Freeze-drying method of long culture growth hormone as well as freeze-drying preparation and injection prepared by freeze-drying method

Abstract

The invention discloses a freeze-drying method of long culture growth hormone, which comprises the following steps: adding a middle plug into a double-cavity clamping bottle, filling the double-cavity clamping bottle with the long culture growth hormone to be freeze-dried, and placing and fixing the double-cavity clamping bottle on a customized freeze-drying bracket; 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 long culture growth hormone 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, and the top plug and the top cover are utilized to complete plug pressing and cover sealing of the double-cavity clamping type bottle, so that the obtained growth hormone freeze-drying preparation for the growth culture 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 for lompexin growth hormone and a freeze-dried preparation and injection prepared therefrom. Background Art

[0002] At present, most of the freeze-dried products on the market use vials as drug containers. Before injection, a sterile syringe must be used to extract the resolvent from another container containing the resolvent, and then the resolvent is injected 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, of 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] Lompex growth hormone, also known as Lompex somatotropin, is a prodrug that is administered once a week and releases unmodified growth hormone. It only needs to be injected once a week. After injection, the connecting structure automatically cleaves at a specific rate and releases unmodified growth hormone in a controllable manner. It is used to treat Chinese children with growth hormone deficiency (GHD). Using double-chamber cartridges to store Lompex growth hormone and reconstitution solvents separately, medical staff can easily reconstitute and administer freeze-dried Lompex growth hormone, and patients can also administer the drug quickly with the help of caregivers. In this way, the administration operation process is simplified, and it also helps to maintain the shelf life stability of the active ingredients in Lompex growth hormone.

[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, self-corrugation and sealing of the lyophilized lompezil growth hormone. 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 cartridge during the freeze-drying process, so that the lyophilized lompezil growth hormone preparation has a good morphology and a lower water content, thereby increasing the effective storage time and maintaining the quality of the drug.

[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 Longpei growth hormone, fill the current gap in the application of double-chamber cartridge bottles in China, and enhance the core competitiveness of the product. 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 Longpei growth hormone, which may include:

[0008] A middle stopper is added to a double-chamber cartridge bottle, and then the lyophilized LOMP somatotropin is poured into the cartridge bottle, and the double-chamber cartridge bottle is placed and fixed on a customized lyophilization rack; a top stopper is placed in a stopper assembly to fix the top stopper at the bottle mouth of the double-chamber cartridge bottle; the lyophilized LOMP somatotropin is frozen, dried once, and dried twice respectively; the top stopper is fixed with a top cover, and the bottle mouth of the double-chamber cartridge bottle is sealed through the top stopper; wherein, placing the top stopper in the stopper assembly to fix the top stopper at the bottle mouth of the double-chamber cartridge bottle comprises 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 lyophilized preparation of Lompezil growth hormone 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 lyophilized preparation of Lompezil growth hormone obtained by the lyophilization method has a good appearance of a lyophilized powder and a low water content, which helps to meet the high-demand freeze-dried product standards, and the preparation product maintains long-term stable quality attributes.

[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 items in the double-chamber cartridge bottle is -60°C to -40°C, which protects the active ingredients of the growth hormone and is also conducive to the formation of crystals with good water sublimation channels, providing a basis for the sublimation of water in the sample; 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, which maintains the sublimation of the growth hormone at an appropriate sublimation rate without affecting its own quality, and quickly removes water from the growth hormone; 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 growth hormone 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 lompexin. By filling the double-chamber cartridge with nitrogen, oxidation of the sample can be prevented and the quality of the finished lompexin freeze-dried preparation can be maintained.

[0013] The present application also provides a lyophilized preparation of Lompezi growth hormone, which is prepared according to any of the above lyophilization methods. The lyophilized preparation of Lompezi growth hormone has the characteristics of high lyophilization quality and low moisture content, and improves the therapeutic effect on patients with growth hormone deficiency.

