Ingredient tank feeding device and aseptic feeding method
By constructing a closed feeding path using sterile containers, tubing, manual diaphragm valves, and peristaltic pumps, and performing in-situ sterilization, the problem of microbial contamination caused by opening the feeding port of the mixing tank is solved, achieving efficient and sterile feeding and convenient operation.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- CHUTIAN HUATONG PHARM EQUIP CO LTD
- Filing Date
- 2026-04-13
- Publication Date
- 2026-06-16
AI Technical Summary
In the existing technology, the raw material and auxiliary material addition method of the mixing tank has a deficiency in aseptic protection. After the feeding port is opened, the internal environment of the tank is directly connected with the external air, resulting in a high risk of microbial contamination.
A closed feeding path is formed by sterile containers, tubing, manual diaphragm valves and peristaltic pumps. The outlet end of the manual diaphragm valve is sterilized in situ by a sterilization component. Combined with sterile connectors and clamps, rapid and reliable aseptic feeding is achieved.
It reduces the risk of microbial contamination, improves the reliability and ease of operation of aseptic feeding, adapts to different forms of raw and auxiliary materials and batch requirements, and meets GMP standards.
Smart Images
Figure CN122209286A_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of biopharmaceutical technology, and more specifically, to a feeding device for a mixing tank and a method for aseptic feeding. Background Technology
[0002] In the pharmaceutical industry, especially in the production of high-value-added sterile drugs, the aseptic addition of raw materials and excipients is a crucial step in ensuring product quality. Currently, the addition of raw materials and excipients to mixing tanks is mostly done manually by opening the tank's feeding port. In practice, operators must open the feeding port cover in a non-sealed environment and directly add the pre-weighed or pre-packaged raw materials and excipients into the tank. However, this method has significant shortcomings in ensuring aseptic performance: once the feeding port is opened, the tank's internal environment is directly exposed to non-sterile external air, resulting in prolonged exposure of the materials to the environment. Airborne microorganisms can easily enter the tank with the airflow, causing contamination. Summary of the Invention
[0003] The purpose of this application is to provide a feeding device for a batching tank and a method for aseptic feeding, addressing at least one of the technical problems mentioned in the background art.
[0004] To achieve the above objectives, this application adopts the following technical solution: One aspect of this application provides a feeding device for a mixing tank, including a feeding assembly and a sterilization assembly. The feeding assembly includes a sterile container, a hose, a peristaltic pump, and a manual diaphragm valve. The sterile container is used to contain raw and auxiliary materials. The outlet end of the manual diaphragm valve is used to connect to the top interface of the mixing tank. One end of the hose is connected to the sterile container, and the other end of the hose is connected to the inlet end of the manual diaphragm valve. The peristaltic pump is installed on the hose to drive the flow of raw and auxiliary materials. The sterilization assembly is connected to the outlet end of the manual diaphragm valve and is used to send pure steam to the outlet end of the manual diaphragm valve to sterilize the outlet end of the manual diaphragm valve in situ.
[0005] Optionally, the sterile container is a sterile bag or a sterile bottle.
[0006] The beneficial effects of this technical solution are as follows: It allows raw materials to be directly stored in flexible sterile bags or rigid sterile bottles after offline sterilization, eliminating the need to transfer them to other containers before feeding and reducing intermediate steps. Furthermore, compared to traditional open-top feeding methods, sterile bags or bottles can be directly and aseptically connected to the tubing, forming a fully enclosed feeding path, reducing the risk of material exposure to ambient air and lowering the possibility of microbial contamination. Simultaneously, sterile bags are suitable for large-volume or single-use applications, while sterile bottles are suitable for small batches or materials requiring rigid protection; the two complement each other, improving the device's adaptability to different raw material forms and batch requirements.
[0007] Optionally, the feeding device for the mixing tank provided in this application further includes a sterile connector and a clamp. One end of the hose is connected to the sterile container through the sterile connector, and the other end of the hose is connected to the inlet end of the manual diaphragm valve through the clamp.
