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Method for purifying lipopetide compound

A purification method and compound technology, applied in the preparation method of peptides, chemical instruments and methods, peptides, etc., to achieve the effect of less waste

Active Publication Date: 2011-11-16
HISUN PHARMACEUTICAL (HANGZHOU) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, no report has disclosed the use of this method to isolate daptomycin

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Embodiment 1: the purification of daptomycin

[0028] Add 30 L of daptomycin fermentation broth, add diatomaceous earth and filter to obtain filtrate, and the filtrate is concentrated to 5 g / L with a nanofiltration membrane, with a volume of about 6 L. Adjust the pH to 3.6 with 1N hydrochloric acid. Add 360g NaCl and 60g diatomaceous earth under stirring, control the temperature at 15°C, stir for 1 hour, filter to obtain 102g of filter cake, redissolve the filter cake and filter to obtain 1L of filtrate, the test result shows that the concentration of daptomycin is 17.9g / L , The calculated yield was 60%.

Embodiment 2

[0029] Embodiment 2: the purification of daptomycin

[0030] The daptomycin fermentation broth was treated according to Example 1 and concentrated to 3.5 L. The analysis results showed that the concentration of daptomycin was 8.2 g / L. Adjust the pH to 4.5 with 1N hydrochloric acid. Add 819g of NaCl and 95g of diatomaceous earth under stirring, control the temperature at 0°C and stir for 1 hour, filter to obtain 171g of filter cake, redissolve the filter cake and filter to obtain 1.2L of filtrate, the test results show that the concentration of daptomycin is 20.8g / L, The calculated yield was 87%.

Embodiment 3

[0031] Embodiment 3: the purification of daptomycin

[0032] The daptomycin fermentation broth was treated according to Example 1 and concentrated to 2.5 L. The analysis results showed that the concentration of daptomycin was 12 g / L. The pH was adjusted to 2.0 with 1N hydrochloric acid. Add 660g of ammonium sulfate under stirring, add 300g of diatomaceous earth, control the temperature at 10°C and stir for 1 hour, filter to obtain 411g of filter cake, redissolve and filter to obtain 1.3L of filtrate, the test results show that the concentration of daptomycin is 21.8g / L, the calculated yield was 94.4%.

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PUM

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Abstract

The invention relates to a method for purifying a lipopetide compound, in particular to a method for precipitating daptomycin. The method comprises the following steps of: concentrating a daptomycin solution and then controlling concentration of the solution, regulating pH, adding a precipitation promoter and a filter aid, stirring and precipitating. The precipitate obtained by the method is redissolved and can be then directly refined by adopting methods such as reversed-phase chromatography, ion exchange and the like. The method provided by the invention has the advantages of economy, environment friendliness, suitability for commercialization and the like.

Description

technical field [0001] The invention relates to a method for purifying lipopeptide compounds, in particular to a method for precipitating daptomycin. Background technique [0002] Gram-positive infections and the rapid increase in bacterial resistance have revived interest in the development of novel antibiotics, one class of which are lipopeptide antibiotics, including daptomycin. Daptomycin is a cyclic lipopeptide antibiotic used to treat complicated skin and skin structure infections, such as abscesses, surgical wound infections, and skin ulcers, caused by some Gram-positive susceptible strains. It can also be used for right-sided infective pericarditis caused by Staphylococcus aureus; bacteremia caused by Staphylococcus aureus complicated by RIE or complicated skin and soft tissue infections. Patents WO01 / 53330 and EP0294990A disclose a method for preparing daptomycin, in which the enrichment of daptomycin from the fermentation broth is mainly accomplished through macro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K1/30C07K7/08C07K7/06
Inventor 杨华剑梁陈宏周永健王玲萍白骅
Owner HISUN PHARMACEUTICAL (HANGZHOU) CO LTD
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