Large-volume injection production process based on large-scale production and concentrated preparation equipment

Abstract

The invention discloses a large-volume injection production process based on large-scale production and concentrated preparation equipment, and relates to the technical field of medical preparation production. Step S1; weighing and burdening raw materials and auxiliary materials, preparing water for injection from drinking water, and carrying out weighing and feeding integrated treatment; s2, performing primary concentrated preparation, performing heating sterilization, and filtering a concentrated solution; s3, adding 50 DEG C water for injection into the concentrated solution to dilute the liquid medicine to a specified concentration, adjusting the pH value, and then filtering again; s4, a filling container is prepared, filling and heat sealing are conducted, and a product is sterilized; s5, after filling is completed, the whole system adopts a cleaning / drying procedure; and S6, the product is subjected to light inspection, labeling and packaging. In the whole technological process, control over the temperature, the humidity and the cleanliness is beneficial for keeping the consistency and stability of the product quality. The whole technological process design considers the requirement of large-scale production, and through automatic and continuous operation, the production efficiency and the yield are improved, and the unit cost is reduced.

Description

Technical Field

[0001] The invention relates to the technical field of medical preparation production. Background Art

[0002] Large-volume injection is a typical sterile preparation produced by terminal sterilization. It has the characteristics of large volume, easy to be contaminated by microorganisms, endotoxins and particulates. The contaminated products will cause serious adverse consequences to patients. The key control points of the large-volume injection production process include common system management, material management, preparation, filtration, bottle washing, rubber stopper washing, filling and plugging, capping, sterilization, light inspection, and packaging. There are many links involved and many risk factors. The preparation process is a link with a relatively high risk of microbial contamination and bacterial endotoxin contamination. In addition to ensuring the uniformity of product content and other physical and chemical properties, this process also needs to consider how to control the level of microbial contamination and bacterial endotoxins before sterilization. For the preparation process, microbial contamination in materials, production equipment, personnel operation and the increase of microorganisms in the product are the main risk factors. During preparation, attention should be paid to the preparation sequence, preparation temperature, stirring time, decarbonization adsorption temperature and time, and preparation time limit of each raw material and auxiliary material, and then the pH value, visible foreign matter, and content should be checked. Only after they are qualified can the next process be carried out, and on-site QA should monitor the whole process. At the same time, in the weighing process of raw materials, traditional manual electronic weighing requires special personnel to operate, and the raw material dust is easy to disperse during the weighing process, causing personnel to inhale dust, and it is also easy to introduce external pollution sources.

[0003] Therefore, it is necessary to start from the production process and equipment of large-volume injections to reduce or eliminate potential risks in the production process. Summary of the invention

[0004] The purpose of the present invention is: in order to solve the above-mentioned technical problems, the present invention provides a large-volume injection production process based on large-scale production, which controls the influence of environmental factors in the production process, reduces external interference, and adopts multiple sterilization treatments, thereby effectively controlling microbial indicators and bacterial endotoxin levels, reducing pollution, and ensuring product quality.

[0005] In order to achieve the above-mentioned purpose, the present invention specifically adopts the following technical solutions:

[0006] A large-volume injection production process based on large-scale production comprises the following steps:

[0007] Step S1: insert a disposable feeding membrane tube, weigh and prepare raw materials and auxiliary materials, and prepare water for injection with drinking water.

[0008] Weighing and feeding are integrated into one process;

[0009] Step S2: preliminary concentration, heating and sterilization, and filtration of the concentrated solution;

[0010] Step S3: Add 50°C water for injection to dilute the concentrated solution to a specified concentration, adjust the pH and filter again;

[0011] Step S4: preparing a filling container, filling and heat-sealing, and sterilizing the product;

[0012] Step S5: After filling, the whole system adopts a cleaning / drying process;

[0013] Step S6: Perform light inspection, labeling and packaging on the products.

