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A kind of preparation technology of vancomycin crystal

A vancomycin and preparation process technology, applied in the field of vancomycin crystallization preparation technology, can solve the problems of difficult filtration of precipitation, deep pigment in precipitation, fine particle size of precipitation, etc., and achieves easy filtration, simple preparation process operation, and avoidance of pollution. Effect

Active Publication Date: 2016-03-30
景德镇富祥生命科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] U.S. Patent Publication No. 4440753 discloses the use of solvents such as isopropanol, ethanol or acetone to precipitate vancomycin, but this method uses a large amount of solvent, resulting in too dark a precipitate color, and the solvent has a large environmental pollution; the U.S. Patent Publication No. 5235037 The Chinese patent with the patent and publication number 101260134A adopts the salting-out method of adding alkali metal salt and ammonium salt to vancomycin solution to precipitate vancomycin respectively. Deep, the sediment particle size is too fine, the sediment is difficult to filter

Method used

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  • A kind of preparation technology of vancomycin crystal
  • A kind of preparation technology of vancomycin crystal

Examples

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Comparison scheme
Effect test

Embodiment 1

[0020] Amycolatopsis orientalis is selected as the production strain, and glucose, cottonseed protein powder and inorganic salts are used as fermentation raw materials to produce vancomycin by fermentation, aeration, agitation and intermediate feeding; After 200h, the fermentation was finished, and the tank was put in, and the concentration of vancomycin in the fermented liquid was 15.13g / L.

[0021] After the vancomycin fermentation broth is microfiltered through a ceramic membrane, it is adsorbed by a polystyrene-based sulfonic acid type strongly acidic cation exchange resin, and eluted with a pH 10 sodium hydroxide solution at a rate of 1 column bed volume / hour , the volume of the eluate was 0.5 times the column volume, and 11L of high-concentration vancomycin eluate was obtained (the concentration of vancomycin was 47.71g / L, the total product was 524.88g, and the purity of vancomycin in liquid phase was 83.4%). Liquid color is black. Use concentrated phosphoric acid to ad...

Embodiment 2

[0026] Produce vancomycin by fermentation method of example 1. After the vancomycin fermentation broth is microfiltered through a ceramic membrane, it is adsorbed by a polystyrene-based sulfonic acid type strongly acidic cation exchange resin, and eluted with a pH 11 sodium hydroxide solution at a rate of 1 column bed volume / hour , the volume of the eluate was 0.5 times the column volume, and 2200L of high-concentration vancomycin eluate was obtained (the concentration of vancomycin was 25.37g / L, the total product was 55.8kg, and the liquid phase purity was 83.4%). The color of the eluate was black. Add 264kg urea to the eluent storage tank (the concentration of urea in the eluent is 120g / L); after stirring and dissolving, filter it with a pipeline filter; quickly adjust the pH of the obtained filtrate to 8.9 with 3mol / L NaOH solution, and then let it stand For crystallization, resuspend and stir the crystals every 2 hours. After 24 hours of crystallization, the crystals wer...

Embodiment 3

[0028] The influence of the amount of urea added on the crystallization yield of vancomycin was investigated. Get the high-concentration vancomycin eluate (wherein the vancomycin concentration is 35.13g / L, liquid phase purity 86.4%) prepared by the method of Example 1, the eluate color is black. Take 5 parts of the above eluent, each 1L, add urea to the concentration of 0, 40, 80, 120, 140g / L respectively; stir and dissolve, filter with filter paper; quickly adjust the pH of the clarified filtrate to 8.5 with 3mol / L NaOH solution After standing still for crystallization, the crystals were resuspended and stirred every 2 hours. After 24 hours of crystallization, the crystals were harvested by filtration with filter paper. The obtained crystals were dissolved with hydrochloric acid aqueous solution, and the purity of the crystal solution was analyzed by high performance liquid chromatography. The effect of urea addition on the vancomycin crystallization yield is shown in Table...

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Abstract

The invention provides a preparation technology for vancomycin crystals. The preparation technology comprises the following steps of after microfiltration of vancomycin fermentation liquor, adsorbing and eluting through cation exchange resin, adding urea into the obtained high concentration eluant of the vancomycin, stirring and dissolving, then filtering and removing suspended particles, standing and crystallizing, and filtering so as to obtain the crude vancomycin crystals. The preparation technology is simple to operate, the obtained crystals are grey white, the grain size of the crystals is large (the average grain diameter detected by a microscope is about 32-47mu m), and the obtained crystals are easy to filter; the crystallization yield is more than 85%, the liquid phase purity of the vancomycin in a crystal dissolving solution is more than 85%, and the color of the solution is light; and the generated urea can be taken as a microorganism nitrogen source, thus avoiding contaminating the environment.

Description

technical field [0001] The invention belongs to the technical field of separation and purification of antibiotics, and in particular relates to a preparation process of vancomycin crystals. Background technique [0002] Vancomycin is a glycopeptide antibiotic isolated from the fermentation broth of a strain of Amycolatopsis orientalis by Micormick et al. in 1956. It was developed by Eli Lilly of the United States and approved by the FDA in 1958. In the 1980s, with the extensive use of β-lactam antibiotics, infections caused by methicillin-resistant Staphylococcus aureus (MRSA) became prevalent. Vancomycin is an important drug used clinically to treat severe infectious diseases caused by MRSA, and it has attracted more and more attention. The chemical structure of vancomycin is shown in the following formula: [0003] [0004] U.S. Patent Publication No. 4440753 discloses the use of solvents such as isopropanol, ethanol or acetone to precipitate vancomycin, but this meth...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K9/00C07K1/14
Inventor 吕祖平吴学华杨斌鹏贾坤刘永刚苗玉武
Owner 景德镇富祥生命科技有限公司
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