Process for producing pravastatin on large scale

A pravastatin and process technology, applied in the field of drug preparation, can solve the problems of operating temperature and time affecting product yield and quality, restricting the large-scale production and application of pravastatin, microorganisms that cannot tolerate addition, etc., to achieve improved drug resistance performance and transformation ability, improve production efficiency and output, and realize the effect of resource reuse

A pravastatin and process technology, applied in the field of drug preparation, can solve the problems of operating temperature and time affecting product yield and quality, restricting the large-scale production and application of pravastatin, microorganisms that cannot tolerate addition, etc., to achieve improved drug resistance performance and transformation ability, improve production efficiency and output, and realize the effect of resource reuse

CN105821086AActive Publication Date: 2016-08-03GUANGDONG BLUE TREASURE PHARMA
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  • Process for producing pravastatin on large scale
  • Process for producing pravastatin on large scale

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Embodiment 1, the technique of large-scale production of pravastatin of the present invention

[0042] Specific steps are as follows:

[0043] S1. Fermentation:

[0044] A1. Seed culture: Use a 5L shaker flask to prepare 3L seed medium. The formulation of the seed medium is as follows: glucose 24g / L, yeast extract 22g / L, soybean peptone 6g / L, K 2 HPO 4 ·3H 2 O2g / L, MgSO 4 ·7H 2 00.5g / L and defoamer 1.0g / L, adjust pH7.0; Inoculate Actinomyces madurai in the seed culture medium, cultivate 48 hours at 33~35 DEG C on a shaker after the inoculation, obtain seed liquid;

[0045] A2. Fermentation culture: Prepare 30L fermentation medium with a 50L automatic fermentation tank. The formula of the fermentation medium is as follows: glucose 56g / L, yeast extract 20g / L, soybean peptone 6g / L, K 2 HPO 4 ·3H 2 O1g / L, MgSO 4 ·7H 2 O1g / L, (NH 4 ) 2 SO 4 1g / L, plant extract 4ml / L and defoamer 1.0g / L, adjust the pH to 7.0; inoculate 2.5L of the seed solution obtained from A1 i...

Embodiment 2

[0059] Embodiment 2, the technique of large-scale production of pravastatin of the present invention

[0060] Specific steps are as follows:

[0061] S1. Fermentation:

[0062] A1. Seed culture: Use a 5L shaker flask to prepare 3L seed medium. The formulation of the seed medium is as follows: glucose 26g / L, yeast extract 20g / L, soybean peptone 8g / L, K 2 HPO 4 ·3H 2 O1g / L, MgSO 4 ·7H 2 O1g / L and defoamer 1.0g / L, adjust pH7.2; Inoculate Actinomyces madurai in the seed culture medium, after the inoculation, cultivate at 33~35 DEG C on a shaker for 72 hours to obtain the seed liquid;

[0063] A2. Fermentation culture: Prepare 30L fermentation medium with a 50L automatic fermentation tank. The formula of the fermentation medium is as follows: glucose 60g / L, yeast extract 24g / L, soybean peptone 8g / L, K 2 HPO 4 ·3H 2 O2g / L, MgSO 4 ·7H 2 O0.5g / L, (NH 4 ) 2 SO 4 2g / L, plant extract 8ml / L and defoamer 1.0g / L, adjust the pH to 7.2; inoculate 2.5L of the seed solution obtaine...

Embodiment 3

[0077] Embodiment 3, the technique of large-scale production of pravastatin of the present invention

[0078] Specific steps are as follows:

[0079] S1. Fermentation:

[0080] A1. Seed culture: Use a 5L shaker flask to prepare 3L seed medium. The formula of the seed medium is as follows: glucose 25g / L, yeast extract 20g / L, soybean peptone 7g / L, K 2 HPO 4 ·3H 2 O1g / L, MgSO 4 ·7H 2 00.5g / L and defoamer 1.0g / L, adjust pH7.0; Inoculate Actinomyces madurai in the seed culture medium, cultivate 72 hours in shaking table at 33~35 ℃ after the inoculation, obtain seed liquid;

[0081] A2. Fermentation culture: prepare 30L fermentation medium with 50L automatic fermentation tank, the formula of fermentation medium is as follows: glucose 58g / L, yeast extract 22g / L, soybean peptone 7g / L, K 2 HPO 4 ·3H 2 O1g / L, MgSO 4 ·7H 2 O0.5g / L, (NH 4 ) 2 SO 4 1g / L, plant extract 6ml / L and antifoaming agent 1.0g / L, adjust the pH to 7.0; inoculate 2.5L of the seed solution obtained from A1...

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Abstract

The invention discloses a process for producing pravastatin on a large scale. The process comprises the steps of fermenting, extracting and refining, wherein a plant extracting solution composed of an exocarpium benincasae extracting solution and a water melon peel extracting solution is used in the fermentation process, drug resistance and the conversion capacity of microorganisms to the substrate compactin and the fermentation level of pravastatin are effectively improved, the yield of pravastatin is increased, and in the steps of extracting and refining, the pH value of the solution, types and dosage of organic solvent, extracting time and temperature, cooling operation and crystallization time are controlled strictly to ensure the yield and purity of pravastatin. The process is stable, cost is low, and large-scale industrial production of pravastatin is achieved.

Description

technical field [0001] The invention relates to the technical field of medicine preparation, in particular to a process for large-scale production of pravastatin. 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. [0003] The production of pravastatin is usually obtained by a two-step fermentation process, although there are also reports or patents (WO99 / 10499, WO2007 / 147827, US6,274,360 and EP1,266,967) describing that the method for one-step fermentation can be used to produce pravastatin, but due to technical For reasons such as complexity and production efficiency, the industrial production of pravastatin is still based on two-step fermentation. [0004] The two-step fermenta...

Claims

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Application Information

Patent Timeline
03 Aug 2016
Publication
CN105821086A
IPC
C12P7/62; C12N1/20; C12N1/38; C07C67/48; C07C67/52; C07C67/56; C07C69/33; C12R1/03
CPC
C07C67/48; C07C67/52; C07C67/56; C12N1/20; C12N1/38; C12P7/62; C07C69/33
Inventors
徐会根; 罗定军