卡维地洛pH敏感性水凝胶智能给药系统研究-药学、药物分析专业毕业论文.docxVIP

兰州大学硕士毕业论文摘要 兰州大学硕士毕业论文 摘要 首次以卡维地洛为主药，壳聚糖及其衍生物Ⅳ-琥珀酰壳聚糖和海藻酸钠为主要 智能载体，采用离子胶凝化法分别制备了卡维地洛pH敏感性壳聚糖一海藻酸钙凝胶 小球和卡维地洛Ⅳ-琥珀酰壳聚糖一海藻酸钙凝胶小球，并通过单因素试验和正交试 验优选了水凝胶制备工艺。利用电子显微镜扫描方法观察了水凝胶小球表面形态， 并用红外光谱对其结构进行了表征。依据水凝胶特性，考察了两种水凝胶在体外不 同介质中的溶胀度和释放性能，并阐明了其在体外不同pH环境中的释放机理。结 果表明卡维地洛壳聚糖一海藻酸钙凝胶小球和卡维地洛Ⅳ-琥珀酰壳聚糖一海藻酸钙 凝胶小球成型效果好，且形状规则；释药行为具有明显的pH敏感性。卡维地洛壳 聚糖一海藻酸钙凝胶小球在pHl．5的盐酸溶液中16 h后药物累积释放度达26．7％， 在pH7．4的磷酸盐缓冲液中可达89．40％；模拟胃肠实验表明，在人工胃液中2 h卡 维地洛平均累积释放达21．1％，转移至pH7．4的磷酸盐缓冲液中23h后，卡维地洛 平均累积释放达到81．7％。卡维地洛Ⅳ-琥珀酰壳聚糖一海藻酸钙凝胶小球在pH2．5 的磷酸盐缓冲液中16 h卡维地洛累积释放度达31．40％，在pH7．4的磷酸盐缓冲液 中可达87．85％：模拟胃肠实验在人工胃液中3h卡维地洛平均累积释放达26．93％， 转移至pH7．4的磷酸盐缓冲液中23 h后，卡维地洛平均累积释放达到95．03％。两 种凝胶小球在不同pH条件下卡维地洛的释放机理用半指数方程分析，发现在 pHl．5．5．0的缓冲液中，药物从水凝胶骨架中释放机制为非Fick扩散，而在 pH6．8．8．0，药物释放为骨架溶蚀机制。结果表明两种凝胶小球能够持续缓慢的释放 药物，可望研究开发为适合肠道给药的pH敏感性智能释药系统，使之经口服后， 预定在肠道部位定位、定量、持续恒定释放药物，达到治疗心血管疾病时用药的智 能化和按需释放药物，减少药物毒副作用，减小给药次数和延长给药周期。 关键词智能给药系统；pH敏感性；水凝胶；壳聚糖；No琥珀酰壳聚糖；卡维地洛 兰州大学硕士毕业论文Abstract 兰州大学硕士毕业论文 Abstract Firstly,using chitosan，N-succinyl chitosan OVsc)and alginate as main intelligent carders，pH sensitive chitosan-alginate hydrogel beads loaded carvedilol and NSC／alginate hydrogel beads loaded carvedilol were prepared respectively by the ionic gelation method in the first time． Secondly，the optimum preparation technique was investigated respectively by single factor design and orthogonal test．The physical and chemical characterizations of the two kinds of hydrogels beads were performed by SEM and FTIR． Finally,swelling behavior and release properties of the two kinds of hydrogel beads in various pH phosphate buffer solutions were investigated，and the release mechanism in vitro was researched． The results showed that the surface morphology of chitosan—alginate hydrogel beads loaded carvedilol and NSC／alginate hydrogel beads loaded carvedilol were spherical and regular,in vitro release behavior presented excellent pH sensitivity．The release of carvedilol from the chitosan—alginate hydrogel beads at pH 1．5 Was relatively low (26．7％)，while this value approached