阅读说明：本技术 一种霉菌脱氢物精品的制备方法 (Preparation method of refined mould dehydrogenated product ) 是由 谭志云 王钱钢 谭建权 熊建国 陈曙 于 2021-08-10 设计创作，主要内容包括：本发明提供一种霉菌脱氢物精品的制备方法,包括：培养霉菌脱氢物种子,得到种子液；将所述种子液发酵得到霉菌脱氢物；对所述霉菌脱氢物进行粗提取,得到霉菌脱氢物粗品；对所述霉菌脱氢物粗品进行精制,得到所述霉菌脱氢物精品。采用本发明技术方案,能够建立霉菌脱氢物种子培养标准操作规程,提高霉菌脱氢物生产过程中的规范性；建立霉菌脱氢物发酵标准操作规程,提高霉菌脱氢物生产过程中的规范性；建立标准操作规程,规范霉菌脱氢物粗品提取岗位的操作；建立标准操作规程,规范霉菌脱氢物精制岗位的操作。(The invention provides a preparation method of a refined mould dehydrogenated substance, which comprises the following steps: culturing mould dehydrogenation seeds to obtain a seed solution; fermenting the seed liquid to obtain a mould dehydrogenation product; carrying out coarse extraction on the mould dehydrogenation product to obtain a crude mould dehydrogenation product; and refining the crude mould dehydrogenation product to obtain a refined mould dehydrogenation product. By adopting the technical scheme, the standard operation procedure for culturing the mould dehydrogenation product seeds can be established, and the standardization in the production process of the mould dehydrogenation product is improved; establishing a standard operating procedure for fermenting the mould dehydrogenation product, and improving the standardability of the mould dehydrogenation product in the production process; establishing a standard operating specification, and standardizing the operation of a mould dehydrogenation product crude product extraction post; and establishing standard operating procedures to standardize the operation of the mould dehydrogenation product refining post.)

1. A preparation method of a refined mould dehydrogenated product is characterized by comprising the following steps: culturing mould dehydrogenation seeds to obtain a seed solution;

fermenting the seed liquid to obtain a mould dehydrogenation product;

carrying out coarse extraction on the mould dehydrogenation product to obtain a crude mould dehydrogenation product;

and refining the crude mould dehydrogenation product to obtain a refined mould dehydrogenation product.

2. The method for preparing a refined mold dehydrogenated product according to claim 1, wherein the culturing of the mold dehydrogenated product seed comprises:

s11, preparing seed raw materials and pouring the seed raw materials and water into a tank, adjusting the pH value of the tank to 8.5-9.0 at 40 ℃, and fastening a tank cover;

s12, performing steam sterilization, adjusting the temperature in the tank to be 112-118 ℃, adjusting the pressure in the tank to be 0.1-0.12 MPa, and maintaining the pressure for 20 min;

and S13, starting mould dehydrogenation seed culture until the inoculation amount in the seed tank is 120-150 Kirschner bottles, and obtaining the seed liquid.

3. The method for preparing a refined mold dehydrogenated product according to claim 2, wherein the seed material comprises the following components in percentage by mass: glucose 0.8%, corn steep liquor 1.35-1.4%, peptone 0.5%, KH₂PO₄0.05%, 0.04% of natural enemy and 0.05% of yeast extract.

4. The method for preparing a refined mold dehydrogenated product according to claim 1, wherein the step of fermenting the seed liquid to obtain the mold dehydrogenated product comprises:

s21, feeding the seed liquid into a fermentation tank, adjusting the pressure in the fermentation tank to be 0.05-0.06 MPa, the temperature in the fermentation tank to be 29-34 ℃, and the air flow in the fermentation tank to be 100-150 m³The stirring speed in the fermentation tank is 120 r/min, and the culture time is 36-56h, so as to obtain fermentation liquor;

s22, adjusting the pH value of the fermentation liquor to 4.5-5.0, reducing the temperature to 75-80 ℃, and discharging to obtain the mould dehydrogenation product.

