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Carbohydrate supplementing method in fermentation process of mycophenolic acid

A fermentation process and mycophenolic acid technology, applied in the field of biomedicine, can solve the problems of limited use by patients and high price, and achieve the effects of simple and easy operation, increased utilization, and reduced cost.

Active Publication Date: 2010-03-17
SHANDONG NEWTIME PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] At present, domestic mycophenolate mofetil preparations mainly rely on imports, which are expensive and limit the use of patients

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Batch feeding in the batch fermentation process of embodiment 1 100L fermentor:

[0025] Prepare 7.5L of seed medium on a 10L fermenter. After the preparation of the seed medium is completed, sterilize at 121°C-123°C for 30 minutes, then cool to 26°C-28°C, and insert 10% of the inoculum into a 12-hour-old shake flask Cultivate for 12h-16h after seeding.

[0026]Prepare 75L of fermentation medium in a 100L fermenter, sterilize at 121°C-123°C for 30 minutes, wait for the medium to cool down to 26°C-28°C, insert 10% of the inoculum into the seed medium, and control the temperature at 25°C during the fermentation process Between -29°C (control temperature at 25°C-26°C during the initial growth period of the bacteria, and control the temperature at 26°C-29°C after the bacteria enter the production type), add defoamer according to the foam generation situation, flow Add 10% ammonia solution or 10% dilute hydrochloric acid to control the pH between 4.5-6.5. According to the ...

Embodiment 2

[0027] Continuous feeding in the batch fermentation process of embodiment 2 100L fermentors:

[0028] Prepare 8L of seed medium in a 10-liter fermenter. After the preparation of the seed medium is completed, sterilize at 121°C-123°C for 30 minutes, then cool to 26°C-28°C, and insert 10% of the inoculum into a 12-hour-old shake flask. Cultivate for 12-16 hours after seeding.

[0029] Prepare 75L of fermentation medium in a 100L fermenter, sterilize at 121°C-123°C for 30 minutes, wait for the medium to cool down to 26°C-28°C, insert 10% of the inoculum into the seed medium, and control the temperature at 25°C during the fermentation process Between -29°C (control temperature at 25°C-26°C during the initial growth period of the bacteria, and control the temperature at 26°C-29°C after the bacteria enter the production type), add defoamer according to the foam generation situation, flow Add 10% ammonia solution and 10% dilute hydrochloric acid to control the pH between 4.5-6.5. A...

Embodiment 3

[0030] The intermittent feeding in the batch fermentation process of embodiment 3 5000L fermentors:

[0031] Prepare 8L of seed medium in a 10-liter fermenter. After the preparation of the seed medium is completed, sterilize at 121°C-123°C for 30 minutes, then cool to 26°C-28°C, and insert 10% of the inoculum into a 12-hour-old shake flask. Cultivate the seeds for 12-16 hours. Prepare 400L of seed medium on a 500-liter fermenter. After the preparation of the seed medium is completed, sterilize at 121°C-123°C for 30 minutes, then cool to 26°C-28°C, and inoculate with 10% inoculum Cultivate 12h-16h after entering the shake flask seeds of 12h seed age.

[0032] Prepare 4000L of fermentation medium in a 5000L fermenter, sterilize at 121°C-123°C for 30 minutes, wait for the medium to cool down to 26°C-28°C, insert 10% of the inoculum into the seed medium, and control the temperature at 25°C during the fermentation process Between -29°C (control temperature at 25°C-26°C during the ...

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PUM

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Abstract

The invention belongs to the field of biological fermentation, more particularly relates to a method for realizing the purpose of producing high-density mycophenolic acid through continuously or intermittently supplementing high-density solution of monosaccharide, disaccharide or polysaccharide into a fermentation liquor to culture penicillium brevicompactum. In the method, high-density solution of monosaccharide, disaccharide or polysaccharide is supplemented as a supplementary carbon source during the fermentation process of mycophenolic acid in a basic culture medium which takes glucose asa carbon source. The carbohydrate supplementing method in the fermentation process provided by the invention is easy to be operated and implemented, can improve the fermentation titer by 80-100 percent, and is very applicable to the demands of industrial production.

Description

technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to a method for producing high-concentration mycophenolic acid by supplementing sugar, more specifically, it relates to culturing by continuously or intermittently adding high-concentration monosaccharide, disaccharide or polysaccharide solutions to fermentation broth Penicillium brevidense, to achieve high concentrations of mycophenolic acid production. Background technique [0002] Mycophenolic acid (mycophenolic acid, MPA, also known as mycophenolic acid) is a fermentation product of certain Penicillium species. MPA is an intermediate, which forms mycophenolate mofetil (MMF) after esterification. Mycophenolate mofetil can inhibit the de novo synthesis pathway of purine nucleotides in lymphocytes. It is a new type of immunosuppressant and is orally bioavailable. High degree, no liver and kidney toxicity and bone marrow suppression and other side effects, clinically can be sa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P17/04C12R1/80
Inventor 赵志全薛国希王洪臣
Owner SHANDONG NEWTIME PHARMA
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