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Method for preparing dexamethasone intermediate product through one-step microbial fermentation and transformation

A technology for dexamethasone and dexamethasone epoxy hydrolyzate, which is applied in the field of biopharmaceuticals, can solve the problems of large yield loss in the production process, long production cycle, and large equipment investment, and achieves high yield and low production cost. , The effect of easy production and operation

Active Publication Date: 2017-03-22
JIANGSU YUANDA XIANLE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, there are extraction, refining, drying, packaging and other processes in each step of the reaction, the production cycle is long, the investment in equipment is large, and the yield loss in the production process is large

Method used

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  • Method for preparing dexamethasone intermediate product through one-step microbial fermentation and transformation
  • Method for preparing dexamethasone intermediate product through one-step microbial fermentation and transformation
  • Method for preparing dexamethasone intermediate product through one-step microbial fermentation and transformation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] A method for preparing a dexamethasone intermediate through one-step fermentation and conversion of microorganisms, the dexamethasone intermediate refers to dexamethasone epoxy hydrolyzate (8DM), comprising the following steps:

[0044] (1) Bacteria culture

[0045] The slant culture of Arthrobacter simplex was inoculated into 200ml seed medium, and the ratio of the used seed medium was: glucose 12g / L, yeast extract powder 10g / L, KH 2 PO 4 1g / L, pH7.0~7.2, cultured on a shaker at 160rpm, 30±1°C for 30hrs;

[0046] Inoculate the slant culture of Bacillus megaterium into another bottle of 200ml seed medium, the ratio of the seed medium used is: glucose 12g / L, yeast extract powder 10g / L, KH 2 PO 4 1g / L, pH7.0~7.2, cultured on a shaker at 160rpm, 30±1°C for 30hrs;

[0047] (2) Fermentation transformation

[0048] Prepare 2000ml of fermentation medium in a 5L Erlenmeyer shaker flask, the ratio of fermentation medium is: glucose 5g / L, corn steep liquor 10g / L, peptone 1g / ...

Embodiment 2

[0052] A method for preparing a dexamethasone intermediate through one-step fermentation and conversion of microorganisms, the dexamethasone intermediate refers to dexamethasone epoxy hydrolyzate (8DM), comprising the following steps:

[0053] (1) Bacteria culture

[0054] Inoculate the slant culture of Arthrobacter simplex into 400ml seed culture medium, the medium ratio used for seed culture is: glucose 12g / L, yeast extract powder 10g / L, KH 2 PO 4 1g / L, pH7.0~7.2, cultured on a shaker at 170rpm, 30±1°C for 24hrs.

[0055] Inoculate the slant culture of Bacillus megaterium into 200ml seed culture medium, the medium ratio used for seed culture is: glucose 12g / L, yeast extract powder 10g / L, KH 2 PO 4 1g / L, pH7.0~7.2, cultured on a shaker at 170rpm, 30±1°C for 24hrs.

[0056] (2) Fermentation transformation

[0057] Prepare 2000ml of fermentation medium in a 5L Erlenmeyer shaker flask, the ratio of fermentation medium is: glucose 5g / L, corn steep liquor 10g / L, peptone 1g / L,...

Embodiment 3

[0061] A method for preparing a dexamethasone intermediate through one-step fermentation and conversion of microorganisms, the dexamethasone intermediate refers to dexamethasone epoxy hydrolyzate (8DM), comprising the following steps:

[0062] (1) Bacteria culture

[0063] Inoculate the slant culture of Arthrobacter simplex into 400ml seed culture medium, the medium ratio used for seed culture is: glucose 12g / L, yeast extract powder 10g / L, KH 2 PO 4 1g / L, pH7.0~7.2, cultured on a shaker at 30±1°C and 170rpm for 18hr.

[0064] Inoculate the slant culture of Bacillus megaterium into 200ml seed culture medium, the medium ratio used for seed culture is: glucose 12g / L, yeast extract powder 10g / L, KH 2 PO 4 1g / L, pH7.0~7.2, cultured on a shaker at 30±1°C and 170rpm for 18hr.

[0065] (2) Fermentation transformation

[0066] Prepare 2000ml fermentation medium in a 5L Erlenmeyer shaker flask, the proportion of fermentation medium is: glucose 5g / L, corn steep liquor 10g / L, peptone...

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Abstract

The invention belongs to the technical field of bio-pharmaceuticals, and in particular relates to a method for producing a dexamethasone epoxide hydrolysate through one-step microbial fermentation and transformation. According to the method, with 16a-methyl-17[alpha],21-dihydroxypregna-4-ene-9,11-epoxy-3,20-dione-21 acetate as a substrate, the dexamethasone epoxide hydrolysate is directly produced mainly by conducting mixed fermentation by virtue of arthrobacter simplex and bacillus megatherium. In comparison with the prior art, the method provided by the invention, on the basis of a synergistic effect between mixed strains, integrally combines two steps of reactions, namely dehydrogenation and hydrolysis, so that the finished dexamethasone epoxide hydrolysate is directly obtained; and the product has the advantages of being short in production cycle, high in bio-transformation rate, high in yield, environment-friendly and low in cost.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and in particular relates to a method for producing dexamethasone epoxy hydrolyzate (namely 8DM) through one-step fermentation conversion of microorganisms. Background technique [0002] Dexamethasone epoxy hydrolyzate (namely 8DM) is a very important pharmaceutical intermediate with a huge market demand. It can be used as a starting material for the synthesis of dexamethasone (Dexamethasone), flumetasone, mometasone furoate, etc. A high-end glucocorticoid and other drugs. Dexamethasone is a glucocorticoid drug widely used clinically. It has various pharmacological effects such as anti-inflammation, anti-allergy, and immune suppression. It is mainly used for collagen diseases, such as rheumatoid arthritis, lupus erythematosus, and rheumatic heart disease. Disease, myocarditis, etc., can also be used for the rescue of dying patients. [0003] The CAS number of dexamethasone epoxy hydr...

Claims

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Application Information

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IPC IPC(8): C12P39/00C12P33/20C12R1/06C12R1/11
CPCC12P33/005C12P33/02C12P33/20C12P39/00
Inventor 杜艳冯永华潘永亮胡雄练梅华刘辉张和明
Owner JIANGSU YUANDA XIANLE PHARMA
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