[0014] Through the above scheme, a disposable feeding membrane tube is inserted to avoid impurities during the feeding process. When the weighing and batching are completed, water for injection is prepared simultaneously. Then the raw materials and water for injection are concentrated, mixed and sterilized at a high temperature to remove the live bacteria in the solution. Then the concentrated solution is filtered of impurities and injected into water for injection for dilution and configuration. Then the pH value is adjusted. After reaching the standard, it is filtered and impurities are removed again. The filling container is prepared simultaneously to fill and heat-seal the configured solution. After filling, the system is cleaned / dried, and the product is subsequently inspected and labeled for packaging. The entire process is reasonably laid out. Through multiple treatments such as heating and sterilization, concentrated solution filtration, dilute solution filtration, and product sterilization, the purity of the product is greatly improved, the microbial indicators and bacterial endotoxin levels are effectively controlled, pollution is reduced, and product quality is guaranteed. At the same time, after filling, the overall system adopts a cleaning / drying process to ensure the purity of the entire system and further improve the overall quality control. In the entire process, the control of temperature, humidity, and cleanliness helps to maintain the consistency and stability of product quality. The entire process design takes into account the needs of large-scale production. Through automated and continuous operations, production efficiency and output are improved and unit costs are reduced.

[0015] Furthermore, in step S2, the mixture is stirred and dissolved and the temperature is raised to boiling, maintained for 10 minutes, and then the temperature is lowered to 50° C. In step S3, the ratio of the concentration of the concentrated drug solution to the concentration of the diluted drug solution is ≤6:1.

[0016] Through the above scheme, the temperature is raised to boiling and maintained for 10 minutes to effectively kill the microorganisms in the solution and keep the solution pure. The solution is then cooled to 50°C for subsequent dilution. The ratio of the concentrated solution concentration to the diluted solution concentration is ≤6:1.

[0017] Furthermore, in step S1, the preparation of water for injection from drinking water includes reverse osmosis, purification, filtration, and distillation to obtain water for injection. The weighing process uses exhaust dust collection and a positive pressure is maintained in the weighing room.

[0018] Through the above scheme, the weighing process adopts exhaust dust collection, and the weighing room maintains positive pressure to prevent external debris from entering the weighing room.

[0019] Furthermore, in the cleaning / drying process in step S5, the cleaning includes firstly delivering purified water along the pipeline to each tank, cleaning through the spray ball in the tank, and discharging the residual water through the valve at the bottom of the tank after the cleaning is completed; ② delivering the cleaning agent to each tank through the pipeline for cleaning and then discharging, and then passing purified water to clean the residual cleaning agent; ③ passing injection water to clean each tank again, and discharging it from the valve at the bottom of the tank after completion, and the cleaning process is completed; drying includes passing compressed air to dry the residual water in the tank, and then passing sterilizing steam into each tank for sterilization, and emptying it through the respirator after sterilization is completed.

[0020] Through the above scheme, purified water is poured into the system in combination with a spray ball for cleaning to wash away the residual liquid medicine, and then a cleaning agent is added for cleaning, and then the residual cleaning agent is cleaned with purified water, and finally the tank is cleaned again with injection water to complete the cleaning process, and finally dried with compressed air and sterilized with high-temperature steam. The whole process is through several cleanings and high-temperature sterilization, and the treatment effect is good, which effectively reduces the residual liquid medicine and microorganisms in the system and cleans it thoroughly.

[0021] Furthermore, in step S4, preparing the filling container includes one of injection blow molding filling or composite film bag making filling, wherein the preparing the filling container and the filling are performed simultaneously.

[0022] Through the above scheme, the preparation of the filling container and the filling are carried out simultaneously, which is convenient for assembly line production and improves production efficiency.

[0023] The second purpose of the present invention is to provide a large-volume injection concentration preparation equipment based on large-scale production, which has a compact structure, a high degree of automation, reduces external interference, reduces impurity intake, and improves the preparation quality of large-volume injections.

