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Glycopeptide antibiotic teicoplanin Extraction Separation Purification process

Classification:
Separation and purification process development
Author:
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Release time:
2019/08/21 17:17
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[Abstract]:
Teicoplanin, also known as Teicomycin A2, is a new glycopeptide antibiotic discovered by Parenti et al. in 1978, produced by Actinoplanes teichomyceticus. It is another important antibiotic for the clinical treatment of multi-drug resistant bacterial infections after vancomycin.

Teicoplanin, also known as Teicomycin A2, is a new glycopeptide antibiotic discovered by Parenti et al. in 1978, produced by Actinoplanes teichomyceticus. It is another important antibiotic for the clinical treatment of multi-drug resistant bacterial infections after vancomycin. Teicoplanin has a molecular weight of about 1900 and is mainly composed of 5 compounds with very similar chemical structures (TA2-1, TA2-2, TA2-3, TA2-4, TA2-5). Teicoplanin crude and refined products also contain another active component TA3-1, which is the deacylated glucosamine product of TA-2. In addition, there are two more lipophilic analogs RS-1 and RS-2 in crude and refined teicoplanin, and two less lipophilic analogs RS-3 and RS-4.

Teicoplanin is named after T-A2, and its molecular structure is similar to vancomycin. It can be seen from the structure of T-A2 that it contains one dichlorotriphenyl ether structural unit, three sugar groups, and multiple amino acids. It has a carboxyl group and an amino group in its structure, which is an amphoteric compound with an isoelectric point of 5.1. According to the structure comparison, the main difference between Teicoplanin and other glycopeptide antibiotics is that it has both D-mannose and D-glucosamine. Teicoplanin is an amphoteric compound and contains multiple hydroxyl groups in its structure, so it is easily soluble in water. In addition, it is easily soluble in dimethylformamide, dimethyl sulfoxide, propylene glycol, soluble in organic solvents such as methanol, ethanol, and insoluble in inorganic acids and non-polar solvents. Because the four phenolic units in the T-A2 structure are easily oxidized, the three sugar groups are easy to form onium salts and degrade under acidic conditions, and T-A2 is easy to isomerize under alkaline conditions. Compared with antibiotics, the large-scale extraction process of T-A2 in industry is more complicated. In order to further simplify the process, reduce costs, and improve product quality, Bona Biological has conducted in-depth research on the purification process of teicoplanin, and developed a new separation and purification layer for the molecular structure of teicoplanin and the structural differences of related substances. Analysis of media and separation and purification process. The yield of separation and purification is greatly improved, more than 40%, the cost is greatly reduced, and the product quality reaches European standards. The process is as follows:

Fermentation broth dilution and alkali adjustment ceramic membrane filtration, adjustment of the filtrate PH to 8.0 HZ816 resin adsorption analysis collection analysis solution concentration, activated carbon decolorization, titanium rod filtration, evaporation to remove the solvent, nanofiltration concentration SKP-10-8300 resin column chromatography to collect the required components To meet the quality standards, SKP-10-8300 resin column removal, acetone crystallization three-in-one dry powder granulation.