BBD-效应面法优选七血酊剂制备工艺及其对小鼠胃肠黏膜刺激的作用

Optimization of preparation technology of Qixue Tincture by BBD-response surface methodology and its stimulating effect on gastrointestinal mucosa in mice

目的:采用BBD-效应面法优选七血酊剂的制备工艺,并研究其口服后对小鼠胃肠黏膜的刺激作用。方法:在单因素试验的基础上,进一步采用BBD-效应面法安排实验,以效应面法预测优化处方并验证,取健康昆明小鼠,随机分为空白组、高剂量组、中剂量组和低剂量组,连续给药7d,对小鼠胃肠道黏膜分别进行肉眼观察、病理切片观察及试剂盒检测。结果:七血酊剂制备工艺为:乙醇浓度为60%,乙醇用量为4倍,提取时间为108h。胃、肠黏膜病理切片及试剂盒检测结果均表明,中、低剂量组在灌胃给药后,未造成小鼠胃肠道黏膜出血、细胞结构变化及组织损伤;但高剂量组老鼠全部胀气死亡。结论:采用BBD-效应面法建立的数学模型预测性良好,结果与其函数预测值之间的偏差<5%。且酊剂中、低剂量连续给药7d后,未出现明显的胃、肠黏膜刺激性;酊剂高剂量对小鼠胃肠刺激严重。

Objective:To optimize the preparation technology of Qixue Tincture by Box-Behnken design(BBD)-response surface methodology and to study its stimulation of mouse’s gastrointestinal mucosal.Methods:BBD-response surface methodology were used to test,optimize and verify on the basis of single-factor experiment.The healthy Kunming mice were randomly divided into blank control group,high dose group of tincture,middle dose group of tincture and low dose group of tincture,after treating for seven days,according to the Guth standard to assess ulcer index,and then observe gastrointestinal mucosal by naked eyes,pathological section and reagent kit.Results:The preparation of Qixue Tincture was that the volume of alcohol was 60%,the concentration of alcohol was 4 times,the time of extracting was 108 h.The test results of pathological section and reagent kit show:middle dose group and low dose group of tincture did not cause gastrointestinal mucosal hemorrhage,structural change of cells and damage of tissue by gastric perfusion.But rats in high dose group died from gastrointestinal flatulence.Conclusion:The optimum mathematic model is established by BBD-response surface methodology is highly predictive.The relative error between the measured value and forecast value is less than 5%.After treating for seven days,middle dose group and low dose group of tincture don’t cause obvious irritation of gastrointestinal mucosal.High dose group of tincture has severe gastrointestinal irritation in mice.