CN118580931A - An integrated sterilization and fermentation device for biopharmaceuticals - Google Patents

Abstract

The present invention discloses an integrated sterilization and fermentation device for biopharmaceuticals, which specifically relates to the field of biopharmaceuticals, including a fermentation tank body, a stirring mechanism, which is arranged inside the fermentation tank body and is used to stir the microorganisms inside the fermentation tank body; a gas control mechanism, which is arranged on the outer wall of the fermentation tank body and is used to adjust the gas inside the fermentation tank body; a temperature control component, which is arranged on the outer wall of the fermentation tank body, and a detection component is fixedly connected to one side of the fermentation tank body, which is used to control the internal temperature of the fermentation tank body. The present invention drives the agitator to rotate and stir the microbial strains, while driving the piston plate to move back and forth in the inner cavity of the buffer bin in an intermittent state, thereby improving the ventilation efficiency, thereby assisting in reducing the gas content in the liquid and reducing the formation of bubbles.

Description

An integrated sterilization and fermentation device for biopharmaceuticals

Technical Field

The present invention relates to the technical field of biopharmaceuticals, and more specifically to an integrated sterilization and fermentation device for biopharmaceuticals.

Background Art

The integrated sterilization and fermentation device for biopharmaceuticals can improve production efficiency, reduce costs, and reduce pollution risks. It is one of the important development trends in the biopharmaceutical industry in terms of production process optimization and upgrading. The integrated sterilization and fermentation device for biopharmaceuticals integrates multiple process steps into one system, reducing the footprint of the equipment, making the production site more efficient, and reducing the risk of pollution from the external environment to production, reducing the possibility of cross-contamination.

The Chinese patent with application number CN202110051108.3 discloses a biopharmaceutical microbial mixed fermentation tank, including a fermentation tank, a feeding mechanism is provided at the front end of the fermentation tank, a feeding mechanism is provided at the bottom of the fermentation tank, a stirring mechanism is provided on the fermentation tank, and the stirring mechanism includes a first rotating shaft rotatably connected to the top of the fermentation tank, an air inlet pipe inserted into the interior of the fermentation tank is provided on the left side of the outer wall of the fermentation tank, and a first push plate is slidably connected to the inner wall of the air inlet pipe through a first spring, and an air outlet pipe is provided on the right side of the interior of the fermentation tank, and the air outlet pipe includes a horizontal pipe and a vertical pipe interconnected with each other, and the left end of the horizontal pipe is connected to the interior of the fermentation tank. However, during the use of this patent, as the tank temperature rises, the organic nitrogen source in the culture medium will produce a large amount of foam due to differences in ratio, variety, and loading, or due to improper use of gas, and the foam will become an insulation layer, and the steam heat is difficult to penetrate, and the bacteria are not easy to be killed.

Moreover, when using the integrated sterilization and fermentation equipment for pharmaceutical use, the microbial strains need to be fully mixed and stirred during the fermentation process. Uneven mixing and stirring can easily lead to insufficient fermentation, resulting in low fermentation efficiency, in order to promote the growth and metabolism of microorganisms. However, continuous high-speed stirring can easily lead to a large number of bubbles or foams inside the equipment, affecting the dissolution of oxygen in the microbial strains and the growth of microorganisms, which is not convenient for actual use. Therefore, the present invention proposes an integrated sterilization and fermentation device for biopharmaceuticals to solve the above problems.

Summary of the invention

In order to overcome the above-mentioned defects of the prior art, an embodiment of the present invention provides an integrated sterilization and fermentation device for biopharmaceuticals, which drives the agitator to rotate and stir the inside of the fermentation tank while driving the piston plate to move back and forth in the inner cavity of the buffer bin in an intermittent state to solve the problems raised in the above-mentioned background technology.

To achieve the above object, the present invention provides the following technical solution: a biopharmaceutical sterilization and fermentation integrated device, comprising a fermentation tank body, and also comprising:

A stirring mechanism, the stirring mechanism is arranged inside the fermentation tank body and is used to stir the microorganisms inside the fermentation tank body;

An air control mechanism, which is arranged on the outer wall of the fermentation tank body and is used to adjust the gas inside the fermentation tank body;

A temperature control component is arranged on the outer wall of the fermentation tank body. A detection component is fixedly connected to one side of the fermentation tank body for controlling the internal temperature of the fermentation tank body.

