CN112481097A - Penicillin fermentation system and process - Google Patents
Penicillin fermentation system and process Download PDFInfo
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- CN112481097A CN112481097A CN201910859853.3A CN201910859853A CN112481097A CN 112481097 A CN112481097 A CN 112481097A CN 201910859853 A CN201910859853 A CN 201910859853A CN 112481097 A CN112481097 A CN 112481097A
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- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/34—Internal compartments or partitions
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- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/06—Nozzles; Sprayers; Spargers; Diffusers
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Abstract
The invention relates to a penicillin fermentation system and a penicillin fermentation process, which comprise the following steps: fermentation cylinder, knockout drum, at least two micro-interface generators and back flow. Compared with the traditional method, the invention forms micron-sized bubbles by crushing air, and mixes the micron-sized bubbles with fermentation raw materials to form gas-liquid emulsion, so as to increase the interfacial area of gas-liquid two phases and achieve the effect of strengthening mass transfer within a lower preset operating condition range; meanwhile, the micron-sized bubbles can be fully mixed with the fermentation raw materials to form gas-liquid emulsion, and the gas-liquid two-phase full mixing can ensure that penicillin producing bacteria in the system can fully absorb oxygen in the materials, so that byproducts are prevented from being generated, and the fermentation efficiency of the system is further improved.
Description
Technical Field
The invention relates to the technical field of bacterial fermentation, in particular to a penicillin fermentation system and a penicillin fermentation process.
Background
Penicillin is an important antibiotic with high efficiency, low toxicity and wide clinical application. The successful development of the antibiotic greatly enhances the capability of human beings to resist bacterial infection and brings birth of an antibiotic family. Its emergence has opened a new era for the treatment of diseases with antibiotics. By the improvement of decades, penicillin injection and oral penicillin can respectively treat pneumonia, meningitis, endocarditis, diphtheria, anthrax and other diseases. Following penicillin, antibiotics such as streptomycin, chloramphenicol, oxytetracycline, tetracycline, and the like are continually produced, enhancing the ability of humans to treat infectious diseases. However, the resistance of some pathogens is also increasing. In order to solve the problem, researchers are developing antibiotics with stronger drug effects at present, exploring how to prevent germs from obtaining resistance genes, and developing antibacterial drugs by taking plants as raw materials.
The penicillin fermentation process mainly comprises the steps of strain selection, spore preparation, seed culture, fermentation, product separation and crystallization and the like. The traditional penicillin fermentation process is two-stage fed-batch fermentation, penicillin spores are inoculated to a seeding tank sterile culture medium through flame, germination and growth are carried out under certain tank temperature and aeration culture conditions, penicillium hyphae grow to reach certain hypha quantity after a certain period, and the penicillium hyphae are transferred to a fermentation tank sterile culture medium for culture until the last logarithmic growth stage. In order to realize a high level fermentation unit by providing a growth environment such as air at a constant temperature in a fermenter, it is necessary to supplement a carbon source, a nitrogen source, a precursor for penicillin synthesis, and the like.
The penicillin fermentation process is divided into a lag phase, a hypha growth phase, a conversion phase from hypha growth to secondary metabolism and a metabolic stabilization phase. The fermentation process is influenced by factors such as fermentation temperature, pH value of culture solution, oxygen amount, foam amount and the like. The aeration and agitation require that enough air is pumped into fine bubbles and uniformly dispersed in the culture solution to ensure that sufficient oxygen is obtained for the growth of the penicillium, so the aeration and agitation have great influence on the culture. The penicillin generates foam during fermentation, which is not beneficial to gas exchange during the metabolism of penicillium to reduce the yield, and simultaneously, the foam overflows and the yield is lost.
Chinese patent publication No.: CN206680461U discloses fermenting installation is used in penicillin production, including a jar body, motor, feed inlet, discharge gate, the internal agitating unit that is equipped with of jar, agitating unit include cavity (mixing) shaft and cavity stirring frame, the cavity (mixing) shaft all links to each other with air intake system with cavity stirring frame, all be equipped with cavity stirring leaf on cavity stirring frame inner wall and the cavity (mixing) shaft, the tip of cavity stirring leaf is equipped with the shower nozzle, be equipped with ventilative waterproof diaphragm in the shower nozzle, cavity (mixing) shaft upper portion is equipped with the horizontal pole, be equipped with a plurality of sawtooth on the horizontal pole, still be equipped with foam breaker on the jar body, foam breaker is including stretching into the internal suction tube of jar, the aspiration pump that sets up on the suction tube and. It can be seen that the device suffers from the following problems:
firstly, the air is broken only by the stirring blades in the device, and the air forms large bubbles after being broken, but the bubbles cannot be fully mixed with the mixed materials due to overlarge volume, so that oxygen is not uniformly absorbed by bacteria, and the fermentation efficiency of the system is reduced.
Secondly, the device is easy to produce by-products under the condition that bacteria are not uniformly contacted with oxygen, so that materials in the system cannot be used, and the energy consumption of the system is increased.
Thirdly, the device uses the stirring leaf to stir bacterium and material, stirs the in-process stirring leaf and can cause the destruction to the bacterium to lead to bacterium quantity reduction in the raw materials, reduce fermentation efficiency.
Disclosure of Invention
Therefore, the invention provides a penicillin fermentation system and a penicillin fermentation process, which are used for solving the problem of low fermentation efficiency caused by the production of byproducts due to incomplete fermentation of penicillin producing bacteria because sterile air cannot be fully mixed with fermentation raw materials in the prior art.
