葛根黄芩黄连方不同提取制备工艺的比较

摘要

目的：通过对葛根黄芩黄连方（简称葛根芩连方）的3种不同提取工艺的药效及毒性的对比实验，为选择合适的葛根连芩方提取制备工艺提供依据。方法小鼠分为空白组、病理组、片剂组、丸剂组、汤剂组，其中后3组又分别分为高、中、低剂量组，除空白组外其余组灌服番泻叶提取液20 mL／kg（4 g／kg）造成病理模型，片剂组、丸剂组、汤剂组灌服葛根芩连方提取物水溶液20 mL／kg。片剂组给药量分别为高剂量组1．60 g／kg，中剂量组0．80 g／kg，低剂量组0．40 g／kg；丸剂组给药量分别为高剂量组6 g／kg，中剂量组3 g／kg，低剂量组1．5 g／kg；汤剂组给药量分别为高剂量组13 g／kg，中剂量组6．5 g／kg，低剂量组3．25 g／kg。以湿粪数积分为评价指标，观察不同提取工艺样品止泻的功效。取30只小鼠分为片剂组、丸剂组、汤剂组，采用最大给药量试验进行不同提取工艺样品的急性毒性试验，最大给药体积均为40 mL／kg；片剂组最大给药浓度为0．66 g／mL、最大给药量折合饮片为67．96 g／kg，丸剂组最大给药浓度为0．63 g／mL、最大给药量折合饮片为89．01 g／kg，汤剂组最大给药浓度为0．74 g／mL、最大给药量折合饮片为177．77 g／kg；分别相当于临床70 kg 人每公斤体重日用量的24倍、9倍和6倍；给药后连续观察7 d，记录小鼠反应情况。结果在药效试验中，按葛根芩连方的3种剂型提取得到的样品，对小鼠的腹泻均有明显治疗效果（P ＜0．001）。其中葛根芩连片的止泻效果最优，且有统计学意义（P ＜0．05），葛根芩连丸次之，葛根芩连汤效果较差。在毒性试验中，在最大剂量下小鼠均未出现死亡且无明显异常表现。结论葛根芩连方的3种制剂，以2015版《中华人民共和国药典》中记录的葛根芩连片的提取制备方法所得提取物对番泻叶引起的腹泻抑制效果最优。%Objective By comparing the efficacy and toxicity of three extraction methods of Gegen Qinlian formula,so as to underline the appropriate technology of its extraction and preparation.Methods Mice were divided into blank group,pathological group,tablet group,pill group and decoction group, in which the latter three groups were divided into high -,mid -and low -dose subgroups respectively. The mice models were induced by i.g.senna decoction 20 mL/kg(4 g/kg).The tablet group were i.g. extract water solution at dose of 1.60,0.80,0.40 g/kg,the pill group were i.g.at dose of 6,3 and 1.5 g/kg,and the decoction group at dose of 13,6.5 and 3.25 g/kg.The number of the wet dung was chosen to evaluate the antidiarrheic effect of Gegen Qinlian formula.Then the acute toxicity test of differ-ent samples was carried out through maximal dosage experiments.Mice were divided into tablet group, pill group and decoction group,with 10 mice in each group.And the maximum dosage were 0.66 g/mL (tablet),0.63 g/mL(pill)and 0.74 g/mL(decoction),equivalent to crude drug pieces of 67.96, 89.01 and 177.77 g/kg,and equivalent to 24,9 and 6 times daily dose of per kilogram of body weight of 70 kg.After the single dose administration,the reactions of the mice were observed for consecutive seven days.Results The sample of three dosage forms of Gegen Qinlian formula had obvious therapeutic effect (P <0.001),among which the antidiarrheic effect of tablets was best (P <0.05),pill less and decoc-tion least.No death or obvious abnormalities was discovered under maximum dosage.Conclusion In the three preparations,Gegen Qinlian tablets extraction preparation method recorded in 2015 Chinese Pharmacopoeia had the best inhibitory effect against diarrhea caused by senna leaves.