Production device for assisted reproduction culture solution

Abstract

The utility model provides an assisted reproduction culture solution production device, which relates to the technical field of assisted reproduction and comprises a disposable stirring bag, the disposable stirring bag is fixed in a stirring container, the top of the disposable stirring bag is provided with a liquid inlet, an exhaust port and a feeding port, the bottom of the disposable stirring bag is provided with an air inlet and a liquid outlet, and the air inlet is connected with an air inlet pipeline; the exhaust port is connected with an exhaust pipeline; a stirring paddle is arranged in the disposable stirring bag; a discharge hole of the glove box is communicated with a feeding hole of the disposable stirring bag; a liquid inlet of the liquid storage bag is communicated with the liquid outlet of the disposable stirring bag, and a liquid outlet of the liquid storage bag is connected with a filling machine; a gas outlet pipe of the dynamic gas distribution instrument is connected to the filling machine, and the dynamic gas distribution instrument is used for introducing protective gas with a set proportion into the filling machine. According to the utility model, the steps of transferring raw materials and semi-finished products in the stirring, filtering and filling processes are simplified, and the pollution risk and the production difficulty in the processes of transferring the raw materials and the semi-finished products and cleaning appliances are reduced.

Description

Technical Field

[0001] The utility model relates to the technical field of assisted reproduction, in particular to a device for producing assisted reproduction culture fluid. Background Art

[0002] Assisted reproduction refers to the use of artificial assistance to help infertile patients realize their desire to have children. The egg and sperm are combined in vitro, cultured for 3-5 days after successful fertilization, and then transplanted into the mother. When the gametes and embryos are in an in vitro environment, they will be placed in a culture medium containing nutrients. The culture medium mainly provides an external environment suitable for the growth of gametes and embryos, such as pH, osmotic pressure, energy, nutrients, etc.

[0003] Culture medium products need to come into direct contact with embryo culture medium, so there are extremely high requirements for this type of product. Therefore, the production process of this type of product is an aspect that deserves great attention and research. The currently known production processes mainly include four major processes: weighing, liquid preparation, filtration, and filling. The external environment, human operation, and incomplete cleaning of production equipment in the liquid preparation and filtration processes will all introduce contamination risks. Utility Model Content

[0004] In view of this, an embodiment of the present application provides an assisted reproductive culture fluid production device, which is a disposable, continuous production device that aims to reduce the direct or indirect contact between the assisted reproductive culture fluid product and the external environment and operators, reduce the cleaning steps of the instruments and pipelines involved in the production process, prevent oxygen-sensitive raw materials from being exposed to the oxygen environment, simplify the transfer steps of raw materials and semi-finished products in the process, and reduce the risk of contamination and production difficulty.

[0005] The embodiment of the present application provides the following technical solution: an assisted reproductive culture fluid production device, comprising:

[0006] A disposable stirring bag, wherein the disposable stirring bag is fixedly arranged in a stirring container, a liquid inlet, an exhaust port and a feeding port are arranged on the top of the disposable stirring bag, an air inlet and a liquid outlet are arranged on the bottom of the disposable stirring bag, the air inlet is connected to an air inlet pipe for introducing a protective gas, and the exhaust port is connected to an exhaust pipe for discharging the protective gas; a stirring paddle is arranged inside the disposable stirring bag;

[0007] A glove box, wherein the discharge port of the glove box is connected to the feeding port of the disposable stirring bag, and is used to directly feed the assisted reproductive culture fluid raw material into the disposable stirring bag through the glove box;

[0008] A liquid storage bag, wherein the liquid inlet of the liquid storage bag is connected to the liquid outlet of the disposable mixing bag, and the liquid outlet of the liquid storage bag is connected to a filling machine;

[0009] A dynamic gas distributor, wherein the gas outlet pipe of the dynamic gas distributor is connected to the filling machine and is used for introducing protective gas of a set ratio into the filling machine.

[0010] According to one embodiment of the present application, it also includes a circulation pipe inside the stirring bag, the circulation outlet of the circulation pipe inside the stirring bag is connected to the bottom of the disposable stirring bag, and the circulation inlet of the circulation pipe inside the stirring bag is connected to the top of the disposable stirring bag; a peristaltic pump is arranged on the circulation pipe inside the stirring bag.

[0011] According to an embodiment of the present application, a support airbag is fixedly provided on one side of the liquid storage bag, so as to make the liquid storage bag present a set slope through the support of the support airbag.