[0008] The beneficial effects of this technical solution are as follows: The use of a sterile connector between the hose and the sterile container enables a rapid and reliable sterile connection in non-clean environments, avoiding the use of complex facilities such as laminar flow hoods and reducing operational requirements. Simultaneously, the use of a clamp connection between the hose and the manual diaphragm valve results in a simple structure that is easy to assemble and disassemble, facilitating disassembly, cleaning, or replacement after use. The different connection methods at both ends of the hose balance sterility assurance with operational convenience; the sterile connector prioritizes preventing microbial intrusion, while the clamp connection prioritizes ease of maintenance.
[0009] Optionally, the sterilization assembly includes a steam pipeline and a pure steam source connected to the steam pipeline, as well as a steam control valve and a temperature transmitter, both installed on the steam pipeline and arranged in sequence. The steam pipeline is connected to the outlet end of the manual diaphragm valve. The steam control valve is located upstream of the outlet end of the manual diaphragm valve, and the temperature transmitter is located downstream of the outlet end of the manual diaphragm valve and close to the outlet end of the manual diaphragm valve. The temperature transmitter is used to monitor the sterilization temperature.
[0010] The beneficial effects of this technical solution are as follows: By setting up a steam pipeline and a pure steam source, and installing a steam control valve upstream of the outlet of the manual diaphragm valve, the on / off state of sterilization steam can be precisely controlled. By installing a temperature transmitter downstream of and close to the outlet of the manual diaphragm valve, the temperature of this critical sterilization point at the outlet of the manual diaphragm valve can be monitored in real time and accurately, avoiding temperature measurement deviations caused by excessive distance.
[0011] Optionally, the sterilization assembly further includes a steam trap installed on the steam pipeline. The steam trap is located downstream of the outlet end of the manual diaphragm valve and is used to discharge pure steam condensate.
[0012] The beneficial effects of this technical solution are as follows: by placing the steam trap at the end of the steam pipeline, it can automatically discharge condensate, maintain a pure steam saturation state in the pipeline, and reduce the possibility of water accumulation affecting the sterilization effect.
[0013] Optionally, the feeding device for the mixing tank provided in this application further includes a gas purging assembly. The gas purging assembly includes a purging pipeline, a gas sterilization filter and a purging control valve, both installed on the purging pipeline. The purging control valve is located downstream of the gas sterilization filter. One end of the purging pipeline is connected to a sterile gas source, and the other end of the purging pipeline is connected to the steam pipeline to purge residual condensate with sterile gas after sterilization.
[0014] The beneficial effects of this technical solution are as follows: After sterilization, sterile gas is introduced through the purge control valve. After passing through the gas sterilization filter to ensure the gas is sterile, it enters the steam pipeline along the purge pipeline to purge the residual pure steam and condensate in the steam pipeline. This effectively removes residual moisture in the pipeline after sterilization, making it less likely for condensate to mix with raw materials or diluted medicine during subsequent feeding. At the same time, it reduces the risk of microbial growth caused by water accumulation. The purge control valve is located downstream of the gas sterilization filter, which can prevent unfiltered gas from entering the pipeline. This ensures that the entire pipeline system remains dry, clean, and sterile before feeding, improving the reliability of the overall process.
[0015] Optionally, an electric heating element is provided on the outside of the housing of the gas sterilization filter, and the electric heating element is used to heat the gas sterilization filter.
[0016] The beneficial effects of this technical solution are as follows: by setting an electric heating element to heat the outer shell of the gas sterilization filter, the filter element is less likely to be clogged or have reduced flow due to moisture after sterilization, thereby stabilizing the purge gas flow rate and reducing the possibility of microbial growth in the moist filter element, thus ensuring the sterility of the purge gas.
[0017] Optionally, the feeding device for the mixing tank provided in this application further includes a metering element and a PLC controller. The PLC controller is electrically connected to the metering element and the peristaltic pump respectively, so as to adjust the speed of the peristaltic pump according to the feedback signal of the metering element; the metering element is a weighing module or a flow meter.
