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Method for producing prednisolone acetate

A technology of prednisolone acetate and a production method is applied in the fields of microbial pharmacy and medical engineering, and can solve the problems such as complicated steps and complicated production process, and achieve the effects of simple process, single product, and overcoming the complicated steps.

Inactive Publication Date: 2008-07-02
TIANJIN UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This kind of production process is complex, the steps are cumbersome, and some toxic reagents need to be used in the production process

Method used

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  • Method for producing prednisolone acetate
  • Method for producing prednisolone acetate
  • Method for producing prednisolone acetate

Examples

Experimental program
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Effect test

Embodiment 1

[0029] A kind of production method of prednisolone acetate, the step of its production method is:

[0030] (1). Arthrobacter simplex is used as the production strain to connect a full ring from the slope to 30ml seed medium, and cultivate it on a rotary shaker at 160r / min at a speed of 160r / min and at a temperature of 30°C for 22 hours to obtain seeds suitable for inoculation culture medium;

[0031] (2). Insert the seed culture solution into the fermentation medium with an inoculation amount of 5% volume ratio, control the shaker rotation speed 200r / min during the fermentation process, keep the pH value at 6.7, and cultivate it under the temperature condition of 32°C for 24 hour, obtain the bacterial cell fermentation liquid;

[0032] (3). Grind hydrocortisone acetate finely, with a particle size of 14μ, and put it into the bacterial fermentation broth under aseptic conditions, and the feeding amount is 5g / L; then add a hydrophilic organic solvent to the bacterial fermentati...

Embodiment 2

[0035] (1). Connect a full ring of Arthrobacter simplex from the slant to 30ml of seed culture medium, and cultivate it at 32°C for 18 hours on a rotary shaker at 180r / min to obtain a seed culture solution suitable for inoculation;

[0036] (2). Insert the well-grown seed culture solution into the 30ml fermentation medium at an inoculum size of 3% (v / v); control the shaking table speed 190r / min during the fermentation process, and keep the pH value at 7.0, 30 Cultivate for 22 hours at ℃ to obtain the cell fermentation broth;

[0037] (3). Grind hydrocortisone acetate finely, with a particle size of 15μ, and put it into the bacterial fermentation broth under aseptic conditions, and the feeding amount is 6g / L; then add a hydrophilic organic solvent to the bacterial fermentation broth 3% ethanol to help dissolve;

[0038] (4). During the conversion process, the shaker speed was controlled at 190r / min, and the pH was maintained at 6.7. The conversion was carried out at a temperat...

Embodiment 3

[0040] (1). Connect a full ring of Arthrobacter simplex from the slant to 30ml of seed culture medium, and cultivate it at 31°C for 20 hours on a rotary shaker at 170r / min to obtain a seed culture solution suitable for inoculation;

[0041] (2). Insert the well-grown seed culture solution into 30ml fermentation medium at an inoculum size of 4% (v / v); control the shaking table speed 180r / min during the fermentation process, and keep the pH value at 7.2, 33 Cultivate for 18 hours at ℃ to obtain the cell fermentation liquid;

[0042] (3). Grind hydrocortisone acetate finely, with a particle size of 16μ, and put it into the bacterial fermentation broth under aseptic conditions, and the feeding amount is 8g / L; then add a hydrophilic organic solvent to the bacterial fermentation broth 5% dimethyl sulfoxide to aid in dissolution;

[0043] (4). During the conversion process, the shaker speed was controlled to 200r / min, and the pH was maintained at 6.8. The conversion was carried out ...

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Abstract

The invention belongs to the field of microbial pharmaceutics and pharmaceutical engineering, specifically relates to a production method of prednisone acetate by microbial transformation with Arthrobacter simplex as bacteria strain and hydrocortisone acetate as substrate. The method uses Arthrobacter simplex as bacteria strain and comprises the following steps of: performing primary seed culture, performing second fermentation culture, adding hydrocortisone acetate into the fermentation liquid of Arthrobacter simplex to transform hydrocortisone acetate into prednisone acetate, filtering, and collecting cake to obtain prednisone acetate. The bacteria can be prepared into double liquid phase, broken cells or protoplast, each of which has high transformation ratio. The inventive production method replaces cortisone acetate with hydrocortisone acetate as raw material, and has the advantages of high yield, simple process, good economical and practical performance, and less use of harmful reagents; and is important for steroids production with biotransformation method.

Description

technical field [0001] The invention belongs to the field of microbial pharmacy and medical engineering, and in particular relates to a method for producing prednisolone acetate by using Arthrobacter simplex as strain, hydrocortisone acetate as substrate and adopting a microbial conversion method. Background technique [0002] The structural formula of prednisolone acetate is shown in the figure below, and its chemical name is: 11β, 17α, 21-trihydroxypregna-1,4-diene-3,20-dione-21-acetate. Prednisolone acetate is an adrenal cortex hormone that can resist the stimulation of bacterial endotoxins on the body to reduce cell damage and fully protect the body. It is suitable for rheumatoid arthritis, rheumatic fever, lupus erythematosus, scleroderma, skin Myositis, acute lymphoblastic leukemia, etc., and it is easily absorbed from the digestive tract. It exists in an active form and exerts its biological effects without being transformed by the liver. [0003] [0004] At pres...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P7/62C12R1/06
Inventor 路福平别松涛杜连祥毛淑红张艺王春霞王建玲
Owner TIANJIN UNIV OF SCI & TECH
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