[0012] According to one embodiment of the present application, a filtering device is further included, and the filtering device is arranged on a connecting pipe between the liquid outlet of the disposable stirring bag and the liquid inlet of the liquid storage bag.

[0013] According to one embodiment of the present application, a peristaltic pump is further included, and the peristaltic pump is arranged on a connecting pipe between the liquid outlet of the disposable stirring bag and the liquid inlet of the filtering device.

[0014] According to an embodiment of the present application, a pressure reducing valve, a pressure sensor and an air filter are arranged on the air intake pipe.

[0015] According to an embodiment of the present application, the discharge port of the glove box and the feeding port of the disposable mixing bag are connected through a feeding pipe, and a connecting knob is provided on the feeding pipe.

[0016] According to an embodiment of the present application, a weighing device is provided in the glove box.

[0017] According to one embodiment of the present application, the liquid storage bag is a disposable sterile liquid storage bag; and the filtering device is a disposable filtering device.

[0018] According to one embodiment of the present application, control valves are provided on the air inlet, the exhaust port, the liquid inlet and the liquid outlet of the disposable mixing bag.

[0019] Compared with the prior art, the at least one technical solution adopted in the embodiments of this specification can achieve the following beneficial effects:

[0020] 1. Since the assisted reproductive culture medium contains a variety of oxygen-sensitive or hygroscopic raw materials, a low-oxygen and low-humidity weighing environment needs to be controlled by a vacuum glove box. Therefore, in this embodiment, the glove box and the disposable mixing bag are detachably connected through a stainless steel pipe. There is a pipe knob in the glove box to control the opening and closing of the pipe. The weighed raw materials can be directly put into the disposable mixing bag through the pipe to reduce the risk of contamination during the transfer process.

[0021] 2. This device has added a gas protection pipeline, and the air inlet is equipped with a pressure reducing valve and a pressure sensor. It can control and adjust the air intake of the protective gas in real time through interconnection with the stirring system. The air inlet of the protective gas is below the liquid surface, which can effectively reduce the dissolved oxygen in the water and achieve a low-oxygen environment during the liquid preparation process to prevent oxidation of oxygen-sensitive raw materials.

[0022] 3. The disposable mixing bag of this device is equipped with an internal circulation pipeline, and a peristaltic pump is used to provide power so that the liquid in the bag can circulate continuously, thereby achieving a more complete mixing effect.

[0023] 4. This device provides an auxiliary platform for the liquid storage bag during the filling process of the liquid storage bag to generate a filling slope, which is beneficial to the filling process and convenient for the liquid storage bag to discharge liquid. This liquid storage bag is equipped with a supporting air bag, which can be achieved without adding additional equipment.

[0024] 5. Since some assisted reproductive fluids (full-course culture fluid, etc.) require the addition of protective gases in different ratios during the filling process, this device can be connected to a dynamic gas distributor, which is connected to the gas source of the required gas to achieve the addition of a single or multiple protective gases.

[0025] 6. The liquid preparation, filtration, liquid storage and pipeline devices in the whole set of equipment of this embodiment are all disposable products, which can achieve zero cleaning work in the whole liquid preparation and filtration process.

[0026] 7. The device is an integrated continuous device. It only needs to adjust the bag body specifications of the bag device according to production needs. It is easy to operate and can complete the sterile product preparation and filtration process in a Class C environmental area. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0028] Figure 1 This is a schematic diagram of the structure of an assisted reproductive culture fluid production device according to an embodiment of the utility model;

[0029] Figure 2 It is a schematic diagram of the structure of the liquid storage bag and the supporting airbag in the embodiment of the utility model;

[0030] In the figure, 1-glove box; 2-connecting knob; 3-feeding port; 4-exhaust pipe; 5-liquid inlet; 6-circulation pipe in the mixing bag; 7-stirring paddle; 8-air inlet pipe; 9-liquid outlet pipe; 10-disposable mixing bag; 11-peristaltic pump; 12-filtering device; 13-liquid inlet pipe of the liquid storage bag; 14-liquid storage bag; 15-support airbag; 16-dynamic gas distributor; 17-liquid outlet pipe of the liquid storage bag; 18-filling machine. DETAILED DESCRIPTION

[0031] The embodiments of the present application are described in detail below with reference to the accompanying drawings.

[0032] The following describes the implementation methods of the present application through specific examples, and those skilled in the art can easily understand other advantages and effects of the present application from the contents disclosed in this specification. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. The present application can also be implemented or applied through other different specific implementation methods, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present application. It should be noted that, in the absence of conflict, the following embodiments and the features in the embodiments can be combined with each other. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without making creative work belong to the scope of protection of the present application.