5. The method for preparing a refined product of a dehydrogenated mold product of claim 4, wherein the conversion rate of the seed liquid in the fermentation tank is greater than or equal to 85%.

6. The method for preparing a refined mold dehydrogenated product of claim 1, wherein the step S2 comprises the following steps:

s31, putting the mould dehydrogenation product into an extraction tank, adjusting the temperature in the extraction tank to be 58-62 ℃ and the pressure in the extraction tank to be 0.06-0.10MPa, starting filter pressing, and pressing the filtrate obtained by filter pressing into a concentration tank A;

s32, collecting mycelia in filter pressing, carrying out filter pressing extraction on the collected mycelia for a plurality of times, and pressing the obtained extracting solution into the concentration tank A to obtain a concentrated solution A;

s33, cooling the concentrated solution A to below 40 ℃, standing for more than 2 hours, and then performing discharging centrifugal separation to respectively obtain mother liquor and the crude product of the mould dehydrogenation product.

7. The method for preparing a refined product of a mold dehydrogenation product according to claim 6, wherein the yield of the crude product of the mold dehydrogenation product is 70-95%,

8. the method for preparing a refined mold dehydrogenated product according to claim 1, wherein the refining of the crude mold dehydrogenated product comprises:

s41, putting the crude mould dehydrogenation product into a refining tank, closing the refining tank, pumping methanol and chloroform, adjusting the pressure in the refining tank to be 0.06-0.10MPa, performing pressure filtration, pressing the filtrate obtained by pressure filtration into a concentration tank B for concentration to obtain a concentrated solution B;

s42, centrifugally drying the concentrated solution B to respectively obtain refined mother liquor and refined mould dehydrogenation product, wherein the drying temperature of the concentrated solution B is 85-95 ℃, and the drying time is 4-6 h.

9. The method for preparing a refined mold dehydrogenated product according to claim 8, wherein the refined mother liquor is concentrated and crystallized, whether the content of mold oxide and mold dehydrogenated product in the refined mother liquor is greater than 95% is detected, and if yes, the refined mother liquor is returned to the step of fermenting the seed liquor to obtain the mold dehydrogenated product; and detecting whether the content of the mold dehydrogenation products is more than 90%, if so, returning to the step S41.

Technical Field

The invention belongs to the technical field of preparation and purification of medical intermediates, and particularly relates to a preparation method of a refined mould dehydrogenated substance.

Background

The mould dehydrogenation product is used as an important medical intermediate and has higher use requirement on the precision. However, due to the complex production process flow, the precision of the mould dehydrogenation product is difficult to ensure by the existing process, the standard operation procedure is lacked, and the product quality is difficult to control due to the lack of the normative process operation.

Disclosure of Invention

Aiming at the problems, the invention provides a preparation method of a fine product of a mould dehydrogenation product, which adopts the following technical scheme:

a preparation method of a refined mould dehydrogenation product comprises the following steps:

culturing mould dehydrogenation seeds to obtain a seed solution;

fermenting the seed liquid to obtain a mould dehydrogenation product;

carrying out coarse extraction on the mould dehydrogenation product to obtain a crude mould dehydrogenation product;

and refining the crude mould dehydrogenation product to obtain a refined mould dehydrogenation product.

Preferably, the cultured mould dehydrogenated seed is specifically:

s11, preparing seed raw materials and pouring the seed raw materials and water into a tank, adjusting the pH value of the tank to 8.5-9.0 at 40 ℃, and fastening a tank cover;

s12, performing steam sterilization, adjusting the temperature in the tank to be 112-118 ℃, adjusting the pressure in the tank to be 0.1-0.12 MPa, and maintaining the pressure for 20 min;

and S13, starting mould dehydrogenation seed culture until the inoculation amount in the seed tank is 120-150 Kirschner bottles, and obtaining the seed liquid.

