羟丙基-β-环糊精对齐墩果酸与熊果酸包合作用的研究

摘要

Objective:To determine the difference in the complex formation processes of oleanolic acid (OA) and ursolic acid (UA) which are insoluble isomers with hydroxypropyl-β-cyclodextrin (HP-β-CD).Methods:The changes in the UV and 1H-NMR spectra of HP-β-CD during interacting with OA and UA were observed respectively.The influences of substitution degree of HP-β-CD,pH and temperature on the inclusion process were evaluated by phase solubility method with complexation efficiency (CE) as an indicator.Meanwhile,the thermodynamic parameters during the complexation were also calculated.Furthermore,the inclusion compounds of OA-and UA-HP-β-CD were prepared by stirring method,and DSC and X-ray were performed to identify the compounds.Results:The UV and 1H-NMR spectra showed that the interaction of HP-β-CD with OA and UA formed hydrogen bond.The CE of OA was higher than UA in the different substitution degree of HP-β-CD,pH and temperature respectively.In addition,there was significant difference between the two inclusion processes according to the thermodynamic parameters.The preparation process is simple and easy to do,and the DSC and X-ray characteristics confirmed that the complexs of OA-and UA-HP-β-CD were formed.Conclusion:HP-β-CD can form inclusion compound with OA and UA to increase the solubility of drugs although there was significant difference between the two inclusion processes due to the different structure of OA and UA.%目的:本文考察了齐墩果酸(oleanolic acid,OA)和熊果酸(ursolic acid,UA)这2种难溶性同分异构体与羟丙基-β-环糊精(hydroxypropyl-β-cyclodextrin,HP-β-CD)包合过程的差异.方法:观察HP-β-CD与OA,UA相互作用时的核磁共振氢谱(1 H-NMR)和紫外吸收图谱的变化.以包合效率(complexation efficiency,CE)为评价指标,采用相溶解度法比较OA和UA在不同取代度的HP-β-CD,pH值和温度时包合过程的差异,并计算在包合过程中出现的热力学参数.通过搅拌法分别制备了OA-HP-β-CD和UA-HP-β-CD包合物,差示扫描热分析(DSC)和X-射线衍射(X-ray)鉴定包合物.结果:在紫外、1 H-NMR图谱中,HP-β-CD与OA和UA相互作用产生氢键.在不同取代度的HP-β-CD,pH值和温度下的包合效率OA高于UA,并且OA和UA的热力学参数表明两者包合过程存在差异.制备工艺简单、易行;DSC和X-ray表征OA-HP-β-CD,UA-HP-β-CD包合物形成.结论:OA和UA可以与HP-β-CD形成包合物,增加药物溶解度.OA和UA的结构不同,两者与HP-β-CD的包合过程存在差异.