WO2022082616A1 - Système de traitement d'érythromycine et procédé de traitement s'y rapportant - Google Patents

Système de traitement d'érythromycine et procédé de traitement s'y rapportant Download PDF

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Publication number
WO2022082616A1
WO2022082616A1 PCT/CN2020/122871 CN2020122871W WO2022082616A1 WO 2022082616 A1 WO2022082616 A1 WO 2022082616A1 CN 2020122871 W CN2020122871 W CN 2020122871W WO 2022082616 A1 WO2022082616 A1 WO 2022082616A1
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liquid
micro
fermentation
erythromycin
processing system
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PCT/CN2020/122871
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English (en)
Chinese (zh)
Inventor
张志炳
周政
张锋
李磊
孟为民
王宝荣
杨高东
罗华勋
杨国强
田洪舟
曹宇
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南京延长反应技术研究院有限公司
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Publication of WO2022082616A1 publication Critical patent/WO2022082616A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/58—Reaction vessels connected in series or in parallel
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B08—CLEANING
    • B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
    • B08B9/00—Cleaning hollow articles by methods or apparatus specially adapted thereto 
    • B08B9/08—Cleaning containers, e.g. tanks
    • B08B9/0804—Cleaning containers having tubular shape, e.g. casks, barrels, drums
    • B08B9/0813—Cleaning containers having tubular shape, e.g. casks, barrels, drums by the force of jets or sprays
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/02—Stirrer or mobile mixing elements
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/06—Nozzles; Sprayers; Spargers; Diffusers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M37/00—Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M39/00—Means for cleaning the apparatus or avoiding unwanted deposits of microorganisms
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/48—Automatic or computerized control
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P19/00—Preparation of compounds containing saccharide radicals
    • C12P19/44—Preparation of O-glycosides, e.g. glucosides
    • C12P19/60—Preparation of O-glycosides, e.g. glucosides having an oxygen of the saccharide radical directly bound to a non-saccharide heterocyclic ring or a condensed ring system containing a non-saccharide heterocyclic ring, e.g. coumermycin, novobiocin
    • C12P19/62—Preparation of O-glycosides, e.g. glucosides having an oxygen of the saccharide radical directly bound to a non-saccharide heterocyclic ring or a condensed ring system containing a non-saccharide heterocyclic ring, e.g. coumermycin, novobiocin the hetero ring having eight or more ring members and only oxygen as ring hetero atoms, e.g. erythromycin, spiramycin, nystatin

Definitions

  • the invention relates to the field of fermentation, in particular, to an erythromycin processing system and a processing method thereof.
  • Industrial fermentation is an industrial process in which fermentation raw materials are converted into microbial products needed by human beings through the life activities of microorganisms.
  • fermentation industry as an important branch of biotechnology, has developed rapidly in recent years, and new fermentation industries (such as amino acids, enzymes, organic acids, single-cell proteins, starch sugars, etc.) are growing at an average annual rate of 21%. So far, my country has formed a large-scale fermentation industry system with a wide variety of varieties, complete categories, and its product applications cover many industries such as medicine, health, light industry, agriculture, energy, and environmental protection.
  • the dissolved oxygen content is the limiting factor for bacterial growth and fermentation, while in the traditional aerobic fermentation process, the dissolved oxygen concentration in the fermentation broth is generally only 7-8 ppm, resulting in low fermentation efficiency. Therefore, it is an important direction for the development of modern fermentation industry to seek fermentation equipment with higher gas-liquid mass transfer efficiency to increase dissolved oxygen concentration and fermentation yield.
  • the first object of the present invention is to provide an erythromycin processing system.
  • the erythromycin processing system is provided with a micro-interface generator and a liquid ejector in the fermentation device.
  • the liquid ejector can efficiently clean the water of the tank. It is broken into micron-sized droplets, and the ejector collides with the top of the fermentation tank to replace manual cleaning.
  • the air is efficiently broken into micron-sized bubbles by the micro-interface generator, and dispersed into the fermentation broth to form a micro-interface system.
  • the PLC (or DCS, PLC and DCS) control system performs remote control of production, which is in line with the intelligence of production.
  • the second object of the present invention is to provide a method for fermentation using the above-mentioned erythromycin processing system.
