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

Preparation method of high-purity high-stability rocuronium bromide

A high-stability, high-purity technology, applied in the field of medicinal chemistry, can solve the problems of long operation time, difficult operation, and inability to completely remove 3-bromopropene, and achieve high stability and reduce the generation of impurity C.

Active Publication Date: 2013-12-11
SHANDONG XINHUA PHARMA CO LTD
View PDF4 Cites 14 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method is not only difficult to operate, but also takes a long time to operate. Rocuronium bromide is in the aqueous solution for a long time without any defense measures, and a large part of the ester group at the 17th position is hydrolyzed.
In addition, this method cannot completely remove 3-bromopropene, and the residual amount of 3-bromopropene is still higher than 100ppm

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 high-stability rocuronium bromide
  • Preparation method of high-purity high-stability rocuronium bromide
  • Preparation method of high-purity high-stability rocuronium bromide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Preparation of crude rocuronium bromide: with reference to Patent US2006 / 0058275 Example 3, the raw material (2β, 3α, 5α, 16β, 17β)-2-(4-morpholino)-16-(1-pyrrolyl)-androgen Add ster-3,17-diol-17-acetate (30g) and 3-bromopropene (78ml) into 120ml of acetonitrile, stir and react at room temperature for 3 hours, after the reaction, slowly add the reaction solution to 720ml Then, filter the precipitated rocuronium bromide and dry it under vacuum at 60°C overnight. After testing, the impurity A content in the crude rocuronium bromide was 0.08%, the impurity C was not detected, the total impurity was 0.35%, the moisture was 3.25%, the acetonitrile residue was 1700ppm, the ether residue was 6600ppm, and the 3-bromopropene residue was 473ppm.

[0036] Step 1: Dissolve 10.0 g of the obtained crude product in 80 ml of dichloromethane, add 8.0 g of alumina, stir vigorously for 2 hours, first filter it with filter paper, then filter it with an organic filter membrane, add the obta...

Embodiment 2

[0043] The rocuronium bromide crude product that makes in embodiment 1 is used for embodiment 2.

[0044] Step 1: Dissolve 10.0 g of the obtained crude product in 80 ml of dichloromethane, add 10.0 g of alumina, stir vigorously for 4 hours, then filter once with filter paper, and then filter again with organic filter membrane, add the obtained filtrate dropwise to 500 ml and stir vigorously In ether, filter under nitrogen protection;

[0045] Step 2: Add 100ml of deionized water to a 500ml single-mouth bottle, carefully add 10% dilute acetic acid to adjust the pH of the solution to 3.8, then add the obtained filter cake to the above solution, shake to dissolve, pour it into a petri dish, and put the petri dish Put it into a freeze-drying box and cool it down to below -45°C within 2 hours to make it freeze quickly. Vacuumize to make the atmospheric pressure in the box reach 2.66pa within 30 minutes. Insulated and vacuum-dried for 48 hours until the moisture content was ≤1.0%,...

Embodiment 3

[0051] The rocuronium bromide crude product that makes in embodiment 1 is used for embodiment 2.

[0052] Step 1: Dissolve 10.0 g of the obtained crude product in 80 ml of dichloromethane, add 18.0 g of alumina, stir vigorously for 4 hours, then filter once with filter paper, then filter again with organic filter membrane, add the obtained filtrate dropwise to 500 ml and stir vigorously In ether, filter under nitrogen protection;

[0053] Step 2: Add 100ml of deionized water to a 500ml single-mouth bottle, carefully add 10% dilute acetic acid to adjust the pH of the solution to 3.8, then add the obtained filter cake to the above solution, shake to dissolve, pour it into a petri dish, and put the petri dish Put it into a freeze-drying box and cool it down to below -45°C within 2 hours to make it freeze quickly. Vacuumize to make the atmospheric pressure in the box reach 6.20pa within 30 minutes. Insulated and vacuum-dried for 48 hours until the moisture content was ≤1.0%, 8.3...

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 belongs to the technical field of medical chemistries, and particularly discloses a preparation method of high-purity high-stability rocuronium bromide. The preparation method comprises the following steps: performing pretreatment on a rocuronium bromide crude product by adopting aluminium oxide for removing most 3-bromopropylene, filtering, dropwise adding an obtained filtrate into diethyl ether stirred violently, wherein during adding process, a great amount of white solid separates out, dissolving the obtained white solids into a dilute acetic acid solution, rapidly freezing the solution into ice, and freeze drying, thus forming the rocuronium bromide. The preparation method provided by the invention has the advantages that the problems that a residual solvent in the prior art exceeds standard, the 3-bromopropylene is hard to remove, and the impurity content is high are successfully solved, and the obtained rocuronium bromide has the high purity and good stability.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a preparation method of high-purity and high-stability rocuronium bromide. Background technique [0002] Rocuronium Bromide (Chinese name: Rocuronium bromide), chemical name 1-[(2β,3α,5α,16β,17β)-17-(acetyloxy)-3-hydroxy-2-(4-morpholinyl) Androstan-16-yl]-1-(2-propenyl)pyrrolidine bromide is a steroidal non-depolarizing muscle relaxant developed by Organon in the Netherlands. It was first listed in the United States in 1994. In the United States, Canada and most European countries, it ranks first in the number of muscle relaxants. This product is a promising muscle relaxant, which is highly valued by the pharmaceutical industry at home and abroad. [0003] The structural formula is as follows: [0004] [0005] Rocuronium bromide is a quaternary ammonium salt, which is very easy to absorb water, and the molecular structure of rocuronium bromide inclu...

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
IPC IPC(8): C07J43/00
Inventor 宋广慧商艳梅郑忠辉郭照奎张滨于小萍
Owner SHANDONG XINHUA PHARMA CO LTD
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