In one aspect, the present invention provides a penicillin fermentation system, comprising:
a fermentation tank for fermenting a material with a penicillin producing microorganism, the fermentation tank comprising: a complete mixed flow biochemical reaction area which is arranged below and used for loading fermentation raw materials and penicillin production bacteria and providing a reaction space for the fermentation of the fermentation raw materials and the penicillin production bacteria, and a plug flow biochemical reaction area which is arranged above and used for conveying fermented materials and separating gas and liquid;
the separation tank is connected with the fermentation tank and is used for separating the materials output by the fermentation tank to generate gaseous strains and fermentation liquor;
at least two micro-interface generators which are respectively arranged at the appointed positions in the fully mixed flow reaction zone, convert the pressure energy of gas and/or the kinetic energy of liquid into the surface energy of bubbles and transmit the surface energy to the sterile air, so that the sterile air is crushed into micron-sized bubbles with the diameter of more than or equal to 1 mu m and less than 1mm to improve the mass transfer area between the fermentation raw material and the sterile air, reduce the thickness of a liquid film and reduce the mass transfer resistance, and the fermentation raw material and the micron-sized bubbles are mixed to form a gas-liquid emulsion after being crushed, so as to strengthen the mass transfer efficiency between the fermentation raw material and the sterile air within the range of preset operation conditions;
and the return pipes are respectively connected with the fermentation tank and the separation tank and used for exchanging heat of the materials output by the fermentation tank and shunting the materials after heat exchange so as to respectively return to the fermentation tank or output to the separation tank.
Further, the micro-interface generator includes:
the first micro-interface generator is a pneumatic micro-interface generator, is arranged in the complete mixed flow biochemical reaction zone and is positioned at the bottom of the reaction zone, and is used for crushing sterile air to form micron-scale bubbles and outputting the micron-scale bubbles to the fermentation tank after the crushing is finished;
and the second micro-interface generator is an air-liquid linkage type micro-interface generator, is arranged in the full-mixed flow biochemical reaction area and is positioned at the top of the reaction area, is used for receiving the material output by the return pipe, uses the material to crush the sterile air to form micron-scale micron-sized bubbles, and mixes the micron-scale bubbles with the material to form an air-liquid emulsion to be output to the full-mixed flow biochemical reaction area.
Further, the complete mixed flow biochemical reaction area in the fermentation tank comprises:
the grating is arranged inside the fermentation tank and is used for filtering insoluble particles in the material;
the pH adjusting liquid feeding port is arranged on the side wall of the fermentation tank, is positioned above the grating and is used for conveying pH adjusting liquid to adjust the pH value of the material;
the fermentation raw material feeding hole is formed in the side wall of the fermentation tank, is positioned below the grating and is used for conveying fermentation raw materials;
the fermentation strain feeding hole is formed in the side wall of the fermentation tank and is positioned below the fermentation raw material feeding hole, and is used for conveying penicillin production bacteria to the interior of the fermentation tank and fermenting the fermentation raw materials;
a first gaseous feed conduit disposed in a side wall of the fermentor and connected to the micro-interface generator for lateral delivery of sterile air into the micro-interface generator within the fermentor;
a residue outlet arranged at the bottom of the fermentation tank and used for discharging fermented residue out of the system;
the baffle, it set up in fermentation cylinder inner wall is located the grid below for block the fermentation raw materials of fermentation raw materials import output with the fluctuation that the penicillin production fungus that the fermentation bacterial feed inlet was exported produced.
Further, the plug flow reaction zone comprises:
the exhaust pipeline is arranged at the top end of the fermentation tank and used for exhausting tail gas generated in the fermentation of the materials in the fermentation tank;
the second gas-phase feeding pipeline is arranged at the top end of the fermentation tank, is connected with the micro-interface generator and is used for conveying the tail gas generated at the top of the fermentation tank into the micro-interface generator in the fermentation tank;
the discharge port is arranged on the side wall of the fermentation tank and used for outputting the fermented materials out of the fermentation tank;
and the backflow feeding pipeline is arranged on the side wall of the fermentation tank and used for outputting part of materials output by the backflow pipe to the micro-interface generator in the fermentation tank.
Further, the return pipe includes:
the circulating pump is connected with the fermentation tank and used for outputting materials fermented in the fermentation tank;
and the heat exchanger is connected with the circulating pump and used for exchanging heat of the material output by the circulating pump so as to enable the material to reach the specified temperature.
Furthermore, the output end of the heat exchanger is provided with a shunt tube, and the shunt tube is respectively connected with the fermentation tank and the separation tank and used for respectively refluxing the materials and outputting the materials to the separation tank.
Further, the separation tank is a sealed tank, and comprises:
the feeding hole is arranged at the top end of the separation tank and used for conveying the material output by the return pipe to the inside of the separation tank;
the exhaust port is arranged at the top end of the separation tank and used for outputting gaseous strains;
and the discharge port is arranged at the bottom end of the separation tank and used for outputting the separated fermentation liquor and conveying the fermentation liquor to the next working section.
In another aspect, the present invention provides a penicillin fermentation process, comprising:
step 1: conveying the specified type of fermentation raw materials to a complete mixed flow biochemical reaction area in the fermentation tank through the fermentation raw material feeding hole, and conveying penicillin production bacteria to the fermentation tank through the fermentation strain feeding hole;
step 2: sterile air is conveyed to the first micro-interface generator through the first gas phase feeding pipeline, the first micro-interface generator breaks the sterile air into micron-sized bubbles and outputs the micron-sized bubbles to the fermentation raw materials in the fermentation tank, and the micron-sized bubbles and the fermentation raw materials are fully mixed to provide an aerobic environment for the penicillin producing bacteria;
and step 3: penicillin producing bacteria and fermentation raw materials react in an aerobic environment, after fermentation is completed, the fermentation tank conveys the fermented materials to the plug flow biochemical reaction area, the materials flow through the grating, residues in the materials are filtered by the grating, and the filtered residues are settled to the bottom of the fermentation tank and are discharged out of the fermentation tank through the residue outlet;
and 4, step 4: the filtered materials flow in the plug flow biochemical reaction area along a designated direction, when the materials flow to the top of the fermentation tank, gas in the materials is output to the fermentation tank through an exhaust pipeline, and the materials are output to the return pipe through a first discharge hole;
and 5: the reflux pipe pumps out the materials in the fermentation tank, and carries out shunting after heat exchange, and part of the materials after heat exchange flows back to the second micro-interface generator to adjust the temperature in the fully mixed flow biochemical reaction area, and the other part of the materials is output to the separation tank for separation;
step 6: after heat exchange, the material flows back and enters the second micro-interface generator through a backflow feeding pipeline, the second micro-interface generator receives tail gas at the top of the fermentation tank through the second gas-phase feeding pipeline, the tail gas is crushed into micron-scale bubbles by using the material, the micron-scale bubbles and the material are mixed to form a gas-liquid emulsion, and after the gas-liquid emulsion is formed, the gas-liquid emulsion is output to the fully-mixed flow biochemical reaction area by the second micro-interface generator so as to adjust the temperature in the fully-mixed flow biochemical reaction area while the material is repeatedly used;
and 7: after heat exchange, the material is output to the separation tank, the separation tank can carry out gas-liquid separation on the material to form gaseous strains and fermentation liquor, after separation, the gaseous strains are discharged out of the separation tank through the exhaust port, and the fermentation liquor is discharged out of the separation tank through the second discharge port and conveyed to the next working section.