  • the processing method is easy to operate, and the obtained fermentation product has high purity and good fermentation effect, and is worthy of widespread application.
  • the invention provides an erythromycin processing system, comprising: a fermentation device and a control system, the control system is connected with the fermentation device to control the working state of the fermentation device, and the fermentation device consists of two fermentation tanks Constructed in parallel with each other, the top of each fermenter is provided with a bacterial liquid inlet and a feed liquid inlet for the entry of bacterial liquid and feed liquid, and the bottom of each of the fermenters is provided with a liquid outlet for fermented products discharge;
  • Each of the fermenters is provided with a liquid injector and a micro-interface generator, the number of the micro-interface generators is two, the number of the liquid injectors is three, and the micro-interface generator is located at the upper part. Close to the top of the fermenter, the micro-interface generator located at the lower part is close to the bottom of the fermenter, and the liquid injectors are all arranged in the upper part of the fermenter, wherein two liquid injectors are respectively arranged on the side of the fermenter.
  • another liquid injector is arranged opposite to the upper micro-interface generator, the side wall of the fermenter is provided with a cleaning water inlet and an air inlet, and the air inlet leads to the micro-interface generator through a pipeline Among them, the air inlet is in one-to-one correspondence with the micro-interface generator, the liquid injector is connected with the cleaning water inlet through a pipeline, and the cleaning water inlet is in one-to-one correspondence with the liquid injector.
  • the fermentation yield is generally not high due to the relatively low gas-liquid mass transfer efficiency.
  • the present invention provides a new type of erythromycin
  • the erythromycin processing system integrates a micro-interface generator and a liquid ejector to fully disperse and crush the air and water, improve the cleaning effect of the fermentation tank, and improve the gas-liquid transfer during the fermentation process. quality effect, so as to finally achieve the effect of improving the fermentation yield.
  • the fermentation device of the present invention is formed by two fermenters connected in parallel, because in the process of fermentation, in order to improve the fermentation effect and improve the mass transfer effect of the fermentation process, the parallel operation of the two fermenters can effectively improve the fermentation effect .
  • the way of working can also increase the fermentation processing capacity and shorten the processing time.
  • the two liquid injectors arranged on the side walls of each fermenter are vertically offset from each other.
  • the liquid ejector is located directly above the upper micro-interface generator.
  • the top of the liquid injector is a semi-circular arc surface
  • a plurality of injection ports are sequentially arranged on the semi-circular arc surface
  • the cleaning water inlet is connected to the bottom of the liquid injector through pipes .
  • the liquid injector of the present invention is mainly connected with the cleaning water inlet through a pipeline, and the cleaning water is introduced into the liquid injector and sprayed out through the spray port on the semicircular arc surface of the liquid injector.
  • the reason why it is designed as a semicircle The structure of the arc-shaped surface is to improve the cleaning effect and ensure that the sprayed cleaning water can clean the wall surface of the fermentation tank in an all-round way.
  • a mesh surface with a plurality of evenly distributed micropores is laid in each of the spray ports. , the water sprayed out in this way is broken and dispersed into mist to improve the mass transfer effect, which is equivalent to the corresponding effect of the micro-interface generator.
  • the liquid injector of the present invention is specifically used in combination with three, one of which is located in the middle, and the other two are located on the inner wall of the fermenter, so that the directions of each liquid injector spraying water mist are in different directions, so as to ensure that the The inside of the fermenter is cleaned.
  • the dislocation of the two liquid injectors on the inner wall is also to prevent the two liquid injectors from interfering with each other.
  • one of the two micro-interface generators is preferably set at a lower position in the fermenter, so that the air can enter and fill the whole fermenter. If the position is too high, it may affect the oxygen and bacterial liquid, The dispersion effect between the materials and liquids, another micro-interface generator is located closer to the upper liquid injector, because the liquid phase entering the micro-interface generator during the working process of the liquid injector can also further It plays the role of dispersing and breaking, so that the liquid dispersion effect is better, so it can be seen that the two micro-interface generators play different roles respectively.
  • each micro-interface generator arranged in each fermenter work in cooperation with each other, and the specific type is preferably a pneumatic micro-interface generator, because the pneumatic type is relatively low in cost and easy to install.
