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Process for preparing antivirus medicine 'Libaweilin'

An antiviral drug and enzyme source technology, which is applied in the field of broad-spectrum antiviral drugs, can solve the problems of industrialization restrictions, ribavirin yield restrictions, and low ribavirin yields, so as to reduce production costs, shorten production cycles, Effect of short fermentation period

Inactive Publication Date: 2002-09-11
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The above shows that the existing technology has certain limitations, and the yield of ribavirin has been limited by the activity of nucleoside phosphorylase
Therefore, when inosine is used as the ribose donor, the yield of ribavirin is lower than 85%; its industrialization is also limited by the cost of bacterial fermentation raw materials and reaction substrates

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] 1. Preparation of nucleoside phosphorylase enzyme source:

[0048] 1.1 Fermentation medium: starch 0.5%, peptone 0.4%, beef extract 0.15%, NaCl 0.03%, K 2 HPO 4 ·3H 2 O 0.33%, KH 2 PO 4 0.10%, defoamer 0.02% (V / V), prepared with tap water. The pH value of the fermentation broth is controlled at 7.0-8.5.

[0049] 1.2 Fermentation control: 170L fermenter, the air flow rate is 1:1.0, the tank pressure is 0.035MPa, the fermentation temperature is 29.5°C, the seed medium and other fermentation process control are roughly the same as the general fermentation control conditions. The fermentation time was 17 hours.

[0050] 1.3 Centrifuge the bacteria out of the tank, resuspend in 20mmol / L phosphate buffer (pH7.0), centrifuge, and weigh the wet weight of the bacteria.

[0051]2. Use 20mmol / L phosphate buffer (pH7.0) to prepare 20mmol / L inosine and 20mmol / L triazole carboxamide as reactants, enzyme dosage: 80mg wet bacteria / ml reaction solution. The reaction conditions ...

Embodiment 2

[0054] Bacterial cells obtained from continuous 3-tank fermentation were used for the reaction.

[0055] 1. Preparation of nucleoside phosphorylase enzyme source:

[0056] 1.1 Fermentation medium: starch 0.45%, peptone 0.55%, beef extract 0.15%, NaCl 0.02%, K 2 HPO 4 ·3H 2 O 0.33%, KH 2 PO 4 0.10%, defoamer 0.02% (V / V), prepared with tap water. During fermentation, the pH value is controlled at 7.0-8.5.

[0057] 1.2 Fermentation control: 170L fermenter, air flow rate 1:0.9, tank pressure 0.025MPa, fermentation temperature 30°C, seed medium and other fermentation process control are roughly the same as general fermentation control conditions. The fermentation times of the three tanks of bacteria were 16h, 19h, and 22h respectively.

[0058] 1.3 Centrifuge the bacteria out of the tank, resuspend in 20mmol / L phosphate buffer (pH7.0), centrifuge, and weigh the wet weight of the bacteria.

[0059] 2. Use 20mmol / L phosphate buffer (pH7.0) to prepare 20mmol / L inosine and 20m...

Embodiment 3

[0067] Using the bacterial cells fermented in the same tank, 60 consecutive reactions were carried out.

[0068] 1. Preparation of nucleoside phosphorylase enzyme source:

[0069] 1.1 Fermentation medium: starch 0.6%, peptone 0.5%, beef extract 0.2%, NaCl 0.03%, K 2 HPO 4 ·3H 2 O 0.33%, KH 2 PO 4 0.10%, defoamer 0.02% (V / V), prepared with tap water. During fermentation, the pH value is controlled at 7.0-8.5.

[0070] 1.2 Fermentation control: 170L fermenter, the air flow rate is 1:1.3, the tank pressure is 0.02MPa, the fermentation temperature is 31.5°C, the seed medium and other fermentation process control are roughly the same as the general fermentation control conditions. The fermentation time is 20h.

[0071] 1.3 Centrifuge the bacteria out of the tank, resuspend in 20mmol / L phosphate buffer (pH7.0), centrifuge, and weigh the wet weight of the bacteria.

[0072] 2. Use 20mmol / L phosphate buffer (pH7.0) to prepare 20mmol / L inosine and 20mmol / L triazole carboxamide...

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Abstract

A process for preparing an antiviral medicine "Libaweilin" uses acetyl bacillus brevis ATCC 39311, with starch, peptone, beef paste, sodium chloride, dipotassium hydrogen phosphate, potassium bihydrogen phosphate, defoaming agent and running water as raw materials, and includes fermenting, and synthesis by using the resultant complete bacteria as enzyme source and the inosine as ribosome doner. Its advantages are simple process, low cost and high output rate.

Description

technical field [0001] The invention relates to a preparation method of antiviral drug ribavirin, which is a broad-spectrum antiviral drug and is suitable for treating influenza, oral herpes and hemorrhagic fever. Background technique [0002] There are three methods for the synthesis of ribavirin, namely chemical method, fermentation method and enzymatic method. [0003] There are many methods for chemically synthesizing ribavirin. However, this type of method has many operation steps, many by-products, low yield and high cost. [0004] For the fermentation method, see literature (Journal of The Agricultural Chemical Society, 50(9), 430-423(1976), Japanese Laid-Open Patent No. 17830 / 1979). The disadvantages of this method are that the bacteria must be cultured every time; the culture time is long and the production efficiency is low; there are many by-products accumulated and the yield is low; the separation and purification of ribavirin is diffi...

Claims

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Application Information

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IPC IPC(8): C12P19/28
Inventor 陈蔚梅冯胜彦郭明雄艾建宇吴斌熊晓然吴显辉
Owner WUHAN UNIV
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