Low-impurity acarbose and preparation method thereof

An acarbose, low impurity technology, applied in the field of biochemical industry, can solve the problems of high removal cost, high impurity A, low yield, etc., and achieve the effect of improving quality

Inactive Publication Date: 2012-07-11
HANGZHOU HUADONG MEDICINE GRP PHARMA RES INST +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The purpose of the present invention is to overcome defects such as the high content of impurity A in the acarbose produced by the prior art, the high cost of removal, and low yield, and provide a low impurity A content, low cost, and easy industrial production. The preparation method of acarbose

Method used

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  • Low-impurity acarbose and preparation method thereof
  • Low-impurity acarbose and preparation method thereof
  • Low-impurity acarbose and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1: The content of impurity A not controlled by dissolved oxygen level

[0027] 10-ton tank, the filling coefficient is controlled at 0.8, and the air flow rate is 8.0m 3 / min (1.0vvm), the speed is controlled at 120 r / min until the end.

[0028] Real-time monitoring of the changes of A impurities with fermentation time and dissolved oxygen level in the fermentation process is shown in Table 3:

[0029]

Embodiment 2

[0031] 10-ton tank, start fermentation at about 72 hours, gradually increase the stirring speed, and the stirring speed will reach 150 r / min within 24 hours, and monitor in real time to keep the dissolved oxygen level at about 100%; start at about 120 hours, maintain the previous Stirring speed of the same, while increasing the air flow to 12.0m 3 / min (1.5vvm), real-time monitoring, keep the dissolved oxygen level at about 100%; in about 144 hours, under the condition of maintaining the stirring speed and air flow, add 400L of sugar water (accounting for about 5% of the total volume of the fermentation broth), The culture medium in the fermenter is diluted and monitored in real time to keep the dissolved oxygen level above 90%.

[0032] The real-time measured content of impurity A is shown in Table 4:

[0033]

Embodiment 3

[0035] 60 tons of tanks, fermentation starts at about 72 hours, and the air flow increases to 12.0m 3 / min (1.5vvm), real-time monitoring, to keep the dissolved oxygen level above 95%; starting at about 120 hours, keep the previous air flow unchanged, and gradually increase the stirring speed to 150 r / min to keep the dissolved oxygen level at More than 90%, in about 144 hours, under the condition of maintaining the constant air flow and stirring speed, add 400L of sugar water (accounting for about 5% of the total volume of the fermentation broth), dilute the medium in the fermenter, monitor in real time, and keep The dissolved oxygen level is above 80%.

[0036] The real-time measured content of impurity A is shown in Table 5:

[0037]

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Abstract

The invention discloses low-impurity acarbose. According to the invention, the metabolism of Actinoplanessp. is regulated and controlled, specifically, the level of dissolved oxygen in fermentation broth during the middle and later periods is controlled to 80-105%, so as to reduce the level of an impurity A in a final metabolin and promote the quality of a product. The invention simultaneously discloses a method for regulating and controlling the metabolism of Actinoplanessp. In the preparation method, the impurity is reduced through industrialized methods such as acceleration of stirring speed, increase of air flow, supplementation of materials to dilute a culture medium in a fermentation tank.

Description

technical field [0001] The invention relates to the field of biochemical industry, more specifically to actinomycetes Actinoplanes sp. Process for the fermentative production of the resulting metabolite acarbose. Background technique [0002] Acarbose, chemical name: O-4,6-dideoxy-4-[(1S, 4R, 5S, 6S) 4, 5, 6-trihydroxy-3-(hydroxymethyl)-2 -Cyclohexenyl-1-amino]-a-D-glucopyranosyl-(1 4)-O-a-D-glucopyranosyl-(1 4)-D-glucopyranosyl, which is released by swimming Mycobacteria Actinoplanes species The metabolites produced are mainly used for the treatment of type Ⅱ diabetes. [0003] regulated motile actinobacteria Actinoplanes sp. Microbial metabolism, that is, the production of acarbose by fermentation. In the microbial fermentation process, as the fermentation process progresses, more and more target products will be produced while some different types of by-products will be produced, especially in the middle and late stages of fermentation, a variety of different impuri...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P19/26C12R1/045
Inventor 谢海松周鲁谨何志勇徐亚强章飞龙李伟伟金海燕王巍
Owner HANGZHOU HUADONG MEDICINE GRP PHARMA RES INST
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