[0033] like Figure 1 As shown, an embodiment of the utility model provides an assisted reproductive culture fluid production device, comprising: a disposable stirring bag 10, wherein the disposable stirring bag 10 is fixedly arranged in a stirring container, a liquid inlet 5, an exhaust port and a feeding port 3 are arranged on the top of the disposable stirring bag 10, an air inlet and a liquid outlet are arranged on the bottom of the disposable stirring bag 10, the air inlet is connected to an air inlet pipe 8 for introducing a protective gas, and the exhaust port is connected to an exhaust pipe 4 for discharging the protective gas; a stirring paddle 7 is arranged inside the disposable stirring bag 10; a glove box 1, wherein the feeding port of the glove box 1 is connected to the feeding port 3 of the disposable stirring bag 10, so as to directly feed the assisted reproductive culture fluid raw material into the disposable stirring bag 10 through the glove box 1; a liquid storage bag 14, wherein the liquid inlet of the liquid storage bag 14 is connected to the liquid outlet of the disposable stirring bag 10, and the liquid outlet of the liquid storage bag 14 is connected to a filling machine 18.

[0034] In order to reduce the risk of contamination introduced by the external environment, human operation and incomplete cleaning of production equipment during the liquid preparation and filtration processes, the embodiment of the utility model proposes an integrated production device for assisted reproductive culture fluid products, which aims to reduce the direct or indirect contact between the product and the external environment and operators, reduce the cleaning steps of the equipment and pipelines involved in the production process, prevent oxygen-sensitive raw materials from being exposed to the oxygen environment, simplify the transfer steps of raw materials and semi-finished products between processes, and reduce the difficulty of production.

[0035] In one embodiment, this embodiment also includes a circulation pipe 6 inside the stirring bag, the circulation outlet of the circulation pipe 6 inside the stirring bag is connected to the bottom of the disposable stirring bag 10, and the circulation inlet of the circulation pipe 6 inside the stirring bag is connected to the top of the disposable stirring bag 10; a peristaltic pump 11 is arranged on the circulation pipe 6 inside the stirring bag.

[0036] In one embodiment, Figure 2 As shown, a support airbag 15 is fixedly provided on one side of the liquid storage bag 14 of this embodiment, so as to make the liquid storage bag 14 present a set slope through the support of the support airbag 15 .

[0037] The device mainly includes a liquid preparation bag (i.e., the disposable stirring bag 10 mentioned above), a vacuum glove box 1, a filter device 12, a liquid storage bag 14, a dynamic gas distributor 16, a filling machine 18, and a connecting pipe. In a further preferred embodiment, it also includes a filter device 12, which is arranged on the connecting pipe between the liquid outlet of the disposable stirring bag 10 and the liquid inlet of the liquid storage bag 14. In a further preferred embodiment, it also includes a peristaltic pump 11, which is arranged on the connecting pipe between the liquid outlet of the disposable stirring bag 10 and the liquid inlet of the filter device 12.

[0038] In specific implementation, the vacuum glove box of this embodiment can provide an environment with an oxygen content of less than 1% and a humidity of less than 10%, so as to effectively ensure a low oxygen and low humidity environment when weighing oxygen-sensitive and hygroscopic raw materials. The top of the disposable stirring bag 10 is provided with a feeding port 3 connected to the glove box 1 through a connecting knob 2, so that the weighed raw materials can be directly put into the disposable stirring bag 10 to reduce contact with the external environment. The disposable stirring bag 10 is a 3D rectangular parallelepiped structure, and the stirring container adopts a stirring support container of a magnetic stirring system. The disposable stirring bag 10 is supported by a rectangular parallelepiped metal support container and is used in conjunction with a magnetic stirring system and a glove box 1. A liquid inlet 5, an exhaust port and a feeding port 3 are provided above the bag body, and a stirring paddle 7, a liquid outlet and an air inlet are provided below the bag body; wherein the air inlet is connected to an air inlet pipe 8 for introducing protective gas, the exhaust port is connected to an exhaust pipe 4, and the feeding port 3 is connected to the discharge port of the glove box 1 through a feeding pipe, wherein valves are provided on the air inlet, exhaust port, liquid inlet 5 and liquid outlet of the disposable stirring bag 10. The disposable stirring bag 10 is also provided with an inner circulation pipe 6 of the stirring bag, and the inner circulation pipe 6 of the stirring bag is connected to a peristaltic pump 11 to increase the stirring effect.