[0014] The present application further provides an injection, which may include: a double-chamber cartridge bottle packaging material for injection, a lyophilized preparation of lompezi somatotropin, and a resolubilizing agent. In one embodiment of the present application, the double-chamber cartridge bottle packaging material for injection may include: a double-chamber cartridge bottle and a bottle cap assembly, wherein the double-chamber cartridge bottle is used to hold the lyophilized preparation of lompezi somatotropin and the resolubilizing agent; the bottle cap assembly includes a top plug and a top cover; the top plug seals the bottle mouth of the double-chamber cartridge bottle; the top plug is pressed by the plug pressing assembly to engage with the double-chamber cartridge bottle to achieve sealing of the double-chamber cartridge bottle; the top cover is used to fix the top plug and seal the bottle mouth of the double-chamber cartridge bottle; wherein the plug pressing assembly includes a pressing jig and a retaining jig.

[0015] 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:

[0016] 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.

[0017] 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.

[0018] In one embodiment of the present application, the lyophilized preparation of Lompezil growth hormone is a lyophilized preparation of Lompezil growth hormone prepared by any of the above-mentioned lyophilization methods or a lyophilized preparation of Lompezil growth hormone provided in the present application.

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

[0020] 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.

[0021] 2. The present application provides the optimal freeze-drying parameters and moisture reduction operation of the freeze-drying process, so that the lyophilized product of Longpei growth hormone obtained by the freeze-drying method of the present application can maintain better quality.

[0022] 3. The present application provides a high-quality lyophilized preparation of Lompezil growth hormone prepared by a lyophilization method.

[0023] 4. The present application provides an injection, which can contain a lyophilized preparation of lompezi growth hormone and a reconstitution solvent based on a double-chamber cartridge bottle packaging material for injection, so as to stably preserve the lyophilized preparation of lompezi growth hormone therein before using the injection. When using the injection, the lyophilized preparation of lompezi growth hormone and the reconstitution solvent are quickly mixed and reconstituted to ensure the accuracy and convenience of the use of the preparation. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] 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.

[0025] Figure 1 The figure shows a schematic diagram of the freeze-dried scaffold of the present application.

[0026] Figure 2 The figure shows a schematic structural diagram of a double-chamber cartridge bottle 1 of the present application.

[0027] Figure 3 The figure shows a schematic structural diagram of the plug assembly of the present application.

[0028] Figure 4 The figure shows a schematic structural diagram of the top cover 4 of the present application.

[0029] Description of Reference Numerals

[0030] 1-Double chamber cartridge bottle 3-Top stopper 4-Top cover 10-Bottle mouth

[0031] 11- Bottle neck 12- Bottle body 13- Inner cavity 20- Holding fixture

[0032] 21-press-in fixture 30-plug cap 31-plug 41-chassis

[0033] 100-bottle opening 120-bypass 200-protrusion 210-pressure column

[0034] 400-top plate 401-annular thread DETAILED DESCRIPTION

[0035] The lonapegsomatropin mentioned in this application is a growth hormone used to treat growth hormone deficiency in children, and can also be called lonapegsomatropin; it should be noted that in this application, lonapegsomatropin and lonapegsomatropin can both refer to products freeze-dried using the freeze-drying method of this application. After once a week of administration, lonapegsomatropin can slowly release unmodified human growth hormone in a controllable manner in the body, and the growth hormone released is consistent with the structure of endogenous growth hormone secreted by the human body, ensuring the safety and effectiveness of lonapegsomatropin.

[0036] The present application discloses a freeze-drying method of lompezi somatotropin, comprising: adding a middle stopper to a double-chamber cartridge bottle 1, then pouring the lompezi somatotropin 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 lompezi somatotropin 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 lyophilized lompezi somatotropin can be any middle plug for a double-chamber cartridge and lyophilizable lompezi somatotropin 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, 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 may not be 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 growth hormone ...