  • each micro-interface generator corresponds to an air inlet, so that each micro-interface generator can achieve the effect of dispersing and breaking the incoming air at the first time, so it is best not to have two micro-interface generators corresponding to the same air inlet at the same time. An air inlet, but the air is blown into the fermenter in a one-to-one correspondence.
  • the micro-interface generator in each fermenter breaks the air into micro-scale micro-bubbles, and releases the micro-bubbles into the fermentation liquid to increase the mass transfer area between the oxygen and the fermentation liquid during the fermentation process, so that the The two phases are fully contacted, the dissolved oxygen concentration in the fermentation broth is increased, the fermentation efficiency is improved, and the fermentation time is shortened.
  • micro-interface generator used in the present invention has been embodied in the inventor's prior patents, such as application numbers CN201610641119.6, CN201610641251.7, CN201710766435.0, CN106187660, CN105903425A, Patents of CN109437390A, CN205833127U and CN207581700U.
  • application numbers CN201610641119.6, CN201610641251.7, CN201710766435.0, CN106187660, CN105903425A, Patents of CN109437390A, CN205833127U and CN207581700U In the previous patent CN201610641119.6, the specific product structure and working principle of the micro-bubble generator (that is, the micro-interface generator) were introduced in detail.
  • the body is provided with an inlet communicating with the cavity, the opposite first and second ends of the cavity are open, wherein the cross-sectional area of the cavity is from the middle of the cavity to the first and second ends of the cavity.
  • the second end is reduced; the secondary crushing piece is arranged at at least one of the first end and the second end of the cavity, a part of the secondary crushing piece is arranged in the cavity, and both ends of the secondary crushing piece and the cavity are open
  • An annular channel is formed between the through holes of the micro-bubble generator.
  • the micro-bubble generator also includes an air inlet pipe and a liquid inlet pipe.” From the specific structure disclosed in the application document, we can know that its specific working principle is: the liquid enters the micron tangentially through the liquid inlet pipe. In the bubble generator, ultra-high-speed rotation and cutting of the gas make the gas bubbles break into micro-bubbles at the micron level, thereby increasing the mass transfer area between the liquid phase and the gas phase, and the micro-bubble generator in this patent belongs to the pneumatic micro-interface generation. device.
  • the previous patent 201610641251.7 records that the primary bubble breaker has a circulating liquid inlet, a circulating gas inlet and a gas-liquid mixture outlet, and the secondary bubble breaker communicates the feed port with the gas-liquid mixture outlet, indicating that the bubble breaker is both It needs to be mixed with gas and liquid.
  • the primary bubble breaker mainly uses circulating liquid as power, so in fact, the primary bubble breaker belongs to the hydraulic micro-interface generator, and the secondary bubble breaker is a gas-liquid breaker. The mixture is simultaneously fed into the elliptical rotating ball for rotation, so that the bubbles are broken during the rotation, so the secondary bubble breaker is actually a gas-liquid linkage type micro-interface generator.
  • both hydraulic micro-interface generators and gas-liquid linkage micro-interface generators belong to a specific form of micro-interface generators.
  • the micro-interface generators used in the present invention are not limited to the above-mentioned forms.
  • the specific structure of the bubble breaker described in the prior patent is only one of the forms that the micro-interface generator of the present invention can take.
  • the previous patent 201710766435.0 records that "the principle of the bubble breaker is to achieve high-speed jets to achieve gas collision", and it is also stated that it can be used in micro-interface enhanced reactors to verify the relationship between the bubble breaker and the micro-interface generator.
  • the top of the bubble breaker is the liquid phase inlet, and the side is the gas phase inlet.
  • the liquid phase entering from the top provides the entrainment power, so as to achieve the effect of crushing into ultra-fine bubbles, which can also be seen in the accompanying drawings.
  • the bubble breaker has a conical structure, and the diameter of the upper part is larger than that of the lower part, so that the liquid phase can provide better entrainment power.
  • micro-interface generator Since the micro-interface generator was just developed in the early stage of the previous patent application, it was named as micro-bubble generator (CN201610641119.6), bubble breaker (201710766435.0), etc., and later changed its name to micro-interface generator with continuous technological improvement.
