Preparation method of high-purity pneumocandin B0

A lung capsule Kangding, high-purity technology, applied in the preparation methods of peptides, chemical instruments and methods, organic chemistry and other directions, can solve the problems of unsuitability for industrial production, cumbersome processes, and high costs, and achieve shortened process cycles. The effect of improving quality

Active Publication Date: 2013-05-01
NCPC NEW DRUG RES & DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Chinese patent CN101659693A discloses a kind of preparation lung capsule Kangding B 0 The method, this method repeatedly extracts Lung Sac Kangding B with two kinds of solvents 0 , the process is cumb

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  • Preparation method of high-purity pneumocandin B0
  • Preparation method of high-purity pneumocandin B0
  • Preparation method of high-purity pneumocandin B0

Examples

Experimental program
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Example Embodiment

[0038] Example 1

[0039] Take the lung capsule Kangding B 0 The fermentation broth was 10.0L, and the fermentation broth unit was 832 μg / mL. 100 g of perlite was added to the fermentation broth, and after stirring for 30 minutes, vacuum filtration was performed to obtain 2.0 kg of fermentation culture. 8 L of industrial ethanol was added to the fermentation culture, and after mechanical stirring for 1 hour, vacuum filtration was performed to collect the extract. The extract was decolorized through a D303 resin column with a diameter-to-height ratio of 1:6, the resin loading was 500 mL, and the flow rate was 1000 mL / h. Collect the decolorizing solution, adjust the solvent concentration to 30%, and introduce into a HZ830 resin column with a diameter-to-height ratio of 1:6 for adsorption. The resin loading is 400 mL, and the flow rate is 800 mL / h. The saturated resin was purified and washed with 40% ethanol, and then desorbed with 80% ethanol at a flow rate of 200 mL / h. The ...

Example Embodiment

[0040] Example 2

[0041] Take the lung capsule Kangding B 0 The fermentation broth was 10.0L, and the fermentation broth unit was 762 μg / mL. 300 g of perlite was added to the fermentation broth, and after stirring for 1 hour, vacuum filtration was performed to obtain 2.2 kg of fermentation culture. 13.2 L of industrial ethanol was added to the fermentation culture, and after mechanical stirring for 2 hours, vacuum filtration was performed to collect the extract. The extract was decolorized through a D303 resin column with a diameter-to-height ratio of 1:6, the resin loading was 500 mL, and the flow rate was 1000 mL / h. Collect the decolorizing solution, adjust the solvent concentration to 40%, and introduce into a HZ830 resin column with a diameter-to-height ratio of 1:6 for adsorption, the resin loading is 400 mL, and the flow rate is 800 mL / h. The saturated resin was purified and washed with 50% ethanol, and then desorbed with 90% ethanol at a flow rate of 200 mL / h. The ...

Example Embodiment

[0042] Example 3

[0043] Take the lung capsule Kangding B 0 The fermentation broth was 20.0L, and the fermentation broth unit was 973 μg / mL. 500 g of perlite was added to the fermentation broth, and after stirring for 1 hour, vacuum filtration was performed to obtain 4.5 kg of fermentation culture. 19 L of industrial ethanol was added to the fermentation culture, mechanically stirred for 1 hour, and then vacuum filtered to collect the extract. The extract was decolorized through a D303 resin column with a diameter-to-height ratio of 1:6, the resin loading was 1000 mL, and the flow rate was 2000 mL / h. Collect the decolorizing solution, adjust the solvent concentration to 30%, and introduce into a HZ830 resin column with a diameter-to-height ratio of 1:6 for adsorption, the resin loading is 1000 mL, and the flow rate is 2000 mL / h. The saturated resin was purified and washed with 40% ethanol, and then desorbed with 90% ethanol at a flow rate of 500 mL / h. The desorbed solutio...

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Abstract

The invention discloses a method for preparing pneumocandin B0 by using a fermentation culture product of filamentous fungi glarea lozoyensis. According to the method, a filter aid is adopted; with steps such as leaching, discoloring, adsorption, crystallization, and the like, a pneumocandin B0 crude extract is obtained; and the crude extract is subjected to chromatographic separation by using polymer microspheres, such that the high-purity pneumocandin B0 product is obtained. The method provided by the invention has the advantages that: pneumocandin B0 is extracted and separated by using macroporous resin; the process is simple and feasible, and is suitable for industrialized productions; the polymer microspheres are used in chromatographic separation of the product for a first time, and high-purity pneumocandin B0 product can be prepared.

Description

technical field [0001] The invention belongs to the technical field of industrial microorganisms, and in particular relates to a high-purity Lung Sac Kangding B 0 method of preparation. Background technique [0002] Echinocandin is a new type of antifungal drug, which is effective against Candida and Aspergillus, and has high safety. Currently there are 3 varieties on the market, namely caspofungin from Merck, micafungin from Fujisawa Pharmaceutical Co., Ltd., and anifungin from Pfizer. Among them, caspofungin is an echinocandin approved by the U.S. FDA for the first time. It was developed by Merck and was first launched in the U.S. in February 2001 for the infection of Candida albicans and Aspergillus fumigatus. [0003] Caspofungin is the first echinocandin antifungal drug approved for the treatment of invasive aspergillosis due to intolerance or poor response to other antifungal drugs (Groll AH, Piscitelli SC, Walsh TJ. Adv Pharmacol, 1998, 44:343-500). Caspofungin ha...

Claims

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Application Information

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IPC IPC(8): C07K7/56C07K1/16
Inventor 李晓露张雪霞任风芝林毅林旸王海燕李宁王健陈书红李丽红成晓迅高月麒张金娟张丽蒋沁段宝玲
Owner NCPC NEW DRUG RES & DEV
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