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New application of Korean mondshood root total alkaloids and guanfu base VIIII

A technology of Guanfunonin and total alkaloids, which is applied in the application field of preparing slow sodium ion channel blockers and antiarrhythmic drugs, and can solve the problem of easily induced ventricular arrhythmia, syncope and sudden death, and action potential plateau phase. extension etc.

Active Publication Date: 2012-10-03
CHINA PHARM UNIV +1
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In recent years, research on long QT syndrome (L-QT, a series of syndromes that easily induce ventricular arrhythmia, syncope and sudden death) and other new targets for the mechanism of arrhythmia. Experiments have shown that the cardiac sodium ion channel gene SCN5A Mutation, resulting in the repeated development of slow sodium current, delaying the current decay, prolonging the plateau period of action potential, and causing L-QT

Method used

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  • New application of Korean mondshood root total alkaloids and guanfu base VIIII
  • New application of Korean mondshood root total alkaloids and guanfu base VIIII
  • New application of Korean mondshood root total alkaloids and guanfu base VIIII

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experiment example 1

[0063] Experimental Example 1: Pharmacological Study on Antiarrhythmic Effects of Total Alkaloid Salts of Guanbaifu

[0064] 1. Experimental materials: Guanbaifu total alkaloid salts, prepared according to Example 3 of the present invention; lidocaine hydrochloride injection, Shandong Yushui Xierkang Pharmaceutical Co., Ltd.; experimental rats are provided by Shanghai Slack Animal Center and Rabbits were provided by the Animal Laboratory of China Pharmaceutical University.

[0065] 2. Protective Effect of Guanbaifu Total Alkali Salt on Arrhythmia Induced by Electrical Stimulation in Rabbit Heart

[0066] 2.1 Experimental method

[0067] Twelve rabbits, weighing 2.4±0.6kg, were divided into two groups, 6 in each group, half male and half male, one group was the total alkaloid group of Guanbaifu, and the other group was the lidocaine group. Urethane 1.2g / kg ear edge was anesthetized iv, the heart was exposed through thoracotomy under artificial respiration, and the Gu's cardi...

experiment example 2

[0083] Experimental Example 2 Study on the blocking effect of Guanfu total alkaloids and Guanfu A hydrochloride on myocardial slow sodium ion channel

[0084] 1 Experimental method

[0085] 1.1 Cardiomyocyte isolation

[0086] Normal guinea pigs (male or female, 250±20g) were stunned, and the heart was quickly removed by chest opening, placed in calcium-free Tyrode solution at 4°C, trimmed and hung on the Langendorff apparatus through the aorta, and kept at Constant temperature perfusion with calcium-free Tyrode solution at a flow rate of 6-8 mL / min. Perfuse for about 5 minutes, wash away the congestion, and then replace with enzyme-containing calcium-free Tyrode's solution for about 10-15 minutes. When the myocardium becomes loose and translucent, cut off the left ventricle and gently blow it in KB solution with a glass dropper. After filtration, the rod-shaped single ventricular myocytes with clear stripes and smooth surface can be obtained, which are stored in KB solution...

experiment example 3

[0098] Experimental Example 3 Study on the Preparation Technology of Total Alkaloids of Guanbaifu

[0099] 1 Comparison of ethanol cold extraction and ethanol heating and reflux extraction of Guanbaifu

[0100] 1.1 Experimental method

[0101]Cold soaking method: crush 500 grams of Guanbaifu granules into 10-20 meshes, soak them in 1000ml 95% ethanol at 25°C for 24 hours, leaching, add 1000ml 95% ethanol for the second time, soaking at 25°C for 12 hours, leaching, add Soak 1000ml of 95% ethanol at 25°C for 4 hours, extract, combine the extracts, filter, and recover ethanol from the filtrate under reduced pressure to obtain a thick alcohol extract, add a small amount of distilled water, place in the refrigerator, cool and filter, remove impurities such as pigments, extract several times with petroleum ether, and Remove the fat-soluble components therein, then extract with chloroform, dehydrate and filter the chloroform extract with anhydrous sodium carbonate, recover chlorofor...

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Abstract

The invention provides a preparation method of Korean mondshood root total alkaloids and applications in preparing a slow sodium-ion passage blocking agent and preparing drugs for resisting arrhythmia. Both the Korean mondshood root total alkaloids and the guanfu base I are provided to have an effect for inhibiting slow sodium current of ventricular muscles of cavies. The invention particularly relates to an application of guanfu base VIIII in preparing a drug-metabolizing enzyme inhibitor. The invention also provides an application of guanfu base VIIII in preparing a slow sodium-ion passage blocking agent.

Description

technical field [0001] The invention relates to the new application of total alkaloids of Guanbaifu and Guanfu nonin. It specifically relates to the application of total alkaloids of Guanbaifu in the preparation of slow sodium ion channel blockers and antiarrhythmic drugs. Background technique [0002] Guanbaifu is the root tuber of Aconitum coreanum (Levl,) Rapaics, a traditional Chinese medicine. It is one of the common Chinese medicines. It is mainly used for heartache and blood stagnation. Its chemical composition is mainly related to Guanfu base G, GFG, Guanfu base A, GFA, Guanfu base I, GFI, etc. All three are diterpenoid alkaloids . Modern pharmacological studies have shown that Guanfu A, Guanfuheptan, and Guanfunonin have antiarrhythmic, anti-inflammatory and analgesic effects. However, because the extraction yield of Guanfu A is about 0.1%, the extraction process cycle is long, the loss of raw materials is large, and the resources of Guanfu A have not been fully ...

Claims

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Application Information

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IPC IPC(8): A61K31/407A61K36/714A61P43/00A61P9/06A61K125/00
Inventor 王广基汤依群董秀华孙建国于鹏刘静涵刘建平杨春华刘巍朱天全徐静孙申国程志国汪旻晖
Owner CHINA PHARM UNIV
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