Further, when the system operates, the pH adjusting liquid feeding port can convey pH adjusting liquid to adjust the pH value of the materials in the fermentation tank.
Further, when the micro-interface generator is used for conveying sterile air, the dissolved oxygen concentration of the materials in the fermentation tank is ensured to be more than or equal to 30%.
Compared with the prior art, the method has the beneficial effects that compared with the traditional method, the method has the advantages that micron-scale micron-sized bubbles are formed by crushing air, so that the micron-scale bubbles are mixed with fermentation raw materials to form gas-liquid emulsion, the phase interface area of gas-liquid two phases is increased, and the effect of strengthening mass transfer within a lower preset operation condition range is achieved; meanwhile, the micron-sized bubbles can be fully mixed with the fermentation raw materials to form gas-liquid emulsion, and the gas-liquid two-phase full mixing can ensure that penicillin producing bacteria in the system can fully absorb oxygen in the materials, so that byproducts are prevented from being generated, and the fermentation efficiency of the system is further improved. Meanwhile, a backflow feeding pipe is arranged in the fermentation tank of the system, and the material after reaction flows back to the fermentation tank, so that the contact time of sterile air and the fermentation raw material is prolonged, and the fermentation efficiency is improved. In addition, the range of the preset operation condition can be flexibly adjusted according to different product requirements or different catalysts, so that the full and effective reaction is further ensured, and the reaction rate is further ensured.
In addition, the range of the preset operation conditions can be flexibly adjusted according to different raw material compositions or different product requirements, so that the full and effective reaction is further ensured, the reaction rate is further ensured, and the purpose of strengthening the reaction is achieved.
Particularly, the full-mixed flow biochemical reaction area is arranged in the fermentation tank, the micro-interface generator is arranged in the full-mixed flow biochemical reaction area, so that the inside of the full-mixed flow biochemical reaction area is closer to a full-mixed flow model, the uniformity of the temperature and the concentration of materials in the reaction area is ensured, and the materials can be quickly and uniformly mixed when entering the reaction area, thereby preventing the penicillin production bacteria in the reaction area from generating byproducts due to insufficient oxygen absorption, and further improving the fermentation efficiency of the system.
Particularly, the invention also arranges a plug flow biochemical reaction area in the fermentation tank, the plug flow biochemical reaction area enables the fermented material to move at a uniform speed along the designated direction, the material is effectively prevented from flowing back in the conveying process, and the plug flow biochemical reaction area can further promote the reaction rate of the material in the fully mixed flow biochemical reaction area, thereby further improving the fermentation efficiency of the system.
Furthermore, the fermentation tank is respectively provided with the pneumatic micro-interface generator and the gas-liquid linkage micro-interface generator, and the micron-sized bubbles and the materials are mixed more uniformly by using different types of micro-interface generators, so that the mixing efficiency of the materials and the sterile air in the fermentation tank is improved, and the fermentation efficiency of the system is further improved.
Furthermore, a grating is arranged in the fermentation tank, and residues in the materials can be effectively filtered and discharged through a residue outlet at the bottom of the fermentation tank, so that the purity of the fermentation liquor is improved.
Especially, the fermentation cylinder lateral wall still is equipped with pH regulator solution feed inlet when the system operation, the pH regulator solution feed inlet can be through adjusting the pH value of the interior material of fermentation cylinder to the mode of carrying pH regulator solution in the fermentation cylinder, when not destroying penicillin production fungus, can effectively adjust the pH value of material to improve penicillin production fungus's reaction efficiency.
Especially, the fermentation cylinder inner wall still is equipped with the baffle, the baffle is located fermentation raw materials feed inlet with the exit of fermentation bacterial feed inlet is through two the feed inlet export is sheltered from to prevent that each feed inlet from producing undulant when export material and penicillin production fungus to be right the second micro-interface generator causes the influence and reduces the mixing efficiency of second micro-interface generator.
Furthermore, a return pipe is further arranged in the system, and the fermented materials are returned to be reused, so that the utilization rate of the materials is improved, and the fermentation efficiency of the system is further improved.
Particularly, the heat exchanger is arranged in the return pipe, when the fermented materials are returned and output, the materials can be subjected to heat exchange through the heat exchanger so as to reach the specified temperature, and the temperature of the materials in the fermentation tank is adjusted, so that a proper fermentation environment is provided for penicillin production bacteria in the fermentation tank, and the fermentation efficiency of the system is further improved.
Drawings
FIG. 1 is a schematic structural diagram of a penicillin fermentation system according to the present invention.
Detailed Description
Preferred embodiments of the present invention are described below with reference to the accompanying drawings. It should be understood by those skilled in the art that these embodiments are only for explaining the technical principle of the present invention, and do not limit the scope of the present invention.
