复方新生颗粒提取工艺的药效评价

Optimization of Process for Compound Xinsheng Granula by Pharmacodynamic Indexes

【目的】通过镇痛和催眠等药效实验筛选复方新生颗粒的提取工艺。【方法】分别从水提、醇提、超临界CO2萃取挥发油中选择不同方法设计4条提取工艺路线。选用昆明种小鼠,随机分为模型组,阿斯匹林组(剂量为0.5 g.kg-1.d-1),工艺路线1、2、3、4组(剂量均为3.74 g.kg-1.d-1),连续给药3 d后,各组小鼠均腹腔注射0.12 mol/L冰醋酸溶液,观察15 min内产生扭体反应的次数及开始出现扭体的时间,计算疼痛抑制率。选用昆明种小鼠,随机分为模型组,舒乐安定组(剂量为5 mg.kg-1.d-1),工艺路线1、2、3、4组(剂量均为3.74 g.kg-1.d-1),连续给药3 d后,各组小鼠均腹腔注射戊巴比妥钠25 mg/kg,计算小鼠入睡数及入睡百分率。【结果】各工艺路线组均对冰醋酸引起的小鼠扭体反应有显著抑制作用(P<0.05或P<0.001),显著延长扭体出现时间(P<0.01或P<0.001),其中工艺路线3、4组作用更佳。工艺路线2、3、4组均能显著提高小鼠戊巴比妥钠阈下剂量的入睡率(P<0.05或P<0.01),且工艺路线3、4组作用更强。【结论】综合药效试验结果与生产实际,确定复方新生颗粒的提取路线为川芎与羌活采用超临界CO2萃取挥发油,其他药物与超临界提取后药渣加水提取。

Objective To screen the extraction technology of Compound Xinsheng granula（CXG） by means of analgesia and hypnosis animal experiment.Methods Four extraction technology routines were designed based on water extraction,ethanol extraction,and supercritical fluid extraction（SFE-CO2）.The analgesia effect of CXG prepared by different extraction technologies was observed through experiment of pain caused by chemical stimulation.In the analgesia experiment,Kunming mice were randomized into model group,aspirin（0.5 g·kg-1·d-1） group,and No.1 to No.4 extraction technology groups（in the dose of CXG 3.74 g·kg-1·d-1）.After treatment for 3 continuous days,the mice were given intraperitoneal injection of acetic acid 0.12 mol/L,then the start time of body writhing and the frequency of body writhing within 15 min were observed,and the inhibitory rate for pain was counted.The hypnotic effect was evaluated by hypnosis test of sub-threshold-dose pentobarbital sodium in mice.In hypnotic experiment,Kunming mice were randomized into model group,estazolam（5 mg·kg-1·d-1） group,and No.1 to No.4 extraction technology groups（in the dose of CXG 3.74 g·kg-1·d-1）.After treatment for 3 continuous days,the mice were given intraperitoneal injection of pentobarbital sodium 25mg/kg,and then the ratio of sleeping was observed.Results Compared with the model group,all CXG groups could significantly inhibit mice writhing response induced by acetic acid（P0.05 or P0.001）,and prolong the onset time of writhing（P0.01 or P0.001）,in particularly in No.3 and No.4 extraction technology groups.No.2,No.3 and No.4 extraction technology groups increased the ratio of sleeping induced by sub-threshold-dose pentobarbital sodium（P0.05 or P0.01）,and the effects in No.3 and No.4 extraction technology groups were more stronger（P0.01）.Conclusion On the basis of the results of efficacy test and industrial production,the optimal extraction technology of CXG is as follows：extracting the volatile oil of Rhizoma Chuanxiong and Rhizoma et Radix Notopterygii by SFE-CO2,and extracting the herb residue and the rest herbs with water.