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A kind of method for preparing doramectin

A technology of doramectin and cyclohexyl carboxylic acid, which is applied in the field of doramectin preparation, can solve the problems of low fermentation yield and slow industrialization process, and achieve the effect of high fermentation yield

Active Publication Date: 2018-11-06
LIVZON NEW NORTH RIVER PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Doramectin fermentation technology not only has the problem of low fermentation yield, but most of them are still in the laboratory stage, and the industrialization process is slow. Therefore, doramectin urgently needs a technology suitable for large-scale industrial production and high fermentation yield

Method used

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  • A kind of method for preparing doramectin
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  • A kind of method for preparing doramectin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Strain: strain Streptomyces avermitilis XJ-8-115, screened and preserved by the Academy of Sciences of the State Grain Administration.

[0029] Doramectin Fermentation Medium

[0030]

[0031] Prepare 350L of fermentation medium and sterilize at 121-123°C for 20 minutes. The inoculum volume is 10%. After inoculation, the tank temperature is 28.0±0.5°C, the tank pressure is 0.04MPa, and the flow rate is 25m 3 / hr at a rotational speed of 80 rpm for 228 hours.

[0032] Feeding strategy: add the precursor cyclohexyl carboxylate twice, the first addition of cyclohexyl carboxylate is added after 40 hours of fermentation, and the supplementary amount is 1.0g / L; the second addition of cyclohexyl carboxylate Salt was added in 180 hours of fermentation, and the supplementary amount was 0.6g / L.

[0033] Add maltodextrin as feeding sugar in the middle and late stages of fermentation, and control the total sugar at 2.5-4.5%; the final tank unit is 773mg / L. Cyclohexyl formate...

Embodiment 2

[0035] Strain: strain Streptomyces avermitilis XJ-8-115, screened and preserved by the Academy of Sciences of the State Grain Administration.

[0036] Doramectin Fermentation Medium

[0037]

[0038] Prepare 350L of fermentation medium and sterilize at 121-123°C for 20 minutes. The inoculum volume is 10%. After inoculation, the tank temperature is 28.0±0.5°C, the tank pressure is 0.04MPa, and the flow rate is 25m 3 / hr at a rotation speed of 80 rpm for 312 hours.

[0039] Maltodextrin is added as feed sugar in the middle and late stage of fermentation, and the total sugar is controlled at 2.5-4.5%.

[0040] Feeding strategy: (1) Experiment 1: The precursor cyclohexyl carboxylate was added twice, the first addition of cyclohexyl carboxylate was added after 40 hours of fermentation, and the supplementary amount was 1.0g / L; the second The second addition of cyclohexyl formate was added at 180 hours of fermentation, and the additional amount was 0.6 g / L.

[0041] (2) Test 2...

Embodiment 3

[0048] Strain: strain Streptomyces avermitilis XJ-8-115, screened and preserved by the Academy of Sciences of the State Grain Administration.

[0049] Doramectin Fermentation Medium

[0050]

[0051] Prepare 350L of fermentation medium and sterilize at 121-123°C for 20 minutes. The inoculum volume is 10%. After inoculation, the tank temperature is 28.0±0.5°C, the tank pressure is 0.04MPa, and the flow rate is 25m 3 / hr at a rotation speed of 80 rpm for 312 hours.

[0052] Maltodextrin is added as feed sugar in the middle and late stage of fermentation, and the total sugar is controlled at 2.5-4.5%.

[0053] Feeding strategy: Add the precursor cyclohexyl carboxylate twice, the first addition of cyclohexyl carboxylate is added at T hours of fermentation, and the supplementary amount is 0.8g / L; the second addition of cyclohexyl carboxylate Salt was added in 180 hours of fermentation, and the additional amount was 0.8g / L. The results are shown in Table 2.

[0054] Table 2:...

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Abstract

The invention provides a new preparation method of doramectin, and in particular relates to a method for fermenting doramectin. The method is characterized by comprising a step of adding cyclohexanol carboxylic acid or salt of the cyclohexanol carboxylic acid twice in a fermentation process, wherein the first addition time of the cyclohexanol carboxylic acid or the salt of the cyclohexanol carboxylic acid is 22-60 hours after fermentation, and the second addition time of the cyclohexanol carboxylic acid or the salt of the cyclohexanol carboxylic acid is 170-194 hours after fermentation. The method is high in fermentation yield and suitable for industrial massive production, and can be applied to production of doramectin by a 500-L fermentation tank in a fermentation manner.

Description

technical field [0001] The present invention relates to the preparation method of doramectin, more specifically, the present invention relates to a kind of fermentation method of doramectin. Background technique [0002] Doramectin is biosynthesized by adding cyclohexanecarboxylic acid in the fermentation process of the bkdFGH gene deletion mutant strain of Streptomyces avermitilis, and is the third generation derivative of abamectin. Doramectin is similar in structure to avermectin, the difference is that the 25th position of doramectin is a cyclohexyl group, while the 25th position of avermectin is a dimethyl group. Doramectin is 25-cyclohexyl-5-O-demethyl-25-de(1-methylpropyl) abamectin Ala, the chemical formula is C 50 h 74 o 14 , the structural formula is as follows: [0003] [0004] Doramectin is a new type of macrolide antiparasitic drug. Compared with avermectin, it has a lower clearance rate in animals, a longer biological half-life, and a higher bioavailabi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P17/18
Inventor 唐阳刚梁春盛倪立俊陈鹰博
Owner LIVZON NEW NORTH RIVER PHARMA
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