It should be noted that in the description of the present invention, the terms of direction or positional relationship indicated by the terms "upper", "lower", "left", "right", "inner", "outer", etc. are based on the directions or positional relationships shown in the drawings, which are only for convenience of description, and do not indicate or imply that the device or element must have a specific orientation, be constructed in a specific orientation, and be operated, and thus, should not be construed as limiting the present invention.
Furthermore, it should be noted that, in the description of the present invention, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations.
Please refer to fig. 1, which is a schematic structural diagram of a penicillin fermentation system according to the present invention, comprising a fermentation tank 1, a micro-interface generator 2 (not shown), a return pipe 3 and a separation tank 4. Wherein, micro-interface generator 2 sets up inside the fermentation cylinder for with the broken micron order bubble that forms micron yardstick of aseptic air and mix the micron order bubble and the material in the fermentation cylinder and form the gas-liquid emulsion thing thereby for penicillin production fungus provides the aerobic environment in the material. The return pipe 3 is connected with the fermentation tank 1 and used for outputting the fermented materials in the fermentation tank 1 and returning part of the output materials to the fermentation tank 1. The separation tank 4 is connected with an output branch in the return pipe 3 and is used for separating and concentrating the material output by the fermentation tank 1 and outputting the treated fermentation liquor to the next working section.
When the system is operated, firstly, fermentation raw materials and penicillin production bacteria are conveyed into the fermentation tank 1, meanwhile, sterile air is conveyed into the fermentation tank 1, the sterile air can enter the micro-interface generator 2, the micro-interface generator 2 breaks the sterile air to form micron-scale micro-bubbles, the micron-scale micro-bubbles are mixed with the fermentation raw materials to form gas-liquid emulsion, so that a uniform aerobic environment is provided for the penicillin production bacteria, after fermentation is completed, the fermentation tank 1 can respectively discharge gas and residues generated in the fermentation process out of the system, and output the fermented materials to the return pipe 3, the return pipe 3 conducts heat exchange on the materials and then shunts the materials, after shunting, a part of the materials flow back to the fermentation tank 1, when the materials are repeatedly used, the temperature of the materials in the fermentation tank is adjusted, the other part of the materials can be output to the separation tank 4, and the separation tank can conduct gas-liquid, discharging residual gaseous bacteria in the materials and outputting the fermentation liquor after separation and concentration to the next working section. It will be understood by those skilled in the art that the fermentation bacteria species used in the system may be penicillin producing bacteria, or other species of bacteria, and the embodiment is not particularly limited as long as the bacteria species are capable of aerobic fermentation.
With continued reference to FIG. 1, the fermenter 1 of the present invention includes a mixed flow biochemical reaction area 11 and a plug flow biochemical reaction area 12. Wherein the complete mixed flow biochemical reaction area 11 is positioned at the lower part of the fermentation tank 1 and is used for fully mixing the penicillin production bacteria and the micron-sized bubbles with the fermentation raw materials. The plug flow biochemical reaction area 12 is located at the upper part of the fermentation tank 1, and is used for conveying fermented materials along a specified direction while promoting the reaction speed in the fermentation tank 1. When the fermentation tank 1 starts to ferment, the mixed flow biochemical reaction area 11 respectively receives the penicillin producing bacteria, the fermentation raw material and the micron-sized bubbles and fully mixes the penicillin producing bacteria, the fermentation raw material and the micron-sized bubbles to enable the penicillin producing bacteria to ferment in an aerobic environment, after the fermentation is finished, the mixed flow biochemical reaction area 11 conveys the fermented material to the plug flow biochemical reaction area 12, and the plug flow biochemical reaction area 12 conveys the material to a designated direction. It is understood that the length-diameter ratio of the plug flow biochemical reaction zone 12 is not particularly limited in this embodiment, as long as the length of the plug flow biochemical reaction zone 12 is sufficient to maintain a continuous and stable flow of the material.
Referring to fig. 1, the mixed flow biochemical reaction area 11 of the present invention includes a grating 111, a pH adjusting liquid inlet 112, a fermentation material inlet 113, a fermentation strain inlet 114, a first gas phase inlet channel 115, a residue outlet 116, and a partition 117. Wherein, the grating 111 is arranged inside the fermentation tank 1 for filtering the residue generated in the fermentation process of the fermentation tank 1. The pH adjusting liquid feeding hole is formed in the inner wall of the fermentation tank 1 and located above the grating 111, and is used for conveying pH adjusting liquid to the fermentation tank 1. The fermentation material inlet 113 is disposed on a sidewall of the fermentation tank 1 and below the grating 111, and is used for delivering fermentation material to the fermentation tank 1. The fermentation strain feed port 114 is arranged on the side wall of the fermentation tank 1 and is positioned below the fermentation raw material feed port 113, and is used for conveying penicillin production bacteria to the fermentation tank 1. The first gas phase feed line 115 is provided in the side wall of the fermenter 1 and connected to the micro-interface generator 2 for supplying sterile air. The residue outlet 116 is disposed at the bottom of the fermentation tank 1 for discharging the residue generated after fermentation out of the fermentation tank 1. The baffle 117 is arranged on the inner wall of the fermentation tank 1 and is positioned at the same side with the fermentation raw material inlet 113, so as to prevent the fermentation raw material from being output by the fermentation raw material inlet 113 and the fluctuation generated when the penicillin-producing bacteria are output by the fermentation strain inlet 114.
When the mixed flow biochemical reaction area is operated, the fermentation material inlet 113 can convey the fermentation material to the inside of the fermentation tank 1, the fermentation strain inlet 114 can convey the penicillin producing bacteria to the inside of the fermentation tank 1, the baffle 117 can block the fluctuation generated when the fermentation material inlet 113 and the fermentation strain inlet 114 output the material, the first gas phase inlet pipeline 115 can convey the sterile air to the micro interface generator 2, the micro interface generator 2 breaks the sterile air to form micron-scale bubbles, and the micron-scale bubbles are mixed with the fermentation material to form gas-liquid emulsion, the gas-liquid emulsion is mixed with the penicillin producing bacteria and then starts to ferment, in the fermentation process, the pH adjusting liquid inlet 113 can convey the pH adjusting liquid to the fermentation tank 1 to adjust the pH value of the mixed material in the fermentation tank 1, after the fermentation is completed, the mixed flow biochemical reaction area 11 can convey the fermented material to the flat plug flow biochemical reaction area 12, during the transportation, the grid 111 will filter out the residues in the material, which after filtering out start to settle and leave the fermentation tank 1 through the residue outlet 116.
