Erythromycin thiocyanate fermentation broth membrane-process impurity-removing purification process

Abstract

The invention discloses an erythromycin thiocyanate fermentation broth membrane-process impurity-removing purification process. The erythromycin thiocyanate fermentation broth membrane-process impurity-removing purification process includes the steps that S1, an erythromycin thiocyanate fermentation broth is subjected to plate frame filter, and then the filtrate is fed into an intermediate tank A; S2, then a feed pump is adopted to deliver the filtrate to a ceramic membrane separation device for concentration, water-added dialysis is performed in batches till the titer U of the concentrated solution is smaller than 400 after the filtrate is concentrated to reach 40%-60%; S3, the concentrated solution is subjected to post-processing, the dialysate treated by the ceramic membrane separation device is fed into an intermediate tank B and then is fed into a spiral-wound ultra-filtration membrane separation device to remove protein and parts of pigments; S4, then the dialysate is fed into an intermediate tank C and is concentrated by using a nanofiltration membrane, the dialysate is discharged or is repeatedly utilized, and finally the concentrated solution is subjected to a subsequent process to obtain a product. The erythromycin thiocyanate fermentation broth membrane-process impurity-removing purification process reduces the unit consumption of an organic solvent by 70% while improving the quality of the concentrated solution, remarkably reduces the production cost and improves the product quality.

Description

technical field [0001] The invention relates to the technical field of medical application, in particular to a process for impurity removal and purification of colomycin fermentation liquid membrane method. Background technique [0002] Introduction of Gaolimycin: Gaolimycin is a derivative of erythromycin base, and erythromycin thiocyanate is an antibiotic specially for livestock. The product name is Galliaycia, chemical name: Erythromycinthiocyanate (Erythromycinthiocyanate), molecular formula: C37H67NO13·HSCN, molecular weight: 793.0 [0003] The current impurity-removing extraction (purification) process of cololimycin fermentation broth mainly adopts acid-base solvent method and thin film concentration method. The existing problems and shortcomings of the impurity removal and purification process of cololimycin fermentation broth are as follows: [0004] 1. Coloxycycline is insoluble in water but soluble in organic solvents. The solvent extraction process of colomycin ...

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Problems solved by technology

[0004] 1. Coloxycycline is insoluble in water but soluble in organic solvents. The solvent extraction process of colomycin (erythromycin thiocyanate) requires the use of solvents such as zinc sulfate, butyl acetate, and lactate and centrifugation Machine equipment, using this extraction process has the following problems and disadvantages: completely using organic solvents to extract colomycin will definitely produce a large amount of solvent residue, which will affect the purity and yield level of the final product, the unit potency is lower than 15000, impurities The level is higher than 5%; emulsification will occur when ethyl ester is extracted, and a clarified concentrated solution can be obtained after flocculation and precipitation, which not only increases production costs, but also reduces product quality and yield; The solvent extraction process needs to be heated, which not only increases the production cost, but also causes thermal damage to colomycin, which affects product quality, and the product potency is lower than 15000γ / mL; the use of concentration equipment such as centrifuges increases production costs

[0005] 2. The existing problems and shortcomings of the film concentration method are: the macromolecular impurities (proteins, sugars, etc.) contained in the feed liquid after film concentration and the eluate treated with macroporous resin cannot be removed, and the color is turbid , still need to purify the acid-base solvent in the post-stage process; the regeneration of macroporous resin requires the use of acid-base solvent, which will cause emulsification during the extraction process; the resin regeneration cycle is long, requiring multiple sets of equipment to be switched and used, which occupies a large area; the film concentration process The consumption of water, electricity and gas is relatively large, and the production and operation costs are relatively high

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