile water for injection (which may contain antibacterial agents, such as phenol, m-cresol, benzyl alcohol, etc.), physiological saline, 5% glucose solution, and other buffers, such as phosphate buffer, citric acid buffer, acetic acid buffer, histidine buffer, succinic acid buffer, tris(hydroxymethyl)aminomethane hydrochloride buffer, etc., which can be used to re-dissolve the lyophilized preparation disclosed in the present application when it is administered.

[0047] In the present application, the packaging material of the double-chamber cartridge bottle for injection includes: a double-chamber cartridge bottle 1 and a bottle cap assembly, wherein the bottle cap assembly includes a top plug 3 and a top cover 4; in particular, the double-chamber cartridge bottle 1 can be placed in a freeze-drying rack used in an existing freeze-drying process, and when the double-chamber cartridge bottle 1 and the bottle cap assembly are fixed and inverted in the freeze-drying rack, the bottle cap assembly can also be adapted to be placed in a freeze-drying rack used in an existing freeze-drying process; the bottle cap assembly can be made of any material adapted to achieve the bottle cap sealing function. The top plug 3 is pressed by the plug pressing assembly to engage with the double-chamber cartridge bottle 1 to achieve sealing of the double-chamber cartridge bottle 1; when the plug pressing assembly presses the top plug 3, the plug pressing assembly can be driven by mechanical compression, air pressure drive, pneumatic clamp drive, or spring pressure.

[0048] In the present application, the top plug 3 is used to seal the bottle mouth 10 of the double-chamber cartridge bottle 1, and the top plug 3 may include a plug cap 30 and a plug column 31. The top cover 4 is used to fix the top plug 3 and seal the bottle mouth 10 of the double-chamber cartridge bottle 1; the top cover 4 may include a main body and a bottom plate 41, and the main body may include a top plate 400 and an annular thread 401. The plug pressing assembly includes a pressing jig 21 and a retaining jig 20, the pressing jig 21 may include a pressing column 210, and the retaining jig 20 may include a protrusion 200. The process of pressing the top plug 3 through the plug pressing assembly to engage with the double-chamber cartridge bottle 1 to achieve sealing of the double-chamber cartridge bottle 1 includes the following steps:

[0049] By fitting the holding jig 20 with the outer wall of the mouth 10 of the double-chamber cartridge bottle 1, the top plug 3 is placed in the holding jig 20 to achieve the positioning of the top plug 3 relative to the mouth 10 of the double-chamber cartridge bottle 1; the top plug 3 is pressed by the pressing jig 21 to fit into the mouth 10 of the double-chamber cartridge bottle 1; and the pressing jig 21 and the holding jig 20 are removed. It should be noted that when the size of part or all of the structure of the double-chamber cartridge bottle 1 changes, the size of the top plug 3, the pressing jig 21 and the holding jig 20 can also be changed accordingly to adapt to the size of the double-chamber cartridge bottle 1 to complete the sealing of the mouth of the bottle.

[0050] In the present application, the double-chamber cartridge bottle 1 comprises: an inner cavity 13, a bottle body 12, a bottleneck 11 and a bottle mouth 10, wherein a bottle mouth opening 100 connected to the inner cavity 13 is arranged at the center of the bottle mouth 10, and the inner diameter of the bottle mouth opening 100 is smaller than the inner diameters of the bottle mouth 10 and the bottleneck 11; and a bypass 120 is arranged on one side of the outer wall of the bottle body 12. It should be noted that the length dimensions of the inner cavity 13, the bottle body 12, the bottleneck 11 and the bottle mouth 10 of the double-chamber cartridge bottle 1 can be adjusted within the size range suitable for placement in the freeze-drying rack without changing its original function, so as to adapt to different bottle cap assemblies for plugging and capping operations, such as increasing the vertical length of one or more parts of the double-chamber cartridge bottle 1, increasing the radial length of one or more parts of the double-chamber cartridge bottle 1, etc. Those skilled in the art can understand that these modifications do not deviate from the protection scope of the present application.

[0051] In the present application, the lyophilized preparation is any lyophilized preparation prepared according to the lyophilization method of the present application or the lyophilized preparation disclosed in the present application.

[0052] Example

[0053] The present invention provides a general and / or specific description of the materials and test methods used in the test. The reagents or instruments used without indicating the manufacturer are all conventional reagent products that can be obtained through commercial purchase.