Specifically, the grating 111 is a sieve plate, which is disposed inside the fermentation tank 1 for filtering the fermented material. After the complete fermentation of the mixed flow biochemical reaction zone 11, the fermented material will flow through the grating 111, and the grating 111 will filter the residue in the material. It is understood that the kind of the grid 111 and the size of the through holes are not particularly limited in this embodiment, as long as the grid 111 can filter solid phase residues in the material.
In particular, the first gas feed line 115 is arranged in the side wall of the fermenter and the outlet of the first gas feed line 115 is connected to the micro-interfacial generator 2 for feeding sterile air to the micro-interfacial generator 2. When the mixed flow biochemical reaction zone 11 is operated, the first gas phase feeding pipe 115 will convey the sterile air to the micro interface generator 2, the micro interface generator 2 will crush the sterile air to form micron-sized bubbles, and the micron-sized bubbles are output to the interior of the fermentation tank 1 and mixed with the fermentation raw material. It is understood that the material and dimensions of first gas feed conduit 115 are not particularly limited in this embodiment, provided that first gas feed conduit 115 is capable of delivering a specified volume of sterile air over a specified period of time.
Specifically, the partition 117 is a baffle plate fixedly connected to the inner wall of the fermentation tank 1 for blocking the fluctuation of the fermentation tank when receiving the material. When the complete mixed flow biochemical reaction zone 11 is operated, the fermentation raw material inlet 113 can convey fermentation raw materials into the fermentation tank 1, the fermentation strain inlet 114 can convey penicillin production strains into the fermentation tank 1, and the partition plate 117 can be blocked at the discharging position, so that the fluctuation of the two materials in the conveying process is prevented, and the influence of the fluctuation on the micro-interface generator is prevented. It will be appreciated that the connection of the partition 117 to the fermenter 1 may be by welding, by integral connection or by other types of connection, provided that the partition 117 is able to reach its designated operating condition.
Referring to fig. 1, the plug flow biochemical reaction area 12 of the present invention is located at the upper portion of the fermentation tank 1, and is used for transporting fermented materials along a designated direction, and includes an exhaust pipe 121, a second gas phase feeding pipe 122, a first discharge port 123 and a return feeding pipe 124. Wherein the exhaust pipeline 121 is arranged at the top of the fermentation tank 1 for exhausting gas generated in the fermentation process. The second gas phase feed line 122 is arranged at the top of the fermenter 1 and connected to the micro-interface generator 2 for feeding the fermenter top off-gas. The first discharge port 123 is arranged on the side wall of the fermentation tank 1 and used for outputting fermented materials. The backflow feeding pipe 124 is disposed on the sidewall of the fermentation tank 1 and below the discharge port 123, and is used for feeding the backflow materials to the fermentation tank 1. When the plug flow reaction zone 12 is in operation, the material is conveyed upward at a constant speed in the reaction zone, when the material reaches the top of the fermentation tank 1, the gas in the material is output from the fermentation tank 1 through the exhaust pipe 121, the liquid-phase material is output to the return pipe 3 through the first discharge port 123, and part of the material is returned through the return pipe 3 and then returned to the fermentation tank 1 through the return feed pipe 124, after the return, the second gas-phase feed pipe 122 conveys the tail gas to the micro-interface generator 2, and the tail gas is mixed with the returned material after being crushed and conveyed to the fully mixed flow biochemical reaction zone 11 for reuse.
Specifically, the second gas phase feeding pipe 122 is disposed at the top of the fermentation tank, and the outlet of the second gas phase feeding pipe 122 is connected to the micro-interface generator 2, so as to convey the tail gas from the top of the fermentation tank to the micro-interface generator 2. When the plug flow biochemical reaction region 12 operates, the second gas phase feeding pipe 122 will feed the tail gas to the micro interface generator 2, and the micro interface generator 2 will crush the tail gas to form micro-bubbles, and the micro-bubbles are output to the inside of the fermentation tank 1 and mixed with the material. It is understood that the material and size of the second gas-phase feed pipe 122 are not particularly limited in this embodiment, as long as the second gas-phase feed pipe 122 can deliver a given volume of off-gas in a given time.
Specifically, the backflow feeding pipe 124 is disposed on the sidewall of the fermentation tank 1, and the outlet of the backflow feeding pipe 124 is connected to the micro-interfacial surface generator 2, so as to convey the backflow materials to the micro-interfacial surface generator 2. When the plug flow biochemical reaction zone is in operation, the return pipe 3 will deliver the returned material to the return feed pipe 124, and the return feed pipe 124 will deliver the material to the micro-interface generator 2 to mix the material with the micro-scale bubbles. It is understood that the material and size of the backflow feeding pipe 124 are not limited in this embodiment, as long as the backflow feeding pipe 124 can deliver a given flow rate of material in a given time.