[0024] A large-capacity injection concentrated preparation equipment based on large-scale production, comprising a frame, the frame is provided with an integrated weighing bin and a preparation tank, the weighing bin and the preparation tank are arranged in a positive pressure room, the weighing bin comprises a feeding mechanism and a weighing mechanism, the preparation tank comprises a configuration mechanism and a conveying mechanism, the weighing bin and the preparation tank are fully enclosed, and a spray cleaning mechanism is arranged in the weighing bin and the preparation tank;

[0025] The feeding mechanism comprises a plurality of feeding pipes arranged on the frame, one end of the feeding pipe extends out of the positive pressure room and is provided with a feeding port at the end, and the other end extends into the weighing bin, and a disposable feeding film tube is arranged in the feeding pipe;

[0026] The weighing mechanism comprises an electronic scale arranged at the bottom of the weighing bin, the bottom of the weighing bin is provided with a bottom plate, the electronic scale is arranged on the bottom plate, the bottom plate is opened and closed by a motor, and the bottom plate opening leads to the preparation tank;

[0027] The configuration mechanism includes a stirring rod and a pure water inlet valve driven by a motor disposed in the preparation tank, and also includes a high-temperature sterilization component disposed in the preparation tank;

[0028] The conveying mechanism comprises a conveying valve arranged at the bottom end of the preparation tank.

[0029] Through the above scheme, a disposable feeding membrane tube is set during the configuration process, which is convenient for feeding along the feeding port at the end of the disposable feeding membrane tube. The raw materials enter the weighing bin and raise the electronic scale for weighing. After weighing, the motor drives the bottom plate to open, and the raw materials are put into the preparation tank. The pure water inlet valve is opened to pass pure water, and the stirring rod is turned on to complete the initial concentration. Then the concentrated solution is heated by the high-temperature sterilization component, and high-temperature sterilization is performed to reduce the number of microorganisms. After high-temperature sterilization, it is cooled and finally transported to the subsequent section through the delivery valve. The whole process is integrated and fully enclosed. The weighing bin and preparation tank are combined in a positive pressure room to effectively avoid personnel entry and exit and the introduction of external impurities, improve the purity of the whole process, and the equipment has a high degree of automation, reduce human interference, reduce external interference, reduce impurity intake, and improve the quality of large-volume injection preparation. Through automated and integrated operations, the links of human operation are reduced, the possibility of human errors is reduced, and the consistency and reliability of products are improved. Through automated and continuous operations, production efficiency and output are improved, and unit costs are reduced.

[0030] Furthermore, the spray cleaning mechanism includes a plurality of porous spray balls arranged in the weighing bin and the preparation tank, and the spray balls are connected to the pure water pipeline.

[0031] Through the above scheme, the spray ball and pure water can be set to flush all positions in the weighing bin and the preparation tank to clean them thoroughly.

[0032] Furthermore, the high-temperature sterilization component includes an electric heating plate arranged in the preparation tank, and also includes a steam pipeline arranged on the preparation tank. The outer periphery of the preparation tank is provided with a cooling circuit with circulating water.

[0033] Through the above scheme, the electric heating plate heats the evenly mixed concentrated solution to boiling, and after high-temperature sterilization, the cooling circuit is used to cool the concentrated solution to facilitate subsequent processing. A steam pipeline is set up, and after the configuration is completed, the device can be steam sterilized.

[0034] Furthermore, the disposable feeding membrane tube uses compressed air to extend into the feeding tube from the feeding port.

[0035] Through the above scheme, the disposable feeding membrane tube uses compressed air to extend into the feeding pipe from the feeding port, that is, the disposable feeding membrane tube is extended into the feeding pipe from the feeding port and compressed air is blown into it, so as to cause the disposable feeding membrane tube to unfold from the feeding pipe, and then form a feeding channel to prevent the raw materials from directly contacting the feeding pipe.

[0036] Furthermore, a negative pressure extraction fan is provided in the preparation tank directly opposite to the weighing bin, and the discharge port of the negative pressure extraction fan directly faces the inside of the preparation tank.

[0037] Through the above scheme, a negative pressure extraction fan is set to facilitate the extraction of residual raw materials in the weighing bin, improve the accuracy of liquid preparation of the device, and avoid dust overflow.

