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Low-toxicity antiarrhythmic medicine and preparation method thereof

A low-toxicity, pharmaceutical technology, applied in the direction of drug combination, pharmaceutical formula, organic chemical method, etc., can solve the problem of unclear component conversion, cardiotoxicity and neurotoxicity, etc.

Active Publication Date: 2021-07-23
CHENGDU UNIV OF TRADITIONAL CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Diterpene alkaloids are the active components of Aconitum that exert analgesic and anti-inflammatory effects, but are also cardiotoxic and neurotoxic
However, in the process of processing, the composition transformation law of aconitum medicinal materials is not yet clear

Method used

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  • Low-toxicity antiarrhythmic medicine and preparation method thereof
  • Low-toxicity antiarrhythmic medicine and preparation method thereof
  • Low-toxicity antiarrhythmic medicine and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] The preparation of embodiment 1 compound 2 of the present invention

[0049] 1. Preparation of Samples for Column Chromatography Separation

[0050] Take 1.83g of aconitin, put it in a 250mL round-bottomed flask, add 25mL of dichloromethane to dissolve, and evaporate the solvent to dryness at 40°C with a rotary evaporator, so that aconitin is evenly attached to the inner wall of the round-bottomed flask, and Put it in an oil bath at 160°C for 30 minutes, take it out, and let it cool to obtain the processed product of aconitin (1.65 g), which is used for column loading.

[0051] 2. Separation and purification

[0052] After dissolving the processed product of aconitin in dichloromethane, it was separated and purified by silica gel column chromatography (200-300 mesh, 120g), and was respectively purified with petroleum ether-acetone-triethylamine 8:1:0.01 (0.4L), 6:1:0.01 (3L), 3:1:0.01 (1.2L) gradient elution, TLC plate inspection, after combining similar fractions, th...

experiment example 1

[0065] Cardiotoxicity Test of Experimental Example 1 Aconitin and its Stir-fried Product Compound 2

[0066] 1. Test method

[0067] Take 20 SD rats of SPF grade, half male and half male, and randomly divide them into aconitin group and compound 2 group (n=10, fasting without food and water for 12 hours before the experiment). Anesthetized by intraperitoneal injection of 20% urethane (dose 1.2g / kg), fixed in the supine position, inserted the needle electrode into the subcutaneous of the extremities, and observed the electrocardiogram of lead II of the rat with a BL-420F multifunctional physiological recorder for 20 minutes. ECG changes within 30 minutes after taking the medicine. Through preliminary preliminary experiments, it was found that 0.10mg / kg of aconitin can cause ventricular premature beat (VPB), ventricular tachycardia (VT) and ventricular fibrillation (VF) in rats, etc. Arrhythmia, by observing whether compound 2 causes the above arrhythmia at the same dose, it c...

experiment example 2

[0074] Study on Antiarrhythmic Activity of Experimental Example 2 Compound 2

[0075] 1. Test method

[0076] Get 125 SD rats, half male and half male, and randomly divided into 8 groups, i.e. blank solvent group (preparation method: get 4mL of 1% hydrochloric acid ethanol, add normal saline to dilute to 100mL), model control group (aconitine; dose 0.03mg / kg), positive control group (lidocaine group, dose 5mg / kg; propafenone group, dose 3.2mg / kg), compound 2 different dose groups (0.05mg / kg, 0.20mg / kg, 0.30mg / kg and 0.40mg / kg). Aconitine, the positive drug and each test drug were prepared by the preparation method of the blank solvent. The blank solvent group was only given an equal volume of the blank solvent to observe whether the solvent had an effect on the ECG of SD rats.

[0077] Before the start of the experiment, SD rats were anesthetized by intraperitoneal injection of 20% urethane (dose 1.2g / kg), fixed in the supine position, needle-shaped electrodes were inserted...

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Abstract

The invention provides a low-toxicity anti-arrhythmia medicine and a preparation method thereof. The structure of the compound is shown as a formula I in the specification. Experimental results show that the compound provided by the invention has excellent anti-arrhythmia activity, can delay the VPB latency period of aconitine induced arrhythmia rats and effectively prevent further development of VPB, and the anti-arrhythmia effect of the compound is even superior to that of a positive drug lidocaine under the dosage of 0.30 mg / kg and 0.40 mg / kg. More importantly, compared with bulleyaconitine A, the cardiotoxicity of the compound disclosed by the invention is obviously reduced; compared with the known sand-fried product delta 15, 16-16-demethoxyindinacitine, the compound disclosed by the invention has the advantages that the acute toxicity is obviously lower, and the safety is higher. The invention provides a new choice for preparing a low-toxicity anti-arrhythmia medicine, and provides a new method for controlling the quality of the sand-fried Aconitum bulleyanum or sand-fried Aconitum crassicaule.

Description

technical field [0001] The invention belongs to the field of pharmacy, and in particular relates to a low-toxicity antiarrhythmic drug and a preparation method thereof. Background technique [0002] Ranunculaceae Ranunculaceae Aconitum L. There are more than 300 species of plants in the world, which are widely distributed in the northern temperate zone and have important medicinal value. There are more than 200 species of Aconitum in my country, which are distributed in various provinces and regions. The main distribution In the high mountain areas of western Sichuan, northwestern Yunnan, and eastern Tibet, there are 76 species that can be used as medicine, and are widely used in traditional Chinese medicine and ethnic minority medicine. For example, Chuanwu, Caowu and Fuzi are commonly used varieties in traditional Chinese medicine, Tiebanghammer and Huangcaowu are commonly used in Tibetan medicine, Qiang medicine and Yi medicine. , joint pain embolism. [0003] Diterpene ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D221/22A61K31/439A61P9/06
CPCC07D221/22A61P9/06C07B2200/07
Inventor 王毓杰陶培
Owner CHENGDU UNIV OF TRADITIONAL CHINESE MEDICINE
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