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

Preparation method of high purity ramoplanin single components

A single-component, filter aid technology, applied in the direction of peptides, etc., can solve the problems of large-scale damage to the downstream purification medium, the inability to realize large-scale production, and the decline of silica gel chromatography, so as to shorten the process cycle, ensure safety technology, and solve the problems of solvent The effect of less consumption

Active Publication Date: 2014-05-14
NCPC NEW DRUG RES & DEV
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method has the following disadvantages: (1) the filtrate is directly obtained without decolorization and impurity removal, and the crude extract contains more impurities, which causes great damage to the downstream purification medium; (2) silica gel column chromatography uses different concentrations of acid water and Acetonitrile gradient elution, water will cause the decline of silica gel chromatography, and it can be reused after regeneration, which cannot realize large-scale production
The medium is expensive, with a price of more than 10,000 yuan per liter, and the preparation cost is very high

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 ramoplanin single components
  • Preparation method of high purity ramoplanin single components
  • Preparation method of high purity ramoplanin single components

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Take 10L of remoplanin fermentation broth, the fermentation unit is 1036μg / mL (calculated as A1+A2+A3), containing 1.55g of A1, 8.08g of A2, and 0.73g of A3. Add 100g of perlite to the fermentation broth at room temperature, stir for 50 minutes, and then filter the plate and frame. The filtrate passes through the macroporous resin D290 column at a flow rate of 1-2BV / h for decolorization, and the decolorization solution is introduced into the macroporous resin D312 column at a flow rate of 1BV / h Carry out adsorption enrichment, after adsorption, use 30% ethanol / water solution and 60% ethanol / water solution for discontinuous gradient desorption, the desorption flow rate is controlled at 0.5BV / h, when HPLC detects that remoplanin flows out, start to collect the desorption liquid, desorption is complete Finally, the stripping solution was concentrated in vacuum at 30°C to a remoplanin concentration of 100g / L-120g / L to obtain a crude extract (see figure 1) 19.2g (51.6% cont...

Embodiment 2

[0039] Take 100L of remoplanin fermentation broth, the fermentation unit is 1137μg / mL (calculated as A1+A2+A3), containing 15.92g of A1, 89.82g of A2, and 7.96g of A3. Add 3Kg of diatomaceous earth to the fermentation broth at room temperature, stir for 90 minutes, and then filter the plate and 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 at a flow rate of 1.5BV / h The macroporous resin HZ816 column is used for adsorption and enrichment. After adsorption, it is desorbed with a discontinuous gradient of 40% methanol / water solution and 60% methanol / water solution. The desorption flow rate is controlled at 0.5BV / h. When HPLC detects that remoplanin flows out, it starts to collect The desorption solution, after the desorption is completed, was concentrated in vacuum at 40°C to a remoplanin concentration of 110g / L-120g / L in the desorption solution to obtain 210.8g of ...

Embodiment 3

[0041] Take 1000L of remoplanin fermentation broth, the fermentation unit is 1058μg / mL (calculated as A1+A2+A3), containing 148.12 grams of A1, 825.24 grams of A2, and 84.64 grams of A3. Add 100Kg of perlite to the fermentation broth at room temperature, stir for 90 minutes, and then filter the plate and 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 macropore at a flow rate of 1.5BV / h Resin D312 column for adsorption and enrichment, after adsorption, use 30% ethanol / water solution and 60% ethanol / water solution for discontinuous gradient desorption, the desorption flow rate is controlled at 0.5BV / h-1BV / h, and when remoplanin flows out as detected by HPLC Start to collect the desorption liquid. After the desorption is completed, the desorption liquid is vacuum concentrated at 50°C to a remoplanin concentration of 110g / L-120g / L to obtain 1978.5g of crude e...

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 of utilizing an Actinoplanes sp. fermentation culture material to prepare three ramoplanin single components. The method includes: conducting decoloration on a ramoplanin fermentation solution through macroporous decolorization resin, then carrying out macroporous resin adsorption, desorption as well as concentration so as to obtain a ramoplanin crude extract containing the three single components: A1, A2, and A3; and dissolving the crude extract with a solvent, then performing chromatographic separation by means of a polymer microsphere, thus obtaining the products of three high purity ramoplanin single components A1, A2 and A3. The invention has the advantage that when using the polymer microsphere to perform chromatographic separation on the product, the sample treatment amount is large, and the obtained single components have high purity. As the price of a polymer microsphere medium is 30% of that of the reverse phase silica gel C18, and the separation effect is equivalent, the preparation cost is greatly reduced.

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 three single components of remoplanin from a fermentation culture. Background technique [0002] The causative organisms of many clinically serious infections are Gram-positive bacteria. Due to the extensive use of antibiotics, the problem of bacterial resistance has become increasingly prominent. Finding new glycopeptide antibiotics has gradually become an urgent need in the pharmaceutical industry. At present, several promising new antibiotics are under development, and remoplanin is one of them. [0003] The structural formulas of the single components A1, A2 and A3 of remoplanin are as follows: [0004] [0005] Component R molecular weight A1 -CO-CH=CH-CH=CH-CH 2 -CH 2 -CH 2 2540 A2 -CO-CH=CH-CH=CH-CH 2 -...

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 Patents(China)
IPC IPC(8): C07K9/00C07K1/16
Inventor 段宝玲张雪霞李宁李晓露任风芝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董爱华
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