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Preparation method of nemadectin

A technology for fermenting and cultivating nimoctine, which is applied in the field of preparation of high-purity nimoctine and antibiotics. It can solve the problems of increased cost of nimoctine extraction, low purity of nimoctine, and a large amount of filtered waste water, etc., and achieves The effect of low cost, significant economic benefits and simple process

Active Publication Date: 2014-05-07
CHONGQING DAXIN PHARMA +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The method described in this invention has the following defects: the fermentation process produces a large amount of nemoctine structural analogues; the fermentation broth uses a large amount of filter aids due to filtration difficulties, resulting in a large amount of filtered waste water, resulting in environmental pollution; using methanol to extract wet Mycelial residue, the amount of methanol used is too large; and, the use of disposable silica gel to separate nemoctine leads to an increase in the cost of nemoctine extraction
Because the mycelium of Streptomyces blue gray is easy to break and autolyze after long-term cultivation, it is very difficult to process the fermented liquid by solid-liquid separation, resulting in low leaching purity and low efficiency of the invention. Therefore, subsequent adsorption by macroporous resin The purity of nemoctine obtained by purification is low

Method used

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  • Preparation method of nemadectin
  • Preparation method of nemadectin
  • Preparation method of nemadectin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] 1. Fermentation production process of nimoctin:

[0017] The components and contents of the fermentation medium are: glucose 4.0%

[0018] Maltose 7.0%

[0019] Soya flour 2.5%

[0020] Yeast extract powder 0.5%

[0021] Magnesium Sulfate 0.3%

[0022] Potassium nitrate 0.5%

[0023] Adjust the pH of the medium to 7.0, then sterilize at 121°C for 30 minutes, and set aside.

[0024] Add 1 L of the prepared Streptomyces coustrigeus seed solution (Note: the bacterial concentration of the seed solution is 18-24%, which is the volume percentage of the bacterial sediment measured after centrifugation) into 30 L of the prepared fermentation medium , cultivated at 28°C for 214h. Then use HPLC to detect the purity of nimoctine in the fermented liquid. The specific method is: take 5 ml of fermented liquid and add 10 ml of meth...

Embodiment 2

[0030] 1. Fermentation production process of nimoctin:

[0031] The components and contents of the fermentation medium are: soluble starch 2%

[0032] Lactose 8%

[0033] Cottonseed meal 3%

[0034] Yeast autodissolving powder 1%

[0035] Magnesium Sulfate 0.3%

[0036] Potassium nitrate 0.5%

[0037] Adjust the pH of the medium to 7.0, then sterilize at 121°C for 30 minutes, and set aside.

[0038] Put 1 L of the prepared Streptomyces coustrigeus seed solution (Note: the bacterial concentration of the seed solution is 18-24%, V / V) into 30 L of the prepared fermentation medium, and culture at 28° C. for 220 h. Using the same method as in Example 1, the fermentation unit of nimoctine in the fermentation broth determined by HPLC was 1.78 g / L, and the purity was greater than 53%.

[0039] 2. Direct spray drying process:

[0040...

Embodiment 3

[0044] 1. Fermentation production process of nimoctin:

[0045] The components and contents of the fermentation medium are: soluble starch 1%

[0046] Lactose 3%

[0047] Cottonseed meal 3%

[0048] Yeast autodissolving powder 1%

[0049] Magnesium Sulfate 0.3%

[0050] Potassium nitrate 0.5%

[0051] Adjust the pH of the medium to 7.0, then sterilize at 121°C for 30 minutes, and set aside.

[0052] Put 1 L of the prepared Streptomyces coustrigeus seed solution (Note: the bacterial concentration of the seed solution is 18-24%, V / V) into 30 L of the prepared fermentation medium, and culture at 28° C. for 220 h. Using the same method as in Example 1, the fermentation unit of nimoctine in the fermentation broth determined by HPLC was 1.66 g / L, and the purity was greater than 50%.

[0053] 2. Direct spray drying process and nem...

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Abstract

The invention discloses a preparation method of nemadectin. According to the invention, a fermentation broth used for producing nemadectin is directly dried by spraying, such that solid powder is obtained; the solid powder is extracted by using an organic solvent, the extract is filtered, and nemadectin in the extract is absorbed by using macroporous resin; nemadectin absorbed by macroporous resin is then eluted; and the eluent is extracted, concentrated, and dried, such that a nemadectin pure product is obtained. According to the invention, a direct spray-drying method is adopted upon the fermentation broth, and the obtained dried solid fermentation bacterium powder is transportation-tolerant, and is easy to store. With the method provided by the invention, the producing of nemadectin degradation product is reduced, the bacterium powder is easy to extract, and the consumption of the extraction solvent is low. The technology is simple, the cost is low, and the method is easy to operate. With the method, the prepared nemadectin has a high HPLC purity of above 90%.

Description

technical field [0001] The invention belongs to the field of animal medicines, and relates to a method for preparing antibiotics, in particular to a method for obtaining high-purity nemoctine by fermenting and cultivating nimoctine-producing bacteria, and then purifying the fermentation product. Background technique [0002] Nemadectin is a sixteen-membered macrolide antibiotic produced by Streptomycescyaneogriseus sp.Noncyanogenus through fermentation. As a member of the milbemycin family, nimoctine is mainly used in the synthesis of the more active anthelmintic drug moxidectin. [0003] European patent EP0170006A2 discloses a production medium and fermentation process for nemoctine. First, inoculate Streptomyces blue gray in a culture medium containing 1.0% glucose, 2.0% dextrin, 0.5% yeast extract, 0.5% NZ amine (enzymatic hydrolyzate of casein) and 0.1% calcium carbonate (note: each The unit of percentage content of a substance is g / mL, for example, 0.1% is 0.001g / mL, ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H19/01C07H1/06C12P19/62C12R1/465
Inventor 何勇崴刘省伟岳光别一刘会明郭明赵德
Owner CHONGQING DAXIN PHARMA
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