紫菀散药效物质基础的研究及新药研制1.docx

中文摘要
紫菀散方出‘千金方》卷十八,由紫菀和款冬花二味中药组成,是一疗效确切的经典名方,适用于咳嗽痰多,咳痰不爽,肺虚燥咳,久咳,痰中带血的治疗。本课题对经典名方紫菀散的药效物质基础进行了深入系统的研究。从三个化学层次,四个药理水平,结合活性追踪的方法确定了其止咳、祛痰的有效部位, 并进一步分离有效成分,从紫菀和款冬花中分离得到57个化合物,其中1个为新化合物,命名为(1a,2a,3a)一1,2-dicaffeoyl—cychopenta-3一ol。并结合分得的化合物性质和得率进行了不同指标的活性筛选。发现祛痰的活性成分至少包括紫菀酮、表木栓醇、山奈酚和槲皮素及总皂苷:对化合物抗肿瘤实验筛选结果表
明槲皮素、表木栓醇及新化合物具有肺癌LA795细胞毒活性。以上述研究为基础,从分子水平对紫菀散作用机理进行了初步探索。认为紫
菀散的平喘途径并非作为B一2受体激动剂实现;利用计算机药物辅助设计分子对接技术对化学成分进行活性筛选,结果表明部分小分子化合物可通过抑制 1LRY,1A4G,1PEO,1AVN四种酶活性而达到抗炎、抗菌、抗病毒及抗组胺的作用,活性较强有黄酮和蒽醌类成分。
根据紫菀散临床用药特点,将其开发为单味药的配方颗粒新型制剂,满足临床辨证论治、随症加减的需要。并对复方进行精制,研制复方有效部位中药新药克咳滴丸,利用正交试验优选出最佳制各工艺、制剂成型工艺并制定了合理的质鼍标准,用于指导工业化生产,严格控制滴丸的质最。
本研究在中医药学理论和实践的指导下,将中药学、药理学、分析化学、统计学、制剂学和计算机技术相结合,初步探讨了紫菀散的药效物质基础和作用机制,并进行了剂型改制和创新中药的研制,优化提取工艺,建立质控方法,为中
药复方现代化做了有意义的探索。
关键词:紫菀散;药效物质基础;作用机制;配方颗粒;克咳滴丸;制备工艺;质量标准
ABSTRACT
"Ziwan Powder",from(Qianjin Fang》volume 18,also named"Kuandonghua Power",composed of Aster tataricus and Tussilago ’S famous traditional chinese medicine prescription with reliable curative has long been used for relieving cough,eliminating phlegm,calming asthma in China.
This theme studied therapeutic basis of‘‘Ziwan Powder'’from three chemical
levels including original preparation,efficient extracts, determined efficient extracts()of relieving COUgIl and eliminating phlegm using activity tracking ,we isolated pounds from .,one of them WaS infered pound by NMR spectroscopic and other spectral analysis. Pharmacological results showed that ponents included at least shionone, epi·friedanol,kaemferol,quercetin and including
-friedanol and(1a,2a,3a)-l'2-dicaffeoyl-eychopenta-3一ol have anti
tumor oflung CanCer activity.
The research explores‘‘Ziwan Powder"’pharmacological function mechanism on
different levels ofinteger,tissue,cell and found that the way ofcalming asthma didn’t call'y out as弘2一receptor Docking techconique was used for pounds’relevant results indi