Preferably, the air control mechanism includes a ventilation pipe connected to the outer wall of the fermentation tank body, the outer wall of the ventilation pipe is connected to a first air pipe, the top of the first air pipe is connected to a buffer bin fixedly connected to the outer wall of the fermentation tank body, the outer wall of the buffer bin is connected to a second air pipe, and one end of the second air pipe is connected to a ventilator.

Preferably, the inner cavity of the buffer bin is slidably connected to a piston plate, and a piston rod is fixedly connected to a side of the piston plate close to the ventilation pipe. The piston rod passes through one end of the buffer bin and extends into the interior of the fermentation tank body.

Preferably, a spring is connected between the side of the piston plate close to the piston rod and the buffer chamber, and the spring is sleeved on the outer wall of the piston rod.

Preferably, the stirring mechanism includes a motor fixedly connected to the top of the fermentation tank body, the output end of the motor is fixedly connected to a rotating shaft rotatably connected to the fermentation tank body, the outside of the rotating shaft is fixedly connected to a cam, and the end of the piston rod is always in contact with the outer wall of the cam under the action of a spring.

Preferably, one end of the rotating shaft extending into the interior of the fermentation tank is fixedly connected to a support frame, and one end of the support frame is rotatably connected to an agitator.

Preferably, the outer wall of the rotating shaft is rotatably connected to a filter plate, the filter plate is located at the bottom of the cam, and the filter plate is fixedly connected to the inner wall of the fermentation tank body, the bottom of the filter plate is fixedly connected to an internal gear, and the inner wall of the internal gear is meshed with a transmission gear fixedly connected to the agitator.

Preferably, the first air pipe is connected to the outer wall of the buffer bin, the second air pipe is connected to the end of the buffer bin away from the fermentation tank body, and a plurality of ventilation holes are provided at the connection between the ventilation pipe and the fermentation tank body.

Preferably, a feed pipe and a discharge pipe are provided on the top of the fermentation tank body, wherein the feed pipe is used to input materials into the fermentation tank body, and the discharge pipe is used to discharge waste liquid from the fermentation tank body.

Technical effects and advantages of the present invention:

1. The present invention can quickly mix and stir the microbial strains through the cooperation of the rotating shaft and the stirrer, which not only allows the gas introduced into the tank to be fully dispersed and increases the gas-liquid contact area, but also prolongs the residence time of the air in the tank to promote the growth and metabolism of the microorganisms;

2. The present invention cooperates with the cam and the piston rod so that the gas can intermittently enter the interior of the fermentation tank body and intermittently intake air, thereby improving the ventilation efficiency, thereby assisting in reducing the gas content in the liquid and reducing the formation of bubbles. The air flow rate is reduced during the fermentation process so that there are no bubbles at the liquid surface inside the fermentation tank body, and the foam is prevented from becoming an insulating layer, so that the steam heat can easily kill the bacteria inside the fermentation tank body. The improvement in ventilation efficiency can reduce the amount of air used, thereby reducing the formation of foam and the chance of contamination by miscellaneous bacteria, thereby ensuring the smooth progress of the fermentation or reaction process and the stability of product quality.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a schematic diagram of the overall structure of the present invention;

Fig. 2 is a schematic diagram of the fermentation tank structure of the present invention;

Fig. 3 is a cross-sectional view of the fermentation tank structure of the present invention;

FIG4 is a schematic diagram of the structure of an agitator of the present invention;

FIG5 is a schematic diagram of the structure of the gas control mechanism of the present invention;

FIG6 is a cross-sectional view of the structure of the gas control mechanism of the present invention;

FIG. 7 is a cross-sectional view of the buffer bin structure of the present invention.

The accompanying drawings are marked as follows: 1. fermentation tank body; 2. stirring mechanism; 21. motor; 22. rotating shaft; 23. support frame; 24. stirrer; 25. filter plate; 26. internal gear; 27. transmission gear; 3. air control mechanism; 31. ventilation pipe; 32. first air pipe; 33. buffer bin; 34. second air pipe; 35. breather; 36. piston plate; 37. piston rod; 38. spring; 39. cam; 310. ventilation hole; 4. temperature control component; 5. detection component; 6. feed pipe; 7. discharge pipe.

DETAILED DESCRIPTION

The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. 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.

Example 1

In the existing sterilization and fermentation devices, uneven mixing and stirring during operation may easily lead to insufficient fermentation, resulting in low fermentation efficiency.

