Method for preparation of vancomycin from benzylamine-propionaldehyde

A vancomycin and n-propionaldehyde technology, applied in the direction of peptides, etc., can solve the problems of difficult crystallization, difficult crystallization, slow growth of vancomycin hydrochloride crystals, etc., and achieve the improvement of effective components, simple production method, and excellent appearance. The effect of color change

Inactive Publication Date: 2017-03-22
江苏海阔生物医药有限公司
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

Among them, the crystallization process can improve the purity of vancomycin and remove some impurities such as pigments. However, due to the slow growth of vancomycin hydrochloride crystals, the crystallization process is easily disturbed by impurities, and the crystallization is difficult. Only the crude extract through ion exchange and decolorization hard to crystallize

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  • Method for preparation of vancomycin from benzylamine-propionaldehyde

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preparation example Construction

[0017] see figure 1 , the invention provides a kind of preparation method that prepares vancomycin by benzylamine-n-propionaldehyde, comprises the following steps:

[0018] a. Fermentation broth pretreatment, including removing high-priced inorganic ions and proteins, using oxalic acid or phosphoric acid to remove high-priced inorganic ions, and the removal method of protein is: use 10% sulfuric acid to adjust pH4.5-5.0 and add 0.05% mass concentration of flocculant method, adding 0.7% diatomaceous earth as a filter aid at the same time, and then filtering through a plate and frame filter for many times;

[0019] b. Use a drum vacuum filter to filter;

[0020] c. Acidify the fermentation filtrate to PH = 2, then add benzylamine-n-propanal equivalent to 1 / 3 of the volume of the fermentation broth, mix and separate in an extraction tank, and perform secondary countercurrent extraction to obtain a primary benzylamine-n-propanal extract, then extract the vancomycin from the benz...

Embodiment 1

[0025] The present invention comprises the following steps:

[0026] a, fermentation broth pretreatment, including removing high-priced inorganic ions and proteins, using oxalic acid or phosphoric acid to remove high-priced inorganic ions, the removal method of protein is: adopt 10% sulfuric acid to adjust pH4.5 and add the method of flocculant of 0.05% mass concentration, At the same time, add 0.7% diatomaceous earth as a filter aid, and then filter through a plate and frame filter for many times;

[0027] b. Use a drum vacuum filter to filter;

[0028] c. Acidify the fermentation filtrate to PH = 2, then add benzylamine-n-propanal equivalent to 1 / 3 of the volume of the fermentation broth, mix and separate in an extraction tank, and perform secondary countercurrent extraction to obtain a primary benzylamine-n-propanal extract, then extract the vancomycin from the benzylamine-n-propionaldehyde extract into the buffer solution with 1.3% sodium bicarbonate under the condition o...

Embodiment 2

[0031] The present invention comprises the following steps:

[0032] a, fermentation broth pretreatment, including removing high-priced inorganic ions and proteins, using oxalic acid or phosphoric acid to remove high-priced inorganic ions, the removal method of protein is: adopt 10% sulfuric acid to adjust pH5.0 and add the method of flocculant of 0.05% mass concentration, At the same time, add 0.7% diatomaceous earth as a filter aid, and then filter through a plate and frame filter for many times;

[0033] b. Use a drum vacuum filter to filter;

[0034] c. Acidify the fermentation filtrate to PH = 2, then add benzylamine-n-propanal equivalent to 1 / 3 of the volume of the fermentation broth, mix and separate in an extraction tank, and perform secondary countercurrent extraction to obtain a primary benzylamine-n-propanal extract, then extract vancomycin from the benzylamine-n-propionaldehyde extract into the buffer solution with 1.9% sodium bicarbonate under the condition of pH...

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Abstract

The invention discloses a method for preparation of vancomycin from benzylamine-propionaldehyde. The method includes fermentation broth pretreatment, which includes removal of high valence inorganic ions and protein, oxalic acid or phosphoric acid is employed to remove high valence inorganic ions, and the protein removal method consists of: using 10% sulfuric acid to adjust the pH to 4.5-5.0, adding a flocculating agent with a mass concentration of 0.05%, at the same time adding 0.7% diatomite as a filter aid, and conducting filtering repeatedly by a plate-and-frame filter. The vancomycin prepared by the method provided by the invention has greatly improved effective components, obviously lowered other impurities, high purity and chromatographic purity up to over 95%, at the same time the product appearance color is significantly improved, and the product is suitable for oral administration or injection administration. The method provided by the invention has the advantages of simple making method and technological process suitable for mass production.

Description

technical field [0001] The invention relates to the technical field of preparation methods of vancomycin, in particular to a preparation method of vancomycin by benzylamine-n-propionaldehyde. Background technique [0002] Vancomycin is an antibiotic with the molecular formula C66H74Cl2N9O24. Its half-life: 4 to 8 hours, 9 days for renal failure, ineffective against anaerobic bacteria and Gram-negative bacteria, and will not be removed by hemodialysis. The "superbug" NDM-1 that appeared in India and other South Asian countries has spread to the United Kingdom, the United States, Canada, Australia, the Netherlands and other countries. Domestic experts say that the South Asian superbug will not become a pandemic, and vancomycin can be effective. [0003] Vancomycin belongs to glycopeptide macromolecular antibiotics. Vancomycin is more powerful and will be used when other antibiotics are ineffective against bacteria. It is mainly used for systemic and intestinal infections cau...

Claims

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Application Information

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IPC IPC(8): C07K9/00
Inventor 苗玉武吕祖平刘永刚王丹丹刘言华
Owner 江苏海阔生物医药有限公司
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