Preferably, the seed raw material comprises the following components in percentage by mass: glucose 0.8%, corn steep liquor 1.35-1.4%, peptone 0.5%, KH₂PO₄0.05%, 0.04% of natural enemy and 0.05% of yeast extract.

Preferably, the fermentation of the seed liquid to obtain the mold dehydrogenated substance specifically comprises:

S21、feeding the seed liquid into a fermentation tank, adjusting the pressure in the fermentation tank to be 0.05-0.06 MPa, the temperature in the fermentation tank to be 29-34 ℃, and the air flow in the fermentation tank to be 100-150 m³The stirring speed in the fermentation tank is 120 r/min, and the culture time is 36-56h, so as to obtain fermentation liquor;

s22, adjusting the pH value of the fermentation liquor to 4.5-5.0, reducing the temperature to 75-80 ℃, and discharging to obtain the mould dehydrogenation product.

Preferably, the conversion rate of the seed liquid in the fermentation tank is more than or equal to 85%.

Preferably, in the step S2, the mold dehydrogenated substance is subjected to a crude extraction, specifically:

s31, putting the mould dehydrogenation product into an extraction tank, adjusting the temperature in the extraction tank to be 58-62 ℃ and the pressure in the extraction tank to be 0.06-0.10MPa, starting filter pressing, and pressing the filtrate obtained by filter pressing into a concentration tank A;

s32, collecting mycelia in filter pressing, carrying out filter pressing extraction on the collected mycelia for a plurality of times, and pressing the obtained extracting solution into the concentration tank A to obtain a concentrated solution A;

s33, cooling the concentrated solution A to below 40 ℃, standing for more than 2 hours, and then performing discharging centrifugal separation to respectively obtain mother liquor and the crude product of the mould dehydrogenation product.

Preferably, the yield of the crude mould dehydrogenated product is 70-95%, wherein,

preferably, the refining of the crude mould dehydrogenated product specifically comprises:

s41, putting the crude mould dehydrogenation product into a refining tank, closing the refining tank, pumping methanol and chloroform, adjusting the pressure in the refining tank to be 0.06-0.10MPa, performing pressure filtration, pressing the filtrate obtained by pressure filtration into a concentration tank B for concentration to obtain a concentrated solution B;

s42, centrifugally drying the concentrated solution B to respectively obtain refined mother liquor and refined mould dehydrogenation product, wherein the drying temperature of the concentrated solution B is 85-95 ℃, and the drying time is 4-6 h.

Preferably, the refined mother liquor is concentrated and crystallized, whether the content of mould oxide and mould dehydrogenation substances in the refined mother liquor is more than 95 percent is detected, if yes, the refined mother liquor is returned to the step of fermenting the seed liquor to obtain the mould dehydrogenation substances; and detecting whether the content of the mold dehydrogenation products is more than 90%, if so, returning to the step S41.

The invention has the following beneficial effects: by adopting the technical scheme, the standard operation procedure for culturing the mould dehydrogenation product seeds can be established, and the standardization in the production process of the mould dehydrogenation product is improved; establishing a standard operating procedure for fermenting the mould dehydrogenation product, and improving the standardability of the mould dehydrogenation product in the production process; establishing a standard operating specification, and standardizing the operation of a mould dehydrogenation product crude product extraction post; and establishing standard operating procedures to standardize the operation of the mould dehydrogenation product refining post.

Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and attained by the structure particularly pointed out in the written description and claims hereof as well as the appended drawings.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and those skilled in the art can also obtain other drawings according to the drawings without creative efforts.