[0039] In the present application, the temperature range set for freezing the lompezi somatotropin in the double-chamber cartridge 1 can be a temperature range suitable for freeze-drying lompezi somatotropin, and when the freezing temperature is between -60°C and -40°C, the freeze-dried raw material generally has a high 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 lompezi somatotropin in the double-chamber cartridge 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 primary 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℃, -35℃,-34℃,-33℃,-32℃,-31℃,-30℃,-29℃,-28℃,-27℃,-26℃,-25℃,-24℃,-23℃,-22℃,-21℃,-20℃,-19℃,-18℃,-17℃,-16℃,-15℃,-14℃,-13℃,-12℃,-11℃,-10℃,-9℃,-8℃,-7℃,-6℃, 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℃.

[0040] Similarly, the primary drying and secondary drying temperatures of the Longpei growth hormone can be any temperature value between -60°C and 0°C and 15°C to 40°C, respectively, to increase the sublimation rate of the drug water. In addition, the pressure range of the primary drying and secondary drying can be any value between 0.02mbar and 0.2mbar. When the primary drying and secondary drying pressure 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.

[0041] In the present application, the top plug 3 is fixed with 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 includes: before sealing the bottle mouth 10, the double-chamber cartridge bottle 1 is filled with nitrogen to maintain the low moisture content of the growth hormone. It can be understood by those skilled in the art that the double-chamber cartridge bottle 1 is filled with nitrogen before sealing the bottle mouth 10, and its purpose 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 growth hormone, 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 bottle 1 fixed.

[0042] In the present application, a lyophilized preparation of lompezotropin is also included, which is prepared according to the above-mentioned lyophilization method. In particular, when different components of the lompezotropin to be lyophilized are poured into the double-chamber cartridge bottle 1, the types of lyophilized preparations of lompezotropin finally obtained can also be different; in addition, when the lyophilization parameters implemented in the lyophilization method of the present application during the lyophilization of lompezotropin, such as the temperature and pressure of the primary drying, are changed, after the same lompezotropin to be lyophilized is poured, lyophilized preparations of lompezotropin of different quality or different properties can also be produced through the lyophilization method, such as preparations with different water contents and different solid forms.

[0043] In the present application, an injection is also included, which includes: a double-chamber cartridge bottle packaging material for injection, a lyophilized preparation of lompezolin and a resolubilizing agent. It should be noted that the lyophilized preparation of lompezolin and the resolubilizing agent can be any lyophilized preparation of lompezolin and the resolubilizing agent suitable for the double-chamber cartridge bottle packaging material for injection and the lyophilization process. Specifically, the resolubilizing agent can be a resolubilizing agent for reconstituting any of the lyophilized preparations of lompezolin prepared above, such as sterile water for injection, etc., which can be used to reconstitute the lyophilized preparation of lompezolin disclosed in the present application when it is administered.

[0044] 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.

[0045] 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:

[0046] 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.

[0047] 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.

[0048] In the present application, the lyophilized preparation of lompezotropin is any lyophilized preparation of lompezotropin prepared according to the lyophilization method of the present application or the lyophilized preparation of lompezotropin disclosed in the present application.

[0049] Example

[0050] 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.

[0051] 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.

[0052] Therefore, in this embodiment, a plugging assembly is used to seal the bottle mouth 10 using the top plug 3. Specifically,

[0053] (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.

[0054] 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.

[0055] 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.

[0056] 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.

[0057] 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.

[0058] (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 4As 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.

[0059] 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 Longpei growth hormone, comprising: Add a middle stopper to the double-chamber cartridge (1), then fill it with the lyophilized lompexin, and place and fix the double-chamber cartridge (1) on a customized lyophilization 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 freezing, primary drying and secondary drying the lyophilized lompeixotropin; 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 lomotropin in the double-chamber cartridge (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 water content of the Lompeix growth hormone.

5. A lyophilized preparation of Lompezil growth hormone, prepared by the lyophilization method according to any one of claims 1 to 4.

6. An injection, comprising: Double-chamber cartridge packaging materials for injection, lyophilized preparations of Lompezil growth hormone and reconstituted 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 bottle (1) is used to contain the lyophilized preparation of lompexin and the reconstituted 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 of lompezotropin is a lyophilized preparation of lompezotropin prepared by the lyophilization method according to any one of claims 1 to 4 or a lyophilized preparation of lompezotropin according to claim 5.

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