蒿鳖养阴软坚方制剂工艺的正交实验与药理筛选比较研究  

Comparative research on orthogonal experiment and pharmacological evaluation on pharmaceutical technology of HaoBieYangYinRuanJian prescription

作　　者：方步武[1] 凌宁生[2] 汪芳[3] 邢伟[1] 郝洁[1] 张玉萍[3] 张永进[1] 刘洁莹[1] 崔志清[1] 

机构地区：[1]天津医科大学药理教研室,天津300070 [2]天津中新药业集团中新制药厂,天津300457 [3]天津中医药大学中药学院,天津300193

出　　处：《中药药理与临床》2010年第4期47-50,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：天津市应用基础研究计划重点项目(06YFJZJC02900)

摘　　要：目的:探讨药理筛选在完善以有效成分的正交实验结果为依据所确立的蒿鳖养阴软坚方制剂工艺中的作用。方法:以复方中辅药的水溶性(丹酚酸B、梓醇)和脂溶性(大黄素)有效成分为评价指标,按HPLC测定其含量,对溶剂倍量、提取次数、提取时间、乙醇浓度等因素各3个水平进行正交实验,据以制定提取工艺共10种方案。0.5mlCCl4/100gwt皮下注射16次(后15次注射用CCl4:橄榄油=4:6,V/V)辅以10%乙醇为饮料引起大鼠肝纤维化,成模后按体重随机区组法分组,分别以蒿鳖养阴软坚方10种提取方案各2个剂量(24.48g/kg,8.16g/kg)治疗用药,每日1次、每周6天灌胃共2个月,模型对照组和正常对照组则灌胃蒸馏水。以肝胶原蛋白含量、肝组织形态及血清中肝纤维化标志物评价疗效。结果:蒿鳖养阴软坚方按方案1-1(水提低含量和醇提低含量)提取,24.48g/kg能明显降低肝胶原蛋白及血清透明质酸和IV型胶原水平(P<0.05),按方案3-2(水提低含量和醇提高含量)提取,8.16g/kg能降低肝胶原蛋白及明显降低血清透明质酸和IV型胶原水平(P<0.05)。结论:对有效成分含量的正交实验基础上以疗效指标进行药理筛选应作为确立复方提取工艺方案的最终依据。Objective：To explore into effect of pharmacological evaluation on improving pharmaceutical technology of Haobieyangyinruanjian prescription（HBYYRJ） based on orthogonal experiment of active principle.Methods：Water-soluble（Salvianolic acid B,Catalnol） and fatsoluble（Emodin） acive components of adjuvant drugs in complex prescription were served as evaluation index and determined with HPLC according to Pharmacopeia of PRC,do orthogonal experiment on 3 levels for solvent multiple,extraction frequency,extraction time,ethanol concentration,10 schemas of extraction craft were established.Hepatic fibrosis was induced by rat sc injection of 0.5ml CCl4/100g first,then 0.5 ml CCl4 in olive-oil（4：6,v：v）/100 g for another 15 frequency,and drinking of 10% ethanol.Rats were grouped by randomized block of weight after model established,remedial administration of HBYYRJ of 24.48 g crude drugs/kg,8.16 g/kg for every extraction schema of 10,per os once a day,6 days a week for 2 months.Model and normal control rats were administered with distilled water.Therapeutic effect was evaluated by liver collagen content,histomorphology and serum markers of hepatic fibrosis.Results：24.48g/kg HBYYRJ extracted by schema 1-1（low cont.extracted with water and low cont.extracted with ethanol） can lower liver collagen,hyaluronic acid and type IV collagen level in sera,so can do 8.16g/kg HBYYRJ extracted by schema 3-2（low cont.extracted with water and high cont.extracted with ethanol）（P〈0.05）.Conclusion：Extraction technology established finally should rest on pharmacological evaluation by index of therapeutic effect based on orthogonal screening of active component cont.

关 键 词：蒿鳖养阴软坚方 正交实验 胶原蛋白 透明质酸 

分 类 号：TQ461[化学工程—制药化工] R285[医药卫生—中药学]