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Process for preparing high-purity rocuronium

A high-purity technology for rocuronium bromide, which is applied in the production of steroids, bulk chemicals, and muscular system diseases, can solve the problems of increasing the complexity and cost of the production process of rocuronium bromide, and achieve high purity and easy operation. simple effect

Active Publication Date: 2012-11-14
刘志亭
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] According to the anti-solvent selected in the prior art scheme, after the anti-solvent treatment, the residual solvent in the rocuronium bromide product needs to be processed through lyophilization and spray drying to meet the GMP principle requirement (below 0.5%), which will greatly increase The complexity and cost of the production process of rocuronium bromide

Method used

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  • Process for preparing high-purity rocuronium

Examples

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Embodiment 1

[0024] The preparation of embodiment 1 high-purity rocuronium bromide:

[0025] Add 18 g of 2β-(4-morpholinyl)-16β-(1-pyrrolidinyl)-5α-androst-3α-ol and 17β-acetate into a single-port reaction flask, add the carapace that is crushed to 80-150 mesh Element 2g, anhydrous magnesium sulfate 1g, dichloromethane 180ml and 3-bromopropene 12ml, stirred at room temperature for 8 hours, carried out with thin layer chromatography (TLC) and HPLC (by the condition that EP6.0 detects rocuronium bromide related impurity) ) to monitor the reaction process, and when the ratio of the peak area of ​​the raw material in the HPLC chromatogram is less than 1%, stop the reaction, filter the reaction mixture, and reclaim dichloromethane to obtain an oil. Dissolve the oily matter with 30 ml of dichloromethane, add the resulting solution to 400 ml of ethyl acetate with constant stirring, and stir for 10 minutes. Filter out the solids and put in CO 2 In a supercritical extraction kettle, the temperatu...

Embodiment 2

[0027] The preparation of embodiment 2 high-purity rocuronium bromide:

[0028] Add 18 g of 2β-(4-morpholinyl)-16β-(1-pyrrolidinyl)-5α-androst-3α-ol and 17β-acetate into a single-port reaction flask, add the carapace that is crushed to 80-150 mesh Element 2g, anhydrous magnesium sulfate 1g, dichloromethane 180ml and 3-bromopropene 12ml, stirred at room temperature for 11 hours, carried out with thin-layer chromatography (TLC) and HPLC (by EP6.0 detecting the condition of rocuronium bromide related impurity) ) to monitor the reaction process, when the ratio of the peak area of ​​the raw material in the HPLC chromatogram is less than 0.5%, the reaction is stopped, the reaction mixture is filtered, and the resulting filtrate is directly dropped into CO 2 In the supercritical extraction kettle, the temperature in the kettle is adjusted to 25°C, carbon dioxide is introduced into the kettle, and the pressure adjustment force is 12MP. 12MP, then adjust the temperature to 30°C, and r...

Embodiment 3

[0030] The preparation of embodiment 3 high-purity rocuronium bromide:

[0031] Add 18 g of 2β-(4-morpholinyl)-16β-(1-pyrrolidinyl)-5α-androst-3α-ol and 17β-acetate into a single-port reaction flask, add the carapace that is crushed to 80-150 mesh Element 2g, dichloromethane 180ml and 3-bromopropene 12ml, room temperature, stir 16 hours under nitrogen protection, monitor the reaction progress with thin-layer chromatography (TLC), after the raw material is substantially consumed, the reaction mixture is filtered, then reclaims two Chloromethane was obtained as an oil. Dissolve the oil with a small amount of 30ml of acetonitrile, and add the resulting solution into 400ml of ethyl acetate under constant stirring, and stir for 10 minutes. Filter out the solids and put in CO 2 In a supercritical extraction kettle, the temperature in the kettle is adjusted to 25°C, carbon dioxide is introduced into the kettle, and the pressure is adjusted to 9MP; g

[0032] Detect according to t...

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Abstract

The invention discloses a process for preparing high-purity rocuronium, comprising the following steps of: mixing a low-boiling anti-solvent with the rocuronium containing organic solvents or / and impurities; and removing the organic solvents or / and the impurities which are contained in the rocuronium by utilizing a principle that the organic solvents or / and the impurities are soluble in the low-boiling anti-solvent and the rocuronium is not or hardly soluble in the low-boiling anti-solvent so that the rocuronium is precipitated or crystallized so as to obtain the high-purity rocuronium without containing the organic solvents or / and the impurities, wherein the low-boiling anti-solvent is a mixture of any one or a few of ethane, propane, butane, ethylene, propylene, trifluoromethane, trifluorochloromethane, carbon dioxide, sulfur dioxide and nitrogen in any proportion. Compared with the traditional extraction method, the process can be used for extracting and separating under the condition of adjacent normal temperature and almost retains all effective components of a product; the quantity of organic solvent residuals can be low not to be detected, and the obtained product has high purity; and in addition, the process is easy to operate and green and saves the energy.

Description

technical field [0001] The invention relates to a process for preparing high-purity rocuronium bromide, in particular to a process for preparing high-purity rocuronium bromide by using a low boiling point anti-solvent. Background technique [0002] Muscle relaxants are necessary adjuvant drugs for anesthesia in surgical operations, and are used in large amounts. At present, the common ones are rocuronium bromide, vecuronium bromide, succinylcholine, and atracurium bromide. Rocuronium has the fastest onset of action and no side effects such as release of histamine, making it the most promising drug of its kind. Since the development of Organon in the Netherlands, it has been marketed in more than 40 countries and regions including the Netherlands, Belgium, Germany, the United States, the United Kingdom, Japan, and Hong Kong, and has been widely recognized and praised. In 1998, it was sold in 500 prescription drugs in the world The amount is in the leading position. [0003]...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J43/00A61P21/02
CPCY02P20/54
Inventor 王加旺
Owner 刘志亭
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