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A kind of purification preparation method of glycopeptide antibiotic dalbavancin intermediate a40926

A glycopeptide antibiotic, the technology of A40926, is applied in the field of biological separation to achieve the effects of easy operation, improved production efficiency and simple preparation process

Active Publication Date: 2021-07-30
鲁南新时代生物技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The main purpose of the present invention is to solve the separation and purification problem of dalbavancin intermediate A40926, and provide high-purity A40926 for the preparation of dalbavancin

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] The A40926 fermented liquid obtained by the prior art fermentation is 30L, the potency is 1087mg / L, and the A40926 is 32.61g. Add a 0.25mol / L sodium hydroxide solution equal to the fermented liquid, fully stir for 60min, and carry out the fermentation at a temperature of 25°C. Ceramic membrane filtration, the pore size of the ceramic membrane is 50nm. After filtration and top washing with pH=11.0 water, 100 L of filtrate was obtained, with a titer of 278.5 mg / L, A40926 of 27.85 g, and a recovery rate of 85.40%.

Embodiment 2

[0029] The A40926 fermented liquid obtained by the prior art fermentation is 30L, the potency is 1087mg / L, and the A40926 is 32.61g. Add a 0.25mol / L potassium hydroxide solution equal to the fermented liquid, fully stir for 120min, and carry out at a temperature of 30°C. Ceramic membrane filtration, the pore size of the ceramic membrane is 30nm. After filtration and top washing with pH=10.0 water, 100 L of filtrate was obtained, with a titer of 276.1 mg / L, A40926 of 27.76 g, and a recovery rate of 85.13%.

Embodiment 3

[0031] The A40926 fermented liquid obtained by prior art fermentation is 30L, the potency is 1087mg / L, and the A40926 is 32.61g. Add 3% ammonia solution equal in volume to the fermented liquid, fully stir for 180min, and carry out ceramic membrane filtration at a temperature of 20°C. The pore size of the ceramic membrane is 20 nm. After filtration and top washing with pH=11.0 water, 100 L of filtrate was obtained, with a titer of 271.0 mg / L, 27.80 g of A40926, and a recovery rate of 85.25%.

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PUM

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Abstract

The present invention relates to a method for the purification and preparation of glycopeptide antibiotic dalbavancin intermediate A40926. A40926 fermented liquid is subjected to alkalization, ceramic membrane filtration, polyamide chromatography, isoelectric precipitation, redissolution and gel chromatography. , to obtain high-purity A40926. The method maximizes the production efficiency of A40926, the purity reaches more than 95%, and the yield reaches more than 65%, thereby realizing the industrialization of high-purity A40926.

Description

technical field [0001] The invention belongs to the technical field of bioseparation, and in particular relates to a method for purifying and preparing a glycopeptide antibiotic dalbavancin intermediate A40926. Background technique [0002] Dalbavancin is a second-generation semi-synthetic glycopeptide antibiotic against multidrug-resistant bacteria after vancomycin and teicoplanin, and has entered phase III clinical trials. Dalbavancin has a similar molecular structure to teicoplanin, but the amide group modification at the end of the carboxypeptide group improves the antibacterial activity of dalbavancin against Staphylococci, especially coagulase-negative staphylococci; while lipophilic Branching and dimer formation enhance the tissue penetration and affinity of dalbavancin to bacterial cell membranes. Compared with vancomycin and teicoplanin, dalbavancin has a broader spectrum and stronger antibacterial activity, and has good antibacterial activity against a variety of ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K9/00C07K1/36C07K1/34C07K1/30C07K1/16
CPCC07K9/008
Inventor 张贵民刘志钰刘治江徐长波
Owner 鲁南新时代生物技术有限公司
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