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Method for preparing 11alpha, 17alpha-dyhydroxyl-pregn-1,4-diene-3,20-dione through microbial co-fermentation

A combined fermentation and microorganism technology, applied in the direction of microorganism-based methods, biochemical equipment and methods, microorganisms, etc., can solve the problems that are not easy to repeat, and the yield and content of the target product do not exceed 50%.

Inactive Publication Date: 2016-07-20
TIANJIN JINYAO GRP
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chinese patent CN201210316179.2 reported a method for preparing 11α-OH-ADD by jointly transforming and fermenting 4-AD using ochrax and Arthrobacter simplex microorganisms. more than 50%
[0008] At present, there is no literature report on the one-step preparation of 11α,17α-dihydroxy-pregna-1,4-diene-3,20-dione using 17α-hydroxyprogesterone as a substrate by combined transformation and fermentation of microorganisms

Method used

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  • Method for preparing 11alpha, 17alpha-dyhydroxyl-pregn-1,4-diene-3,20-dione through microbial co-fermentation

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Effect test

Embodiment 1

[0038] The selection of embodiment 1 fermentation medium

[0039] In the following examples, the influence of the fermentation medium on the conversion rate of the target product was investigated. Incline, seed cultivation method as described in the summary of the invention.

Embodiment 1-1

[0041] In 1L of water, 30g of the fermentation substrate 17α-hydroxyprogesterone, 15g of the components of the fermentation medium, glucose, 5g of silkworm chrysalis powder, 30g of corn steep liquor, 1g of ammonium sulfate, 2g of potassium dihydrogen phosphate, 5g of sodium dihydrogen phosphate, and 0.4 g, pH 6.0. For the secondary culture of Arthrobacter simplex, after 24 hours of primary seed culture, insert 10% of the inoculum into the secondary seed medium, and after 22 hours of secondary culture, insert 15% of the inoculum into the above fermentation medium ; After 24 hours of culturing the primary seeds of Ochraus ochratum, they were inserted into the above-mentioned fermentation medium according to 30% inoculum amount. Use a 5-ton fermenter for conversion, with a liquid volume of 80%, a tank pressure of 0.05MPa, and an air flow of 40m 3 / hr, temperature 28°C, stirring 180rpm, conversion for 72 hours, sampling by TLC analysis, the conversion of the substrate was complet...

Embodiment 1-2

[0044] In 1L of water, 30g of the fermentation substrate 17α-hydroxyprogesterone, 30g of the components of the fermentation medium, glucose, 5g of silkworm chrysalis powder, 30g of corn steep liquor, 1g of ammonium sulfate, 2g of potassium dihydrogen phosphate, 5g of sodium dihydrogen phosphate, and 0.4 g, pH 6.0. For the secondary culture of Arthrobacter simplex, after 24 hours of primary seed culture, insert 10% of the inoculum into the secondary seed medium, and after 22 hours of secondary culture, insert 15% of the inoculum into the above fermentation medium ; After 24 hours of culturing the primary seeds of Ochraus ochratum, they were inserted into the above-mentioned fermentation medium according to 30% inoculum amount. Use a 5-ton fermenter for conversion, with a liquid volume of 80%, a tank pressure of 0.05MPa, and an air flow of 40m 3 / hr, temperature 28°C, stirring 180rpm, conversion for 72 hours, sampling by TLC analysis, the conversion of the substrate was complet...

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Abstract

The invention relates to a method for preparing 11alpha, 17alpha-dyhydroxyl-pregn-1,4-diene-3,20-dione by taking 17alpha-hydroxyprogesterone as a starting material and through mixed one-step fermentation adopting aspergillus ochraceus and arthrobacter simplex.

Description

technical field [0001] The present invention relates to a production method of steroidal drugs, specifically, the preparation of 11α, 17α-dihydroxy-pregna-1,4-diene-3,20-dione by joint transformation and fermentation of 17α-hydroxyprogesterone by microorganisms method. Background technique [0002] Steroid drugs are an important class of drugs, with anti-inflammatory, anti-immune, contraceptive, anti-cancer, endocrine regulation and other functions, widely used in rheumatism, cardiovascular disease, collagen disease, lymphatic leukemia, human organ transplantation, Treatment of bacterial encephalitis, skin diseases, endocrine disorders, senile diseases, hormone-dependent tumors and other diseases. [0003] In the production of steroid hormone drugs, multiple groups of the steroid nucleus need to be modified by chemical methods and microorganisms, among which C 11 α-hydroxylation and C 1,2 The introduction of double bonds by dehydrogenation is an important steroid transfor...

Claims

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Application Information

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IPC IPC(8): C12P39/00C12P33/10C12P33/02C12R1/66C12R1/06
Inventor 赵春霞王淑丽
Owner TIANJIN JINYAO GRP
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