As shown in FIG1 , a sterilization and fermentation integrated device for biopharmaceuticals includes a fermentation tank body 1, and also includes: a stirring mechanism 2, which is arranged inside the fermentation tank body 1 and is used to stir the microorganisms inside the fermentation tank body 1; an air control mechanism 3, which is arranged on the outer wall of the fermentation tank body 1 and is used to adjust the gas inside the fermentation tank body 1; a temperature control component 4, which is arranged on the outer wall of the fermentation tank body 1, and a detection component 5 is fixedly connected to one side of the fermentation tank body 1 for controlling the internal temperature of the fermentation tank body 1. In actual use, the detection component 5 can control the sterilization component inside the fermentation tank body 1 to perform sterilization treatment to ensure the sterile conditions of the fermentation process, and is also used to monitor and control various parameters in the fermentation process, such as temperature, pH value, stirring speed, etc., to ensure that the fermentation process can proceed smoothly. In order to carry out the fermentation and achieve the expected production target, in the specific implementation, the selected microbial strains are inoculated into the interior of the fermentation tank body 1, and the fermentation tank body 1 is disinfected and sterilized by its own sterilization component before fermentation, and then the temperature, humidity, gas composition, pH and other parameters of the fermentation tank body 1 are synchronously adjusted to a suitable environment to meet the requirements of microbial growth and metabolism, and the control system monitors and adjusts the temperature, stirring speed, ventilation volume, pH value and other parameters during the fermentation process according to the preset fermentation conditions to maintain the best growth environment, and the microorganisms grow, metabolize and synthesize products under suitable fermentation conditions to produce the target product. A feed pipe 6 and a discharge pipe 7 are provided on the top of the fermentation tank body 1, and the feed pipe 6 is used to input materials into the interior of the fermentation tank body 1, and the discharge pipe 7 is used to discharge the waste liquid inside the fermentation tank body 1.

As shown in Figures 2 to 4, the stirring mechanism 2 includes a motor 21 fixedly connected to the top of the fermentation tank body 1, the output end of the motor 21 is fixedly connected to a rotating shaft 22 rotatably connected to the fermentation tank body 1, one end of the rotating shaft 22 extending into the fermentation tank body 1 is fixedly connected to a support frame 23, the center of the support frame 23 is fixedly connected to the rotating shaft 22, one end of the support frame 23 is rotatably connected to an agitator 24, and the agitator 24 can rotate in a circle inside the fermentation tank body 1 when rotating, the outer wall of the rotating shaft 22 is rotatably connected to a filter plate 25, the filter plate 25 is located at the bottom of the cam 39, and the filter plate 25 is fixedly connected to the inner wall of the fermentation tank body 1, the bottom of the filter plate 25 is fixedly connected to an internal gear 26, and the inner wall of the internal gear 26 is meshed with a transmission gear 27 fixedly connected to the agitator 24.

When the driving shaft 22 drives the support frame 23 to rotate, the agitator 24 rotates around the inner wall of the fermentation tank body 1. At the same time, the transmission gear 27 and the internal gear 26 are meshed with each other, so that the agitator 24 as a whole rotates synchronously at the bottom of the support frame 23, and the agitator 24 rotates in a circle inside the fermentation tank body 1. The agitator 24 stirs and flips the microbial strains at the vertical center line position of the fermentation tank body 1 and the microbial strains near the inner wall position of the fermentation tank body 1, and fully mixes and stirs the microbial strains. Driven by the rotating shaft 22, the agitator 24 can quickly mix and stir the microbial strains. Since the solubility of oxygen in water is very small, so is the solubility in the fermentation liquid. Therefore, continuous ventilation and stirring are required to meet the oxygen requirements of different fermentation processes. In order to meet the needs of the present invention, the stirring speed is increased, which not only makes the gas introduced into the tank fully dispersed and increases the gas-liquid contact area, but also prolongs the residence time of the air in the tank to promote the growth and metabolism of microorganisms. Compared with the existing sterilization and fermentation device, the agitator 24 is located at the center of the device, and the stirring is rotated by the center, which is easy to cause foam, and it is difficult to drive the microorganisms at the edge of the inner wall of the device, resulting in uneven fermentation and poor fermentation quality. The agitator 24 of the device is located on the side of the device. When the agitator 24 rotates, it can rotate in a circle inside the fermentation tank body 1. The agitator 24 stirs and flips the microorganisms at the vertical center line of the fermentation tank body 1 and the microorganisms near the inner wall of the fermentation tank body 1, so as to fully mix and stir the microorganisms, improve the fermentation effect, and improve the fermentation quality.

Through the cooperation between the rotating shaft 22 and the agitator 24, the microbial strains can be quickly mixed and stirred, which not only allows the gas introduced into the tank to be fully dispersed and increases the gas-liquid contact area, but also prolongs the residence time of the air in the tank to promote the growth and metabolism of the microorganisms.