Referring still to fig. 1, the micro-interface generator 2 of the present invention includes a first micro-interface generator 21 and a second micro-interface generator 22. Wherein the first micro-interface generator 21 is disposed at the bottom of the mixed flow biochemical reaction zone 11 for breaking the sterile air to form micro-scale bubbles. The second micro-interface generator 22 is disposed on the top of the mixed flow biochemical reaction region 11 and connected to the grid 111, and is used for breaking the sterile air into micro-bubbles and mixing the micro-bubbles with the backflow material. When the fermentation tank 1 is in operation, the first micro-interface generator 21 can crush the sterile air to form micron-sized bubbles, and mix the micron-sized bubbles with the fermentation raw material to form a gas-liquid emulsion, and the second micro-interface generator 22 receives the returned material and the sterile air respectively, crushes the sterile air into the micron-sized bubbles, and mixes the micron-sized bubbles with the material to form the gas-liquid emulsion. It is understood that the micro-interface generator 2 of the present invention can also be used in other multi-phase reactions, such as multi-phase fluid, micro-nano-scale particle, micro-bubble micro-emulsion, micro-flow, micro-dispersion, two micro-mixed flow, micro-turbulence, micro-bubble flow, micro-bubble, micro-bubble micro-bubble flow, micro-nano-scale bubble flow, micro-bubble flow, micro-nano-scale particle, micro-bubble micro-fluid, micro-bubble micro-bubble flow, micro-bubble micro-, Or multiphase fluid (micro interface fluid for short) formed by micro-nano-scale particles, thereby effectively increasing the phase boundary mass transfer area between the gas phase and/or the liquid phase and/or the solid phase in the reaction process.
Specifically, the first micro-interface generator 21 of the present invention is a pneumatic micro-interface generator, which is connected to the first gas phase feeding pipe 115, and is used for breaking up the air conveyed by the first gas phase feeding pipe 115 and forming micron-sized bubbles. When the fermentation tank 1 is in operation, the first gas phase feeding pipe 115 will feed the sterile air to the first micro-interface generator 21, the first micro-interface generator 21 will break the sterile air and form micron-sized bubbles, and after the breaking, the first micro-interface generator 21 will output the micron-sized bubbles to the inside of the fermentation tank 1 and mix with the fermentation raw material to provide an aerobic environment for the penicillin producing bacteria.
Specifically, the second micro-interface generator 22 of the present invention is a gas-liquid linkage micro-interface generator, which is connected to the second gas-phase feeding pipe 122 and the backflow feeding pipe 124, respectively, for receiving the tail gas and the backflow material, respectively, and crushing the tail gas into micron-sized micro-bubbles through the pressure of the backflow material. When the second micro-interface generator 22 operates, it will receive the tail gas and the backflow material, respectively, and utilize the pressure energy of the backflow material to break the tail gas into micron-sized bubbles, and form a gas-liquid emulsion by mixing the micron-sized bubbles with the backflow material and output the gas-liquid emulsion to the complete mixed flow biochemical reaction zone 11 for repeated fermentation.
With continued reference to fig. 1, the return line 3 according to the invention comprises a circulation pump 31 and a heat exchanger 32. Wherein the circulating pump 31 is connected with the first material outlet 123 for pumping out the fermented material in the fermentation tank 1. The heat exchanger 32 is connected with the circulating pump 31 and used for exchanging heat for the material output by the circulating pump 31. After the fermentation of the materials in the fermentation tank 1 is completed, the circulation pump 31 starts to operate, the materials are pumped out through the first material outlet 123, and the materials are conveyed to the heat exchanger 32, the heat exchanger 32 exchanges heat with the materials and splits the heat exchanged materials, a part of the materials is refluxed to the reflux feeding pipeline 124, and another part of the materials is output to the separation tank 4. It is understood that the type and power of the circulating pump 31 are not particularly limited in this embodiment, as long as the circulating pump 31 can reach its designated operating state.
Specifically, a diversion pipeline is arranged at the outlet of the heat exchanger 32, one end of the diversion pipeline is connected with the backflow feeding pipeline 124 for returning a part of the materials output by the heat exchanger 32, and the other end of the diversion pipeline is connected with the separation tank 4 for outputting another part of the materials output by the heat exchanger 32 to the separation tank 4 for separation.
With reference to fig. 1, the separating tank 4 of the present invention is a sealed tank, and a feeding port is disposed at the top end of the sealed tank, and the feeding port is connected to the heat exchanger 32 for receiving the material after completion of waste heat; the top end of the separation tank 4 is also provided with an exhaust port for exhausting gaseous bacteria during separation; and a second discharge hole is formed in the bottom end of the separation tank 4 and used for outputting the separated fermentation liquor to the next working section. When the heat exchanger 32 outputs the heat-exchanged material, the material enters the separation tank 4 through the feed inlet and is subjected to gas-liquid separation, after the separation, penicillin-producing bacteria remaining in the material and gas are discharged out of the separation tank 4 through the exhaust port, and the material is separated to form fermentation liquor and is output to the next working section through the second discharge port. It is understood that the material and size of the separation tank 4 are not limited in this embodiment, as long as the separation tank 4 can reach its designated working state.
In order that the objects and advantages of the invention will be more clearly understood, the invention is further described below with reference to examples; it should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
A penicillin fermentation process comprises the following steps:
step 1: conveying the specified type of fermentation raw materials to a complete mixed flow biochemical reaction area in the fermentation tank through the fermentation raw material feeding hole, and conveying penicillin production bacteria to the fermentation tank through the fermentation strain feeding hole;
step 2: sterile air is conveyed to the first micro-interface generator through the first gas phase feeding pipeline, the first micro-interface generator breaks the sterile air into micron-sized bubbles and outputs the micron-sized bubbles to the fermentation raw materials in the fermentation tank, and the micron-sized bubbles and the fermentation raw materials are fully mixed to provide an aerobic environment for the penicillin producing bacteria;
and step 3: penicillin producing bacteria and fermentation raw materials react in an aerobic environment, after fermentation is completed, the fermentation tank conveys the fermented materials to the plug flow biochemical reaction area, the materials flow through the grating, residues in the materials are filtered by the grating, and the filtered residues are settled to the bottom of the fermentation tank and are discharged out of the fermentation tank through the residue outlet;
and 4, step 4: the filtered materials flow in the plug flow biochemical reaction area along a designated direction, when the materials flow to the top of the fermentation tank, gas in the materials is output to the fermentation tank through an exhaust pipeline, and the materials are output to the return pipe through a first discharge hole;
and 5: the reflux pipe pumps out the materials in the fermentation tank, and carries out shunting after heat exchange, and part of the materials after heat exchange flows back to the second micro-interface generator to adjust the temperature in the fully mixed flow biochemical reaction area, and the other part of the materials is output to the separation tank for separation;
step 6: after heat exchange, the material flows back and enters the second micro-interface generator through a backflow feeding pipeline, the second micro-interface generator receives tail gas through the second gas phase feeding pipeline, the tail gas is crushed by the material to form micron-scale bubbles, the micron-scale bubbles and the material are mixed to form a gas-liquid emulsion, and after the gas-liquid emulsion is formed, the gas-liquid emulsion is output to the fully mixed flow biochemical reaction area by the second micro-interface generator so as to regulate the temperature in the fully mixed flow biochemical reaction area while the material is repeatedly used;
and 7: after heat exchange, the material is output to the separation tank, the separation tank can carry out gas-liquid separation on the material to form gaseous strains and fermentation liquor, after separation, the gaseous strains are discharged out of the separation tank through the exhaust port, and the fermentation liquor is discharged out of the separation tank through the second discharge port and conveyed to the next working section.