FIG. 1 shows a process flow diagram for culturing mold dehydrogenate seeds according to the invention;

FIG. 2 shows a process flow diagram for the crude extraction of the mould dehydrogenate in step S2 according to the invention;

FIG. 3 shows a process flow diagram for refining the crude mould dehydrogenate according to the invention.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

A preparation method of a refined mould dehydrogenation product comprises the following steps:

s1, culturing mould dehydrogenation seeds to obtain a seed solution;

s2, fermenting the seed liquid to obtain the mold dehydrogenated substance, wherein the reaction formula is as follows:

s3, performing coarse extraction on the mould dehydrogenation product in the step S2 to obtain a crude mould dehydrogenation product;

s4, refining the crude mould dehydrogenation product to obtain a refined mould dehydrogenation product.

Further, regarding the cultivation of the mold dehydrogenated seed in step S1, as shown in fig. 1, the following process flow is specifically described:

1. adopting glucose, corn steep liquor, peptone and yeast extract as seed raw materials, preparing reagent KH₂PO₄The specification and the proportion of various seed raw materials, such as the dunking (polyether), the sodium hydroxide and the like are shown in the table 1 according to the volume of a 6T (ton) seed tank.

TABLE 1 seed materials and proportions

2. The preparation and sterilization of the seed liquid culture medium comprises the following specific processes:

2.1 preparation work, as follows: opening the tank cover, checking whether the tank is clean and has accumulated water, draining the tank from the bottom if the tank has accumulated water, and washing the tank with process water; checking whether each pipeline valve is intact and whether mechanical equipment is normal; checking whether the materials are intact, whether the package is damaged, whether the quantity is consistent with the batching list, and the like.

2.2 preparation of seed liquid culture Medium, exemplarily, the procedure is as follows:

2.2.1 weighing the corn steep liquor according to the mixture ratio.

2.2.2 opening the water valve for the process, and adding the water for the process to the required amount of mark according to the proportion. The condensed water of the steam is considered when the process water is put in, and the water is less than 10 percent of the required water when the process water is added.

2.2.3 the raw materials (seed raw materials) are poured into a pot according to the proportion, the distribution list in the bag is taken out to check the conformity of variety and quantity, and the distribution list and the material receiving list can be poured into the pot after the distribution list and the material receiving list are checked to be correct.

2.2.4 taking a small amount of process water to wash the tank opening and the raw material powder on the tank inner wall, sealing the tank cover after washing, heating to 40 ℃, adjusting the pH value by using a 20% sodium hydroxide aqueous solution, measuring the pH value to be 8.5-9.0, adding the molinate, tightening the tank cover, and preparing for sterilization.

2.3 Sterilization of seed liquid culture Medium, exemplarily, the procedure is as follows:

2.3.1 starting stirring to uniformly stir the materials.

2.3.2 the drain valve of the coil pipe (jacket) is opened firstly, the steam inlet valve of the coil pipe (jacket) is opened, and finally the steam valve is opened, and the condensed water in the coil pipe (jacket) is drained. When a large amount of steam is discharged, the drain valve of the coil pipe (jacket) is closed, the drain valve is kept slightly opened, condensed water is discharged, and meanwhile, the waste of the steam is prevented. The pressure of the coil (jacket) is controlled to be less than 0.2 MPa.

2.3.3 opening each path of emptying valve at the top of the tank to discharge cold air in the tank.

2.3.4 when the temperature in the tank rises to above 90 ℃, the steam inlet valve of the coil (jacket) is closed, and the stirring is closed. And opening a drain valve on the steam pipe to drain the condensed water until the white steam emerges. The main steam valve is slowly opened to allow the pressure to slowly rise, which cannot be too fast, so as to avoid damaging the steam filter. When the pressure rises to 0.3MPa, the steam inlet valve of the sampling pipe, the steam inlet valve of the air distribution pipe and the steam inlet of the bottom discharge pipe are opened, and the three paths of steam inlets are kept for sterilization.

2.3.5 when the temperature rises to above 100 ℃, a large amount of steam is emitted, each emptying valve is closed, and partial steam is kept to pass through. The pressure and temperature of the tank are raised in balance.