[0054] A double-chamber cartridge bottle packaging material for injection, comprising a double-chamber cartridge bottle 1 and a bottle cap assembly, wherein the bottle cap assembly comprises a top plug 3 and a top cover 4, and is used to seal the double-chamber cartridge bottle 1. The structure of the double-chamber cartridge bottle 1 is as follows: Figure 2 As shown, the top plug 3 is used to seal the bottle mouth 10 of the double-chamber cartridge bottle 1. The double-chamber cartridge bottle 1 uses a plugging assembly to seal the bottle mouth 10 with the top plug 3, wherein the plugging assembly includes a pressing fixture 21 and a holding fixture 20, and its structure is as shown in FIG. Figure 3 As shown, the double-chamber cartridge bottle 1 has a bottle mouth 10, a bottle neck 11, a bottle body 12 and an inner cavity 13 extending from the bottle mouth 10 to the bottle body 12; the top plug has a plug cap 30 and a plug rod 31, and the plug rod 31 needs to be completely embedded in the bottle mouth opening 100 at the center of the bottle mouth 10, and the lower surface of the plug cap 30 is completely fitted with the upper surface of the bottle mouth 10 to achieve sealing of the bottle mouth 10.

[0055] Therefore, in this embodiment, a plugging assembly is used to seal the bottle mouth 10 using the top plug 3. Specifically,

[0056] (1) First, the plugging assembly includes a holding fixture 20, the upper and lower ends of which are both open. The inner wall of the holding fixture 20 is attached to the outer surface of the bottle mouth 10 and the bottle body 12, and the holding fixture 20 is pressed until it is completely attached to the upper end of the bottle body 12. The holding fixture 20 is tightly attached to the bottle mouth 10 and the bottle body 12, and has a large friction force. Therefore, the holding fixture 20 is not easy to fall off from the double-chamber cartridge bottle 1; in addition, the upper end of the holding fixture 20 protrudes from the bottle mouth 10.

[0057] Next, the top plug 3 is placed in the holding fixture 20. Specifically, the top plug is placed on the convex portion 200 protruding from the upper end of the holding fixture 20. The convex portion 200 can support the plug cap 30 to fix the position of the top plug 3, so that the plug 31 is aligned with the bottle mouth opening 100, so as to facilitate the plug 31 to be inserted into the bottle mouth opening 100 when moving downward. In particular, there are two convex portions 200, which are respectively arranged on both sides of the upper end of the holding fixture 20.

[0058] Then, the inner wall of the pressing jig 21 of the plug assembly is fitted against the outer wall of the retaining jig 20 and slid downward. The lower end of the pressing jig 21 is open, the upper surface is closed and the center is recessed downward, and a pressing column 210 protruding along the axial direction of the pressing jig 21 is provided on one side of the inner wall of the recess. When the pressing jig 21 slides downward, the pressing column 210 can contact and apply downward pressure to the plug cap 30 to press the top plug 3 as a whole to move toward the bottle mouth 10 until the plug column 31 is fully embedded in the bottle mouth 10; after the plug column 31 is fully embedded in the bottle mouth 10, the plug cap 30 can be clamped at the lower end of the protrusion 200, so that the protrusion 200 can further clamp the top plug 3 to prevent it from falling off.

[0059] It should be noted that before the plug 31 is completely embedded in the bottle mouth 10, the height of the holding fixture 20 protruding from the bottle mouth 10 is less than the height of the outer side of the upper surface of the pressing fixture 21 protruding from the bottle mouth 10; therefore, before the plug 31 is completely embedded in the bottle mouth 10, the pressing fixture 21 will not be hindered by the holding fixture 20 and cannot move downward, thus avoiding incomplete engagement of the top plug 3 with the bottle mouth 10. In particular, there are two pressing columns 210, which are respectively arranged on both sides of the inner wall of the concave part of the upper surface of the pressing fixture 21, so as to apply uniform downward pressure to the top plug 3.

[0060] Finally, the pressing jig 21 and the holding jig 20 are removed. The plugging assembly is only used to seal the bottle mouth 10 with the top plug 3. Therefore, it needs to be removed after the sealing is completed to facilitate the subsequent capping and sealing.