[0018] The beneficial effects of this technical solution are as follows: the metering device detects the feed amount in real time, and the PLC controller dynamically adjusts the speed of the peristaltic pump according to the feedback signal, so that the actual feed amount is close to the target value, avoiding the problem of inaccurate metering in traditional manual feeding; at the same time, the weighing method or flow method can be flexibly selected according to the type of batching tank or the characteristics of the material to adapt to different accuracy requirements and process conditions.
[0019] Another aspect of this application provides an aseptic feeding method, implemented using the ingredient tank feeding device provided in this application, the method comprising: The aseptic container, tubing and manual diaphragm valve in the feeding assembly are sterilized offline. Under aseptic conditions, the raw materials and excipients are loaded into the sterile container that has been sterilized offline and then sealed. Connect one end of the tubing to the sterile container, connect the other end of the tubing to the inlet of the manual diaphragm valve, connect the outlet of the manual diaphragm valve to the top interface of the mixing tank, and install the peristaltic pump on the tubing. Start the sterilization assembly and introduce pure steam into the outlet end of the manual diaphragm valve to sterilize the outlet end of the manual diaphragm valve in situ. After sterilization, open the manual diaphragm valve and start the peristaltic pump to pump the raw materials and auxiliary materials in the sterile container into the mixing tank through the hose.
[0020] Optionally, after in-situ sterilization of the outlet end of the manual diaphragm valve and before opening the manual diaphragm valve for feeding, the method further includes: Sterile gas is introduced into the outlet of the manual diaphragm valve to purge the residual pure steam and condensate in the pipeline to the discharge pipeline.
[0021] The beneficial effects of this technical solution are: it can prevent residual moisture from mixing into raw and auxiliary materials, reducing the risk of dilution; at the same time, it can prevent condensate from breeding microorganisms in the pipeline system, ensuring a sterile state before feeding.
[0022] The technical solution provided in this application can achieve at least one of the following beneficial effects: The feeding device and aseptic feeding method for the mixing tank provided in this application use aseptic containers, hoses, manual diaphragm valves and peristaltic pumps to form a closed feeding path, which avoids environmental exposure caused by opening the feeding port, thereby reducing the risk of microorganisms entering the mixing tank through air or operation.
[0023] The additional technical features and advantages of this application will become more apparent from the following description or from practical application. Attached Figure Description
[0024] To more clearly illustrate the technical solutions of the specific embodiments of this application, the accompanying drawings used in the description of the specific embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.
[0025] Figure 1This is a schematic diagram of the structure of the feeding device for the batching tank provided in this application embodiment, showing the connection between the pipeline where the third air path pneumatic ball valve 18 is located and the material inlet pipe. The pipeline where the third air path pneumatic ball valve 18 is located and the material inlet pipe intersect but are not connected. Figure 2 This is a flowchart of one embodiment of the aseptic feeding method provided in this application.
[0026] Figure label: 01. First air path pneumatic ball valve; 02. Second air path pneumatic ball valve; 03. Diaphragm pressure gauge; 04. Gas sterilization filter; 05. Purge control valve; 06. Top interface; 07. Second auxiliary pneumatic diaphragm valve; 08. First auxiliary steam control valve; 09. Second auxiliary steam control valve; 10. Steam control valve; 11. First auxiliary pneumatic diaphragm valve; 12. Pneumatic diaphragm valve; 13. Manual diaphragm valve; 14. Peristaltic pump; 15. Tubes; 16. Sterile containers; 17. Pneumatic ball valve; 18. Third-line pneumatic ball valve; 19. Feeding assembly; 20. Temperature transmitter; 21. Steam trap; 22. Batching tank; 23. Pure steam source; 24. Sterile gas source; 25. Material inlet pipe. Detailed Implementation
[0027] The technical solutions of this application will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this application. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.
[0028] In the description of this application, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this application. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.
[0029] In the description of this application, it should be noted that, unless otherwise expressly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection between two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.