[0038] The beneficial effects of the present invention are as follows:

[0039] 1. Insert a disposable feeding membrane tube to avoid impurities during the feeding process. When weighing and batching, prepare water for injection at the same time. Then, concentrate the raw materials and water for injection, heat and sterilize after mixing, remove live bacteria in the solution, filter the impurities from the concentrated solution and inject water for injection for dilution, then adjust the pH value, filter and remove impurities again after reaching the standard, prepare the filling container at the same time, fill the prepared solution and heat seal and sterilize, clean / dry the system after filling, and carry out subsequent light inspection, labeling and packaging of the product. The whole process is reasonably laid out. Through multiple treatments such as heating and sterilization, concentrated solution filtration, dilute solution filtration, and product sterilization, the purity of the product is greatly improved, the microbial indicators and bacterial endotoxin levels are effectively controlled, pollution is reduced, and product quality is guaranteed. At the same time, after filling, the whole system adopts the cleaning / drying process to ensure the purity of the whole system and further improve the overall quality control. In the whole process, the control of temperature, humidity and cleanliness helps to maintain the consistency and stability of product quality. The entire process design takes into account the needs of large-scale production. Through automated and continuous operations, production efficiency and output are improved and unit costs are reduced.

[0040] 2. During the configuration process, a disposable feeding membrane tube is set up to facilitate feeding along the feeding port at the end of the disposable feeding membrane tube. The raw materials enter the weighing bin and the electronic scale is raised for weighing. After weighing, the motor drives the bottom plate to open, and the raw materials are put into the preparation tank. The pure water inlet valve is opened to pass pure water, and the stirring rod is turned on to complete the initial concentration. Then the concentrated solution is heated by the high-temperature sterilization component for high-temperature sterilization to reduce the number of microorganisms. After high-temperature sterilization, it is cooled and finally transported to the subsequent section through the delivery valve. The whole process is integrated and fully enclosed. The weighing bin and preparation tank are combined with the positive pressure room to effectively avoid personnel entry and exit and the introduction of external impurities, which improves the purity of the whole process. The equipment has a high degree of automation, reduces human interference, reduces external interference, reduces impurity intake, and improves the quality of large-volume injection preparation. Through automated and integrated operations, the links of human operation are reduced, the possibility of human errors is reduced, the consistency and reliability of products are improved, and the production efficiency and output are improved through automated and continuous operations. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1is a system schematic diagram of Embodiment 1 of the present invention;

[0042] Figure 2 is a schematic diagram of a system of Embodiment 2 of the present invention;

[0043] Figure 3 It is a structural schematic diagram of embodiment 1 of the present invention.

[0044] Figure numerals: 11, frame; 12, weighing bin; 13, preparation tank; 14, feeding pipe; 15, feeding port; 16, disposable feeding membrane tube; 17, electronic scale; 18, bottom plate; 19, stirring rod; 20, pure water inlet valve; 21, delivery valve; 22, spray ball; 23, electric heating plate; 24, steam pipeline; 25, cooling circuit; 26, negative pressure extraction fan. DETAILED DESCRIPTION

[0045] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Generally, the components of the embodiments of the present invention described and shown in the drawings here can be arranged and designed in various different configurations.

[0046] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the invention claimed for protection, but merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0047] Example 1

[0048] like Figure 1 and Figure 3 As shown, this embodiment provides a large-volume injection production process based on large-scale production, comprising the following steps:

[0049] Step S1: insert the disposable feeding membrane tube 16, weigh the raw and auxiliary materials, prepare the water for injection with drinking water, conduct quality inspection on the raw materials and water for injection, and ensure that they meet the pharmaceutical production standards. Weighing and feeding are integrated;

[0050] Step S2: Preliminary concentration preparation, using online analytical equipment to monitor the concentration of the drug solution, heating and sterilization, and filtering the concentrated solution;

[0051] Step S3: Add 50°C water for injection to the concentrated solution to dilute the drug solution to a specified concentration to maintain drug stability, adjust the pH and filter again;

[0052] Step S4: Prepare filling containers, fill and heat seal, and sterilize the product. The heat sealing process from step S1 to step S4 is all produced in a Class C environment;

[0053] Step S5: After filling, the whole system adopts a cleaning / drying process;

[0054] Step S6: Perform light inspection, labeling and packaging on the products.

