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A kind of refining method of Fasudil hydrochloride

A technology of fasudil hydrochloride and a refining method, applied in the direction of organic chemistry and the like, can solve the problems of inability to stabilize, not obtain satisfactory results, poor dimer removal effect, etc., and achieve excellent effects.

Active Publication Date: 2016-08-24
TIANJIN CHASE SUN PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

CN103030629A, CN102020635A adopt the method of methanol + poor solvent to drop the poor solvent at room temperature, and the removal effect on the dimer is not good
[0011] The patent application whose publication number is CN101973981A points out that the water-methanol, water-ethanol, methanol-ether systems reported in the literature are used to recrystallize the crude product of fasudil hydrochloride, but no satisfactory results have been obtained, and it is impossible to stably recrystallize the crude product of fasudil hydrochloride. The single impurity in Er is controlled within 0.1%
In paragraph 0007 of the document, it states that the crude product of Fasudil hydrochloride was recrystallized using water-methanol, water-ethanol, and methanol-ether systems, but no satisfactory results were obtained, and the single impurity of Fasudil hydrochloride could not be stably controlled. Within 0.1%

Method used

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  • A kind of refining method of Fasudil hydrochloride
  • A kind of refining method of Fasudil hydrochloride
  • A kind of refining method of Fasudil hydrochloride

Examples

Experimental program
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Effect test

Embodiment 1

[0027] Example 1: Weigh 10 grams of the crude product of Fasudil hydrochloride, dissolve it in 80 ml of refluxing methanol, add 80 ml of diethyl ether dropwise under reflux, cool to 10° C., let it stand for crystallization for 1 hour, filter, and use methanol-diethyl ether The 1:1 mixture was washed and dried to obtain 9.1 g of the refined product of Fasudil hydrochloride. Its content is 99.90%, and a single impurity is 0.01%. Yield 91%

Embodiment 2

[0028] Example 2: Weigh 10 grams of the crude product of Fasudil hydrochloride, dissolve it in 80 ml of refluxed methanol, add dropwise 240 ml of acetone under the reflux state, after the addition is completed, cool to 10° C., let stand for crystallization for 1 hour, filter, Wash with methanol-acetone 1:3 mixture, and vacuum-dry to obtain 9.1 g of the refined product of Fasudil hydrochloride. Its content is 99.89%, and a single impurity is 0.01%. Yield 91%

Embodiment 3

[0029] Embodiment 3: Weigh 10 grams of the crude product of Fasudil hydrochloride, dissolve it in 80 ml of refluxed anhydrous methanol, add dropwise 400 ml of acetone under the reflux state, after the addition is completed, cool to 10° C., and stand for crystallization for 1 hour. Filter, wash with methanol-acetone 1:5 mixture, and vacuum-dry to obtain 9.0 g of refined fasudil hydrochloride. Its content is 99.82%, a single impurity is 0.02%, and the yield is 90%.

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Abstract

The invention relates to a refining method for hydroxyfasudil. The refining method is characterized in that the hydroxyfasudil is dissolved in a heated solvent A, and a solvent B is added dropwise at a certain temperature; the combination is cooled to be below 10 DEG C, stood for devitrification, filtered, washed by the mixed liquor of A and B with the proportion the same as that of the added A and B, and dried to a hydroxyfasudil refined product. According to the invention, a high purity hydroxyfasudil crystal can be obtained, the content is greater than 99.8%, and the single impurity of the hydroxyfasudil can be stably controlled not to be greater than 0.1%.

Description

technical field [0001] The present invention relates to a refining method of fasudil hydrochloride, in particular to a production process of the drug fasudil hydrochloride crude drug used for improving the symptoms of ischemic cerebrovascular disease caused by cerebral vasospasm after subarachnoid hemorrhage Refining process in. Background technique [0002] Fasudil hydrochloride is a sulfonylisoquinoline derivative, its English name is Fasudil Hydrochloride, and its chemical name is hexahydro-1-(5-sulfonylisoquinoline)-1-(H)-1,4 -Diazepine hydrochloride, the molecular formula is C 14 h 17 N 3 o 2 .. HCl, the chemical structural formula is as follows: [0003] [0004] It is an intracellular calcium ion antagonist developed by Asahi Kasei Co., Ltd. of Japan. It has the effects of dilating cerebral blood vessels and is clinically used for cerebral spasm caused by subarachnoid hemorrhage. It was launched in Japan in June 1995 and is currently widely used in clinical....

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D401/12
CPCC07D401/12
Inventor 姚小青孙长海侯文锋干浩周喜泽孙福亮李振重张福杰常淑梅
Owner TIANJIN CHASE SUN PHARM CO LTD