L-isovalerylspiramycin iii, its preparation, preparation method and application

A technology of L-isovaleryl spiramycin and rot-isovaleryl spiramycin is applied in the field of macrolide genetic engineering new antibiotics, and can solve problems such as difficulty in reaching chemical quality control standards and the like

Active Publication Date: 2011-11-30
SHENYANG TONGLIAN GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For the multi-component antibiotics produced by fermentation, it is difficult to meet the quality control standards of chemical drugs for injections. However, for clinical critically ill patients or patient...

Method used

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  • L-isovalerylspiramycin iii, its preparation, preparation method and application
  • L-isovalerylspiramycin iii, its preparation, preparation method and application
  • L-isovalerylspiramycin iii, its preparation, preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0084] Example 1 Separation and preparation of L-isovalerylspiramycin III

[0085] (1) Biological fermentation: the helicase-producing bacteria clone strain WSJ-195 containing the 4″-isovaleryltransferase gene was mixed with soybean meal 2%, glucose 1%, starch 3%, CaCO 3 0.5%, NaCl 0.4% and agar 2% on the slant medium, cultured at pH 6.5-7.5, temperature 28-38 ℃ for 8-15 days, inoculated with soybean cake powder 1.5%, starch 3.0%, NaCl 0.4%, CaCO 3 0.5%, fish peptone 0.3% and KH 2 PO 4 0.05% seed medium, cultured at pH 6.5-7.5, 25-30°C for 40-80 hours, inoculated with 0.1-20% inoculum containing 0.5% glucose, 6.0% starch, 0.5% yeast powder, Fishmeal 2.0%, NH 4 NO 3 0.6%, NaCl 1.0%, CaCO 3 0.5%, KH 2 PO 4 0.05%, MgSO 4 0.1%, 0.5% soybean oil and 0.02% anti-foaming agent fermentation medium, cultivated under the conditions of pH 6.5-7.5, 26-30 ℃ for 72-120 hours to obtain the fermentation liquid;

[0086] Among them, through the adjustment and optimization of the...

Embodiment 2

[0098] Embodiment 2: Separation and preparation of L-isovalerylspiramycin III

[0099] (1) Biological fermentation: the helicase-producing bacteria clone strain WSJ-195 containing the 4″-isovaleryltransferase gene was mixed with soybean meal 2%, glucose 1%, starch 3%, CaCO 3 0.5%, NaCl 0.4% and agar 2% on the slant medium, cultured at pH 7.2, temperature 32 ℃ for 12 days, inoculated with soybean meal 1.5%, starch 3.0%, NaCl 0.4%, CaCO3 0.5 %, 0.3% fish peptone and 0.05% KH2PO4 seed medium, cultured at pH 7.2 and 27°C for 70 hours, planted with 12% inoculum containing 0.5% glucose, 6.0% starch, 0.5% yeast powder, Fishmeal 2.0%, NH4NO3 0.6%, NaCl 1.0%, CaCO3 0.5%, KH2PO4 0.05%, MgSO4 0.1%, soybean oil 0.5% and defoamer 0.02% of the fermentation medium, at pH6.0~9.0, 26℃ Cultivate under high temperature for 100 hours to obtain fermentation broth; ferment under the condition of pH 6.0-8.0, the fermentation time is 110h, and the change curve of pH value with time presents three c...

Embodiment 3

[0111] Example 3 Separation and preparation of L-isovalerylspiramycin III

[0112] (1) Cultivation and fermentation: the spiramycin-producing bacteria clone strain WSJ-195 containing the 4″-isovaleryltransferase gene is cultivated on the slant medium, and then inoculated into the seed medium. After cultivation, the It is inoculated in the fermentation medium, the fermentation process is controlled by glucose and citric acid, and the fermentation is carried out under the condition of pH 6.0-7.5. The fermentation time is 115 hours, and the change curve of pH value with time presents three consecutive stages. One stage satisfies the equation y 1 =0.0682x 1 +6.0, where 01 2 =-0.0294x 2 +8.147, where 222 3 =0.0078x 3 +6.06, where 563 Figure 4 , to obtain the fermentation broth.

[0113] (2) Extraction of biological fermentation liquid: the fermentation liquid that step (1) obtains is treated with aluminum sulfate to obtain filtrate, adjusts pH to 8.6, extracts with butyl aceta...

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Abstract

The invention relates to levorotatory isovaleryl spiramycin III, and also relates to a preparation, a preparation method and application thereof. The preparation consists of the levorotatory isovaleryl spiramycin III and a pharmaceutically acceptable carrier and/or auxiliary materials, and the purity of the levorotatory isovaleryl spiramycin III is over 90 weight percent, preferably over 95 weight percent and further preferably over 98 weight percent. The levorotatory isovaleryl spiramycin III has good antibacterial activity; the preparation of the levorotatory isovaleryl spiramycin III comprises water injection for injection, powder injection for injection and freeze-dried powder injection, fills up a blank of a single-component preparation of the isovaleryl spiramycin III in the current market and provides a new quick-response way for treating infectious diseases. The single-component preparation of the isovaleryl spiramycin III has the advantages of stable production process, easily controlled quality standard, and suitability for large-scale industrial production.

Description

technical field [0001] The invention relates to a new antibiotic of macrolide genetic engineering, especially L-isovalerylspiramycin III, its medicinal preparation, preparation method and application in anti-infective disease medicine. Background technique [0002] Macrolide antibiotics occupy an important position clinically, because they have good activity against Gram-positive bacteria and mycoplasma, and also have effects on some Gram-negative bacteria, and they are effective against some increasingly popular Toxoplasma and Legionella It has good antibacterial activity and tissue permeability for pathogens that are difficult to control, fast oral absorption, less adverse reactions, basically no effect on liver and kidney functions, and has potential immunomodulatory effects. In the 1990s, it was considered to be effective in the treatment of adult respiratory tract infections. will compete with β-lactam drugs. [0003] Chirality is the basic property of three-dimensiona...

Claims

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Application Information

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IPC IPC(8): C07H17/08A61K31/7048C12P19/62A61P31/00A61P31/04A61P31/10
CPCY02A50/30
Inventor 姜洋郝玉有
Owner SHENYANG TONGLIAN GRP CO LTD
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