[0030] like Figure 1 As shown, one aspect of this application provides a feeding device for a mixing tank, including a feeding assembly 19 and a sterilization assembly. The feeding assembly 19 includes a sterile container 16, a hose 15, a peristaltic pump 14, and a manual diaphragm valve 13. The sterile container 16 is used to contain raw and auxiliary materials, and the outlet end of the manual diaphragm valve 13 is used to connect with the top interface 06 of the mixing tank 22 (e.g., ...). Figure 1 As shown (represented by a horizontal line), one end of the hose 15 is connected to the sterile container 16, and the other end of the hose 15 is connected to the inlet end of the manual diaphragm valve 13. The peristaltic pump 14 is installed on the hose 15 to drive the flow of raw materials and auxiliary materials. The sterilization assembly is connected to the outlet end of the manual diaphragm valve 13. The sterilization assembly is used to send pure steam to the outlet end of the manual diaphragm valve 13 to sterilize the outlet end of the manual diaphragm valve 13 in situ.
[0031] The manual diaphragm valve 13 is preferably a sterile stainless steel handle valve, that is, the manual diaphragm valve 13 is preferably a sanitary manual diaphragm valve 13 that can withstand pure steam sterilization at 121℃; the top interface 06 of the mixing tank 22 is connected to the material inlet pipe 25 that extends into the mixing tank 22.
[0032] The feeding device for the ingredient tank 22 provided in this application involves offline sterilization of the manual diaphragm valve 13, the hose 15 (preferably a sanitary hose 15), and the sterile container 16 during use. After offline sterilization, the raw materials and excipients are loaded into the sterile container 16 and sealed in a laminar flow environment to maintain an internal sterile state. One end of the hose 15 is connected to the manual diaphragm valve 13, and the other end of the hose 15 is aseptically connected to the sterile container 16 containing the raw materials and excipients via a sterile connector or under a laminar flow hood. The hose 15 is then installed on the peristaltic pump 14, and the raw materials are fed into the container. The outlet end of the manual diaphragm valve 13 is connected to the top interface 06 of the mixing tank 22 via a feed pipe; pure steam is introduced into the feed pipe at the top of the tank, so that the pure steam flows through the inlet end of the manual diaphragm valve 13 (which has an exposed end face), and the sterilization temperature is controlled by temperature detection to reach 121°C and maintained for 30 minutes to complete the online sterilization of the exposed end face of the manual diaphragm valve 13; the manual diaphragm valve 13 is opened, the peristaltic pump 14 is started, and the raw and auxiliary materials in the sterile container 16 are quantitatively pumped into the mixing tank 22 through the hose 15 to complete the aseptic addition.
[0033] The feeding device for the mixing tank 22 provided in this application uses a sterile container 16, a hose 15, a manual diaphragm valve 13, and a peristaltic pump 14 to form a closed feeding path, avoiding environmental exposure caused by opening the feeding port, thereby reducing the risk of microorganisms entering the mixing tank 22 through air or operational contact; at the same time, the sterilization component can sterilize the outlet end of the manual diaphragm valve 13 connected to the mixing tank 22 in situ, making up for the deficiency that this key interface cannot be sterilized online in the traditional method, which helps to improve the sterility assurance level of the feeding process; moreover, the use of the peristaltic pump 14 to drive the feeding speed can realize the adjustment of the feeding speed, which is conducive to stable material conveying.
[0034] Optionally, the sterile container 16 is a sterile bag or a sterile bottle. This allows raw materials to be stored directly in flexible sterile bags or rigid sterile bottles after offline sterilization, eliminating the need to transfer them to other containers before feeding and reducing intermediate operation steps. Furthermore, compared to traditional open-top feeding methods, sterile bags or bottles can be directly and aseptically connected to the tubing 15 to form a fully enclosed feeding path, reducing the risk of material exposure to ambient air and lowering the possibility of microbial contamination. At the same time, sterile bags are suitable for large-volume or single-use scenarios, while sterile bottles are suitable for small batches or materials requiring rigid protection. The two complement each other, improving the adaptability of the device to different raw material forms and batch requirements.
