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New process for preparing meleumycin

A kind of melemycin, a new process technology, applied in the field of microbial production of melemycin, can solve the problems of backwardness, high cost of extraction process, complicated organic solvent recovery process, etc.

Inactive Publication Date: 2013-05-15
贯虹科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, the production of mebelamycin raw materials mainly adopts microbial fermentation method, but the industrial production process is relatively backward compared with foreign countries. High, easy to cause environmental pollution, etc., difficult to meet the needs of formulation development

Method used

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  • New process for preparing meleumycin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0010] seed culture

[0011] Medium: 13% indica rice flour hydrolyzate, 1% sucrose, 0.2% peptone, 0.1% ammonium sulfate, 0.1% potassium dihydrogen phosphate, and the rest is distilled water.

[0012] ①Incline seed culture

[0013] The preserved strains were inoculated on the slant medium with an inoculation needle, and cultured at 28°C for 7 days.

[0014] ② Primary seed culture medium

[0015] Add 50mL of seed medium into a 250mL shake flask, sterilize and cool down, then connect a ring of well-grown slant culture, and cultivate at 28°C and 200r / min for 48h.

[0016] ③ Secondary seed culture solution

[0017] Add 3L of seed culture medium into a 5L shake flask, sterilize and cool, add 60mL of primary seed culture medium, and cultivate at 28°C and 200r / min for 48h.

[0018] ④Tertiary seed culture solution

[0019] Add 9L of seed culture medium into a 15L shake flask, sterilize and cool, add 2.7L of secondary seed culture medium, and cultivate at 28°C and 200r / min for 48h....

Embodiment 2

[0032] Seed culture is the same as example 1

[0033] Fermentation culture

[0034] Fermentation medium: 15% of indica rice flour hydrolyzate, 0.3% of ammonium sulfate, 0.1% of potassium dihydrogen phosphate, 0.08% of calcium carbonate, and the rest is distilled water.

[0035] Add 50L of fermentation medium and an appropriate amount of defoamer to a 100L automatic fermentation tank, sterilize at 0.1MPa for 30 minutes, cool to 28°C, insert 16.0L of tertiary seed culture medium, and the ventilation rate is 1.1-1.2V / V / min, the stirring speed is 500-700r / min, the fermentation temperature is 28°C, and after 72 hours of fermentation, centrifuge to obtain the melemycin fermentation broth.

[0036] Extraction of melelamycin

[0037] ①Extraction

[0038] Add a quantitative amount of mebamycin fermentation broth to the extraction tank, adjust the pH value to 8.0-9.0 with a saturated solution of sodium bicarbonate, and then add 1.5 times the volume of the extraction solution of isop...

Embodiment 3

[0045] Seed culture is the same as example 1

[0046] Fermentation culture

[0047] Fermentation medium: 17% of indica rice flour hydrolyzate, 0.5% of ammonium sulfate, 0.7% of potassium dihydrogen phosphate, 0.2% of calcium carbonate, and the rest is distilled water.

[0048] Add 50L fermentation medium and an appropriate amount of defoamer to a 100L fully automatic fermentation tank, sterilize at 0.1MPa for 30min, cool to 28°C, insert 16.0L of tertiary seed culture medium, and the ventilation rate is 1.0-1.2V / V / min, the stirring speed is 500-700r / min, the fermentation temperature is 28°C, and centrifuged to obtain the mebamycin fermentation broth.

[0049] Extraction of melelamycin

[0050] ①Extraction

[0051] Add a quantitative amount of mebamycin fermentation broth to the extraction tank, adjust the pH value to 8.0-9.0 with a saturated solution of sodium bicarbonate, and then add 3 times the volume of the extraction solution of octanol and aviation kerosene (V / V=5:2) ...

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Abstract

The invention discloses a method for preparing meleumycin through fermentation of streptomyces mycarofaciens. The method comprises the following steps of: fermenting streptomyces mycarofaciens through a new fermenting base formula, to improve contents of medemycin A1 and kitasamycin back A6; after fermentation, through an extraction and a back extraction, extracting by a new mixing extracting agent, to improve extracting rate; and automatically crystallizing, to separate out the meleumycin. The process disclosed by the invention, which produces the meleumycin through a new fermenting base formula, simplifies meleumycin extraction process, and has characteristics of simple and convenient operation, energy conservation and the like; and the meleumycin produced by the process disclosed by the invention is accordant with related requirements of Chinese Pharmacopoeia 2010 version, and is applicable to industrial mass production.

Description

1. Technical field [0001] The invention belongs to the field of microbial fermentation technology, in particular to a method for producing mebamycin by microorganisms. 2. Background technology [0002] Mebemycin belongs to macrolide multi-component antibiotics, the active ingredients are mainly two components of midecamycin A1 and kitasamycin A6, according to the requirements of the 2005 edition of Chinese Pharmacopoeia The content of medemycin A1 in melelamycin should not be lower than 35.0%, and the 2010 edition of China’s requirements has raised the requirement that the component of midecamycin A1 in mebelamycin should not be lower than 48%, and the component of kitamycin A6 should not be lower than 12%. For this reason, new requirements have been brought to mebelamycin production enterprises. [0003] Mebemycin is a 16-membered cyclic lactone antibiotic produced during the metabolic process of Streptomyces mika. It is a broad-spectrum antibacterial drug commonly used in...

Claims

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Application Information

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IPC IPC(8): C12P19/62C07H17/08C07H1/08C12R1/465
Inventor 许荔新朱睿
Owner 贯虹科技有限公司
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