  • the micro-interface generator in the present invention is equivalent to the previous micro-bubble generator, bubble breaker, etc., but the names are different.
  • the micro-interface generator of the present invention belongs to the prior art, although some micro-interface generators belong to the type of pneumatic micro-interface generators, some micro-interface generators belong to the type of hydraulic micro-interface generators, and some are of the type of hydraulic micro-interface generators. It belongs to the type of gas-liquid linkage micro-interface generator, but the difference between the types is mainly selected according to the specific working conditions.
  • the connection between the micro-interface generator and the reactor and other equipment including the connection structure, connection position, It depends on the structure of the micro-interface generator, which is not limited.
  • the erythromycin processing system includes a liquid bacterial strain premixing device and a bacterial liquid tank, the bacterial liquid tank is communicated with the bacterial liquid inlet, and the bacterial strains premixed by the liquid bacterial strain premixing device are stored. in the bacterial liquid tank.
  • the liquid bacterial strain premixing device includes a split premixing pipe and a confluence premixing pipe, and different types of bacterial liquids are merged into the confluent premixing pipe through the splitting premixing pipe for premixing, and the confluent premixing pipe is connected with the confluence premixing pipe.
  • the bacterial liquid tank is communicated.
  • the bacterial strain premixing device is designed to realize the premixing of various liquid strains. Different types of bacterial liquids first pass through different shunt premixing pipes, and then are aggregated into the confluence premixing pipe for mixing between different bacterial liquids. , so as to realize the mixing of different bacterial liquids to improve the pre-mixing rate of bacterial species, and also improve the subsequent fermentation effect.
  • the erythromycin processing system includes a feed liquid tank, and the feed liquid tank is communicated with the feed liquid inlet through a pipeline.
  • the feed liquid stored in the feed liquid tank enters the fermentation tank through the feed liquid inlet.
  • both sides of the bottom of the fermenter are flat, and a bulge is formed upward at the center position, and the liquid outlets are respectively provided at the flat positions on both sides of the bottom of the fermenter.
  • the reason why the center position is raised upwards is to efficiently discharge the fermented products generated by aerobic fermentation from the outlet.
  • the center of the bottom of the fermenter is raised upwards.
  • a stirring paddle is provided at the center bulge of the inner bottom of the fermentation tank to accelerate the discharge.
  • the stirring paddle is also arranged in the raised position to improve the discharge efficiency of the fermentation product, and the fermentation efficiency can also be improved by stirring.
  • the erythromycin processing system of the present invention further comprises a plurality of high-temperature steam pipelines for sterilizing the fermentation tank, respectively sterilizing the feed liquid, the bacterial liquid and the cleaning water.
  • the fermenter is provided with an ultrasonic sterilization device, and the ultrasonic sterilization device is close to the inner wall of the fermenter, so that while steam is passed into the fermenter through the steam pipeline, the ultrasonic sterilization device can be used to assist sterilization. .
  • the cleaning water inlet is provided near the bottom of the fermenter to clean the inner bottom of the fermenter. This can not only have the effect of cleaning the upper part of the fermentation tank, but also the effect of cleaning the lower part of the fermentation tank.
  • the present invention also provides a processing method, comprising the following steps:
  • the cleaning water is broken into micron-sized droplets to clean the inside of the fermentation device;
  • the air micro-interface After the air micro-interface is dispersed and broken, it is mixed with bacterial liquid and feed liquid for aerobic fermentation, and the fermentation product is discharged and collected.
  • a micro-interface generator is arranged inside each fermentation tank in the fermentation device, so that before the air and the fermentation liquid are fermented, the micro-interface generator breaks the air into a diameter of 1 ⁇ m or more and a diameter of less than 1 ⁇ m.
  • 1mm microbubbles make the air contact with the fermentation liquid in the state of microbubbles, so as to increase the mass transfer area of the phase boundary between the oxygen and the fermentation liquid during the fermentation process, so that the two phases are fully contacted, and the dissolved oxygen concentration in the fermentation liquid is increased. , improving the fermentation efficiency and shortening the fermentation time, thereby solving the problem of low fermentation efficiency in the prior art.