[0035] Optionally, the feeding device for the mixing tank 22 provided in this embodiment further includes a sterile connector and a clamp. One end of the hose 15 is connected to the sterile container 16 via the sterile connector, and the other end of the hose 15 is connected to the inlet end of the manual diaphragm valve 13 via the clamp. In this embodiment, preferably, the sterile connector includes the Lynx S2S sterile connector manufactured by Merck Millipore. Thus, the use of a sterile connector between the hose 15 and the sterile container 16 enables a rapid and reliable sterile connection in non-clean environments, avoiding the use of complex facilities such as laminar flow hoods and reducing operational requirements. Simultaneously, the clamp connection between the hose 15 and the manual diaphragm valve 13 is simple in structure, easy to assemble and disassemble, and convenient for disassembly, cleaning, or replacement after use. The different connection methods at both ends of the hose 15 balance sterility and operational convenience; the sterile connector focuses on preventing microbial intrusion, while the clamp connection focuses on ease of maintenance.
[0036] Optionally, the sterilization assembly includes a steam pipeline and a pure steam source 23 connected to the steam pipeline, as well as a steam control valve 10 and a temperature transmitter 20, both installed on the steam pipeline and arranged in sequence. The steam pipeline is connected to the outlet end of the manual diaphragm valve 13. The steam control valve 10 is located upstream of the outlet end of the manual diaphragm valve 13, and the temperature transmitter 20 is located downstream of the outlet end of the manual diaphragm valve 13 and close to the outlet end of the manual diaphragm valve 13. The temperature transmitter 20 is used to monitor the sterilization temperature. Thus, by setting up a steam pipeline and a pure steam source 23, and installing a steam control valve 10 upstream of the outlet of the manual diaphragm valve 13, the on / off state of sterilization steam can be precisely controlled. A temperature transmitter 20 is installed downstream of and near the outlet of the manual diaphragm valve 13, enabling real-time and accurate monitoring of the temperature at this critical sterilization point, avoiding temperature measurement deviations due to excessive distance and ensuring that the sterilization temperature meets the 121℃ requirement. In this embodiment, the steam pipeline is preferably connected between the outlet of the manual diaphragm valve 13 and the top interface 06 of the mixing tank 22. This pipeline connects the outlet of the manual diaphragm valve 13 and the top interface 06 of the mixing tank 22. Figure 1 As shown, the steam control valve 10 is preferably a pneumatic diaphragm valve. In this embodiment, the sterilization assembly also includes a first auxiliary steam control valve 08, a second auxiliary steam control valve 09, and a pneumatic ball valve 17 (such as PBV9103). The first auxiliary steam control valve 08 and the second auxiliary steam control valve 09 are used to control the flow direction of pure steam so that it can flow through the outlet end face of the manual diaphragm valve 13. The pneumatic ball valve 17 is located at the end of the steam pipeline and is used to discharge condensate after sterilization.
[0037] A pneumatic diaphragm valve 12 is installed on the pipeline between the outlet end of the manual diaphragm valve 13 and the top interface 06 of the mixing tank 22 to prevent steam from entering the mixing tank 22 during the sterilization process. The pneumatic diaphragm valve 12 is opened when materials are fed into the mixing tank 22 to allow raw materials and auxiliary materials to enter the mixing tank 22.
[0038] Optionally, the sterilization assembly further includes a steam trap 21 installed in the steam pipeline. The steam trap 21 is located downstream of the outlet end of the manual diaphragm valve 13 and is used to discharge pure steam condensate. Thus, by placing the steam trap 21 at the end of the steam pipeline, it can automatically discharge condensate, maintain a saturated state of pure steam in the pipeline, and reduce the possibility of water accumulation affecting the sterilization effect. Preferably, the steam trap 21 is a thermostatic steam trap 21 (such as ST9101); the distance between the steam trap 21 and the temperature transmitter 20 is preferably greater than 400 mm.
