Extraction method of tobramycin

A technology of tobramycin and extraction method, applied in the field of biomedicine, can solve the problems of long production cycle, difficult quality control of production process, complicated process, etc., to simplify production process, reduce environmental protection discharge and processing pressure, and shorten production effect of cycles

Active Publication Date: 2019-05-03
NEW FOUNDER HLDG DEV LLC +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These three types of substances are aminoglycoside antibiotics with very similar properties. The entire tobramycin purification process is complicated, the production cycle is long, and the quality control of the production process is difficult.

Method used

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  • Extraction method of tobramycin
  • Extraction method of tobramycin
  • Extraction method of tobramycin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] The extraction method of embodiment 1 tobramycin

[0028] 1. Adjust the fermentation filtrate (fermentation filtrate sample) of Streptomyces obscurus with ammonia water, control the pH=7.05, put the macroporous cationic resin HZ-3C into the filtrate for static adsorption, and add the resin according to 40,000 adsorption units. After the adsorption is finished, collect the resin and put it into a resin column, wash it with purified water for 8h, and then elute it with a concentration of 0.3mol / L ammonia water. During the elution process, use thin layer chromatography (TLC) to detect components. When 5 For 'carbamoyl tobramycin, replace 1.0 mol / L ammonia water for elution and collect 5' carbamoyl tobramycin (fermentation crude product 1 sample).

[0029] 2. Concentrate the collected liquid in step 1 with an ultra-nanofiltration system (first filter with an ultrafiltration membrane with a molecular weight cut-off of 5000Da, and then concentrate with a nanofiltration membra...

Embodiment 2

[0034] The extraction method of embodiment 2 tobramycin

[0035] 1. Use ammonia water to mediate the fermentation filtrate of Streptomyces obscurus, control the pH=7.20, put macroporous cationic resin HZ-3C into the filtrate for static adsorption, and calculate and add the resin according to 45,000 adsorption units. After the adsorption is completed, collect the resin and put it into the resin column, wash it with purified water for 8 hours, and then elute it with ammonia water at a concentration of 0.4mol / L. During the elution process, use TLC for component detection. When carbamoyl tobramycin appears , replace 1.5mol / L ammonia water to elute and collect carbamoyl tobramycin (fermentation crude product 2 samples).

[0036]2. Concentrate the collected liquid in step 1 with an ultra-nanofiltration system (first filter with an ultrafiltration membrane with a molecular weight cut-off of 5000Da, and then concentrate with a nanofiltration membrane with a molecular weight cut-off of...

Embodiment 3

[0041] The extraction method of embodiment 3 tobramycin

[0042] 1. Use ammonia water to mediate the fermentation filtrate of Streptomyces obscurus, control the pH=7.50, put macroporous cationic resin HZ-3C into the filtrate for static adsorption, and calculate and add the resin according to 50,000 adsorption units. After the adsorption is completed, collect the resin and put it into the resin column, wash it with purified water for 8 hours, and then elute it with ammonia water at a concentration of 0.5mol / L. During the elution process, use TLC for component detection. When carbamoyl tobramycin appears , replace 2.0mol / L ammonia water for elution and collect carbamoyl tobramycin (fermentation crude product 3 samples).

[0043] 2. Concentrate the collected liquid in step 1 with an ultra-nanofiltration system (first filter with an ultrafiltration membrane with a molecular weight cut-off of 5000Da, and then concentrate with a nanofiltration membrane with a molecular weight cut-of...

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Abstract

The present invention provides an extraction method of tobramycin. The extraction method comprises the following steps: (1) pH of a 5'carbamoyl tobramycin fermentation filtrate is adjusted to be 7.0-7.5, a cationic resin is added for absorption, water and ammonia water are used for rinsing, and an ammonia water eluent is collected; (2) the eluent is concentrated; (3) the obtained concentrate is hydrolyzed at an alkaline condition, pH of a hydrolyzate is adjusted to be 5.0-6.0, a cationic resin is used for decolorizing, a decoloring solution is connected, pH is adjusted to be 7.0-7.5, a medium-pressure chromatography self-prepared column equipped with a cationic resin is eluted with the water and ammonia water to collect an ammonia water eluent, then a strong alkaline anion resin is used for decoloring, and a decoloring solution is connected; and (4) the obtained decoloring solution is concentrated and then decolorized with activated carbon, and then spray-drying is conducted to obtaina finished product of the tobramycin. The method simplifies production processes, uses super nanofiltration, combines the medium-pressure chromatography self-prepared column technology, shortens production cycle, is free of solvent crystals and residual solvents, and reduces environmental discharge and treatment pressure.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a method for extracting tobramycin. Background technique [0002] Tobramycin (Tobramycin) is an aminoglycoside antibiotic, which is a product obtained by fermentation of Streptomyces darkerus. At present, the fermentation process of tobramycin mainly produces 3 products of 5' carbamoyl tobramycin, apramycin and carbamycin karamycin B (kb), each accounting for about 30%, and about 10% Left and right other impurity products are hydrolyzed to produce tobramycin and kanamycin B and other by-products. These three types of substances are aminoglycoside antibiotics with very similar properties. The entire tobramycin purification process is complicated, the production cycle is long, and the quality control of the production process is difficult. Therefore, the existing tobramycin extraction method needs to be improved. Contents of the invention [0003] The purpose of the pres...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H1/00C07H15/234
Inventor 蔡丽张葵
Owner NEW FOUNDER HLDG DEV LLC
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