Method for separating and purifying daptomycin

A technology for separation and purification of daptomycin, applied in the field of biomedicine, can solve problems such as complex operation, achieve the effect of reducing side effects and excellent raw materials

Active Publication Date: 2012-10-10
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

In prior art reports on the purification method of daptomycin, the purity is all below 98%, and the operation is complicated

Method used

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  • Method for separating and purifying daptomycin

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Receive 20L of fermentation broth to be put into the tank, the fermentation titer is 1200mg / L, and dilute the fermentation broth with 18L of purified water. After dilution, the fermentation unit is 631.5mg / L, the feed liquid temperature is 25°C, and the ceramic membrane is filtered. When concentrated to 6L, add 2.5L of purified water to the non-permeated liquid of the ceramic membrane, stir for 5min, and continue to filter through the ceramic membrane. When concentrated to 6L again, add 2.5L of purified water to the ceramic membrane impermeate, stir for 5min, and continue ceramic membrane filtration. This operation was repeated 8 times, and a total of 20 L of purified water was added. Sampling, HPLC detection of daptomycin 48mg / L in ceramic membrane permeate liquid, ceramic membrane filtration ends. A total of 52 L of ceramic membrane permeate was collected, containing 21.8 g of daptomycin.

[0043]Load the collected ceramic membrane permeate into a macroporous adsorp...

Embodiment 2

[0051] Receive 25L of fermentation broth to be put into the tank, the fermentation titer is 1320mg / L, and dilute the fermentation broth with 25L of 5% ethanol. After dilution, the fermentation unit is 660mg / L, the temperature of the feed liquid is 25°C, and the ceramic membrane is filtered. When concentrated to 8L, add 3L of 5% ethanol to the non-permeated liquid of the ceramic membrane, stir for 5min, and continue to filter through the ceramic membrane. When concentrated again to 8L, add 3L of 5% ethanol to the impermeate liquid of the ceramic membrane, stir for 5min, and continue to filter through the ceramic membrane. This operation was repeated 8 times, and a total of 24 L of 5% ethanol was added. Sampling, HPLC detection of daptomycin 42mg / L in the ceramic membrane permeate, ceramic membrane filtration ends. A total of 65 L of ceramic membrane permeate was collected, containing 30.1 g of daptomycin.

[0052] The collected ceramic membrane permeate was applied to a macro...

Embodiment 3

[0060] Receive 27L of fermentation broth to be put into the tank, the fermentation titer is 1180mg / L, and dilute the fermentation broth with 15L of 30% ethanol. After dilution, the fermentation unit is 758mg / L, the temperature of the feed liquid is 40°C, and the ceramic membrane is filtered. When concentrated to 9L, add 3L of 30% ethanol to the non-permeate liquid of the ceramic membrane, stir for 5min, and continue to filter through the ceramic membrane. When concentrated again to 9L, add 3L of 30% ethanol to the impermeate liquid of the ceramic membrane, stir for 5min, and continue to filter through the ceramic membrane. This operation was repeated 8 times, and a total of 24 L of 30% ethanol was added. Sampling, HPLC detection of daptomycin 40mg / L in the ceramic membrane permeate, ceramic membrane filtration is completed. A total of 56 L of ceramic membrane permeate was collected, containing 28.8 g of daptomycin.

[0061] Load the collected ceramic membrane permeate into a...

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Abstract

The invention provides a method for separating and purifying daptomycin. The method overcomes the defects of the exiting extraction technology of the daptomycin, the purity of the daptomycin is improved, and the final purity of the daptomycin reaches higher than 99.2, so a method capable of industrially purifying the daptomycin is provided.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a method for separating and purifying daptomycin. Background technique [0002] Daptomycin is a cyclolipopeptide substance extracted from the fermentation broth of Streptomyces roseospora. It was originally developed by Lily Company of the United States in the 1980s. In November 1997, Lily Company exclusively developed Daptomycin globally, Production and sales rights were transferred to Cubist Pharmaceuticals. On September 12, 2003, FDA approved Cubicin (Daptomycin injection) for the first time. It is the first cyclolipopeptide antibiotic drug approved for marketing for the treatment of complicated skin and skin structure infections caused by some Gram-positive sensitive strains. In 2006, it was listed in Australia, Germany, the Netherlands, Spain, and the United Kingdom, and in 2007 in Switzerland. It was subsequently registered in more than 10 countries includ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C07K1/36C07K1/34C07K1/20C07K1/18C07K1/16
Inventor 赵志全朱海洋孙颖张培训邵长阔武猛王蒙
Owner 鲁南新时代生物技术有限公司
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