[0039] Optionally, the feeding device for the mixing tank 22 provided in this application embodiment further includes a gas purging assembly. The gas purging assembly includes a purging pipeline, a gas sterilization filter 04 and a purging control valve 05 both installed on the purging pipeline. The purging control valve 05 is located downstream of the gas sterilization filter 04. One end of the purging pipeline is connected to a sterile gas source 24, and the other end of the purging pipeline is connected to the steam pipeline to purge residual condensate with sterile gas after sterilization. In this way, after sterilization, sterile gas is introduced through the purge control valve 05. After passing through the gas sterilization filter 04 to ensure the gas is sterile, it enters the steam pipeline along the purge pipeline to purge any residual pure steam and condensate in the steam pipeline. This effectively removes residual moisture from the pipeline after sterilization, making it less likely for condensate to mix with raw materials or diluted pharmaceutical solutions during subsequent feeds. It also reduces the risk of microbial growth due to water accumulation. The purge control valve 05 is located downstream of the gas sterilization filter 04 to prevent unfiltered gas from entering the pipeline, thus keeping the entire pipeline system dry, clean, and sterile before feed, improving the overall reliability of the process. Preferably, the gas sterilization filter 04 is 5 inches long and uses a single filter element with a pore size of 0.22 μm, which can intercept microorganisms in the gas, ensuring that the purge gas itself is sterile and does not disrupt the established sterile state of the pipeline. The gas purging assembly also preferably includes a diaphragm pressure gauge 03 for monitoring the purging pressure; the gas purging assembly also includes a first auxiliary pneumatic diaphragm valve 11, a second auxiliary pneumatic diaphragm valve 07, a first pneumatic ball valve 01, a second pneumatic ball valve 02, and a third pneumatic ball valve 18.
[0040] Optionally, an electric heating element is provided on the exterior of the outer shell of the gas sterilization filter 04 to heat the gas sterilization filter 04. By using an electric heating element to heat the outer shell of the gas sterilization filter 04, the filter element is less likely to become clogged or have reduced flow rate due to moisture after sterilization, thereby stabilizing the purge gas flow rate and reducing the possibility of microbial growth on the moist filter element, ensuring the sterility of the purge gas. In this application example, the electric heating element is preferably a heating mantle or similar device, which has an insulation layer, a temperature sensor, and a temperature controller, enabling precise temperature control. The gas sterilization filter 04 itself may also have an electric heating function.
[0041] Optionally, the feeding device for the mixing tank 22 provided in this embodiment further includes a metering element and a PLC controller. The PLC controller is electrically connected to the metering element and the peristaltic pump 14 respectively, so as to adjust the rotation speed of the peristaltic pump 14 according to the feedback signal of the metering element. The metering element is a weighing module or a flow meter. Preferably, the weighing module is installed at the support foot of the mixing tank 22 (e.g., a strain gauge weighing sensor) to detect changes in the weight of the material in the tank; the flow meter (e.g., a mass flow meter or an electromagnetic flow meter) is installed on the hose 15 to detect the instantaneous flow rate. The metering device monitors the feed rate in real time, and the PLC controller dynamically adjusts the speed of the peristaltic pump 14 based on the feedback signal, so that the actual feed rate accurately approaches the target value, avoiding the problem of inaccurate metering in traditional manual feeding. At the same time, the weighing method or flow rate method can be flexibly selected according to the type of batching tank 22 or the characteristics of the material to adapt to different accuracy requirements and process conditions. Moreover, the automated metering control reduces manual intervention, lowers operational errors and the risk of contamination, and can be linked with the host computer system to form a traceable electronic record, meeting the GMP (Good Manufacturing Practice) requirements for data integrity.
[0042] The PLC controller (which can use the existing PLC system in the mixing tank 22) is electrically connected to the metering device and the peristaltic pump 14. Specifically, the PLC controller receives signals from the weighing module or flow meter. The target amount of raw materials to be added is preset in the PLC controller program. During the feeding process, the PLC controller reads the detection value of the metering device in real time. When the liquid level change detected by the weighing module (or the cumulative flow detected by the flow meter) gradually approaches the preset target amount, the PLC controller controls the drive motor of the peristaltic pump 14 through a 4-20mA electrical signal to gradually reduce the speed of the peristaltic pump 14, thereby slowing down the addition rate of raw materials and achieving deceleration and slow filling. When the detection value reaches the target amount, the PLC controller issues a stop signal, shuts down the peristaltic pump 14 and closes the manual diaphragm valve 13, completing the precise quantitative addition. In this embodiment, the peristaltic pump 14 can be steplessly speed-adjusted within the range of 80-3500ml / min, meeting the dual requirements of precise addition in small batches and rapid delivery in large batches. The PLC controller is used to control the sterilization temperature and sterilization time of the sterilization components, and to record the temperature data during the sterilization process.
