【作者】 李文超；

【导师】 双少敏；

【作者基本信息】 山西大学 ， 药物分析学， 2009， 硕士

【摘要】 第一章:本章简要综述了环糊精包合技术的研究进展,着重阐述了环糊精及其衍生物在药物方面的应用研究,并概述了异槲皮苷的基本化学性质和药理作用。第二章:采用共沉淀法制备了异槲皮苷的β-环糊精固体包合物,并用紫外光谱、红外光谱和核磁共振法表征了包合物。利用紫外-可见分光光度法建立了包合物中异槲皮苷的含量测定方法,低、中、高三种浓度的异槲皮苷溶液的日内和日间精密度分别为1.66%、1.42%、0.28%和1.99%、1.34%、1.26%,回收率分别为102.60±0.19%、102.61±0.59%、103.19±0.61%。在此基础上,对异槲皮苷在β-环糊精中的相溶解度进行研究,发现异槲皮苷与β-环糊精形成了1:1型包合物。溶解度研究显示异槲皮苷被制备成固体包合物后,其溶解度提高了822倍。溶出度研究发现异槲皮苷被β-环糊精包合后其溶出度得到显著增强,在30min内,溶出度由原来的41.48%提高至89.80%。第三章:采用共沉淀法、超声法和研磨法制备了异槲皮苷的β-环糊精固体包合物,以包封率、载药率以及溶解度为主要参考指标,优选出共沉淀法做为IQ-β-CD包合物制备的最佳方法。并利用正交试验设计优选出包合物制备的最佳条件为主客体分子比2:1,搅拌时间6 h,搅拌温度55℃。第四章:采用搅拌法对异槲皮苷的羟丙基-β-环糊精固体包合物进行制备,利用紫外光谱、红外光谱和核磁共振法表征了包合物。采用紫外-可见分光光度法建立了包合物中异槲皮苷的含量测定方法,日内和日间精密度均小于2%,回收率分别为100.73±0.82%、101.84±1.12%、103.11±0.93%。通过相溶解度的研究,发现异槲皮苷与羟丙基-β-环糊精之间形成A_L型的1:1型包合物。溶解度研究发现异槲皮苷被制备成固体包合物后,其溶解度提高了15.66倍,与此同时,异槲皮苷的溶出度研究显示其溶出度由原来的30min内累积溶出41.48%提高至15min内累积溶出98.96%。第五章:以收率、包封率、载药率和溶解度为考察指标,通过对搅拌法、超声法和研磨法三种包合物制备方法的评价,优选出包合物制备的最佳方法,并利用正交试验设计优化出包合物制备的最佳条件为主客体分子比3:1,搅拌时间6h,搅拌温度55℃。更多还原

【Abstract】 Chapter 1:The recent development of cyclodextrins inclusion technique has been reviewed and especially focused on the application of cyclodextrins and their derivatives in pharmaceutical industry.The chemical and biological properties of isoquercitrin(IQ) were summarized.Chapter 2:The inclusion complex of IQ withβ-cyclodextrin(β-CD) was prepared and characterized by UV-vis absorption spectroscopy(UV),Fourier transformation-infrared(FTIR) spectroscopy and ~1H Nuclear magnetic resonance(~1H-NMR) spectroscopy.An exact and precise method for UV-vis absorption spectroscopy determination of IQ was developed.The precision experiments within-day and between-day were 1.66%,1.42%,0.28%and 1.99%,1.34%,1.26%,respectively.Results of recovery experiment were 102.60±0.19%,102.61±0.59%and 103.19±0.61%,respectively.The phase solubility diagram of IQ withβ-CD was classified as A_L-type,which suggested IQ was inserted into theβ-CD cavity to form a 1:1 inclusion complex.Further,it is found that the water solubility and dissolution rate of IQ were significantly increased by forming an inclusion complex withβ-CD. The aqueous solubility of IQ-β-CD was 8.22 times higher than that of IQ.The dissolution rate of IQ-β-CD complex was 89.80%within 30 min,while the dissolution rate of IQ was 41.48%which was evidently enhanced by the complex of IQ withβ-CD.Chapter 3:The solid inclusion complex of IQ withβ-CD was prepared by using coprecipitation,ultrasonic and kneading method,respectively.The recovery,inclusion rate,load drug and solubility of IQ were adopted as index to optimize the best method for inclusion preparation.The orthogonal experiment design was applied to optimize the preparation process of inclusion complex.The optimum entrapment conditions were as follows:the reaction time was 6 h,the molar ratio of IQ intoβ-CD was 1:2,the reaction temperature was 55℃.Chapter 4:The inclusion complex of IQ with hydroxypropy-β-cyclodextrin (HP-β-CD) was prepared and characterized by UV,Fourier FTIR and ~1H-NMR.An exact and precise method for UV-vis absorption spectroscopy determination of IQ was developed.The precision experiments within-day and between-day were not more than 2%,respectively.Results of recovery experiment were 100.73±0.82%,101.84±1.12%and 103.11±0.93%, respectively.The phase solubility diagram of IQ with HP-β-CD was classified as A_L-type,which suggested IQ was inserted into the HP-β-CD cavity to form a 1:1 inclusion complex.Further,it is found that the water solubility and dissolution rate of IQ were significantly increased by forming an inclusion complex with HP-β-CD.The solubility of IQ-HP-β-CD was 15.66 times higher than that of IQ.The dissolution rate of IQ-HP-β-CD complex was 98.96%within 15 min,while the dissolution rate of IQ was 41.48%within 30 min which was evidently enhanced by the complex of IQ with HP-β-CD.Chapter 5:The solid inclusion complex of IQ with HP-β-CD was prepared by using stirring,ultrasonic and kneading method,respectively.The recovery, inclusion rate,load drug and solubility of IQ were adopted as index to optimize the best method for inclusion preparation.The orthogonal experiment design was applied to optimize the preparation process of inclusion complex.The optimum entrapment conditions were as follows:the reaction time was 6h,the molar ratio of IQ into HP-β-CD was 1:3,the reaction temperature was 55℃.更多还原