Separation purification method and use of echinocandin B

A technology of echinocandin and mycelium, which is applied in the field of separation of echinocandin B from fermentation broth, can solve the problems of inability to remove pigments well, the separation medium is expensive, and the quality of antibacterial drugs is affected, and the operation is achieved. Simple, mild separation conditions, easy to operate, suitable for large-scale production

Active Publication Date: 2014-04-16
CHONGQING QIANTAI BIOLOGICAL MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Most of the separation techniques for echinocandin B in the prior art are separated by macroporous resin and silica gel chromatography, as US Patent No. 4,968,608 discloses a method of using Macroporous resin HP20, dextran gel LH20 and normal phase silica gel to separate and purify the method to obtain ECB from the fermentation broth. The adaptability of the extraction liquid is poor; U.S. Patent US6506726 improves this, and uses macroporous resins such as HP20, SP825, SP207 and CG-161 to separate and purify ECB after acidifying the fermented liquid. This method is relatively simple but the separation effect is not good, and the product purity is lower than 80%, there is also the disadvantage of poor ada

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  • Separation purification method and use of echinocandin B
  • Separation purification method and use of echinocandin B
  • Separation purification method and use of echinocandin B

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Take 1000ml of echinocandin B fermentation broth, adjust the pH to 5.0 with oxalic acid, add 20g of perlite and stir for 2 hours, filter, wash mycelium with 500ml of water, and collect 352g of mycelium after drying.

[0059] Take 352g of mycelium, add 1000ml of ethanol solution, soak and stir for 6 hours, filter to obtain about 980ml of extract, concentrate the extract at 50°C to a volume of 100ml; filter the obtained mycelium after extraction Add it to 750ml ethanol solution, stir for 4 hours while soaking, filter to obtain about 730ml of extract, concentrate the extract at 50°C to a volume of 75ml, cool to room temperature, combine the two extracts at 25°C, vacuum Concentrate the extract at a temperature of -0.08 Mpa until the ethanol content in the solution is 25%.

[0060] Take 100ml of the extract, add 10ml of petroleum ether to shake, let it stand for 2 hours, collect 92ml of the organic layer solution, and concentrate to 9ml at 40°C.

[0061] Take 300 mL of ...

Embodiment 2

[0063] Take 1000ml of echinocandin B fermentation broth, adjust the pH to 4.0 with acetic acid, add 15g of talcum powder and stir for 2 hours, filter, wash mycelium with 500 ml of water, and collect 350g of mycelium after drying.

[0064] Take 350g of mycelium, add 1000ml of methanol solution, stir for 4 hours while soaking, filter to obtain about 970ml of extract, concentrate the extract at 50°C to a volume of 100ml; filter the obtained mycelium after leaching Add it to 750ml of methanol solution, stir for 3 hours while soaking, filter to obtain about 725ml of extract, concentrate the extract at 50°C to a volume of 72ml, cool to room temperature, and combine the two extracts. Concentrate the extract solution at 25°C with a vacuum of -0.08 Mpa until the methanol content in the solution is 20%.

[0065] Take 100ml of the extract, add 10ml of n-hexane to shake, let it stand for 2 hours, collect 90ml of the organic layer solution, and concentrate to 9ml at 40°C.

[0066] Take 3...

Embodiment 3

[0068] Take 1000ml of echinocandin B fermentation broth, adjust the pH to 6.0 with carbonic acid, add 35g of micropowdered silica gel and stir for 2 hours, filter, wash mycelium with 500 ml of water, and collect 355g of mycelium after drying.

[0069] Take 355g of mycelium, add 1000ml of acetone solution, soak and stir for 6 hours, filter to obtain about 985ml of extract, concentrate the extract at 50°C to a volume of 100ml; filter the obtained mycelium after extraction Add it to 750ml of acetone solution, stir for 3 hours while soaking, filter to obtain about 735ml of extract, concentrate the extract at 50°C to a volume of 75ml, cool to room temperature, and combine the two extracts. Concentrate the extract solution at 25°C with a vacuum of -0.08 Mpa until the acetone content in the solution is 28%.

[0070] Take 100ml of the extract, add 10ml of n-heptane to shake, let it stand for 2 hours, collect 90ml of the organic layer solution, and concentrate to 9ml at 35°C.

[0071]...

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Abstract

The invention provides a method for separating echinocandin B from fermentation broth and a use of echinocandin B. The method comprises the following steps that through fermentation broth acidification, extraction and concentration, concentrated liquid is obtained; and the concentrated liquid is fed into a reverse phase silica gel column and then is subjected to separation and concentration so that echinocandin B is obtained. The echinocandin B separated by the method has high purity and is a good raw material for preparation of echinocandin cyclopeptide parent nucleus and antifungal drugs. The method has a high finished product yield, utilizes safe and cheap solvent and instruments, has a low production cost and simple processes and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a method for separating echinocandin B from fermentation broth and its application. Background technique [0002] Echinocandins are a group of natural products discovered in the late 1970s. They have similar structural features of cyclic polypeptide cores and different fatty acid side chains, and can non-competitively inhibit fungal cell walls. β -1,3-glucan synthase activity, clinically used as an antifungal drug. [0003] Echinocandin B (ECB for short) is produced by Aspergillus nidulans ( Aspergilus nidulans ) metabolism, is one of echinocandins, and its structure is as follows: [0004] [0005] Echinocandin B is subjected to deacylase to obtain the cyclic peptide core, and the cyclic peptide core can be chemically modified to prepare the antifungal drug Anidulafungin. In order to improve the efficiency of deacylation of ECB and the quality of ECB nuclei, ...

Claims

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Application Information

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IPC IPC(8): C07K7/56C07K1/36C07K1/20A61K38/12A61P31/10
Inventor 袁建栋刘明川郭明张杰
Owner CHONGQING QIANTAI BIOLOGICAL MEDICINE
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