Specifically, when the micro-interface generator is used for conveying sterile air, the dissolved oxygen concentration of the materials in the fermentation tank is ensured to be more than or equal to 30%. It can be understood that the range of the preset operation conditions can be flexibly adjusted according to different raw material compositions or different product requirements, so as to ensure the full and effective reaction, further ensure the reaction rate and achieve the purpose of strengthening the reaction.
Example one
The above system and process are used for the biological fermentation of penicillin, wherein:
the temperature of the solution in the fermentation tank is 26 ℃, the pH is 6.5, the pH regulating solution is sugar and ammonia water, and the pH can be controlled by adding sugar when the pH is higher; when the pH is lower, ammonia water can be added for adjustment.
When the micro-interface generator is used for conveying sterile air, the dissolved oxygen concentration of materials in the fermentation tank is ensured to be more than or equal to 30 percent.
The penicillin prepared by the system has the purity of 99.63 percent through detection.
Example two
The above system and process are used for the biological fermentation of penicillin, wherein:
the temperature of the solution in the fermentation tank is 26 deg.C, pH is 6.8, and the pH regulating solution is selected from sugar and CaCO3When the pH is higher, the pH can be controlled by adding sugar; CaCO may be added when the pH is low3And (6) carrying out adjustment.
When the micro-interface generator is used for conveying sterile air, the dissolved oxygen concentration of materials in the fermentation tank is ensured to be more than or equal to 30 percent.
The penicillin prepared by the system has the purity of 99.89 percent through detection.
EXAMPLE III
The above system and process are used for the biological fermentation of penicillin, wherein:
the temperature of the solution in the fermentation tank is 27 deg.C, pH is 7.0, and the pH regulating solution is natural oil and CaCO3When the pH value is higher, the pH value can be controlled by adding natural oil; CaCO may be added when the pH is low3And (6) carrying out adjustment.
When the micro-interface generator is used for conveying sterile air, the dissolved oxygen concentration of materials in the fermentation tank is ensured to be more than or equal to 30 percent.
The penicillin prepared by the system has the purity of 99.75 percent through detection.
So far, the technical solutions of the present invention have been described in connection with the preferred embodiments shown in the drawings, but it is easily understood by those skilled in the art that the scope of the present invention is obviously not limited to these specific embodiments. Equivalent changes or substitutions of related technical features can be made by those skilled in the art without departing from the principle of the invention, and the technical scheme after the changes or substitutions can fall into the protection scope of the invention.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention; various modifications and alterations to this invention will become apparent to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A penicillin fermentation system, comprising:
a fermentation tank for fermenting a material with a penicillin producing microorganism, the fermentation tank comprising: a complete mixed flow biochemical reaction area which is arranged below and used for loading fermentation raw materials and penicillin production bacteria and providing a reaction space for the fermentation of the fermentation raw materials and the penicillin production bacteria, and a plug flow biochemical reaction area which is arranged above and used for conveying fermented materials and separating gas and liquid;
the separation tank is connected with the fermentation tank and is used for separating the materials output by the fermentation tank to generate gaseous strains and fermentation liquor;
at least two micro-interface generators which are respectively arranged at the appointed positions in the fully mixed flow reaction zone, convert the pressure energy of gas and/or the kinetic energy of liquid into the surface energy of bubbles and transmit the surface energy to the sterile air, so that the sterile air is crushed into micron-sized bubbles with the diameter of more than or equal to 1 mu m and less than 1mm to improve the mass transfer area between the fermentation raw material and the sterile air, reduce the thickness of a liquid film and reduce the mass transfer resistance, and the fermentation raw material and the micron-sized bubbles are mixed to form a gas-liquid emulsion after being crushed, so as to strengthen the mass transfer efficiency between the fermentation raw material and the sterile air within the range of preset operation conditions;
and the return pipes are respectively connected with the fermentation tank and the separation tank and used for exchanging heat of the materials output by the fermentation tank and shunting the materials after heat exchange so as to respectively return to the fermentation tank or output to the separation tank.
2. Penicillin fermentation system according to claim 1, wherein said micro-interface generator comprises:
the first micro-interface generator is a pneumatic micro-interface generator, is arranged in the complete mixed flow biochemical reaction zone and is positioned at the bottom of the reaction zone, and is used for crushing sterile air to form micron-scale bubbles and outputting the micron-scale bubbles to the fermentation tank after the crushing is finished;
and the second micro-interface generator is an air-liquid linkage type micro-interface generator, is arranged in the full-mixed flow biochemical reaction area and is positioned at the top of the reaction area, is used for receiving the material output by the return pipe, uses the material to crush the sterile air to form micron-scale micron-sized bubbles, and mixes the micron-scale bubbles with the material to form an air-liquid emulsion to be output to the full-mixed flow biochemical reaction area.
