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Method for producing nucleoside medicine intermediate cytosine arabinoside through biotransformation process

A kind of cytarabine, biotransformation technology

Inactive Publication Date: 2014-08-06
山东斯递尔化工科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] It can be seen from the above that the production of cytarabine by the chemical method has many steps, harsh conditions, a large amount of organic solvents are used, the environmental pollution is serious, and the production cost is high and the process is complicated.
[0005] At present, there are few literature reports on the production of cytarabine by biotransformation at home and abroad.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Embodiment 1, biotransformation method produces cytarabine

[0025] (1) Bacteria slant culture

[0026] Lactobacillus helveticus (Lac tobacco helveticus) CGMCC1.1877 (General Microbiology Center of China Microbiological Culture Collection Management Committee) was inoculated into the slant medium, 37 ° C, pH value 6.5, and cultivated for 24 hours to make slant strains; the slant medium was prepared by The component composition of following parts by weight:

[0027] 10 parts of yeast extract powder, 1 part of glucose, 5 parts of peptone, 5 parts of dipotassium hydrogen phosphate, 0.5 parts of corn steep liquor, 2 parts of sodium chloride, 15 parts of agar and 1000 parts of water.

[0028] (2) Inoculation fermentation

[0029] Insert the slant bacterial strain into the fermentation medium and expand the cultivation as the seed solution; the seed solution is inserted into the fermentor equipped with the fermentation medium at 10% (volume percentage) inoculum at 37°C, 160...

Embodiment 2

[0038] Embodiment 2, biotransformation method produces cytarabine

[0039] (1) Lactobacillus helveticus CGMCC 1.1877 was inoculated into the slant culture medium, 40 DEG C, pH6.5, cultivated for 24 hours to make the slant strain; the slant medium was composed of the following components by weight:

[0040] 12 parts of yeast extract powder, 1.5 parts of glucose, 2.5 parts of peptone, 5 parts of dipotassium hydrogen phosphate, 0.75 parts of corn steep liquor, 2 parts of sodium chloride, 17 parts of agar and 1000 parts of water.

[0041] (2) Inoculation fermentation

[0042] Insert the slant bacterial strain into the fermentation medium and expand the cultivation as the seed liquid; the seed liquid is inserted into the fermenter equipped with the fermentation medium with an inoculum of 20% (volume percentage) at 37°C, 140 rpm, and the pH value is 6.5, fermented for 36 hours; the fermentation medium was composed of the following components by weight:

[0043] Yeast extract powde...

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Abstract

The invention discloses a method for producing cytosine arabinoside through a biotransformation process. The method comprises the following steps: inoculating a Lactobacillus helveticus seed liquid into a fermentation culturing medium, carrying out fermentation culturing to obtain crude thalli, adding a buffer solution to the crude thallik to prepare a cell suspension, adding Spongouridine and cytosine into the cells suspension, and carrying out an enzymatic reaction to obtain cytosine arabinoside. The fermentation culturing medium comprises, by mass, 10-50 parts of yeast extract powder, 1-10 parts of glucose, 1-15 parts of peptone, 1-7 parts of ammonium sulfate, 2-12 parts of dipotassium hydrogen phosphate, 2-17 parts of a corn steep liquor, 0.5-6 parts of calcium chloride and 1000 parts of water. The method fully uses the high effectiveness, the specificity and the mildness of an enzyme; and compared with traditional chemical synthesis methods, the method disclosed in the invention has the advantages of high selectivity, mild conditions, simple process, low cost, small pollution and the like.

Description

technical field [0001] The invention relates to a method for producing cytarabine by a biotransformation method. Background technique [0002] Cytarabine is currently one of the effective first-line drugs for the treatment of acute non-lymphoid leukemia. It belongs to pyrimidine analogs in anti-metabolic chemotherapy drugs, is a structural analog of 2'-deoxycytidine, and is also a cell cycle-specific drug. It is mainly used for acute leukemia, among which the curative effect is the best for acute myeloid leukemia, and it is also effective for acute monocytic leukemia and acute lymphoblastic leukemia. In clinical application, it is generally used in combination with other drugs, and it has a certain effect on malignant lymphoma, lung cancer, digestive tract cancer, head and neck cancer, and also has a certain effect on viral keratitis and epidemic conjunctivitis. [0003] At present, the preparation method of cytarabine is mainly chemical synthesis. Hunan Institute of Pharm...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P19/38C12R1/225
Inventor 朱嘉震史峻嵩李海存王颖赵新远尹传祥王金才
Owner 山东斯递尔化工科技有限公司
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