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Method for preparing high-purity doramectin

A doramectin, high-purity technology, applied in the field of doramectin preparation, can solve the problems of increased operation steps and production costs, low purity, environmental pollution, etc., to reduce process operations and equipment requirements, improve Product quality, the effect of reducing production costs

Active Publication Date: 2015-06-10
CHONGQING QIANTAI BIOLOGICAL MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the face of increasing market demand and product quality requirements, the existing separation technology is difficult to achieve, mainly has the following disadvantages: 1) The purity of the obtained fine product is 92.2%, which is relatively low and cannot meet the quality standards of drugs (according to anhydrous According to the calculation, the doramectin content should not be less than 95.0%); 2) silica gel chromatography separation after resin adsorption will reduce the product yield, and increase the operation steps and production costs; 3) the resin chromatography desorption process requires A large amount of organic solvent poses a threat to the health of operators and pollutes the environment, so it is not suitable for large-scale industrial production

Method used

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  • Method for preparing high-purity doramectin
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  • Method for preparing high-purity doramectin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] The doramectin fermentation broth was placed in a tank of 32.7L, and the fermentation unit was 1257ug / ml (41.1g). Add 490g of diatomaceous earth to it, stir for half an hour, perform plate and frame pressure filtration after uniformity, and obtain 4.2kg of wet mycelium residue, which is dried in a 45°C oven until the moisture content is 20%, and a 3.0kg block is obtained dry mycelium residue. Grind the mycelium residue into powder and extract with 9L butyl acetate, stir for 12 hours and filter to obtain about 9L extract (see HPLC spectrum figure 1 and its data are shown in Table 1), the unit is 3633ug / ml (32.7g). Concentrate the extract at 55°C until it is in the form of an extract, add a beating solution (methyl tert-butyl ether:ethanol=1.5:1 (v / v)) equal to the mass of the extract, stir at room temperature for 3 hours and then let it stand Overnight, filter to obtain light yellow crude product A (HPLC spectrum see figure 2 And its data are shown in Table 2) 87.3g...

Embodiment 2

[0048] Put the doramectin fermentation broth in a 35L tank, and the fermentation unit is 1000ug / ml (35g). Add 1.5 kg of diatomaceous earth therein, stir for half an hour, perform plate and frame pressure filtration after uniformity, and obtain 4.5 kg of wet mycelia residue. Grind the mycelial residue into powder and extract with 13.5L of ethanol, stir for 8 hours and then filter to obtain about 13.5L of extract with a unit of 2145ug / ml (29g). Concentrate the extract at 50°C until it is in the form of an extract, add a beating solution (methyl tert-butyl ether:ethanol=2:1 (v / v)) equal to the mass of the extract, stir at room temperature for 3 hours and then let it stand After overnight, it was filtered to obtain 78.6 g of pale yellow crude product A with a content of 36.5% (28.7 g) and a purity of 84.1%.

[0049] Add 700 ml of crystallization solution (isobutanol: acetone = 9:1 (v / v)) to the crude product A, stir at 50°C until the crude product A is just completely dissolved, ...

Embodiment 3

[0051] The doramectin fermentation broth was put into a tank of 31.2L, and the fermentation unit was 1100ug / ml (34.3g). Add 690g of diatomaceous earth to it, stir for half an hour, and perform plate and frame pressure filtration after uniformity to obtain 4.6kg of wet mycelium residue, which is dried in an oven at 45°C until the moisture content is 18%, and 3.2kg of block Dried mycelium residue, ground into powder, extracted with 13L of methanol, stirred for 15 hours and then filtered to obtain about 13L of extract, with a unit of 2110ug / ml (27.4g). Concentrate the extract at 55°C until it is in the form of an extract, add a beating solution (methyl tert-butyl ether:ethanol=1:1 (v / v)) equal to the mass of the extract, stir at room temperature for 3 hours and then let it stand After overnight, it was filtered to obtain 77.4 g of light yellow crude product A with a content of 32.8% (25.4 g) and a purity of 83.5%.

[0052] Add 470ml of crystallization solution (ethanol solution)...

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Abstract

The invention discloses a method for preparing a high-purity doramectin. The method comprises the steps of extracting the fermenting solution, condensing, pulping, crystallizing and the like to obtain the high-purity doramectin. The doramectin can be extracted by adopting a pulping and crystallizing process, and the method has the advantages of simple and easy process, high yield, high product quality, low production cost, and suitability for industrial production.

Description

technical field [0001] The invention belongs to the technical field of industrial microorganisms, and in particular relates to a preparation method of high-purity doramectin. Background technique [0002] Parasitic diseases are one of the most serious zoonotic diseases at present, seriously affecting the healthy development of animal husbandry and the safety of human life. Among the many anti-parasitic drugs in animals, avermectins are currently the most excellent broad-spectrum and high-efficiency veterinary anti-parasitic drugs. Ivermectin, Doramectin and Eprinomectin. Among them, doramectin is a new generation of macrolide antiparasitic drug developed by Pfizer of the United States in the 1990s, and is considered to be one of the best drugs among avermectins. Doramectin is produced by genetically recombined Streptomyces avermitilis ( Streptomyces avermitilis ) The new strain is a sixteen-membered macrolide semi-synthetic antibiotic formed by fermenting the precursor su...

Claims

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Application Information

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IPC IPC(8): C07H17/08C07H1/08
CPCC07H1/08C07H17/08
Inventor 杨久林袁增良唐恒郭明袁建栋
Owner CHONGQING QIANTAI BIOLOGICAL MEDICINE
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