环糊精及其衍生物对药物溶出影响-药物分析学专业论文.docxVIP

摘要环糊精具有“空腔”结构可与药物形成“主客体”包合物。利用环糊精的包合物技术， 改善难溶性药物溶出，备受研究者关注。本论文初步考察环糊精及其衍生物对药物溶出 影响，主要内容如下：本文选取 β-环糊精（β-CD）和亲水羟丙基-β-环糊精（HP-β-CD）作为改善药物溶 出的辅料，分别选取模型药物诺氟沙星和格列美脲，利用正交实验设计优化片剂处方， 采用研磨法混合药物与环糊精等辅料，湿法制粒压片压制自制诺氟沙星或格列美脲片 剂，分别对压制片进行质量考察。结果表明两种自制片的片重差异、脆碎度、崩解时限 均符合中国药典要求。环糊精诺氟沙星片剂的溶出相比诺氟沙星片剂对照组，诺氟沙星 溶出有明显改善；而 HP-β-CD 辅料引入，能促进难溶性格列美脲药物溶出，其效果同 样优于对照格列美脲片。为拓展环糊精应用，本文在环糊精母体结构上进行化学修饰，经酯化反应自制乙酰 化-β-环糊精（AT-β-CD），并用红外色谱仪（FT IR）和核磁共振仪（H NMR）对材料 进行表征。选择抗癌药米托蒽醌（MTO）为模型药，以 AT-β-CD 为载体，采用透析法 包载 MTO，经透射电镜、粒度分析仪、FT IR 和 XRD 对 AT-β-CD 空白纳米粒及载药纳 米粒进行表征，考察 MTO 的 AT-β-CD 载药纳米粒的体外释放行为，结果显示负载 MTO 药物达到缓慢释放，故 AT-β-CD 材料可能成为潜在抗肿瘤药物缓释载体。乙酰化环糊精 衍生物合成丰富了环糊精及其衍生物在医药领域中的应用。关键词环糊精羟丙基-β-环糊精 乙酰化-β-环糊精 溶出 释放IAbstractAbstractCyclodextrins (CDs) are oligosaccharides with a hydrophilic outer surface and a somewhat lipophilic central cavity, and they can formed into “host-guest” inclusion complexes with drugs due to their special “molecular cages” structure. Cyclodextrins have captivated many scientists, because it can be used as excipients for solubilization of drugs in aqueous formulations. The dissertation preliminary investigated that the solubility changed of drugs whether adding cyclodextrin derivatives or not, main content as follows:HP-β-CD and β-CD were chosen as adjuvant which could improve the dissolution rate of poorly soluble drugs. Norfloxacin and glimepiride were chosen as model drugs in the study. Orthogonal test was used to optimize the conditions for the technology of preparation the tablets, kneading method was used to mix the drug and adjuvant, and then the tablets was prepared by the wet granulation tableting. According to the Chinese Pharmacopoeia (2010), the weight differences, friability, disintegration and dissolution rate of tablets were met the requirements respectively. Moreover, the dissolution rate of norfloxacin or glimepiride tablets were improved when β-CD or HP-β-CD were added.In order to expend its application, acetylate-β-CD (AT-β-CD) was synthesized by esterification reaction