Method for preparing mycophenolate sodium from mycophenolic acid strains

A technology for mycophenolic acid bacteria and mycophenolic acid sodium, which is applied in the field of preparing mycophenolic acid sodium from mycophenolic acid strains, can solve the problem of "mycophenolic acid sodium, long synthesis route and environmental pollution that cannot be directly prepared to obtain the final product". and other problems, to achieve the effect of reducing the harm to the environment and human body, the preparation route is short, and the operation procedure is simple

Active Publication Date: 2017-01-25
WUXI FORTUNE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

This non-inert carrier will produce a large amount of waste in the industrial application of passing vehicles, which will cause certain pollution to the environment; longer route
At the same time, in the current liquid fermentation method, the metabolites of microbial cells and the microbial environment will also have adverse effects on the precursor of mycophenolate sodium (ie "mycophenolic acid")

Method used

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  • Method for preparing mycophenolate sodium from mycophenolic acid strains

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Experimental program
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Effect test

Embodiment 1

[0024] The method for preparing mycophenolate sodium from mycophenolic acid bacterial strains comprises the following steps.

[0025] Step (1): Take the spore suspension of mycophenolic acid-producing bacteria, inoculate it on the seed medium, and cultivate it at 28° C. for 4 days. The components in the seed medium are (unit: g / L): 5 soybean cake powder, 40 lactose, 20 corn steep liquor powder, 1 ammonium nitrate, 1 potassium dihydrogen phosphate, 1 calcium carbonate, and the balance is water.

[0026] In step (2), the seed medium is inoculated in a fermenter, and a fermentation medium is added, and cultured at 26° C. for 10 days. Components in the fermentation medium (unit: g / L): 15 soybean cake powder, 5 corn starch, 45 glucose, 70 fructose, 45 corn steep liquor powder, 1 calcium carbonate, 2 methionine, 0.5 potassium dihydrogen phosphate, and The amount is water. After the fermentation is completed, the tank is put into the tank to extract the fermentation liquid.

[002...

Embodiment 2

[0032] The method for preparing mycophenolate sodium from mycophenolic acid bacterial strains comprises the following steps.

[0033] Step (1), take the spore suspension of mycophenolic acid-producing bacteria, inoculate it on the culture medium, and cultivate it for 3 days at 26°C; each component in the seed culture medium is (unit: g / L): soybean meal powder 10. Lactose 50, corn steep liquor dry powder 25, ammonium nitrate 2, potassium dihydrogen phosphate 2, calcium carbonate 2, and the balance is water.

[0034] In step (2), the seed medium is inoculated in a fermenter, and a fermentation medium is added, and cultured at 26° C. for 9 days. The components in the fermentation medium are (unit: g / L): soybean cake powder 20, corn starch 10, glucose 50, fructose 80, corn steep liquor powder 50, calcium carbonate 1, methionine 3, potassium dihydrogen phosphate 0.5, The balance is water. After the fermentation is completed, the tank is put into the tank to extract the fermentati...

Embodiment 3

[0040] The method for preparing mycophenolate sodium from mycophenolic acid bacterial strains comprises the following steps.

[0041] Step (1), take the spore suspension of mycophenolic acid-producing bacteria, inoculate it on the culture medium, and cultivate it for 4 days at 28°C; each component in the seed culture medium is (unit: g / L) soybean cake powder 15 , lactose 60, corn steep liquor dry powder 40, ammonium nitrate 3, potassium dihydrogen phosphate 3, calcium carbonate 3, and the balance is water.

[0042]In step (2), the seed medium is inoculated in a fermenter, and a fermentation medium is added, and cultured at 28° C. for 11 days. The components in the fermentation medium are (unit: g / L): soybean cake powder 25, corn starch 15, glucose 65, fructose 90, corn steep liquor powder 55, calcium carbonate 3, methionine 4, potassium dihydrogen phosphate 1.5, The balance is water. After the fermentation is completed, the tank is put into the tank to extract the fermentati...

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Abstract

The invention provides a method for preparingmycophenolate sodium from mycophenolic acid strains, comprising the following steps: selecting the mycophenolic acid strains to produce strain spore suspension liquid, inoculating the strain spore suspension liquid in a seed medium and cultivating for 2-4 days at a temperature of 26-28 DEG C; inoculating the seed medium in a fermentation tank, adding a fermentation medium, and fermenting for 9-11 days at a temperature of 26-28 DEG C; adding acid into fermentation liquid in such a manner that pH value of the fermentation liquid is 3-4, adding a sodium hydroxide solution into the fermentation liquid in such a manner that pH value of the fermentation liquid is 8-9, decolorizing and recrystallizing to obtain mycophenolic acid; and synthesizing the mycophenolic acid and sodium hydroxide or sodium methylate in alcohols solvent to obtain the mycophenolate sodium. According to the method provided by the invention, the fermentation liquid obtained by cultivating the mycophenolic acid strains is subjected to acid and alkali treatment, and the sodium hydroxide or the sodium methylate is adopted to synthesize the mycophenolate sodium; and therefore the method has the advantages of short preparation route, simple operating procedure and lower production cost; meanwhile, the application of ketones organic solvent is avoided, and harm to the environment and human body is reduced.

Description

technical field [0001] The invention relates to the technical field of biopharmaceuticals, in particular to a method for preparing mycophenolate sodium from mycophenolic acid strains. Background technique [0002] Mycophenolate Sodium, also known as Mycophenolate Sodium, is an immunosuppressant synthesized from Mycophenolate Mofetil, molecular formula: C 17 h 19 NaO 6 , molecular weight: 342.3. The chemical structural formula of mycophenolate sodium is shown in the following formula (1). [0003] [0004] Mycophenolate Sodium (MPS) is the sodium salt of mycophenolic acid (MPA). Mycophenolic acid is a selective, non-competitive, reversible inhibitor of hypoxanthine monophosphate dehydrogenase (IMPDH), which can inhibit the classical synthesis pathway of guanine nucleotides without damaging DNA synthesis. Mycophenolate Sodium is suitable for use in combination with cyclosporine and corticosteroids for the prevention of acute rejection in adult patients receiving alloge...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P17/04
CPCC12P17/04
Inventor 游云龙付静曹峥杨亮赵永俊蔡云洁金丹甜
Owner WUXI FORTUNE PHARMA
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