[0043] like Figure 2 As shown, another aspect of this application provides an aseptic feeding method, implemented using the feeding device of the mixing tank 22 provided in the embodiments of this application. The method includes: S100: The aseptic container 16, hose 15 and manual diaphragm valve 13 in the feeding assembly 19 are sterilized offline. S200: Under aseptic conditions, the raw materials and excipients are loaded into the sterile container 16 that has been sterilized offline and then sealed. S300: Connect one end of the hose 15 to the sterile container 16, connect the other end of the hose 15 to the inlet end of the manual diaphragm valve 13, connect the outlet end of the manual diaphragm valve 13 to the top interface 06 of the mixing tank 22, and install the peristaltic pump 14 on the hose 15. S400: Start the sterilization assembly and introduce pure steam into the outlet end of the manual diaphragm valve 13 to sterilize the outlet end of the manual diaphragm valve 13 in situ. S500: After sterilization, open the manual diaphragm valve 13 and start the peristaltic pump 14 to pump the raw materials and auxiliary materials in the sterile container 16 into the mixing tank 22 through the hose 15.
[0044] The aseptic feeding method provided in this application is implemented using the feeding device of the mixing tank 22 provided in this application. It uses an aseptic container 16, a hose 15, a manual diaphragm valve 13 and a peristaltic pump 14 to form a closed feeding path, avoiding environmental exposure caused by opening the feeding port, thereby reducing the risk of microorganisms entering the mixing tank 22 through air or operational contact. At the same time, the sterilization component can sterilize the outlet end of the manual diaphragm valve 13 connected to the mixing tank 22 in situ, making up for the deficiency of the inability to sterilize this key interface online in the traditional method, which helps to improve the aseptic assurance level of the feeding process. Moreover, the use of the peristaltic pump 14 to drive the feeding speed can be adjusted, which is beneficial to the stable material conveying.
[0045] Optionally, after in-situ sterilization of the outlet end of the manual diaphragm valve 13 and before opening the manual diaphragm valve 13 for feeding, the method further includes: S600: Sterile gas is introduced into the outlet of the manual diaphragm valve 13 to purge residual pure steam and condensate in the pipeline to the discharge pipeline. This avoids residual moisture from mixing with raw materials and reduces the risk of dilution; at the same time, it prevents the growth of microorganisms in the condensate in the pipeline system, ensuring a sterile state before feeding.
[0046] In this application example, the sterile gas is clean compressed air or nitrogen; in the in-situ sterilization step, the sterilization temperature is monitored by a temperature transmitter 20, and timing begins when the temperature reaches 121°C, maintaining the sterilization time for 30 minutes; in the feeding step, the feeding amount is detected in real time by a weighing module or flow meter, and the PLC controller adjusts the speed of the peristaltic pump 14 according to the detection value feedback until the preset addition amount is reached and feeding stops; the aseptic loading step is carried out in a laminar flow hood or laminar flow system, with a laminar flow level of ISO 5 (Class A); the aseptic feeding method also includes a sterilization verification step: before in-situ sterilization, a biological indicator is placed in the pipeline near the outlet of the manual diaphragm valve 13, and after sterilization, it is taken out and cultured to verify the sterilization effect; the purging step continues until no visible condensate is discharged from the pipeline; after feeding, the peristaltic pump 14 is stopped, the manual diaphragm valve 13 is closed, and the connection between the hose 15 and the sterile container 16 is disconnected in sequence.
[0047] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.
