摘要
目的:开展生乌头与制乌头提取物的药理研究与处方原料选择的评价,促进乌头类制剂的发展和临床应用。方法:按照乌头注射液的工艺,制得生草乌与生川乌(合称生乌头)以及制草乌与制川乌(合称制乌头)的混合提取物,以生药0.152 5 mg·g^-1为基础,配得生乌头与制乌头的不同剂量组,开展了镇痛、减慢心率、抑癌等药效和急性毒性、脏器观察等毒理实验,进行系统的分析与评价。结果:与空白组比较,生乌头与制乌头提取物均具有显著的镇痛作用,给药剂量相同时,生乌头注射液的疼痛抑制率(60.91%)比制乌头注射液的(53.42%)大,口服给药的生乌头提取物疼痛抑制率(73.94%)远大于制乌头提取物(29.97%)(P<0.01)。减慢心率实验,大鼠给药后第30 min的心率与0 min心率相比,随着给药剂量的增加,生乌头组依次呈现减慢、平稳、加快的趋势,制乌头组则表现为平稳、减慢、加快的顺序,表明生乌头提取物低剂量时可达到减慢心率的作用。噻唑蓝(MTT)比色法结果显示,生乌头与制乌头提取物均具有明显抑制胃癌AGS细胞增殖的作用,剂量相同时,生乌头提取液的抑制作用较制乌头的更强。大鼠急性毒性实验测得生乌头与制乌头提取液的半数致死量(LD50)分别为3.9,21.0 g·kg^-1,相当于临床剂量的4,20倍,制乌头的LD50是生乌头的5倍。中毒致死大鼠的解剖发现,肝、肾等脏器均已发黑,中毒症状明显,而临床及其以下剂量的大鼠,各脏器均为正常。结论:生乌头安全性比制乌头的小,但镇痛、减慢心率与抑癌作用来的大,建议乌头注射液等制剂在治疗胃、肝癌晚期等重症疼痛时,原料选用生乌头,治疗一般疼痛的乌头制剂选用制乌头提取物为处方,做到真正安全与疗效相结合地辨证施治。
Objective: To carry out the studies of pharmacological action for extracts of Aconiti Radix and Aconiti Radix Cocta,and evaluate the selection of raw materials in prescriptions, in order to promote the development and clinical application of preparations.Method: The mixed extracts of Aconiti Radix and Aconiti Radix Cocta were prepared respectively according to the technique of aconitum injection,and different dose groups of Aconiti Radix and Aconiti Radix Cocta were established based on the dose of Aconiti Radix 0.152 5 mg·g^-1,and then applied in such pharmacodynamic tests as analgesia,heart rate reduction,antitumor effect and toxicology tests,such as acute toxicity and organ observation.The data were analyzed systematically on the basis of literatures.Result: Compared with blank group,the extracts of both Aconiti Radix and Aconiti Radix Cocta had a significantly analgesic effect.At the same dose,the pain inhibition rate of Aconiti Radix injection(60.91%) was higher than that of Aconiti Radix Cocta injection(53.42%),and the pain inhibition rate of Aconiti Radix extract for oral administration(73.94%) was also much higher than that of Aconiti Radix Cocta extract(29.97%),with significant differences(P<0.01).In terms of heart rate reduction test,the heart rate of rats at 0 min was compared with that at 30 thmin after administration,the heart rate of the Aconiti Radix group was decreased first,then stabilized,and finally increased with the rise of the dose,while for the Aconiti Radix Cocta group showed a different trend of first stability,then decrease and finally increase.The result indicated the Aconiti Radix group had the effect in reducing heart rate in rats at a low dose.The survival inhibition rate was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT).The extracts of both Aconiti Radix and Aconiti Radix Cocta had a significantly inhibitory effect on the proliferation of AGS gastric cancer cells,in which Aconiti Radix was stronger than that of Aconiti Radix Cocta at the same dose.In the acute toxicity test of rats,lethal dose50%(LD50) of Aconiti Radix and Aconiti Radix Cocta were 3.9 g·kg^-1 and 21.0 g·kg^-1 respectively,which were equivalent to 4 times and 20 times of the clinical dose.LD50 of the extract of Aconiti Radix Cocta was 5 times than that of Aconiti Radix.The liver and kidney of dead rats were dark with obvious symptoms of poisoning after dissection,while all the organs of rats at the clinical and lower dose were normal.Conclusion: The safety of Aconiti Radix is lower than that of Aconiti Radix Cocta,but with greater analgesic,bradycardic and anticancerous effect.Therefore,it is suggested that the preparations,such as aconitum injection,should be prepared with Aconiti Radix in the treatment of severe pain of patients with advanced gastric and liver cancer,and the preparations for general pain can be prepared with Aconiti Radix Cocta,so as to achieve a truly safe and effective dialectical treatment.
作者
杨苗苗
陈燕
杨霖
李孝栋
YANG Miao-miao;CHEN Yan;YANG Lin;LI Xiao-dong(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2019年第16期44-49,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
福建省科技厅引导性项目(2017Y0052)
关键词
乌头注射液
生乌头
制乌头
安全有效
处方评价
Aconiti Radix injection
Aconiti Radix
Aconiti Radix Cocta
safety and effectiveness
prescription evaluation