  • the automatic fermentation tank cleaning process and the intelligent control process are realized by adding the control system, which further saves the production cost.
  • a micro-interface generator and a liquid ejector are arranged in the fermenter.
  • the top of the collision fermentation tank replaces manual cleaning.
  • the air is efficiently broken into micron-sized bubbles by the micro-interface generator, and dispersed into the fermentation liquid to form a micro-interface system to increase the gas-liquid in the anti-gas liquid dozens of times.
  • the area of the phase interface greatly improves the mass transfer rate of oxygen to the fermentation broth, the concentration of dissolved oxygen and the macroscopic fermentation rate;
  • the erythromycin processing system of the present invention uses an intelligent cleaning device to replace manual cleaning, and adopts a PLC (or DCS, PLC and DCS) control system to remotely control the production, which is in line with the intelligence of production;
  • PLC or DCS, PLC and DCS
  • the processing method of the present invention is easy to operate, the obtained fermentation product has high purity and good fermentation effect, and is worthy of widespread application.
  • FIG. 1 is a schematic structural diagram of an erythromycin processing system provided in an embodiment of the present invention.
  • Fig. 2 is the internal structure diagram of each fermentation tank in Fig. 1;
  • FIG. 3 is a schematic structural diagram of a mesh surface of an erythromycin processing system provided by an embodiment of the present invention.
  • the terms “installed”, “connected” and “connected” should be understood in a broad sense, unless otherwise expressly specified and limited, for example, it may be a fixed connection or a detachable connection Connection, or integral connection; can be mechanical connection, can also be electrical connection; can be directly connected, can also be indirectly connected through an intermediate medium, can be internal communication between two elements.
  • installed should be understood in a broad sense, unless otherwise expressly specified and limited, for example, it may be a fixed connection or a detachable connection Connection, or integral connection; can be mechanical connection, can also be electrical connection; can be directly connected, can also be indirectly connected through an intermediate medium, can be internal communication between two elements.
  • FIG. 1 it is an erythromycin processing system according to an embodiment of the present invention, which mainly includes a fermentation device and a control system 20.
  • the fermentation device is composed of two fermenters 10 in parallel with each other.
  • each fermenter 10 is provided with three liquid injectors 103 and two micro-interface generators 104.
  • the upper micro-interface generator 104 is close to the top of each fermenter 10, and the lower one is close to the top of each fermenter 10.
  • the micro-interface generator 104 is close to the bottom of each fermenter 10, and the liquid injectors 103 are arranged in the upper part of each fermenter 10, wherein two liquid injectors 103 are respectively arranged on the side wall of each fermenter 10, and are mutually offset Another liquid injector 103 is arranged opposite to the upper micro-interface generator 104, and is arranged directly above the micro-interface generator 104.
  • the side wall of the fermentation tank 10 is provided with a cleaning water inlet 106 and an air inlet 105.
  • the fermentation tank The top of 10 is provided with a bacterial liquid inlet 101 and a material liquid inlet 102 for the entry of bacterial liquid and material liquid, the micro-interface generator 104 is connected with the air inlet 105 through a pipeline, and the cleaning water inlet 106 corresponds to the liquid ejector 103 one-to-one. , used to disperse and crush the cleaning water in the liquid ejector 103, and the air inlet 105 corresponds to the micro-interface generator 104 one-to-one.
  • the air is broken into micro-bubbles with a diameter of microns to increase the During the fermentation process, the mass transfer area of the phase boundary between the oxygen and the fermentation liquid makes the two phases fully contact, increases the dissolved oxygen concentration in the fermentation liquid, improves the fermentation efficiency, and shortens the fermentation time.
  • the fermentation system includes a liquid strain premixing device 112, a bacterial liquid tank 110 and a material liquid tank 111.
  • the liquid strain premixing device 112 includes a shunt premixing pipe 1121 and a confluence premixing pipe 1122.
  • the mixing pipe 1121 is merged into the confluence premixing pipe 1122 for premixing, the confluence premixing pipe 1122 is connected with the bacterial liquid tank 110, the material liquid tank 111 is connected with the material liquid inlet 102 through a pipeline, and the bacterial liquid tank 110 is connected with the bacterial liquid inlet 101 through a pipeline. Pipeline connection.