2.3.6 when the temperature rises to 112-118 ℃ and the tank pressure is about 0.1-0.12 MPa, closing each steam inlet valve, closing the emptying valve and maintaining the pressure for 20 min.

And 2.3.7, steam is introduced into the butt joint pipe for sterilization when pressure is maintained. During sterilization, the steam is required to pass through all parts of the pipeline, and dead corners which are not reached by the steam are avoided.

2.3.8 maintaining pressure, opening condensed water to cool the culture medium, opening an exhaust valve to exhaust steam in the tank, introducing sterile air when the pressure of the tank is reduced to 0.05MPa, starting stirring, and cooling to 30 +/-1 ℃ for later use.

2.3.9 the sterilized culture medium should be kept at positive pressure all the time to prevent contamination. And sterilizing the sampling tube, sampling the culture medium by using a triangular flask, marking the batch number of the culture medium, and sending the culture medium into a sterile room for storage for later use.

3 inoculation of seed liquid medium, the specific process is exemplarily as follows:

3.1 preparation: tearing a small amount of cotton into strips or soaking gauze strips in alcohol, and placing the strips or gauze strips into the gap of the can cover; taking out the hot air ring, and soaking the hot air ring in alcohol for later use; preparing two sets of wrenches; a towel strip soaked by basin water or water is prepared for extinguishing the wind and fire circle.

3.2 inoculation

3.2.1 ignite the cotton on the can lid and let it burn for 1 minute to sterilize the can lid.

3.2.2 the screw of the tank cover is quickly disassembled by a wrench, and when the tank cover is opened, the emptying valve is closed at the same time, so that air is discharged from the tank opening, and the contamination of bacteria is avoided.

3.2.3 when the can cover is completely disassembled, the air-fire ring is ignited, and when the can cover is opened, the air-fire ring is placed at the can opening.

3.2.4 pouring the mixed strains into a pot quickly through a wind-fire ring;

3.2.5 burning the cover on the wind-fire ring for about 20 s, removing the wind-fire ring, and putting into water or putting out with wet towel. The tank cover is quickly tightened, the evacuation valve is opened, and the air flow is regulated to a specified flow.

3.2.6 recording time, starting seed culture to obtain seed liquid, wherein the inoculation amount of a seeding tank is 120-150 Kirschner bottles, and the process conditions of the seeding tank culture process control used for culturing the mould dehydrogenation seeds are shown in Table 2.

The corresponding process parameters of the above process steps are shown in Table 3.

TABLE 2 seeding tank culture Process control parameters (1 ton seeding tank)

TABLE 3 Process parameters corresponding to the various steps of culturing mould dehydrogenation seeds

The process method for culturing the mould dehydrogenation seeds can establish a standard operation procedure for culturing the mould dehydrogenation seeds and improve the standardization in the production process of the mould dehydrogenation.

Further, in step S2, the seed solution is fermented to obtain the mold dehydrogenated substance, after the steps of culturing the mold dehydrogenated substance seeds, the seed tank is sampled for the first time at 8 hours, and when the bacteria are not infected in microscopic examination, the fermentation tank can be fed and sterilized for later use. The seeds can be transferred when the pH value is 7.0-7.2. The time for transferring seeds can be properly prolonged, but the culture time of the primary seeds can not exceed 15 hours at most, if the culture time is not reached, the seeds can be transferred to a fermentation tank without being infected with bacteria for secondary fermentation. Exemplarily, specifically:

1 transplanting of seeds

1.1 the culture medium of the fermenter (30 tons) before the seed transfer is sterilized by the sterilization method and cooled for further use.

1.2 the transfer line is also sterilized before transfer for use.

1.3 after the fermentation liquor in the seed tank is detected to be qualified, transferring the seed liquid into the fermentation tank according to a seed transferring operation method, and performing fermentation culture.

1.4 after the seeds are transplanted, the seed tank and the pipeline need to be washed clean by water and are emptied for 30 minutes.

