Fermentation process for producing pravastatin by transforming compactin by using actinomadura yumaense

A technology of actinomycetes madura and pravastatin, which is applied in the field of preparation of pravastatin and fermentation technology, and achieves the effects of low cost, beneficial to mass proliferation of bacterial cells, and improvement of fermentation level

Active Publication Date: 2012-10-31
GUANGDONG BLUE TREASURE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] At present, the fermentation production level of pravastatin is mostly around 10g / L. As a commercial scale production, there is still a lot of room for improvement in such a production level.

Method used

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  • Fermentation process for producing pravastatin by transforming compactin by using actinomadura yumaense

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] A kind of fermenting process of using actinomycetes madura to transform compatin to produce pravastatin of the present embodiment, the concrete steps of this fermenting process are as follows:

[0053] The trace element solution of the present embodiment is prepared according to the following formula:

[0054] Sodium molybdate (Na 2 MoO 4 2H 2 O) 0.1g / L;

[0055] boric acid (H 3 BO 3 ) 1.0g / L;

[0056] Manganese chloride (MnCl 2 ·H 2 O) 0.1g / L;

[0057] Zinc sulfate (ZnSO 4 ·7H 2 O) 5.0g / L;

[0058] Ferrous Sulfate (FeSO 4 ·7H 2 O) 1.5g / L;

[0059] Sodium nitrate (NaNO 3 ) 3.0g / L;

[0060] Citric acid (C 6 h 8 o 7 ) 1.5g / L;

[0061] Copper Sulfate (CuSO 4 ·5H 2 O) 0.2g / L.

[0062] Step 1 Seed Culture

[0063] First prepare 350mL seed medium in a 1L shake flask according to the following formula:

[0064] Glucose 30g / L, yeast extract 20g / L, soybean peptone 5g / L, K 2 HPO 4 ·3H 2 O2g / L, MgSO 4 ·7H 2 O 0.5g / L and antifoaming agent 1.0g / L.

[0...

Embodiment 2

[0072] In this embodiment, a 50L fully automatic fermenter is used to transform conbatin into pravastatin with actinomycetes madura, and the specific steps of the fermentation process are as follows:

[0073] The trace element solution of the present embodiment is prepared according to the following formula:

[0074] Sodium molybdate (Na 2 MoO 4 2H 2 O) 0.2g / L;

[0075] boric acid (H 3 BO 3 ) 1.5g / L;

[0076] Manganese chloride (MnCl 2 ·H 2 O) 0.2g / L;

[0077] Zinc sulfate (ZnSO 4 ·7H 2 O) 5.5g / L;

[0078] Ferrous Sulfate (FeSO 4 ·7H 2 O) 2.0g / L;

[0079] Sodium nitrate (NaNO 3 ) 3.3g / L;

[0080] Citric acid (C 6 h 8 o 7 ) 2.0g / L;

[0081] Copper Sulfate (CuSO 4 ·5H 2 O) 0.3g / L.

[0082] Seed culture method is the same as embodiment 1.

[0083] The fermentation culture operation is as follows:

[0084] First prepare 30L fermentation medium according to the following formula: glucose 60g / L, yeast extract 25g / L, soybean peptone 5g / L, K 2 HPO 4 ·3H 2 O...

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Abstract

The invention discloses a fermentation process for producing pravastatin by transforming compactin by using actinomadura yumaense. According to the fermentation process based on the conventional fermentation process, the transformation ability of the microbial substrate and the fermentation level of the pravastatin are improved by adding trace element solution into a fermentation culture medium and utilizing the effect of the trace elements completely; the transformation ability of the microbial transformation bacteria-actinomadura yumaense on the compactin and the fermentation level of the pravastatin are effectively improved by controlling the culture temperature of the actinomadura yumaense and the transformation temperature of the compactin by using actinomadura yumaense; and the fermentation level is far higher than that of the prior art. The fermentation process is simple and convenient to operate, low in cost and suitable for large-scale production.

Description

technical field [0001] The invention relates to the field of medicine preparation, in particular to the preparation of pravastatin, and in particular to a fermentation process capable of improving the yield of pravastatin produced by a two-step fermentation method. Background technique [0002] Pravastatin is a 3-hydroxy 3-methylglutaryl-CoA reductase inhibitor, initially used to treat hyperlipidemia and familial hypercholesterolemia, and later the indications continued to expand, it can slow down the development of atherosclerosis, reduce Coronary atherosclerotic lesions and clinical cardiovascular events. Long-term use of pravastatin, regardless of whether the patient suffers from coronary heart disease or not, can reduce the mortality rate caused by various causes. of patients on drugs for primary and secondary defense of heart attack and stroke. [0003] Studies have also shown that pravastatin can also reduce the incidence of diabetes and Alzheimer's disease; it can i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P7/42C12R1/03
Inventor 徐会根罗定军黄智勇韩明活陈继敏
Owner GUANGDONG BLUE TREASURE PHARMA
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