  • the liquid injector 103 is connected with the cleaning water inlet 106 through a pipeline.
  • the top surface of the liquid injector 103 is a semi-circular arc surface, and a number of injection ports 1031 are arranged in sequence on the semi-circular arc surface.
  • 106 is connected to the bottom of the liquid injector 103 through a pipeline, and the cleaning water is broken into micro-droplets with a diameter of micrometers, and sprayed from the ejection port 1031 raised on the surface to collide with the inside of the tank for efficient cleaning.
  • a mesh surface 1032 with a plurality of micropores evenly distributed is laid in the spray port 1031, and the number of the mesh surface 1032 is not limited.
  • the structure of the mesh surface 1032 refer to FIG. 3 for details.
  • the bottom of the fermentation tank 10 is provided with a liquid outlet 107 for discharging waste water and waste gas and discharging products. Both sides of the bottom of the fermentation tank 10 are flat, and the center position is upward to form a bulge.
  • the liquid outlet 107 is respectively provided at the flat position on both sides of the bottom of the fermentation tank 10, and the center bulge of the inner bottom of the fermentation tank 10 is provided with a stirring device.
  • the paddle 108 plays the role of accelerating the discharge, the direction of the blade is upward, and is used for stirring at the bottom of the fermentation tank 10 during washing, fermentation and liquid drainage, and the rotational speed can be adjusted steplessly.
  • a cleaning water inlet 106 is also correspondingly provided at the bottom of the side wall of the fermentation tank 10 . In this way, effective cleaning can be achieved for various positions inside the fermenter 10 .
  • the fermenter 10 of the present invention can also realize the sterilization function.
  • a steam line is correspondingly arranged on each feed line, and an ultrasonic sterilization device 109 is correspondingly arranged on the inner side wall of the fermenter 10 to assist the steam line in sterilization. .
  • This embodiment also includes a PLC (or DCS, PLC and DCS) control system 20: connected to the sensor of the fermenter 10, for intelligently controlling process operations and parameters, realizing remote control of production, and conforming to the intelligence of production.
  • PLC or DCS, PLC and DCS
  • the cleaning water above the fermentation tank 10 is transported to the inside of the liquid ejector 103 and sprayed out through the jet port 1031 on the arc surface, and is efficiently broken into micron-level (1 ⁇ m ⁇ d ⁇ 1mm) through the mesh surface 1032 ) droplets are ejected from the protruding ejection port 1031 on the surface of the liquid ejector 103 , collide with the inside of the fermenter 10 and clean the top.
  • the cleaned droplets form a liquid level at the bottom of the tank. When the liquid level rises to the middle of the tank, close the upper water delivery valve and open the stirring paddle at the bottom at 108 to 200 rpm.
  • the installation direction of the blades of the stirring paddle 108 is downward, the liquid above the blades will be pumped to the lower sides, and a vortex will be formed on both sides of the stirring paddle 108 to wash and clean the lower two sides of the fermentation tank 10 .
  • the lower waterway is opened, so that the flowing water enters from the lower cleaning water inlet 106, and the input water flow cleans the high-side tank wall under the action of the stirring paddle 108.
  • the water delivery valve is closed, and the speed is reduced to 100rpm. /min, and discharge the waste water through the liquid outlet 107 on both sides of the lower end of the tank, close the liquid outlet 107, and reduce the speed to 50 rpm.
  • Feeding Open the feed liquid inlet 102 at the top of the fermentation tank 10, and feed erythromycin from the feed liquid inlet 102 through the pipeline. When the liquid level reaches a certain height, the feeding is completed, and the valve is closed to stop feeding.
  • Ventilation after the feed liquid is cooled to room temperature, the fermented fungi are introduced from the bacterial liquid inlet 101, the stirring speed is increased to 100 rpm, the bacteria feeding pipeline is closed, and the air inlet 105 begins to introduce air into the micro-interface generator 104 .
  • the micro-interface generator 104 breaks the air into micro-bubbles of micron scale, and releases the micro-bubbles into the fermentation liquid, so as to increase the mass transfer area of the phase boundary between the oxygen and the fermentation liquid during the fermentation process, so that the two phases are fully contacted, The dissolved oxygen concentration in the fermentation broth is increased, the fermentation efficiency is improved, and the fermentation time is shortened.