Example 2

On the basis of the above embodiments, during the working process, as the tank temperature rises, the organic nitrogen source in the culture medium will produce a large amount of foam due to differences in ratio, variety, loading amount, or due to improper use of gas. The foam will become an insulating layer, making it difficult for steam heat to penetrate and the bacteria to be difficult to kill.

As shown in Figures 5 to 7, the gas control mechanism 3 includes a vent pipe 31 connected to the outer wall of the fermentation tank body 1, and a plurality of vent holes 310 are opened at the connection between the vent pipe 31 and the fermentation tank body 1. The vent pipe 31 is connected to the fermentation tank body 1 through the vent holes 310. The outer wall of the vent pipe 31 is connected to a first air pipe 32, and the top of the first air pipe 32 is connected to a buffer bin 33 fixedly connected to the outer wall of the fermentation tank body 1. The buffer bin 33 is used for gas regulation, and the outer wall of the buffer bin 33 is connected to a second The air pipe 34 is connected to the outer wall of the buffer bin 33, and the second air pipe 34 is connected to the end of the buffer bin 33 away from the fermentation tank body 1. One end of the second air pipe 34 is connected to the ventilator 35, which is used to filter the gas. In actual use, the ventilator 35 is used to provide an air source, so that the external gas enters the interior of the vent pipe 31 through the second air pipe 34, the buffer bin 33, and the first air pipe 32 in sequence, and the vent hole 310 evenly distributes the gas in the inner cavity of the vent pipe 31. To the interior of the fermentation tank body 1, the inner cavity of the buffer bin 33 is slidably connected with a piston plate 36, and the side of the piston plate 36 close to the ventilation pipe 31 is fixedly connected with a piston rod 37, the piston rod 37 passes through one end of the buffer bin 33 and extends into the interior of the fermentation tank body 1, and a spring 38 is connected between the side of the piston plate 36 close to the piston rod 37 and the buffer bin 33, and the spring 38 is sleeved on the outer wall of the piston rod 37, and moves to the side close to the fermentation tank body 1 through the piston plate 36, so that the gas can flow freely into the interior of the ventilation pipe 31. With the stirring of the stirring mechanism 2, the liquid in the inner cavity of the fermentation tank body 1 will gather and increase a large amount of foam due to continuous stirring, and the piston plate 36 moves back and forth up and down in the inner cavity of the buffer bin 33, and the piston plate 36 sequentially and reciprocally blocks the connection between the buffer bin 33 and the second air pipe 34, so as to realize intermittent air intake and improve ventilation efficiency, thereby helping to reduce the gas content in the liquid and reduce the formation of bubbles, so as to ensure the smooth progress of the fermentation or reaction process and the stability of product quality.

As shown in Figures 6 and 7, the stirring mechanism 2 includes a motor 21 fixedly connected to the top of the fermentation tank body 1, and the output end of the motor 21 is fixedly connected to a rotating shaft 22 rotatably connected to the fermentation tank body 1, and the outside of the rotating shaft 22 is fixedly connected to a cam 39. The end of the piston rod 37 is always in contact with the outer wall of the cam 39 under the action of the spring 38. The maximum push stroke of the cam 39 contacts the end of the piston rod 37, which can enable the piston plate 36 to block the second air pipe 34, the ventilation pipe 31 is not ventilated, and the ventilation of the fermentation tank body 1 is stopped.

The motor 21 is started, so that the rotating shaft 22 drives the cam 39 to rotate, and the piston rod 37 slides as a whole on the outer wall of the rotating cam 39. At the same time, under the action of the spring 38, the piston rod 37 is moved back and forth as a whole, so that the piston rod 37 drives the piston plate 36 to move back and forth in the inner cavity of the buffer bin 33, so that the piston plate 36 reciprocates to open and close the connection between the buffer bin 33 and the second air pipe 34. At the same time, the ventilator 35 allows the external air to enter the interior of the ventilation pipe 31 through the second air pipe 34, the buffer bin 33, and the first air pipe 32 in sequence, and the vent hole 310 is ventilated. The gas in the inner cavity of the tube 31 is evenly distributed to the interior of the fermentation tank body 1. The ventilation tube 31 intermittently intakes air into the fermentation tank body 1 to improve the ventilation efficiency, thereby assisting in reducing the gas content in the liquid and reducing the formation of bubbles. The air flow rate is reduced during the fermentation process so that there are no bubbles at the liquid surface inside the fermentation tank body 1, avoiding the foam from becoming an insulating layer, so that the steam heat can easily kill the bacteria inside the fermentation tank body 1. The improvement in ventilation efficiency can reduce the amount of air used, thereby reducing the formation of foam and the chance of contamination by miscellaneous bacteria, so as to ensure the smooth progress of the fermentation or reaction process and the stability of product quality.

