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Non-depolarizing muscle relaxant composition as well as preparation method and application thereof

A composition and compound technology, applied in the directions of drug combination, pharmaceutical formulation, muscular system diseases, etc., can solve problems such as affecting the cardiovascular system, allergies, skin flushing, etc., achieving good storage stability, small release effect of histamine, and effective fast effect

Pending Publication Date: 2018-12-04
SICHUAN CREDIT PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to reports, the release of histamine from mivacurium chloride causes adverse reactions such as skin flushing and allergies, and even affects the cardiovascular system of the human body.

Method used

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  • Non-depolarizing muscle relaxant composition as well as preparation method and application thereof
  • Non-depolarizing muscle relaxant composition as well as preparation method and application thereof
  • Non-depolarizing muscle relaxant composition as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0052] Weigh 100.0g (R)-5'-methoxylaudansu, 63.0g 3-chloropropanol, 115.0g sodium iodide, 10.0g anhydrous sodium carbonate, add solvent acetone 1500mL, reflux for 24h. After the reaction is complete, stop heating, cool down and filter, concentrate the filtrate to dryness, add purified water to dissolve, then add dichloromethane to extract, separate liquid, pass the water layer through an ion exchange resin column, collect the liquid, add sodium chloride to saturate, and dichloromethane extract , concentrated to dryness to give 6,7-dimethoxy-2-(3-hydroxypropyl)-2-methyl-1-[(3,4,5-trimethoxyphenyl)methyl]-1 ,2,3,4-tetrahydroisoquinoline chloride. The purity determined by HPLC was 99.72%.

preparation example 2

[0054] Weigh 100.0g (R)-5'-methoxylaudansu, 63.0g 3-chloropropanol, 115.0g sodium iodide, 10.0g anhydrous sodium carbonate, add solvent acetone 1000mL, reflux for 20h. After the reaction is complete, stop heating, cool down and filter, concentrate the filtrate to dryness, add purified water to dissolve, then add chloroform to extract, separate liquid, pass the water layer through an ion exchange resin column, collect the liquid, add sodium chloride to saturate, extract with dichloromethane, and concentrate to dry to obtain 6,7-dimethoxy-2-(3-hydroxypropyl)-2-methyl-1-[(3,4,5-trimethoxyphenyl)methyl]-1,2 ,3,4-tetrahydroisoquinoline chloride. The purity determined by HPLC was 99.72%.

preparation example 3

[0056] Weigh 100.0g (R)-5'-methoxylaudansu, 63.0g 3-chloropropanol, 115.0g sodium iodide, 10.0g anhydrous sodium carbonate, add solvent acetone 800mL, reflux for 18h. After the reaction is complete, stop heating, cool down and filter, concentrate the filtrate to dryness, add purified water to dissolve, add 1,2-dichloroethane to extract, separate liquid, pass the water layer through an ion exchange resin column, collect the liquid, add sodium chloride to saturate , extracted with dichloromethane, and concentrated to dryness to give 6,7-dimethoxy-2-(3-hydroxypropyl)-2-methyl-1-[(3,4,5-trimethoxyphenyl) Methyl]-1,2,3,4-tetrahydroisoquinoline chloride. The purity was determined to be 99.75% by HPLC.

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Abstract

The invention discloses a mivacurium chloride composition as well as a preparation method and an application thereof. The mivacurium chloride composition consists of mivacurium chloride, a compound A,a compound B as well as an optional compound C and an optional compound D, wherein in terms of total weight of the mivacurium chloride composition, the compound A accounts for 0.001-0.15wt%, preferably 0.001-0.13wt%, and more preferably 0.001-0.1wt%; and the compound B accounts for 0.001-0.15wt%, preferably 0.006-0.15wt%, and more preferably 0.01-0.15wt%. The mivacurium chloride composition provided by the invention is good in stability in long-term preservation, relatively low in histamine release action and low in toxic and side effects.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a mivacurium chloride composition, a preparation method and application thereof. Background technique [0002] Neuromuscular blocking agents inhibit the interaction between acetylcholine released from autonomic nerve fibers and nicotinic acetylcholine receptors on the cell membrane of skeletal muscle cells, disrupt the chemical signal transmission at the neuromuscular junction, and play a role in muscle relaxation. According to different pharmacological effects, neuromuscular blocking agents can be divided into depolarizing and non-depolarizing types. The depolarizing type has poor selectivity and obvious side effects; the non-depolarizing type itself has no biological activity and can be rescued by neostigmine in case of overdose. It is easy to regulate and safe in surgical anesthesia, and is more and more favored by clinicians. [0003] Mivacurium chloride belongs to the cla...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4725A61P21/02
CPCA61K31/4725
Inventor 蒋春霞宿磊李晓莉陈刚
Owner SICHUAN CREDIT PHARMA
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