【作者】 王钰涵；

【导师】 韩光；

【作者基本信息】 河南大学 ， 中药学， 2011， 硕士

【摘要】 穿心莲是一种常用的清热解毒类中草药,现代研究表明,穿心莲具有显著的抗肿瘤作用,其有效成分是以穿心莲内酯、脱水穿心莲内酯、14-去氧穿心莲内酯为代表的二萜内酯类化合物。穿心莲内酯和脱水穿心莲内酯在2010版中国药典中是穿心莲药材及其制剂含量测定的重要指标。韩光等采用超分子技术富集穿心莲醇提物,得到的穿心莲超分子提取物中二萜内酯类成分的含量达到50%以上,具有显著的体内抗肿瘤作用,且明显优于穿心莲内酯单体及穿心莲乙醇粗提物。为提高穿心莲超分子提取物在水中的溶解度,本课题采用现代靶向制剂技术,以泊洛沙姆188为载体材料,将穿心莲超分子提取物制备成胶束给药系统。制备方法采用薄膜分散法,以包封率、载药量为主要指标,考察投药量、水化体积、旋转蒸发温度、水相pH值等影响因素,选择影响较大的三个因素,即投药量、水化体积、旋转蒸发温度进行正交设计,得到最优处方为:投药量15mg,ploxamer 188 120mg,水化体积8mL。优化得到的胶束溶液均一澄明,平均粒径为190nm。包封率为(85.7+2.1)%,载药量(3.9±0.1)%。以超分子提取物溶液为对照,胶束的释放实验结果显示其具有一定的缓释效果。以超分子提取物的PEG溶液为对照组,穿心莲超分子提取物胶束为样品,小鼠尾静脉注射后,不同时间测定小鼠组织中穿心莲内酯、脱水穿心莲内酯的浓度,并与原药对比,评价组织分布特点。结果显示与对照组相比,胶束在血液中的浓度降低,在组织器官中的浓度相对增加,其中肝脏、肺部的浓度相对增加较为显著。提示胶束有利于肝、肺部的抗肿瘤治疗。结果表明poloxamer188胶束可作为难溶性药物载体,提高在特定组织中的靶向性。更多还原

【Abstract】 Andrographis is one of commonly used cleaning heat and detoxificating Chinese herbal medicine. Modern research shows that Andrographis has significant anti-tumor effect. It’s major active ingredient is andrographolide,dehydroandrographolide and 14-deoxyandrographolide. andrographolide and dehydroandrographolide are important indicators of the quality inspection in the 2010 edition Chinese Pharmacopoeia.By using supermolecule techniques to enrich ethanol extract of Andrographis paniculata, Han Guang obtained supramolecular extract of Andrographis (SEA), which contained more than 50% of andrographolides.The topic was based on SEA to prepare micelles,which used modern targeting drug delivery system technology,and took poloxamer 188 as carrier material. The SEA-loaded micelles were prepared by thin-film hydration method.The entrapment efficiency was taken as the index to evaluate the effects of the amount of SEA,volume of water phase,temperature of rotary evaporation,and pH of water phase on the characteristics of micelles.Chosing the most influential three factors: the amount of SEA,volume of water phase,temperature of rotary evaporation,to design Orthogonal experiment, the final optimized formulation was 15mg of Andrographis supramolecular extract,120mg ploxamer 188 and 8mL of water phase.The optimized supramolecular micelles solution was uniform and clear : arerage particle size was 198nm;entrapment efficiency was (85.7±2.1)% ;drug loading was (3.9±0.1)% . Compared with SEA solution,in vitro release results of SEA-loaded micelles indicated that the drug release slowly from micelles.Using the original extract as the control group, giving tail vein injection, measuring the concentration of andrographolide and dehydroandrographolide in the organization at different time an d comparing it with the original drug to evaluate the tissue distribution characteristics. The results showed that the relative increase in the concentration of liver and lung was more significant compared with the PEG original drug, so it was beneficial to the treatment of liver cancer and lung cancer.The results showed that poloxamer188 micelle as the carrier of insoluble drugs can improve the targeting of specific tissues.更多还原