[0055] In step S1, the preparation of water for injection from drinking water includes reverse osmosis, purification, filtration, and distillation to obtain water for injection. The weighing process uses exhaust dust collection, and the weighing room maintains positive pressure. The weighing process uses exhaust dust collection, and the weighing room maintains positive pressure to prevent external debris from entering the weighing room.

[0056] In step S4, preparing the filling container includes one of injection molding blow bottle filling or composite film bag filling, wherein the preparation of the filling container is carried out simultaneously with the filling. In this embodiment, injection molding blow bottle filling is adopted, and the specific steps are as follows: the molten plastic particles are injected into the extruder to prepare the required parison by injection molding. Then the prepared parison is placed in the blow molding mold, and compressed air is injected into the parison to blow it into a hollow shape. During the inflation process, the parison is close to the cooling surface of the mold, so that it solidifies and forms. After inflation molding, the product is cooled to solidify and maintain the desired shape and size. After cooling is completed, the product is removed from the mold, and the plastic bottle is transported to the filling workshop to be filled with sterile liquid medicine, and the valve group cover is automatically heat-sealed with the combination cover.

[0057] In step S4, the filling and heat sealing are performed. The product sterilization process is as follows: the filled medicine bottles are placed on the sterilization tray according to the prescribed arrangement and stacked on the RGV sterilization vehicle; the sterilization vehicle is transferred to the sterilization cabinet and maintained at 121°C for 30 minutes using the water bath method: after the sterilization is completed, the medicine bags are cooled to 50°C using cooling circulating water.

[0058] The process of light inspection, labeling and packaging in step S6 is as follows: the sterilized medicine bottles (bags) are loaded into the sterilization vehicle and transferred to the conveyor line to enter the light inspection machine. After the full-automatic light inspection machine performs light inspection (the unqualified products rejected by the machine undergo manual light inspection), they are then labeled, sprayed with codes, and packed. The finished products are then transferred to the normal temperature warehouse for storage. (Packing specifications: 100mL plastic bottles, 100 bottles / box; 250mL plastic bottles, 50 bottles / box; 500mL plastic bottles, 30 bottles / box.)

[0059] In the cleaning / drying process of step S5, the cleaning includes firstly conveying purified water to each tank along the pipeline, cleaning through the spray ball 22 in the tank, and the residual water is discharged through the valve at the bottom of the tank after the cleaning is completed; ② conveying the cleaning agent to each tank through the pipeline for cleaning and then discharging, and then passing purified water to clean the residual cleaning agent; ③ passing injection water to clean each tank again, and then discharging from the valve at the bottom of the tank after completion, and the cleaning process is completed; drying includes passing compressed air to dry the residual water in the tank, and then passing sterilizing steam into each tank for sterilization, and emptying through the respirator after sterilization. Therefore, by pouring purified water into the system and cleaning with the spray ball 22, the residual liquid medicine is washed away, and then the cleaning agent is added for cleaning, and then the residual cleaning agent is cleaned with purified water, and finally the tank is cleaned again with injection water to complete the cleaning process, and finally dried with compressed air and sterilized with high-temperature steam. The whole process is washed several times with high-temperature sterilization, and the treatment effect is good, and the residual liquid medicine and microorganisms in the system are effectively reduced, and the cleaning is thorough.

