Separating and purifying method for obtaining highly pure teicoplanin

A technology for separation and purification of teicoplanin, which is applied in the field of separation and purification of high-purity teicoplanin, can solve the problems of expensive chromatographic packing material, high production cost, unfavorable industrial application, etc., and achieve the effect of high separation purity and low cost

Inactive Publication Date: 2013-12-25
江苏海阔生物医药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the large amount of solvent used, the poor separation and purification effect and the low purity of the final product prepared by the solvent extraction method, this method is rarely used at present.
Ion exchange method, because the use of acidic ion exchange resin will increase the degradation of T-A2 glycosyl moiety, but strong basic ion exchange resin is

Method used

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  • Separating and purifying method for obtaining highly pure teicoplanin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Pass 70L of teicoplanin fermentation broth through a microfiltration membrane (pore size 0.1 μm, ceramic microfiltration membrane) to remove solids in the fermentation broth. After the fermentation broth is fed, add 2 times the volume of water to wash the solids to recover Teicoplanin product. Combined to obtain 180L of filtrate, the filtrate was concentrated to 70L by nanofiltration (molecular weight cut-off 700-800Da), the concentration of the concentrated solution was 6.02g / L, and the content of teicoplanin was 421.4g.

[0024] Take 17L nanofiltration concentrate (teicoplanin content 102.34g), and install 9L AMBERLITE XAD 7HP resin on it for adsorption, and the sample loading flow rate is 9L / h. After loading the column, wash the resin with 27L deionized water to remove unadsorbed impurities, and the cleaning flow rate is 18L / h; continue to use 50L 15% acetone aqueous solution (containing 20g / LNaH 2 PO 4 , phosphoric acid to adjust the pH to 4.5) to clean th...

example 2

[0030] Take 30L nanofiltration concentrated liquid (teicoplanin content: 180.6g) in Example 1, and install 10L HZ801 resin on it for adsorption, and the sample loading flow rate is 10L / h. After loading the column, wash the resin with 30L deionized water to remove unadsorbed impurities, and the cleaning flow rate is 20L / h; continue to use 50L 16% acetonitrile aqueous solution (containing 20g / LNaH 2 PO 4 , phosphoric acid to adjust the pH to 4.5) to clean the resin to remove impurities with weak adsorption capacity, the flow rate is 10L / h; finally use 30% acetonitrile aqueous solution (containing 20g / L NaH 2 PO 4 , phosphoric acid to adjust pH4.5) elution, flow rate 10L / h. A total of 14.6 L of eluent was collected, the potency was 11.4 g / L, and 166.44 g of teicoplanin was recovered, the process yield was 92.1%, and the purity of the product by liquid chromatography was 81.5%.

[0031] The teicoplanin eluate was diluted with deionized water until the concentration of ac...

Embodiment 3

[0036] Take 20L nanofiltration concentrated liquid (teicoplanin content: 120.4g) in Example 1, and install 6L AMBERLITE XAD 1180N resin on it for adsorption, and the sample loading flow rate is 6L / h. After loading the column, wash the resin with 24L deionized water to remove unadsorbed impurities, and the cleaning flow rate is 12L / h; continue to use 24L 22% isopropanol aqueous solution (containing 20g / L 2 PO 4 , phosphoric acid to adjust the pH to 4.5) to clean the resin to remove impurities with weak adsorption capacity, the flow rate is 10L / h; finally use 34% isopropanol aqueous solution (containing 20g / L NaH 2 PO 4 , phosphoric acid to adjust pH4.5) elution, flow rate 6L / h. A total of 13.8 L of eluent was collected, the potency was 7.59 g / L, and 104.86 g of teicoplanin was recovered, the process yield was 87.1%, and the purity of the product by liquid chromatography was 85.5%.

[0037] The teicoplanin eluate was diluted with deionized water until the concentratio...

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Abstract

The invention discloses a separating and purifying method for obtaining highly pure teicoplanin. The method comprises the following steps: removing solids in a teicoplanin fermenting liquid through using a microfiltration membrane, and concentrating an obtained teicoplanin-containing micro-filtrate through a nanofiltration membrane to obtain a teicoplanin concentrate; carrying out adsorption elution of the concentrate through a macroporous adsorption resin twice to obtain a highly pure teicoplanin eluate; carrying out nanofiltration concentration of the eluate, adding a protein precipitating agent acetone to the concentrate for precipitating proteins of the concentrate, and filtering for removing the proteins to obtain a filtrate; adding active carbon to the filtrate for decoloring, and filtering to obtain a decolored liquid; and adding acetone to the decolored liquid, carrying out low temperature crystallization, and carrying out vacuum drying of obtained crystals to obtain finally obtained highly pure teicoplanin having a purity of above 96%. The method has the advantages of low cost, high separation purity of teicoplanin, and suitableness for the commercial production.

Description

technical field [0001] The invention relates to a high-purity teicoplanin separation and purification method, which belongs to the technical field of antibiotic separation and purification. Background technique [0002] Teicoplanin (Teicoplanin) is a group of glycopeptide antibiotics produced by the fermentation of Actinomycetes teicoplanin. It is another glycopeptide against drug-resistant bacteria developed after the internationally recognized antibiotic vancomycin against drug-resistant bacteria Antibiotics, which mainly have strong antibacterial activity against Gram-positive aerobic and anaerobic bacteria, especially for infections caused by methicillin-resistant Staphylococcus aureus (MRSA). One of the most active drugs against multidrug-resistant Staphylococcus aureus and Enterococci. [0003] Teicoplanin is composed of 5 compounds with very similar chemical structures, Teicoplanin A2 (TA2-1, TA2-2, TA2-3, TA2-4, TA2-5) and deacylglucosamine Teicoplanin A...

Claims

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Application Information

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IPC IPC(8): C07K9/00C07K1/36C07K1/34C07K1/30
Inventor 吴学华贾坤吕祖平苗玉武
Owner 江苏海阔生物医药有限公司
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