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Method for preparing declomycin by fermentation method

A technology of demethyltetracycline and fermentation method, which is applied in the field of preparing demethyltetracycline by fermentation method, can solve the problems of high requirements on equipment and operation precision, high production cost, high production difficulty, etc., and achieves reduction of equipment investment and yield. The effect of increasing and reducing production costs

Pending Publication Date: 2020-05-05
HEBEI SHENGXUE DACHENG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Demethyltetracycline is the intermediate of the first step in the synthesis of minocycline hydrochloride. The traditional synthesis method is to ferment and purify demethyltetracycline, and then synthesize demethyltetracycline through dechlorination reaction, with a total yield of 80%; the reaction Hydrogen needs to be introduced, the reaction pressure is as high as 4MPa, the temperature is close to 60°C, and the expensive palladium carbon catalyst is used at the same time, so this process has a very high safety risk, and it will cause an explosion if you are not careful, which will affect the equipment and operation accuracy. High requirements, difficult production, high production cost

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  • Method for preparing declomycin by fermentation method

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Embodiment 1

[0020] Example 1: Use engineering bacteria to cultivate the seed liquid according to the standard formula, put the seed liquid into the sterilized seed tank for cultivation, the cultivation temperature is 28°C, the tank pressure is 0.03MPa, the ventilation rate is 1vvm, the dissolved oxygen is controlled in linkage to ≥30%, and the rotation speed 800rpm; after the cultivation of the seed tank is completed, it is connected to the fermenter tank, the culture temperature is 28°C, the tank pressure is 0.03MPa, the ventilation volume is 1vvm, the dissolved oxygen is controlled by linkage control ≥ 30%, and the speed is 800rpm; the transplant volume is 20%, and the culture period is 9 days. The tank titer is 9300u / mL and the volume is 60L.

[0021] After putting in the tank, heat the fermentation broth to 70°C, keep it warm for 60 minutes, cool it to room temperature, filter it with a plate frame, drain the filtrate, and keep the filter residue for use; add the filter residue to the ...

Embodiment 2

[0023] Example 2: Use engineering bacteria to cultivate the seed liquid according to the standard formula, put the seed liquid into a sterilized seed tank for cultivation, the cultivation temperature is 28°C, the tank pressure is 0.04MPa, the ventilation rate is 1vvm, the linkage control dissolved oxygen is ≥ 30%, and the rotation speed is 600rpm After the cultivation of the seed tank is completed, it is connected to the fermenter, the culture temperature is 28°C, the tank pressure is 0.04MPa, the ventilation volume is 1vvm, the dissolved oxygen is ≥ 30% in linkage control, the rotation speed is 600rpm, the transplant volume is 20%, and the culture period is 9 days. The potency is 10200u / mL and the volume is 57L.

[0024] After putting in the tank, heat the fermentation broth to 65°C, keep it warm for 40 minutes, cool it to room temperature, filter it with a plate frame, drain the filtrate, and keep the filter residue; add the filter residue to the purified water equal to the f...

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Abstract

The invention discloses a method for preparing declomycin by a fermentation method. The method comprises the following steps of step a, culturing seed liquid through engineering bacteria according toa standard recipe; step b, inoculating a sterilization seed tank with the seed liquid, and performing culturing; step c, after culturing of the seed tank is completed, inoculating a fermentation tankwith the obtained cultured seeds to obtain fermentation liquid; step d, after release of the fermentation liquid, firstly filtering the fermentation liquid, and remaining filter residues for use; stepe, adding purified water to the filter residues to obtain suspension, adding a purifying agent and a flocculant, and performing standing and filtration so as to obtain purifying liquid; step f, concentrating the purifying liquid, performing crystallization, and performing drying so as to obtain crude products; step g, adding activated carbon, performing stirring for decolourization, and performing filtration so as to obtain decolourized liquid; and step h, reducing the temperature, performing crystallization and performing drying so as to obtain finished products. According to the method disclosed by the invention, the whole extraction course is performed under the condition of normal low temperature and normal pressure, and a general-purpose solvent is used, so that security risk is reduced; and the declomycin is directly obtained through fermentation and refinement, and the yield is increased to 90% or above.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a method for preparing demethyltetracycline by fermentation. Background technique [0002] Demethyltetracycline is the intermediate of the first step in the synthesis of minocycline hydrochloride. The traditional synthesis method is to ferment and purify demethyltetracycline, and then synthesize demethyltetracycline through dechlorination reaction, with a total yield of 80%; the reaction Hydrogen needs to be introduced, the reaction pressure is as high as 4MPa, the temperature is close to 60°C, and the expensive palladium carbon catalyst is used at the same time, so this process has a very high safety risk, and it will cause an explosion if you are not careful, which will affect the equipment and operation accuracy. The requirements are high, the production is difficult, and the production cost is high. Contents of the invention [0003] In order to solve the p...

Claims

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Application Information

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IPC IPC(8): C12P29/00
CPCC12P29/00
Inventor 常国栋袁昉王绘砖徐珍曹建全
Owner HEBEI SHENGXUE DACHENG PHARMA