[0060] Therefore, a disposable feeding membrane tube 16 is inserted to avoid impurities during the feeding process. When the weighing and batching are completed, water for injection is prepared simultaneously. Then the raw materials and water for injection are concentrated, mixed and sterilized to remove live bacteria in the solution. Then the concentrated solution is filtered for impurities and injected into water for injection for dilution and configuration. Then the pH value is adjusted. After reaching the standard, it is filtered and impurities are removed again. The filling container is prepared simultaneously to fill the configured solution and heat-seal and sterilize. After filling, the system is cleaned / dried, and the product is subsequently inspected and labeled for packaging. The entire process is reasonably laid out. Through multiple treatments such as heating and sterilization, concentrated solution filtration, dilute solution filtration, and product sterilization, the purity of the product is greatly improved, the microbial indicators and bacterial endotoxin levels are effectively controlled, pollution is reduced, and product quality is guaranteed. At the same time, after filling, the overall system adopts a cleaning / drying process to ensure the purity of the entire system and further improve the overall quality control. In the entire process, the control of temperature, humidity, and cleanliness helps to maintain the consistency and stability of product quality. The entire process design takes into account the needs of large-scale production. Through automated and continuous operations, production efficiency and output are improved and unit costs are reduced.

[0061] The present invention also provides a large-volume injection concentration preparation device based on large-scale production, which has a compact structure, a high degree of automation, reduces external interference, reduces impurity intake, and improves the preparation quality of large-volume injections.

[0062] Reference Figure 1 and Figure 3 A large-volume injection concentration preparation device based on large-scale production includes a frame 11, on which an integrated weighing bin 12 and a preparation tank 13 are arranged, and the weighing bin 12 and the preparation tank 13 are arranged in a positive pressure room. Figure 3The weighing bin 12 includes a feeding mechanism and a weighing mechanism, and the preparation tank 13 includes a configuration mechanism and a conveying mechanism. The weighing bin 12 and the preparation tank 13 are fully enclosed, and a spray cleaning mechanism is provided in the weighing bin 12 and the preparation tank 13;

[0063] The feeding mechanism includes a plurality of feeding pipes 14 arranged on the frame 11, one end of the feeding pipe 14 extends out of the positive pressure room and is provided with a feeding port 15 at the end, and the other end extends into the weighing bin 12, and a disposable feeding film tube 16 is provided in the feeding pipe 14;

[0064] The weighing mechanism includes an electronic scale 17 disposed at the bottom of the weighing bin 12. A bottom plate 18 is disposed at the bottom of the weighing bin 12. The electronic scale 17 is disposed on the bottom plate 18. The bottom plate 18 is opened and closed by a motor. The opening of the bottom plate 18 leads to the preparation tank 13.

[0065] The configuration mechanism includes a motor-driven stirring rod 19 and a pure water inlet valve 20 disposed in the preparation tank 13, the pure water inlet valve 20 is connected to the injection water preparation section, and also includes a high-temperature sterilization component disposed in the preparation tank 13;

[0066] The delivery mechanism includes a delivery valve 21 disposed at the bottom of the preparation tank 13, and the delivery valve 21 is connected to the subsequent filtration section, wherein an online analysis device (the online analysis device is a common device in the industry and is not shown) is used to monitor the concentration of the drug solution.

[0067] Reference Figure 3 In order to improve the convenience of operation and further reduce external pollution, the disposable feeding membrane tube 16 uses compressed air to extend from the feeding port 15 into the feeding pipe 14, and a negative pressure extraction fan 26 is provided at the preparation tank 13 directly inside the weighing bin 12, and the discharge port of the negative pressure extraction fan 26 is directly facing the preparation tank 13. The disposable feeding membrane tube 16 uses compressed air to extend from the feeding port 15 into the feeding pipe 14, that is, the disposable feeding membrane tube 16 extends from the feeding port 15 into the feeding pipe 14 and blows compressed air, so that the disposable feeding membrane tube 16 is expanded from the feeding pipe 14, and then a feeding channel is formed to prevent the raw materials from directly contacting the feeding pipe 14. The negative pressure extraction fan 26 is provided to facilitate the extraction of residual raw materials in the weighing bin 12, improve the accuracy of the liquid preparation of the device, and avoid dust overflow.

