Levo-isovaleryl spiramycin I and preparation, preparation method and application thereof

A technology of L-isovalerylspiramycin and Isovalerylspiramycin, which is applied in the field of macrolide genetic engineering new antibiotics, and can solve the problems that it is difficult to meet the quality control standards of chemicals

Active Publication Date: 2011-11-02
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 patients w

Method used

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  • Levo-isovaleryl spiramycin I and preparation, preparation method and application thereof
  • Levo-isovaleryl spiramycin I and preparation, preparation method and application thereof
  • Levo-isovaleryl spiramycin I and preparation, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] Example 1 Separation and preparation of L-isovalerylspiramycin I

[0083] (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;

[0084] Among them, through the adjustment and optimization of the ...

Embodiment 2

[0096] Embodiment 2: Separation and preparation of L-isovalerylspiramycin I

[0097] (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 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 7.2, 27°C for 70 hours, inoculated with 12% inoculum containing 0.5% glucose, 6.0% starch, 0.5% yeast powder, 2.0% fish meal, 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 6.0-9.0, 26 ℃ for 100 hours to obtain the fermentation broth; fermented under the conditions of pH 6.0-8.0, The time is 110h, and the change curve of pH valu...

Embodiment 3

[0109] Example 3 Separation and preparation of L-isovalerylspiramycin I

[0110] (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.

[0111] (2) Extraction of biological fermentation liquid: the fermentation liquid obtained in step (1) is treated with aluminum sulfate to obtain a filtrate, adjust the pH to 8.6, extract with butyl acet...

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Abstract

The invention relates to levo-isovaleryl spiramycin I and a preparation, a preparation method and application thereof. The preparation consists of the levo-isovaleryl spiramycin I and pharmaceutically acceptable carriers and/or excipient, wherein the purity of the levo-isovaleryl spiramycin I is over 90 weight percent, preferably over 95 weight percent and further preferably over 98 weight percent. The levo-isovaleryl spiramycin I has good antimicrobial activity; the preparation of the levo-isovaleryl spiramycin I comprises water injection, powder injection or freeze dried powder injection; the preparation fills the blank of the single component preparation of the isovaleryl spiramycin I at present market, and provides a new path with quick response for treating anti-infective diseases; and the production process for the preparation of single component of the isovaleryl spiramycin I is stable, standard and easily controlled in quality and suitable for large-scale industrialized production.

Description

technical field [0001] The invention relates to a new antibiotic of macrolide genetic engineering, especially L-isovalerylspiramycin I, 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-dimensional ...

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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