Through the cooperation between the cam 39 and the piston rod 37, gas can intermittently enter the interior of the fermentation tank body 1, intermittently intake air, improve ventilation efficiency, thereby helping to reduce the gas content in the liquid, reduce the formation of bubbles, reduce the air flow rate during the fermentation process, so that there are no bubbles at the liquid surface inside the fermentation tank body 1, avoid foam from becoming an insulating layer, so that the steam heat can easily kill the bacteria inside the fermentation tank body 1. The improvement of ventilation efficiency can reduce the amount of air used, thereby reducing the formation of foam and the chance of contamination by miscellaneous bacteria, so as to ensure the smooth progress of the fermentation or reaction process and the stability of product quality.

The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, which fall within the scope of the present invention. The scope of protection claimed by the present invention is defined by the attached claims and their equivalents.

Claims (9)

1. A biopharmaceutical sterilization and fermentation integrated device, comprising a fermentation tank, characterized in that it also includes: A stirring mechanism, the stirring mechanism is arranged inside the fermentation tank body and is used to stir the microorganisms inside the fermentation tank body; An air control mechanism, which is arranged on the outer wall of the fermentation tank body and is used to adjust the gas inside the fermentation tank body; A temperature control component is arranged on the outer wall of the fermentation tank body. A detection component is fixedly connected to one side of the fermentation tank body for controlling the internal temperature of the fermentation tank body. 2. A biopharmaceutical sterilization and fermentation integrated device according to claim 1, characterized in that: the air control mechanism includes a ventilation pipe connected to the outer wall of the fermentation tank body, the outer wall of the ventilation pipe is connected to a first air pipe, the top of the first air pipe is connected to a buffer bin fixedly connected to the outer wall of the fermentation tank body, the outer wall of the buffer bin is connected to a second air pipe, and one end of the second air pipe is connected to a ventilator. 3. A biopharmaceutical sterilization and fermentation integrated device according to claim 2, characterized in that: the inner cavity of the buffer bin is slidably connected to a piston plate, and the side of the piston plate close to the ventilation pipe is fixedly connected to a piston rod, and the piston rod passes through one end of the buffer bin and extends into the interior of the fermentation tank. 4. A biopharmaceutical sterilization and fermentation integrated device according to claim 3, characterized in that: a spring is connected between the side of the piston plate close to the piston rod and the buffer chamber, and the spring is sleeved on the outer wall of the piston rod. 5. A biopharmaceutical sterilization and fermentation integrated device according to claim 4, characterized in that: the stirring mechanism includes a motor fixedly connected to the top of the fermentation tank body, the output end of the motor is fixedly connected to a rotating shaft rotatably connected to the fermentation tank body, the outside of the rotating shaft is fixedly connected to a cam, and the end of the piston rod is always in contact with the outer wall of the cam under the action of a spring. 6. A biopharmaceutical sterilization and fermentation integrated device according to claim 5, characterized in that one end of the rotating shaft extending into the fermentation tank is fixedly connected to a support frame, and one end of the support frame is rotatably connected to a stirrer. 7. A biopharmaceutical sterilization and fermentation integrated device according to claim 6, characterized in that: the outer wall of the rotating shaft is rotatably connected to a filter plate, the filter plate is located at the bottom of the cam, and the filter plate is fixedly connected to the inner wall of the fermentation tank body, the bottom of the filter plate is fixedly connected to an internal gear, and the inner wall of the internal gear is meshed with a transmission gear fixedly connected to the agitator. 8. A biopharmaceutical sterilization and fermentation integrated device according to claim 2, characterized in that: the first air pipe is connected and arranged on the outer wall of the buffer bin, the second air pipe is connected and arranged at one end of the buffer bin away from the fermentation tank body, and a plurality of ventilation holes are provided at the connection between the ventilation pipe and the fermentation tank body. 9. A biopharmaceutical sterilization and fermentation integrated device according to claim 1, characterized in that a feed pipe and a discharge pipe are provided on the top of the fermentation tank body, the feed pipe is used to input materials into the fermentation tank body, and the discharge pipe is used to discharge waste liquid from the fermentation tank body.