Claims
1. A feeding device for a batching tank, characterized in that, The device includes a feeding assembly and a sterilization assembly. The feeding assembly includes a sterile container, a hose, a peristaltic pump, and a manual diaphragm valve. The sterile container is used to hold raw materials and excipients. The outlet end of the manual diaphragm valve is used to connect to the top interface of the mixing tank. One end of the hose is connected to the sterile container, and the other end of the hose is connected to the inlet end of the manual diaphragm valve. The peristaltic pump is installed on the hose to drive the flow of raw materials and excipients. The sterilization assembly is connected to the outlet end of the manual diaphragm valve and is used to send pure steam to the outlet end of the manual diaphragm valve for in-situ sterilization of the outlet end of the manual diaphragm valve.
2. The feeding device for the batching tank according to claim 1, characterized in that, The sterile container is a sterile bag or a sterile bottle.
3. The feeding device for the batching tank according to claim 1, characterized in that, It also includes a sterile connector and a clamp, one end of the hose is connected to the sterile container through the sterile connector, and the other end of the hose is connected to the inlet end of the manual diaphragm valve through the clamp.
4. The feeding device for the batching tank according to claim 1, characterized in that, The sterilization assembly includes a steam pipeline and a pure steam source connected to the steam pipeline, as well as a steam control valve and a temperature transmitter, both installed on the steam pipeline and arranged in sequence. The steam pipeline is connected to the outlet end of the manual diaphragm valve. The steam control valve is located upstream of the outlet end of the manual diaphragm valve, and the temperature transmitter is located downstream of the outlet end of the manual diaphragm valve and close to the outlet end of the manual diaphragm valve. The temperature transmitter is used to monitor the sterilization temperature.
5. The feeding device for the batching tank according to claim 4, characterized in that, The sterilization assembly also includes a steam trap installed on the steam pipeline. The steam trap is located downstream of the outlet end of the manual diaphragm valve and is used to discharge pure steam condensate.
6. The feeding device for the batching tank according to claim 4, characterized in that, It also includes a gas purging assembly, which includes a purging pipeline, a gas sterilization filter and a purging control valve, both installed on the purging pipeline. The purging control valve is located downstream of the gas sterilization filter. One end of the purging pipeline is connected to a sterile gas source, and the other end of the purging pipeline is connected to the steam pipeline to purge residual condensate with sterile gas after sterilization.
7. The feeding device for the batching tank according to claim 6, characterized in that, An electric heating element is provided on the outside of the outer shell of the gas sterilization filter, and the electric heating element is used to heat the gas sterilization filter.
8. The feeding device for the batching tank according to any one of claims 1 to 7, characterized in that, It also includes a metering device and a PLC controller. The PLC controller is electrically connected to the metering device and the peristaltic pump respectively, so as to adjust the speed of the peristaltic pump according to the feedback signal of the metering device. The metering device is a weighing module or a flow meter.
9. A sterile feeding method, characterized in that, The method comprises: using the feeding device for the batching tank as described in any one of claims 1 to 8 The aseptic container, tubing and manual diaphragm valve in the feeding assembly are sterilized offline. Under aseptic conditions, the raw materials and excipients are loaded into the sterile container that has been sterilized offline and then sealed. Connect one end of the tubing to the sterile container, connect the other end of the tubing to the inlet of the manual diaphragm valve, connect the outlet of the manual diaphragm valve to the top interface of the mixing tank, and install the peristaltic pump on the tubing. Start the sterilization assembly and introduce pure steam into the outlet end of the manual diaphragm valve to sterilize the outlet end of the manual diaphragm valve in situ. After sterilization, open the manual diaphragm valve and start the peristaltic pump to pump the raw materials and auxiliary materials in the sterile container into the mixing tank through the hose.
10. The aseptic feeding method according to claim 9, characterized in that, After in-situ sterilization of the outlet end of the manual diaphragm valve and before opening the manual diaphragm valve for feeding, the method further includes: Sterile gas is introduced into the outlet of the manual diaphragm valve to purge the residual pure steam and condensate in the pipeline to the discharge pipeline.