Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method of high-purity cyclosporin A derivative

A technology for cyclosporin and derivatives, which is applied in the preparation of pharmaceutical raw materials, separation and purification of cyclosporin A derivatives, and achieves the effects of high sample yield, improved filtration speed, and controllable quality

Active Publication Date: 2013-05-01
NCPC NEW DRUG RES & DEV
View PDF6 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This patent only involves fermentation culture to improve the biotransformation rate of cyclosporine A, and does not involve the separation and purification process of cyclosporin A derivatives

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of high-purity cyclosporin A derivative
  • Preparation method of high-purity cyclosporin A derivative
  • Preparation method of high-purity cyclosporin A derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Take 10L of cyclosporine A derivative fermentation liquid, and the fermentation unit is 422 μg / mL. Add 200g of perlite to the fermentation broth, stir for 50 minutes, and then filter the plate and frame. The filtrate passes through the macroporous resin SD-2 column at a flow rate of 1-2BV / h for decolorization, and the decolorization solution is introduced into the macroporous resin D312 at a flow rate of 1BV / h. The column is subjected to adsorption and enrichment. After adsorption, use 40% ethanol / water solution and 95% ethanol / water solution for discontinuous gradient desorption. The desorption flow rate is controlled at 0.5BV / h. When HPLC detects that cyclosporine A derivatives flow out, start to collect and desorb After the desorption is completed, the desorption liquid is vacuum concentrated to a concentration of cyclosporine A derivatives of 100g / L-120g / L, slowly cooled to -5-0°C, crystallized for 12 hours, filtered, washed, and dried to obtain a coarse powder (see...

Embodiment 2

[0039] Take 100 L of cyclosporin A derivative fermentation liquid, and the fermentation unit is 457 μg / mL. Add 3Kg of diatomaceous earth to the fermentation broth, stir for 90 minutes, and filter the plate frame. The filtrate passes through the macroporous resin LX-700 column at a flow rate of 1.5BV / h for decolorization, and the decolorization solution is introduced into the macroporous resin at a flow rate of 1.5BV / h. HZ816 column is used for adsorption and enrichment. After adsorption, use 40% ethanol / water solution and 95% ethanol / water solution for discontinuous gradient desorption. The desorption flow rate is controlled at 0.5BV / h. When HPLC detects that cyclosporin A derivatives flow out, they start to collect Desorption liquid, after the desorption is completed, vacuum concentrate the desorption liquid to the concentration of cyclosporin A derivatives 110g / L-120g / L, slowly cool down to -5-0°C, crystallize for 12 hours, suction filter, wash and dry to obtain crude Powder...

Embodiment 3

[0041] Take 1000L of cyclosporin A derivative fermentation liquid, and the fermentation unit is 428 μg / mL. Add 40Kg of perlite to the fermentation broth, stir for 90 minutes, and then filter the plate and frame. The filtrate passes through the macroporous resin SD-2 column at a flow rate of 1.5BV / h for decolorization, and the decolorization solution is introduced into the macroporous resin HZ816 at a flow rate of 1.5BV / h. The column is subjected to adsorption and enrichment. After adsorption, use 40% ethanol / water solution and 95% ethanol / water solution for discontinuous gradient desorption. The desorption flow rate is controlled at 0.5BV / h-1BV / h. HPLC detects that cyclosporin A derivatives flow out After the desorption is completed, the desorption liquid is concentrated in vacuum to the concentration of cyclosporin A derivatives of 110g / L-120g / L, slowly cooled to -5-0°C, crystallized for 12 hours, suction filtered, washed and dried , to obtain 638.1 g of coarse powder. Add 7...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a method for preparing a cyclosporin A derivative by using a fermentation culture product of filamentous fungi tolypocladium inflatum. According to the method, a filter aid is adopted; with steps such as leaching, discoloring, adsorption, crystallization, and the like, a cyclosporin A derivative crude extract is obtained; and the crude extract is subjected to chromatographic separation by using polymer microspheres, such that the high-purity cyclosporin A derivative product is obtained. The method provided by the invention has the advantages that: cyclosporin A derivative is extracted and separated by using macroporous resin; the process is simple and feasible, and is suitable for industrialized productions; the polymer microspheres are used in chromatographic separation of the product for a first time, and high-purity cyclosporin A derivative product can be prepared.

Description

technical field [0001] The invention belongs to the technical field of industrial microorganisms, and relates to a preparation method of pharmaceutical raw materials, in particular to a preparation method of separating and purifying cyclosporin A derivatives from fermentation cultures. Background technique [0002] Cyclosporine A (Cyclosporine A, CsA) is a cyclic peptide composed of 11 amino acids isolated from the culture fluid of filamentous fungi (Tolypocladium inflatum). Since CsA was used clinically as an immunosuppressant in the 1980s, it has played an important role in the treatment of organ transplantation, laying the foundation and promoting the development of organ transplantation. At present, more than 200,000 patients in the world have used cyclosporin A as an anti-rejection drug during organ transplantation (edited by Chen Daijie. Microbial Pharmacology [M]. Shanghai: East China University of Science and Technology Press, 1999, 140) . In addition, cyclosporin ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/64C07K1/16C07K1/14
Inventor 张雪霞董爱华任风芝李晓露李宁陈书红成晓迅林毅王海燕李丽红张金娟林旸张丽张艳立高月麒张艳哲蒋沁段宝玲
Owner NCPC NEW DRUG RES & DEV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com