[0061] (2) The top cover 4 is used to fix the top plug 3 and seal the bottle mouth 10 of the double-chamber cartridge bottle 1 through the top plug 3. The structure of the top cover 4 is as follows: Figure 4 As shown, it includes a main body and a bottom plate 41, the main body has a top plate 400 located at the center of the upper end of the top cover 4 and an annular thread 401 located at the edge of the upper end of the top cover 4, which is arranged above the bottom plate 41, and the bottom of the bottom plate 41 is an opening; after the top plug 3 is completely embedded in the bottle mouth 10, the top cover 4 is pressed downward and sleeved on the bottle mouth 10. During this process, the inner walls of the main body and the bottom plate 41 are in contact with the bottle mouth 10 and the bottleneck 11; therefore, after the top cover 4 is pressed until the bottom plate 41 is completely in contact with the upper surface of the bottle body 12, there is a large friction between the top cover 4 and the double-chamber cartridge bottle 1, which can prevent the top cover 4 from falling off, so as to improve the sealing performance of the double-chamber cartridge bottle 1.

[0062] The top plate 400 is a double-layer structure, the upper layer of which is a hollow cylinder, and the lower layer of which 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 41 is completely fitted with the upper surface of the bottle body 12, the top plate 400 can support the top plug 3 embedded in the bottle mouth 10 through the lower cylinder to prevent the top plug 3 from escaping from the bottle mouth 10, thereby improving the airtightness of the double-chamber cartridge bottle 1.

Claims

1. A freeze-drying method for a product for pharmaceutical, cosmetic or medical aesthetic applications, comprising: Adding a middle stopper to the double-chamber cartridge (1), then filling the product to be freeze-dried, and placing and fixing the double-chamber cartridge (1) on a customized freeze-drying stand; Placing a top plug (3) in a plug pressing assembly to fix the top plug (3) at the bottle mouth (10) of the double-chamber cartridge bottle (1); Respectively performing freezing, primary drying and secondary drying on the product to be freeze-dried; The top plug (3) is fixed with a top cover (4), and the bottle mouth (10) of the double-chamber cartridge bottle (1) is sealed through the top plug (3); The process of placing the top plug (3) in the plug pressing assembly to fix the top plug (3) at the bottle mouth (10) of the double-chamber cartridge bottle (1) comprises the following steps: The top plug (3) is placed in the holding fixture (20) by fitting the holding fixture (20) of the plug pressing assembly to the outer wall of the bottle mouth (10) of the double-chamber cartridge bottle (1), so as to achieve the fixing of the top plug (3) relative to the bottle mouth (10) of the double-chamber cartridge bottle (1); The top plug (3) is pressed by a pressing jig (21) of the plug pressing assembly so as to be inserted into the bottle mouth (10) of the double-chamber cartridge bottle (1); The pressing jig (21) and the holding jig (20) are removed.

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

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

4. The freeze-drying method according to claim 1, wherein The top plug (3) is fixed by the top cover (4), and the bottle mouth (10) of the double-chamber cartridge bottle (1) is sealed through the top plug (3), and further comprises: The double-chamber cartridge bottle (1) is filled with nitrogen before the bottle mouth (10) is sealed to maintain a low moisture content of the freeze-dried product.

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

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

7. The injection according to claim 6, wherein The double-chamber cartridge bottle packaging material for injection comprises: a double-chamber cartridge bottle (1) and a bottle cap assembly, wherein: The double-chamber cartridge (1) is used to contain the lyophilized preparation and the reconstitution solution; The bottle cap assembly comprises the top plug (3) and the top cover (4); The top plug (3) seals the bottle mouth (10) of the double-chamber cartridge bottle (1); The top plug (3) is pressed by the plug pressing assembly to engage with the double-chamber cartridge bottle (1) to achieve sealing of the double-chamber cartridge bottle (1); The top cover (4) is used to fix the top plug (3) and seal the bottle mouth (10) of the double-chamber cartridge bottle (1); Wherein, the pressing plug assembly comprises the pressing jig (21) and the retaining jig (20).

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

9. The injection according to claim 7 or 8, wherein The process of pressing the top plug (3) through the plug pressing assembly to engage with the double-chamber cartridge bottle (1) to seal the double-chamber cartridge bottle (1) comprises the following steps: The top plug (3) is placed in the holding jig (20) by fitting the holding jig (20) to the outer wall of the bottle mouth (10) of the double-chamber cartridge bottle (1), so as to achieve positioning of the top plug (3) relative to the bottle mouth (10) of the double-chamber cartridge bottle (1); The top plug (3) is pressed by the pressing jig (21) to be inserted into the bottle mouth (10) of the double-chamber cartridge bottle (1); The pressing jig (21) and the holding jig (20) are removed.

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

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