The process can establish a standard operation procedure for fermenting the mould dehydrogenation product and improve the standardization of the mould dehydrogenation product in the production process.

Further, regarding step S3, the crude extraction of the mold dehydrogenated material in step S2 is exemplarily shown in fig. 2, specifically:

1. the specifications and the proportions of raw materials such as mold dehydrogenated substances, methanol and the like are shown in Table 4.

2. The process operation for extracting the crude mould dehydrogenated product is as follows:

2.1 checking whether the extraction tank, the accessory equipment and the pipeline thereof are intact and normal.

2.2 inspecting the production environment, clearing qualification certificate, extracting tank and its accessory facilities and cleaning the pipeline.

2.3, the name, batch number and quantity of the fed materials are checked to be accurate and correct.

2.4 the labor insurance product is worn correctly.

2.5, 20 plus or minus 2kg of the crude mould dehydrogenation product is put into an extraction tank, and the tank cover is closed.

2.6 open the vacuum and pump the metered amount of methanol into the extraction tank.

2.7 close the vacuum and the unclosed valve on the canister. The condenser is opened to allow brine to enter and exit, the exhaust pipe valve is opened, and the steam pipe exhaust valve is opened. Slowly opening a steam valve, heating to dissolve until reflux appears, controlling the steam quantity to prevent flushing, keeping the temperature at 60 +/-2 ℃, and preserving the heat for refluxing for 1 hour.

2.8 after the reflux is finished, stopping stirring, closing the exhaust valve, and preparing the filter system for filter pressing.

2.9 checking whether the concentration tank is clean and has no impurities, and whether a tank bottom valve is closed.

2.10 starting a vacuum pump, opening the vacuum of a lower storage tank of the concentration tank, and starting a cooler on the side of the concentration tank to enter a brine return valve. Opening the extraction tank to compress air, and adjusting the pressure of the extraction tank to 0.06-0.10 MPa. And opening connecting valves at two sides of the filter, starting filter pressing, and pressing the filtrate into a concentration tank.

2.11 collecting mycelium, and when about 20kg of mycelium is collected, intensively extracting for 1-2 times, wherein the operation is the same as the first extraction.

2.12 pressing the extract into a concentration tank, starting stirring, starting steam, and carrying out reduced pressure concentration and crystallization. And the steam quantity is controlled to prevent the material from being flushed.

2.13 when the solution is concentrated to 60-100 liters, closing the steam, opening the interlayer for cooling, and cooling the solution to below 40 ℃. Standing for more than 2 hours, and discharging.

2.14 check if the centrifuge is clean and intact. And laying filter cloth of the centrifuge.

2.15 putting the material into a centrifuge for spin-drying, collecting mother liquor, weighing wet products and obtaining a crude product of the mould dehydrogenation product.

2.16 methanol recovery sent to recovery plant.

2.17 concentrating, crystallizing and centrifuging the mother liquor after centralized batching, refining the mother liquor to a content of more than 90 percent separately through content detection, and putting the refined mother liquor as a crude product into the concentration and crystallization operation.

The process parameters for the above steps are shown in table 5. It should be noted that:

the reflux time for extraction must be more than 1 hour so that the product is fully dissolved in the solvent; during filter pressing, the pressure of the tank body is controlled not to exceed 0.1MPa, so that the filter paper is prevented from being crushed and safety accidents are prevented; the steam amount is not too large during concentration, so that the material is prevented from being washed; the retention of the concentrated solution is controlled within the range of 60-100 liters so as to control the quality and yield of the product; methanol is a toxic substance, and labor protection products are worn during operation.

Yield range of crude extraction of mold dehydrogenated material: 70% -95%; the standard yield thereof was found to be 80%. Batch yield range: 14 kg-19 kg; standard yield 16 kg.

TABLE 4 raw material specification and compounding ratio for crude extraction of mold dehydrogenated material

TABLE 5 Process parameters for the various steps

By adopting the technical scheme in the embodiment, a standard operation procedure can be established, and the operation of a mould dehydrogenation crude product extraction post is standardized.