[0039] The liquid outlet is connected to the peristaltic pump 11 through the liquid outlet pipe 9, and the peristaltic pump 11 is connected to the filter device 12. The peristaltic pump 11 provides power to pass the culture solution into the filter device 12 for filtration. The filter device 12 is connected to the liquid storage bag 14 through the liquid storage bag liquid inlet pipe 13, and the filtered culture solution is passed into the liquid storage bag 14 for temporary storage. The liquid storage bag 14 is connected to the filling machine 18 through the liquid storage bag liquid outlet pipe 17, and the filling machine 18 performs the final filling.

[0040] In this embodiment, a weighing device is provided in the glove box 1, and the weighing device in this embodiment adopts an electronic balance. The glove box 1 is a laboratory equipment that fills a high-purity inert gas into the box body and circulates and filters out the active substances therein. It is also called a vacuum glove box, an inert gas protection box, a dry box, etc. It is mainly used for the removal of O2, H2O, and organic gases. It is widely used in anhydrous, oxygen-free, and dust-free ultra-pure environments. The weighing process of various raw materials for assisted reproduction in this embodiment needs to control a low-oxygen and low-humidity environment. After the raw materials are weighed in the vacuum glove box 1, they can be directly put into the liquid preparation bag through a pipeline to reduce the risk of contamination during the transfer process. In addition, a protective pipeline is added in this embodiment, that is, the air inlet of the disposable stirring bag 10 is passed through the protective gas nitrogen, and a pressure reducing valve, a pressure sensor, and an air filter element are provided on the air inlet pipeline 8. The air intake of nitrogen can be controlled and adjusted in real time through the interconnection with the stirring system to achieve a low-oxygen environment and prevent oxidation of oxygen-sensitive raw materials.

[0041] In this embodiment, the filtering device 12 is a disposable filter. In the direction of liquid flow, the filtering device 12 is connected to a disposable stirring bag 10 in front and to a disposable sterile liquid storage bag 14 in the back. A peristaltic pump 11 is arranged in front of the filter to provide power to pass the culture fluid in the liquid preparation bag through the filter into the liquid storage bag 14. This process can achieve a sterilization filtration effect.

[0042] In this embodiment, the liquid storage bag 14 is a disposable sterile liquid storage bag with a 2D rectangular structure; the disposable sterile liquid storage bag is connected to the filtering device 12 in front and connected to the filling machine 18 in the back, receiving the culture solution after sterilization and filtration by the primary filtering device, and plays a temporary storage function between the filtering and filling processes. The liquid storage bag 14 is equipped with a supporting air bag 15, which can make the liquid storage bag 14 present a certain slope, which helps to reduce the loss of the culture solution in the bag.

[0043] The dynamic gas distributor 16 is a gas mixing device. In a specific implementation, different gas source air inlet pipes can be connected to the dynamic gas distributor 16. The dynamic gas distributor 16 outputs mixed protective gas with different gas proportions set as required. The air outlet pipe is connected to the filling machine 18, so that the protective gas can be filled during filling.

[0044] The filling machine 18 is a device for filling the filtered culture solution into the primary package. The filling machine 18 is connected to the liquid storage bag outlet pipe 17 and the gas outlet pipe of the dynamic gas distributor 16, so that a certain proportion of mixed protective gas can be filled into the packaging bottle while the culture solution is canned.

[0045] In this embodiment, the process of using the assisted reproductive culture fluid production device to produce egg retrieval fluid products is as follows:

[0046] 1. Place the disposable stirring bag in the support container of the magnetic stirring system, connect it to the glove box with a stainless steel pipe, open the air inlet and exhaust pipes, introduce nitrogen, and after the disposable stirring bag is filled with nitrogen, adjust the nitrogen flow rate to a low rate, and add water into the disposable stirring bag through the liquid inlet pipe connected to the liquid inlet, and stop when the set weight is reached.

[0047] 2. Weigh the raw materials, open the connection knob, put the weighed raw materials in the glove box into the disposable mixing bag through the connecting pipe and the feeding port, turn on the magnetic stirrer, stir evenly, and after all the raw materials are added and stirred, open the circulation pipeline in the mixing bag to stir fully;

[0048] 3. After all the raw materials are put into the bag and stirred evenly, open the control valve and peristaltic pump of the liquid outlet pipeline, select the appropriate pump speed to filter the culture solution through the filter and transfer it into the sterile liquid storage bag, then connect the liquid storage bag outlet to the filling machine, turn on the gas source and dynamic gas distributor, adjust the gas ratio to the target value, and perform product filling and protective gas charging in a Class A environment.

