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Preparation method for mivacurium chloride

A technology of mivacurium chloride and mivacurium chloride dihydrochloride, applied in the field of biomedicine, can solve problems such as small side effects, histamine release, and cardiovascular system damage, and achieve small changes in impurity content, low impurity content, The effect of high chiral purity

Inactive Publication Date: 2018-09-28
北京六盛合医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Clinical studies have shown that when the chiral carbon atom of mivacurium chloride is in the R configuration, the side effects are relatively small; while when the carbon atom is in the S configuration, it is very likely to cause damage to the cardiovascular system and cause adverse reactions such as the release of histamine

Method used

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  • Preparation method for mivacurium chloride
  • Preparation method for mivacurium chloride
  • Preparation method for mivacurium chloride

Examples

Experimental program
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Effect test

Embodiment 1

[0028] (1) Get 10g of ricecuronium chloride crude product and add in 500ml tetrahydrofuran, add dropwise hydrochloric acid solution (concentration is 36%) to solid dissolution under stirring, evaporate to dryness under reduced pressure, obtain ricecuronium chloride dihydrochloride crude product 9.79g;

[0029] (2) Add 9.79 g of the crude product of mivacuronium chloride dihydrochloride into 500 ml of ethyl acetate, stir at 30° C. for 2 hours, and filter with suction to obtain 9.12 g of mivacuronium chloride dihydrochloride;

[0030] (3) 9.12g of prepared ricecuronium chloride dihydrochloride is added in 100ml ethanol, and 30ml of propylene oxide is added, and the solid is precipitated under stirring, suction filtered, and dried to obtain 7.03g ricecuronium chloride; total yield 70.3 %.

Embodiment 2

[0032] (1) Get 10g of ricecuronium chloride crude product and add in 1000ml of n-hexanol, add dropwise hydrochloric acid solution (concentration is 36%) to solid dissolution under stirring, evaporate to dryness under reduced pressure, get ricecuronium chloride dihydrochloride crude product 9.71g;

[0033] (2) Add 9.71 g of the crude product of mivacuronium chloride dihydrochloride into 600 ml of ethyl acetate, stir at 30° C. for 2 hours, and filter with suction to obtain 9.01 g of mivacuronium chloride dihydrochloride;

[0034] (3) 9.01g of prepared ricecuronium chloride dihydrochloride is added in 100ml ethanol, and 30ml of propylene oxide is added, and the solid is precipitated under stirring, suction filtered, and dried to obtain 7.1g ricecuronium chloride; total yield 71.0 %.

Embodiment 3

[0036] (1) Get 10g of ricecuronium chloride crude product and add in the mixture that 100ml tetrahydrofuran and 500ml n-hexanol form, add dropwise hydrochloric acid solution (concentration is 36%) to solid dissolving under stirring, evaporate to dryness under reduced pressure, get ricecuronium chloride disalt Salt crude product 9.89g;

[0037] (2) Add 9.89 g of the crude product of mivacuronium chloride dihydrochloride into 1000 ml of ethyl acetate, stir at 30° C. for 2 hours, and filter with suction to obtain 9.29 g of mivacuronium chloride dihydrochloride;

[0038] (3) 9.29g of prepared ricecuronium chloride dihydrochloride is added in 100ml ethanol, 30ml of propylene oxide is added, and the solid is precipitated under stirring, suction filtered, and dried to obtain 7.62g ricecuronium chloride; total yield 76.2 %.

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Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to a preparation method for mivacurium chloride. The method comprises the following steps: taking a crudeproduct of the mivacurium chloride to prepare a crude product of mivacurium chloride dihydrohydrochloride, performing recrystallization on the crude product of the mivacurium chloride dihydrohydrochloride to obtain the mivacurium chloride dihydrohydrochloride, and adding epoxy propane into the mivacurium chloride dihydrohydrochloride in ethanol to prepare the mivacurium chloride. According to themethod provided by the invention, the mivacurium chloride obtained by the method has a high content of effective ingredients and a low content of impurities; and through stability tests, the contentof the impurities of the mivacurium chloride prepared by the preparation method has small change, and the content of the effective ingredients is almost unchanged.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a preparation method of mivacurium chloride. Background technique [0002] Mivacurium Chloride is a benzylisoquinoline short-acting non-depolarizing neuromuscular blocking drug and a new type of short-acting non-depolarizing muscle relaxant. Chemical name: (E)-(1R,1'R)-2,2'-[4-occedenoylbis(oxypropylene)]bis[1,2,3,4-tetrahydro-6, 7-dimethoxy-2 methyl-1-(3,4,5 trimethoxybenzyl)isoquinoline] dichloride, its structural formula is as follows: [0003] [0004] Mivacurium chloride was developed by Abbott lab and first launched in the United States in 1992. It is the muscle relaxant with the shortest action time found so far, only 1 / 3-1 / 2 of cis-besylate atracurium and vecuronium bromide . Because of its unique advantages of quick onset and short duration of action, mivacurium chloride is often used to maintain muscle relaxation during endotracheal intubation and ...

Claims

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Application Information

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IPC IPC(8): C07D217/20
CPCC07D217/20
Inventor 李霞王燕
Owner 北京六盛合医药科技有限公司
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