Further, step S4 is to refine the crude mold dehydrogenated product, for example, referring to fig. 3, specifically:

1. the raw materials of the mould dehydrogenation product crude product, methanol, chloroform and the like are adopted, and the specification and the proportion of the raw materials are shown in table 6.

2. The process operation comprises the following steps of firstly dissolving materials for the first time:

2.1 checking whether the refining tank, the accessory equipment and the pipeline thereof are intact and normal.

2.2 inspecting the production environment, the site cleaning qualification certificate, the refining tank and the accessory facilities thereof and the clean site cleaning condition of the pipeline.

2.3, the name, batch number and quantity of the fed materials are checked to be accurate and correct.

2.4 the labor insurance product is worn correctly.

2.5 putting 12 plus or minus 3kg of the mould dehydrogenation crude product into a refining tank, and closing the tank.

2.6 opening vacuum, pumping in methanol and chloroform according to the mixture ratio, and closing vacuum.

2.7 opening a brine inlet valve and a brine outlet valve of the cooler beside the refining tank. Starting stirring, slowly starting steam, raising temperature and refluxing for 60 minutes.

2.8 after the backflow is finished, closing the exhaust valve, starting the vacuum pump, opening the vacuum of the lower storage tank of the concentration tank, and starting the brine inlet and return valve of the cooler beside the concentration tank. Starting the refined compressed air, and adjusting the pressure of the tank to be 0.06-0.10 MPa. And opening connecting valves at two sides of the filter, starting filter pressing, and pressing the filtrate into a concentration tank.

2.9 starting the concentration tank to stir, starting steam, and concentrating. Concentrating the solution to a certain amount under normal pressure, standing, and concentrating together after the secondary material dissolution.

Dissolving the materials for the second time, and repeating the steps 2.1-2.8

2.10 pressing the material liquid after the two times of material dissolving and primary concentration into the same concentration tank, starting the concentration tank to stir, starting steam to concentrate, and obtaining concentrated solution B. Concentrating the concentrated solution B to about 50L under normal pressure, stopping concentrating, cooling to below 40 deg.C with cold water, and standing for 1 hr.

2.11 checking whether the centrifuge is clean and intact. And laying filter cloth of the centrifuge.

2.12 after standing, placing the concentrated solution B into a centrifuge for centrifugal drying to respectively obtain mother liquor and solid products, sampling and testing the solid products to be qualified, drying at 90 +/-5 ℃ for 4-6 hours, weighing and warehousing to obtain the refined mould dehydrogenation product. And refining for the second time when the content is unqualified, wherein the method is the same as the first time.

2.13 the refined mother liquor is concentrated to about 30 liters, cooled, crystallized and dried by spinning, the content of the detected mould oxide and mould dehydrogenation substance is more than or equal to 95 percent and then returned to a fermentation workshop, and the content of the mould dehydrogenation substance is more than or equal to 90 percent and then sleeved in the step of concentration and crystallization.

The above operations need to be noted: during refluxing, the materials are observed to be completely dissolved and then concentrated; during filter pressing, the pressure of the tank body is controlled not to exceed 0.1MPa, so that the filter paper is prevented from being crushed and safety accidents are prevented; the steam amount is not too large during concentration, so that the material is prevented from being washed; the retention of the concentrated solution is controlled to be about 50 liters so as to control the quality and the yield of the product; methanol and chloroform are toxic substances, and the labor protection product is worn during operation.

The batch yield range of the obtained refined mould dehydrogenation product is 20 +/-5 kg, and the quality standard is shown in Table 7.

TABLE 6 refined raw material specification and compounding ratio

TABLE 7 quality standards for fine products of dehydrogenated mold

The technological process of the fine mould dehydrogenation product can establish standard operating specifications and standardize the operation of a mould dehydrogenation product refining post.

Although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.