[0068] Reference Figure 3 In order to improve the purity of the system, the spray cleaning mechanism includes a plurality of porous spray balls 22 arranged in the weighing bin 12 and the preparation tank 13. The spray balls 22 are connected to the pure water pipeline produced by the injection water preparation section. The spray balls 22 and the pure water can be used to flush all directions in the weighing bin 12 and the preparation tank 13 to clean them thoroughly.

[0069] In order to facilitate understanding and avoid cluttering the drawings, other common pipelines and mechanisms on the weighing bin 12 and the preparation tank 13 in this application are not drawn in this figure.

[0070] Reference Figure 3 The high-temperature sterilization component includes an electric heating plate 23 arranged in the preparation tank 13. The electric heating plate 23 is embedded in the preparation tank 13 and only the area is marked in the figure. It also includes a steam pipeline 24 arranged on the preparation tank 13. The steam pipeline 24 is coiled in the preparation tank 13. When there is a need, steam can be introduced into the preparation tank 13 for sterilization. The steam pipeline 24 is connected to the distillation section produced by the preparation of water for injection section and supplies steam. A cooling circuit 25 with circulating water is provided on the periphery of the preparation tank 13. The cooling circuit 25 is also connected to the preparation of water for injection section. Pure water or filtered water can be used. The electric heating plate 23 heats the evenly mixed concentrated solution to boiling. After high-temperature sterilization, the cooling circuit 25 is used to cool the concentrated solution to facilitate subsequent processing. The steam pipeline 24 is set, and the device can be steam sterilized after configuration. During the configuration process, a disposable feeding membrane tube 16 is set, which is convenient for feeding along the feeding port 15 at the end of the disposable feeding membrane tube 16. The raw materials enter the weighing bin 12 and the electronic scale 17 is raised for weighing. After weighing, the motor drives the bottom plate 18 to open, and the raw materials are put into the preparation tank 13. The pure water inlet valve 20 is opened to pass pure water, and the stirring rod 19 is turned on to complete the initial concentration. Then the concentrated solution is heated by the high-temperature sterilization component, and high-temperature sterilization is performed to reduce the number of microorganisms. After high-temperature sterilization, it is cooled and finally transported to the subsequent section through the delivery valve 21 for filtration. The whole process is integrated and fully enclosed. The weighing bin 12 and the preparation tank 13 are combined in a positive pressure room to effectively avoid personnel entering and exiting and the introduction of external impurities, thereby improving the purity of the entire process. The equipment has a high degree of automation, reduces human interference, reduces external interference, reduces impurity intake, and improves the quality of large-volume injection preparation. Through automated and integrated operations, the links of human operation are reduced, the possibility of human errors is reduced, the consistency and reliability of the product are improved, and through automated and continuous operations, the production efficiency and output are improved, and the unit cost is reduced.

[0071] Embodiment 2

[0072] Reference Figure 2 The structure and method of the second embodiment are similar to the basic box of the first embodiment, except that in the second embodiment, in step S4, the preparation of the filling container adopts the composite film bag filling, wherein the preparation of the filling container and the filling are carried out simultaneously. In this embodiment, the composite film is used as the raw material to prepare the injection soft bag, and the injection soft bag is combined with the valve group cover for filling. The heat sealing process in steps S1 to S4 is all produced in a C-level environment.

Claims

1. A large-volume injection production process based on large-scale production, characterized in that: The steps include: Step S1; A disposable feeding membrane tube (16) is inserted, and raw materials and auxiliary materials are weighed and mixed, and drinking water is used to prepare water for injection, and weighing and feeding are processed in one piece; Step S2: preliminary concentration, heating and sterilization, and filtration of the concentrated solution; Step S3: Add 50°C water for injection to dilute the concentrated solution to a specified concentration, adjust the pH and filter again; Step S4: preparing a filling container, filling and heat-sealing, and sterilizing the product; Step S5: After filling, the whole system adopts a cleaning / drying process; Step S6: Perform light inspection, labeling and packaging on the products.

2. A large-volume injection production process based on large-scale production according to claim 1, characterized in that: In step S2, the mixture is stirred to dissolve and heated to boiling, maintained for 10 minutes, and then cooled to 50° C. In step S3, the ratio of the concentration of the concentrated drug solution to the concentration of the diluted drug solution is ≤6:

1.