[0049] The above-mentioned liquid preparation process is protected by nitrogen to avoid oxidation of oxygen-sensitive raw materials and effectively avoid pollution from the outside air. The circulation system in the stirring bag is used to achieve full dissolution and mixing of the raw materials. After liquid preparation, the solution is directly filtered into a sterile liquid storage bag through a filter without contacting the external environment to avoid the possibility of re-contamination. A certain proportion of protective gas is filled in during the filling process to effectively protect the product from contact with the air.

[0050] The utility model combines the weighing process, liquid preparation process, filtration process and filling process required for the production of assisted reproductive culture fluid to design an integrated continuous device, which simplifies and optimizes the weighing, stirring, filtering and filling steps. It only needs to adjust the bag body specifications of the bag device according to production needs. It is easy to operate and can achieve gas protection for raw materials and intermediates, reducing the pollution risk and production difficulty during the transfer of raw materials and intermediates and the cleaning of equipment. It can meet the requirements of weighing, liquid preparation and filtration of sterile products in a Class C environmental area, and greatly reduces the pollution risks introduced by the external environment, human operation and incomplete cleaning of production equipment in the liquid preparation and filtration processes.

[0051] The above is only a specific implementation of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed in the present application should be included in the protection scope of the present application. Therefore, the protection scope of the present application shall be based on the protection scope of the claims.

Claims

1. An assisted reproductive culture fluid production device, characterized in that: include: A disposable stirring bag, wherein the disposable stirring bag is fixedly arranged in a stirring container, a liquid inlet, an exhaust port and a feeding port are arranged on the top of the disposable stirring bag, an air inlet and a liquid outlet are arranged on the bottom of the disposable stirring bag, the air inlet is connected to an air inlet pipe for introducing a protective gas, and the exhaust port is connected to an exhaust pipe for discharging the protective gas; a stirring paddle is arranged inside the disposable stirring bag; A glove box, wherein the discharge port of the glove box is connected to the feeding port of the disposable stirring bag, and is used to directly feed the assisted reproductive culture fluid raw material into the disposable stirring bag through the glove box; A liquid storage bag, wherein the liquid inlet of the liquid storage bag is connected to the liquid outlet of the disposable mixing bag, and the liquid outlet of the liquid storage bag is connected to a filling machine; A dynamic gas distributor, wherein the gas outlet pipe of the dynamic gas distributor is connected to the filling machine and is used for introducing protective gas of a set ratio into the filling machine.

2. The assisted reproductive culture fluid production device according to claim 1, characterized in that: It also includes a circulation pipe in the stirring bag, the circulation outlet of the circulation pipe in the stirring bag is connected to the bottom of the disposable stirring bag, and the circulation inlet of the circulation pipe in the stirring bag is connected to the top of the disposable stirring bag; a peristaltic pump is arranged on the circulation pipe in the stirring bag.

3. The assisted reproductive culture fluid production device according to claim 1, characterized in that: A support airbag is fixedly arranged on one side of the liquid storage bag, and is used for making the liquid storage bag present a set slope through the support of the support airbag.

4. The assisted reproductive culture fluid production device according to claim 1, characterized in that: It also includes a filtering device, which is arranged on a connecting pipe between the liquid outlet of the disposable stirring bag and the liquid inlet of the liquid storage bag.

5. The assisted reproductive culture fluid production device according to claim 4, characterized in that: It also includes a peristaltic pump, which is arranged on a connecting pipe between the liquid outlet of the disposable stirring bag and the liquid inlet of the filtering device.

6. The assisted reproductive culture fluid production device according to claim 1, characterized in that: The air intake pipeline is provided with a pressure reducing valve, a pressure sensor and an air filter element.

7. The assisted reproductive culture fluid production device according to claim 1, characterized in that: The discharge port of the glove box is connected to the feeding port of the disposable mixing bag through a feeding pipe, and a connecting knob is arranged on the feeding pipe.

8. The assisted reproductive culture fluid production device according to claim 1, characterized in that: A weighing device is arranged in the glove box.

9. The assisted reproductive culture fluid production device according to claim 4, characterized in that: The liquid storage bag is a disposable sterile liquid storage bag; the filtering device is a disposable filtering device.

10. The assisted reproductive culture fluid production device according to claim 1, characterized in that: Control valves are arranged on the air inlet, the air outlet, the liquid inlet and the liquid outlet of the disposable mixing bag.

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