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Levorotary isovaleryl spiramycin II as well as 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: 2012-01-11
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 who are not suitable for oral medication, injections are effective quickly. Therefore, a single group of isovalerylspiramycin was developed. The preparation of the fraction has a very far-reaching significance

Method used

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  • Levorotary isovaleryl spiramycin II as well as preparation, preparation method and application thereof
  • Levorotary isovaleryl spiramycin II as well as preparation, preparation method and application thereof
  • Levorotary isovaleryl spiramycin II as well as preparation, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

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

[0085] (1) Biological fermentation: the helicinase-producing bacteria clone strain WSJ-195 containing 4″-isovaleryltransferase gene was added to soybean meal containing 2%, glucose 1%, starch 3%, CaCO 3 On a slant medium of 0.5%, 0.4% NaCl, and 2% agar, culture for 8-15 days at pH 6.5-7.5, temperature 28-38°C, and inoculate it with 1.5% soybean meal powder, 3.0% starch, NaCl 0.4%, CaCO 3 0.5%, fish peptone 0.3% and KH 2 PO 4 0.05% seed culture medium, cultured at pH 6.5~7.5, 25~30℃ for 40~80 hours, inoculated with 0.1~20% inoculum containing 0.5% glucose, 6.0% starch, 0.5% yeast powder, Fish meal 2.0%, NH 4 NO 3 0.6%, NaCl 1.0%, CaCO 3 0.5%, KH 2 PO 4 0.05%, MgSO 4 Fermentation medium containing 0.1%, 0.5% soybean oil and 0.02% defoamer is cultured for 72-120 hours at pH 6.5-7.5 and 26-30°C to obtain fermentation broth;

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

Embodiment 2

[0098] Example 2: Separation and preparation of L-isovalerylspiramycin II

[0099] (1) Biological fermentation: the helicinase-producing bacteria clone strain WSJ-195 containing 4″-isovaleryltransferase gene was used to contain soybean meal 2%, glucose 1%, starch 3%, CaCO3 0.5%, NaCl On the slant medium of 0.4% and 2% agar, cultured for 12 days at pH 7.2 and temperature 32°C, inoculated into soybean meal containing 1.5% starch, 3.0% starch, 0.4% NaCl, and CaCO 3 0.5%, fish peptone 0.3% and KH 2 PO 4 A 0.05% seed culture medium was cultured at pH 7.2 and 27°C for 70 hours, and 12% inoculum was seeded with 0.5% glucose, 6.0% starch, 0.5% yeast powder, fish meal 2.0%, NH4NO3 0.6%, Fermentation medium containing NaCl 1.0%, CaCO3 0.5%, KH2PO4 0.05%, MgSO4 0.1%, soybean oil 0.5% and defoamer 0.02%, cultured for 100 hours under the conditions of pH 6.0~9.0 and 26℃ to obtain fermentation broth ; Fermentation is carried out under the condition of pH 6.0~8.0, the fermentation time is 110h...

Embodiment 3

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

[0112] (1) Cultivation and fermentation: the spiramycin-producing bacteria clone strain WSJ-195 containing the 4″-isovaleryltransferase gene is cultivated on a slant medium, and then inoculated into a seed medium. After cultivation, the It is inoculated into the fermentation medium, and the fermentation process is controlled by glucose and citric acid. The fermentation is carried out under the condition of pH 6.0-7.5. The fermentation time is 115h, and the pH curve with time shows three consecutive stages. One stage satisfies the equation y 1 =0.0682x 1 +6.0, where 01 2 = -0.0294x 2 +8.147, where 223 =0.0078x 3 +6.06, where 563 Figure 4 , Obtain the fermentation broth.

[0113] (2) Extraction of biological fermentation broth: the fermentation broth obtained in step (1) is treated with aluminum sulfate to obtain the filtrate, adjusted to pH 8.6, and extracted with butyl acetate, and the butyl acetate extrac...

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Abstract

The invention relates to a levorotary sovaleryl spiramycin II, and also relates to a preparation, a preparation method and an application thereof. The preparation is composed of the levorotary sovaleryl spiramycin II and a pharmaceutically acceptable carrier and / or auxiliary material, and the purity of the levorotary sovaleryl spiramycin II is greater than 90wt%, preferably 95wt%, and further preferably 98wt%. The levorotary sovaleryl spiramycin II has good antibacterial activity; the preparation comprises a water injection, a powder injection, and a freeze-dried powder injection; the preparation provided by the invention fills up the blank of an isovaleryl spiramycin II individual component preparation in the markets at present, thereby providing a rapid-acting way for treating anti-infection diseases; and the isovaleryl spiramycin II individual component preparation provided by the invention has the advantages that the production process is stable, the quality standard is easy to control, and the preparation is suitable for large-scale industrial production.

Description

Technical field [0001] The present invention relates to a new antibiotic of macrolide genetic engineering, especially L-isovalerylspiramycin II, its medicinal preparation, preparation method and application in anti-infective medicine. Background technique [0002] Macrolide antibiotics occupies an important clinical position, because they have good activity against gram-positive bacteria and mycoplasma, and also have an effect on some gram-negative bacteria, and have an effect on some increasingly popular Toxoplasma and Legionella Other pathogens that are difficult to control have good antibacterial activity and tissue permeability, fast oral absorption, few adverse reactions, basically no effect on liver and kidney function, and potential immunomodulatory effects. They were considered to be treating adult respiratory tract infections in the 1990s It will compete with β-lactam drugs. [0003] Chirality is the basic attribute of three-dimensional objects and one of the essential at...

Claims

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Application Information

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