3. Penicillin fermentation system according to claim 1, wherein said complete mixed flow biochemical reaction zone in said fermentor comprises:
the grating is arranged inside the fermentation tank and is used for filtering insoluble particles in the material;
the pH adjusting liquid feeding port is arranged on the side wall of the fermentation tank, is positioned above the grating and is used for conveying pH adjusting liquid to adjust the pH value of the material;
the fermentation raw material feeding hole is formed in the side wall of the fermentation tank, is positioned below the grating and is used for conveying fermentation raw materials;
the fermentation strain feeding hole is formed in the side wall of the fermentation tank and is positioned below the fermentation raw material feeding hole, and is used for conveying penicillin production bacteria to the interior of the fermentation tank and fermenting the fermentation raw materials;
a first gaseous feed conduit disposed in a side wall of the fermentor and connected to the micro-interface generator for lateral delivery of sterile air into the micro-interface generator within the fermentor;
a residue outlet arranged at the bottom of the fermentation tank and used for discharging fermented residue out of the system;
the baffle, it set up in fermentation cylinder inner wall is located the grid below for block the fermentation raw materials of fermentation raw materials import output with the fluctuation that the penicillin production fungus that the fermentation bacterial feed inlet was exported produced.
4. The penicillin fermentation system of claim 1, wherein said plug flow reaction zone comprises:
the exhaust pipeline is arranged at the top end of the fermentation tank and used for exhausting tail gas generated in the fermentation of the materials in the fermentation tank;
the second gas-phase feeding pipeline is arranged at the top end of the fermentation tank, is connected with the micro-interface generator and is used for conveying the tail gas generated at the top of the fermentation tank into the micro-interface generator in the fermentation tank;
the discharge port is arranged on the side wall of the fermentation tank and used for outputting the fermented materials out of the fermentation tank;
and the backflow feeding pipeline is arranged on the side wall of the fermentation tank and used for outputting part of materials output by the backflow pipe to the micro-interface generator in the fermentation tank.
5. Penicillin fermentation system according to claim 1, wherein said return line comprises:
the circulating pump is connected with the fermentation tank and used for outputting materials fermented in the fermentation tank;
and the heat exchanger is connected with the circulating pump and used for exchanging heat of the material output by the circulating pump so as to enable the material to reach the specified temperature.
6. Penicillin fermentation system according to claim 1, wherein the output of said heat exchanger is provided with a shunt tube, said shunt tube being connected to said fermentation tank and said separation tank, respectively, for performing a back flow of the material and for outputting the material to the separation tank, respectively.
7. Penicillin fermentation system according to claim 1, wherein said separation tank is a sealed tank comprising:
the feeding hole is arranged at the top end of the separation tank and used for conveying the material output by the return pipe to the inside of the separation tank;
the exhaust port is arranged at the top end of the separation tank and used for outputting gaseous strains;
and the discharge port is arranged at the bottom end of the separation tank and used for outputting the separated fermentation liquor and conveying the fermentation liquor to the next working section.
8. A penicillin fermentation process is characterized by comprising the following steps:
step 1: conveying the specified type of fermentation raw materials to a complete mixed flow biochemical reaction area in the fermentation tank through the fermentation raw material feeding hole, and conveying penicillin production bacteria to the fermentation tank through the fermentation strain feeding hole;
step 2: sterile air is conveyed to the first micro-interface generator through the first gas phase feeding pipeline, the first micro-interface generator breaks the sterile air into micron-sized bubbles and outputs the micron-sized bubbles to the fermentation raw materials in the fermentation tank, and the micron-sized bubbles and the fermentation raw materials are fully mixed to provide an aerobic environment for the penicillin producing bacteria;
and step 3: penicillin producing bacteria and fermentation raw materials react in an aerobic environment, after fermentation is completed, the fermentation tank conveys the fermented materials to the plug flow biochemical reaction area, the materials flow through the grating, residues in the materials are filtered by the grating, and the filtered residues are settled to the bottom of the fermentation tank and are discharged out of the fermentation tank through the residue outlet;
and 4, step 4: the filtered materials flow in the plug flow biochemical reaction area along a designated direction, when the materials flow to the top of the fermentation tank, gas in the materials is output to the fermentation tank through an exhaust pipeline, and the materials are output to the return pipe through a first discharge hole;
and 5: the reflux pipe pumps out the materials in the fermentation tank, and carries out shunting after heat exchange, and part of the materials after heat exchange flows back to the second micro-interface generator to adjust the temperature in the fully mixed flow biochemical reaction area, and the other part of the materials is output to the separation tank for separation;
step 6: after heat exchange, the material flows back and enters the second micro-interface generator through a backflow feeding pipeline, the second micro-interface generator receives tail gas at the top of the fermentation tank through the second gas-phase feeding pipeline, the tail gas is crushed into micron-scale bubbles by using the material, the micron-scale bubbles and the material are mixed to form a gas-liquid emulsion, and after the gas-liquid emulsion is formed, the gas-liquid emulsion is output to the fully-mixed flow biochemical reaction area by the second micro-interface generator so as to adjust the temperature in the fully-mixed flow biochemical reaction area while the material is repeatedly used;
and 7: after heat exchange, the material is output to the separation tank, the separation tank can carry out gas-liquid separation on the material to form gaseous strains and fermentation liquor, after separation, the gaseous strains are discharged out of the separation tank through the exhaust port, and the fermentation liquor is discharged out of the separation tank through the second discharge port and conveyed to the next working section.
9. The penicillin fermentation process of claim 8, wherein said pH adjustment feed port delivers a pH adjustment liquid for adjusting the pH of the contents of said fermentor during operation of said system.
10. The penicillin fermentation process according to claim 8, wherein the dissolved oxygen concentration of the materials in the fermenter is ensured to be more than or equal to 30% when the micro-interface generator is used for delivering sterile air.
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| CN201910859853.3A CN112481097A (en) | 2019-09-11 | 2019-09-11 | Penicillin fermentation system and process |
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| CN201910859853.3A CN112481097A (en) | 2019-09-11 | 2019-09-11 | Penicillin fermentation system and process |
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