  • control system 20 of PLC or DCS, PLC and DCS.
  • micro-interface generators 104 there are two micro-interface generators 104.
  • the bubbles are broken into pieces with a diameter of 1 ⁇ m or more and less than 1 mm.
  • Micro-bubbles of micron level are classified into pneumatic micro-interface generator 104, hydraulic micro-interface generator 104 and gas-liquid linkage micro-interface generator 104 according to the energy input method or gas-liquid ratio, wherein the pneumatic micro-interface generator 104 is driven by gas, and the input
  • the gas volume is much greater than the liquid volume
  • the hydraulic micro-interface generator 104 is driven by liquid, and the input gas volume is generally less than the liquid volume
  • the gas-liquid linkage micro-interface generator 104 is driven by gas and liquid simultaneously, and the input gas volume is close to the liquid volume.
  • the micro-interface generator 104 selects one or more of the pneumatic micro-interface generator 104, the hydraulic micro-interface generator 104 and the gas-liquid linkage micro-interface generator 104.
  • micro-interface generators 104 can also be added.
  • the installation position is not limited. It can be external or built-in. When built-in, it can also be installed on the side wall of the kettle. , so as to achieve hedging of the micro-bubbles coming out of the outlet of the micro-interface generator 104 .
  • the fermentation temperature can be normal temperature or the temperature required by the bacterial species
  • the fermentation pressure is normal pressure
  • the fermented substances can be citric acid, penicillin and the like in addition to erythromycin.

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Abstract

La présente invention concerne un système de traitement d'érythromycine et un procédé de traitement s'y rapportant. Le système de traitement d'érythromycine comprend : un dispositif de fermentation et un système de régulation, le dispositif de fermentation étant formé en reliant deux cuves de fermentation en parallèle, la partie supérieure de chaque cuve de fermentation étant pourvue d'une entrée de solution bactérienne et d'une entrée de liquide d'alimentation pour laisser entrer une solution bactérienne et un liquide d'alimentation et le fond de chaque cuve de fermentation est pourvu d'une sortie de liquide pour évacuer un produit de fermentation. Chaque réservoir de fermentation est doté à l'intérieur d'éjecteurs de liquide et de générateurs de micro-interface, les générateurs de micro-interface positionnés au niveau d'une partie supérieure sont proches de la partie supérieure du réservoir de fermentation, les générateurs de micro-interface positionnés au niveau d'une partie inférieure sont proches du fond du réservoir de fermentation, les éjecteurs de liquide sont disposés au niveau de la partie supérieure dans le réservoir de fermentation, deux éjecteurs de liquide sont disposés respectivement sur une paroi latérale de chaque cuve de fermentation et un autre éjecteur de liquide est disposé à l'opposé du générateur de micro-interface au niveau de la partie supérieure. Le procédé de traitement comprend les étapes suivantes : décomposer l'eau de nettoyage en micro-gouttelettes de taille micrométrique pour nettoyer l'intérieur d'un dispositif de fermentation ; disperser et fragmenter une micro-interface d'air, mélanger la micro-interface d'air avec une solution bactérienne et un liquide d'alimentation pour la fermentation aérobie et décharger et collecter un produit de fermentation. Le système de traitement d'érythromycine résout le problème dans l'état de la technique de l'air et d'un liquide de fermentation qui ne peuvent se mélanger complètement dans un réservoir de fermentation.
PCT/CN2020/122871 2020-10-21 2020-10-22 Système de traitement d'érythromycine et procédé de traitement s'y rapportant WO2022082616A1 (fr)

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CN113058403B (zh) * 2021-04-02 2023-03-14 河北首朗新能源科技有限公司 一种工业尾气连续发酵装置
CN113512483A (zh) * 2021-07-14 2021-10-19 南京延长反应技术研究院有限公司 一种超高效低压气源微界面强化生物发酵的装置及方法

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CN204723426U (zh) * 2015-05-27 2015-10-28 河北宇泽环保科技有限公司 一种节能型连续灭菌系统
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