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Quality control method for fasudil hydrochloride

A technology of fasudil hydrochloride and a quality control method, applied in the field of quality control of fasudil hydrochloride, can solve the problem of quality detection and control of dimer and homopiperazine, influence the production and quality assurance of fasudil hydrochloride , can not completely effectively and accurately control the quality of fasudil hydrochloride and other problems to achieve the effect of improving product quality, high precision and accuracy, and improving quality

Active Publication Date: 2016-08-17
SICHUAN SUNNYHOPE PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] Homopiperazine is also used in the synthesis process of the dimer, so it will affect the production and quality assurance of Fasudil hydrochloride, and the content of dimer and homopiperazine is not tested in the above-mentioned published patent and control, the existing technology cannot fully effectively and accurately control the quality of Fasudil Hydrochloride

Method used

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  • Quality control method for fasudil hydrochloride
  • Quality control method for fasudil hydrochloride
  • Quality control method for fasudil hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1: Synthesis of 1,4-bis(5-isoquinolinesulfonyl)-pentahydro-1,4 diazepine dimer

[0037] Add 50.0g of isoquinoline-5-sulfonyl chloride hydrochloride and 150ml of dichloromethane into a 500ml reaction flask, mix and cool to 0°C, dropwise add aqueous sodium bicarbonate (16.5g / 250mlH 2O) adjust the pH to 5, then keep stirring for 25min, let stand for stratification, separate the dichloromethane layer, extract the water layer with dichloromethane, combine the organic layers, and dry with anhydrous magnesium sulfate at a temperature of 0°C to obtain a dry solution ;

[0038] Dissolve 18.8g of homopiperazine in 150ml of anhydrous tetrahydrofuran, add dropwise to the dry solution at 0°C, keep stirring for 1.5h, adjust the pH to 5, stir for 1h, concentrate the reaction solution to dryness under reduced pressure, add 500ml of water, stirred at 50°C for 2h, filtered and collected the filter cake, took a 500ml flask, added the above solid, added 250ml of methanol, heated t...

Embodiment 2

[0040] Example 2: Synthesis of 1,4-bis(5-isoquinolinesulfonyl)-pentahydro-1,4 diazepine dimer

[0041] Add 50.0g of isoquinoline-5-sulfonyl chloride hydrochloride and 150ml of dichloromethane into a 500ml reaction flask, mix and cool down to 5°C, dropwise add aqueous sodium bicarbonate (16.5g / 250mlH 2 O) adjust the pH to 6, then keep stirring for 35 minutes, let stand to separate the layers, separate the dichloromethane layer, extract the water layer with dichloromethane, combine the organic layers, and dry with anhydrous magnesium sulfate at a temperature of 5°C to obtain a dry solution ;

[0042] Dissolve 18.8g of homopiperazine in 150ml of anhydrous tetrahydrofuran, add dropwise to the dry solution at 5°C, keep stirring for 2.5h, adjust the pH to 5, stir for 1h, concentrate the reaction solution to dryness under reduced pressure, add 500ml of water, stirred at 50°C for 2h, filtered and collected the filter cake, took a 500ml flask, added the above solid, added 250ml of met...

Embodiment 3

[0044] Example 3: Synthesis of 1,4-bis(5-isoquinolinesulfonyl)-pentahydro-1,4 diazepine dimer

[0045] Add 50.0g of isoquinoline-5-sulfonyl chloride hydrochloride and 150ml of dichloromethane into a 500ml reaction flask, mix and cool to 3°C, dropwise add aqueous sodium bicarbonate (16.5g / 250mlH 2 O) Adjust the pH to 5.5, heat and stir for 28 minutes, let stand to separate the layers, separate the dichloromethane layer, extract the water layer with dichloromethane, combine the organic layers, and dry with anhydrous magnesium sulfate at a temperature of 2°C to obtain a dry solution ;

[0046] Dissolve 18.8g of homopiperazine in 150ml of anhydrous tetrahydrofuran, add dropwise to the dry solution at 3°C, keep stirring for 2 hours, adjust the pH to 5, stir for 1 hour, concentrate the reaction solution to dryness under reduced pressure, add 500ml water, stir at 50°C for 2 hours, filter and collect the filter cake, take a 500ml flask, add the above solid, add 250ml of methanol, hea...

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Abstract

The invention discloses a quality control method for fasudil hydrochloride. The quality control method comprises the following steps: observation of properties; identification of contents; inspection of the contents; and determination of the contents of components included in the contents; wherein inspection of the contents comprises determination of the contents of related substances and determination of the content of homopiperazine. In the process of a synthesis reaction, fasudil hydrochloride is prone to generation of degradation impurities and to a side reaction for production of a dimer impurity and a starting reaction material homopiperazine is hard to thoroughly remove, so purity and security of fasudil hydrochloride are influenced; thus, the contents of impurities in fasudil hydrochloride should be determined in time in the production process so as to control product quality in the production process. The method provided by the invention has additional steps of determination of dimer content and determination of homopiperazine content on the basis of conventional control method, so the quality control method further improves the quality of fasudil hydrochloride, perfects current industrial standards, has the advantages of simplicity, easy practicability and high precision and accuracy and is of great significance to improvement of product quality.

Description

technical field [0001] The invention relates to a quality control method of pharmaceutical preparations, in particular to a quality control method of fasudil hydrochloride. Background technique [0002] Fasudil hydrochloride, chemical name: hexahydro-1-(5-isoquinolinesulfonyl)-1H-1,4-diazepine hydrochloride, molecular formula: C 14 h 17 N 3 o 2 S·HCl, molecular weight 327.83, English name: Fasudil Hydrochloride. [0003] Its chemical structural formula is as follows: [0004] [0005] Fasudil hydrochloride is an isoquinoline sulfonamide drug developed by Japan's Asahi Kasei (Asahi Kasei) Co., Ltd. in the 1980s. It is a protein kinase RHO inhibitor (intracellular calcium ion antagonist) that blocks vasoconstriction. The final stage of the process, that is, by increasing the activity of myosin hydrogen chain phosphatase, dilating blood vessels (inhibiting vasospasm), reducing the tension of endothelial cells to exert the drug effect, thereby improving the microcirculat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N21/3563
CPCG01N21/3563G01N30/02G01N2030/025G01N2030/027
Inventor 黄筱萍陈开军姚欣刘建廷杨群慧杨波蒲洪橙
Owner SICHUAN SUNNYHOPE PHARM CO LTD
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