3. A large-volume injection production process based on large-scale production according to claim 1, characterized in that: In step S1, the preparation of water for injection from drinking water includes reverse osmosis, purification, filtration, and distillation to obtain water for injection. The weighing process uses exhaust dust collection and a positive pressure is maintained in the weighing room.

4. A large-volume injection production process based on large-scale production according to claim 1, characterized in that: In the cleaning / drying process of step S5, the cleaning includes firstly delivering purified water to each tank along the pipeline, cleaning through the spray ball (22) in the tank, and discharging the residual water through the valve at the bottom of the tank after the cleaning is completed; 2. Delivering the cleaning agent to each tank through the pipeline for cleaning and then discharging, and then passing purified water to clean the residual cleaning agent; 3. Passing injection water to clean each tank again, and discharging it from the valve at the bottom of the tank after completion, and the cleaning process is completed; drying includes passing compressed air to dry the residual water in the tank, and then passing sterilizing steam into each tank for sterilization, and emptying it through the respirator after the sterilization is completed.

5. The large-volume injection production process based on large-scale production according to claim 1, characterized in that: In step S4, preparing the filling container includes one of injection blow molding filling or composite film bag making filling, wherein the preparation of the filling container and the filling are performed simultaneously.

6. A large-volume injection preparation device based on large-scale production according to any one of claims 1 to 5, comprising a frame (11), characterized in that: The frame (11) is provided with an integrated weighing bin (12) and a preparation tank (13), the weighing bin (12) and the preparation tank (13) are arranged in a positive pressure room, the weighing bin (12) includes a feeding mechanism and a weighing mechanism, the preparation tank (13) includes a configuration mechanism and a conveying mechanism, the weighing bin (12) and the preparation tank (13) are fully enclosed, and a spray cleaning mechanism is arranged in the weighing bin (12) and the preparation tank (13); The feeding mechanism comprises a plurality of feeding pipes (14) arranged on the frame (11), one end of the feeding pipe (14) extends out of the positive pressure room and is provided with a feeding port (15), and the other end extends into the weighing bin (12), and a disposable feeding film tube (16) is arranged in the feeding pipe (14); The weighing mechanism comprises an electronic scale (17) arranged at the bottom end of the weighing bin (12); a bottom plate (18) is arranged at the bottom end of the weighing bin (12); the electronic scale (17) is arranged on the bottom plate (18); the bottom plate (18) is opened and closed by a motor, and the opening of the bottom plate (18) leads to the preparation tank (13); The configuration mechanism comprises a stirring rod (19) and a pure water inlet valve (20) driven by a motor and arranged in the preparation tank (13), and also comprises a high temperature sterilization component arranged in the preparation tank (13); The conveying mechanism comprises a conveying valve (21) arranged at the bottom end of the preparation tank (13).

7. The large-volume injection preparation equipment based on large-scale production according to claim 6 is characterized in that: The spray cleaning mechanism comprises a plurality of porous spray balls (22) arranged in the weighing bin (12) and the preparation tank (13), and the spray balls (22) are connected to a pure water pipeline.

8. The large-volume injection preparation equipment based on large-scale production according to claim 6 is characterized in that: The high-temperature sterilization component comprises an electric heating plate (23) arranged in the preparation tank (13), and also comprises a steam pipeline (24) arranged on the preparation tank (13). The outer periphery of the preparation tank (13) is provided with a cooling circuit (25) through which circulating water flows.

9. The large-volume injection preparation equipment based on large-scale production according to claim 6, characterized in that: The disposable feeding membrane tube (16) is extended into the feeding tube (14) from the feeding port (15) by compressed air.

10. The large-volume injection preparation equipment based on large-scale production according to claim 6, characterized in that: A negative pressure extraction fan (26) is provided in the preparation tank (13) directly facing the weighing bin (12), and the discharge port of the negative pressure extraction fan (26) is directly facing the inside of the preparation tank (13).

Images