【作者】 李正艳；

【导师】 何应；

【作者基本信息】 天津大学 ， 药剂学， 2007， 硕士

【摘要】 壳聚糖来源于虾蟹类壳,在我国资源丰富,产量高,价格低,是自然界中存在的唯一的碱性多糖。近几年壳聚糖作为新型药用辅料得到广泛研究。缓释制剂是一种新型的、具有很多优点的制剂,疗效显著,毒副作用少,用药方便,病人依从性好。应用壳聚糖制备的缓释制剂不仅缓释作用效果显著,且在体内不会蓄积。本文以牛血清白蛋白(BSA)为模型药物,以三聚磷酸钠(Tripolyphosphate sodium, TPP)为凝聚剂,采用离子凝胶法制备了BSA壳聚糖纳米粒(Chitosan nanoparticles, CS-NPS),该方法无需有机溶剂,制备条件温和,有利于保持蛋白多肽类药物的生物活性的稳定性。通过控制不同的反应条件,制备出50nm～683nm之间不同粒度范围的壳聚糖载药纳米粒,用扫描电镜观察纳米粒子的形貌,傅立叶红外光谱表征其结构。并采用紫外分光光度法分析药物含量,纳米粒最大包封率为58.45%,其制备工艺条件具体如下:壳聚糖浓度0.3%,三聚磷酸钠浓度0.15%,壳药比2:1,pH5.1～6.0,搅拌时间30min。载药纳米粒体外药物释放动力学检测表明,壳聚糖浓度、TPP浓度、载药率的高低及冷冻干燥工艺是影响纳米粒释放的主要因素。粒细胞巨噬细胞集落刺激因子(GM-CSF)是作用于造血祖细胞和免疫系统的细胞因子,能刺激单核粒细胞的增殖和分化,在体内半衰期约为1小时,因此在治疗过程中需要频繁注射,为了延长的作用时效,减少给药次数,降低不良反应,制备出GM-CSF缓释纳米新剂型,透射电镜显示纳米粒平均粒径小于200nm。采用荧光分光光度法进行含量分析得出GM-CSF-CS-NPS平均载药量为155.01ug/100mg。持续7d的药物体外释放试验显示,释放初期1h, GM-CSF释放达19.01%,7h释放34.29%。随后药物释放逐渐平缓,至药物释放7d, GM-CSF释放达到62.13%。更多还原

【Abstract】 Chitosan come from the shell of shrimp and crab. In our country, the resources of chitosan is abundant, the yield is high, and the price is low. It is a kind of alkalescence amylase that existed in the nature exclusively, no poisonous and biodegradable. In the last few years chitosan conduct and actions as the new medicine complements is in the ascendant. Sustaine-release preparations is a new product with many advantage. It includes accurate curative effect, badly respond to reduce, patients compliance. Sustained–release preparations used chitosan is not only function of sustained -release markednessly, but also can’t accumulate in the body.Chitosan-BSA is prepared by ioncrosslinking in this paper. The preparation method is mild without organic solvent, so it is suitable for keeping the integrity and biological stability of the albumen and polypeptide. Nanoparticles from 50nm to 683nm are prepared in this paper by modifying the parameter. It determined loading efficiency of chitosan-BSA sustained-release nanoparticles is 58.45% by UV. The content of CS is 0.3%, the content of TPP is 0.15%, Chitosan:BSA =2:1,pH is 5.1-6.0 and time of stirring is 30 min. It shows that the diameter is uniform and the dispersion is good by SEM. The in vitro release test showed that the effects of the drug loading, chitosan content, TPPcontent and freeze drying on the release rate were much.Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine which exhibits activity in the hematopoietic and immune systems. GM-CSF was originally cloned based on its ability to stimulate the proliferation and differentiation of hematopoetic precursors of the granulocyte monocyte lineage. The serum elimination half-life of human GM-CSF in humans is approximately one hour, and therefore daily injections are required to achieve therapeutic effects, To induce the frequency of GM-CSF administration and improve the therapeutic efficency, Chitosan-GM-CSF sustained-release nanoparticles was prepared. It shows the diameter of GM-CSF is less than 200nm by TEM. It determined drug loading of chitosan-GM-CSF sustained-release nanoparticle is 155.01ug/100mg by SPF. The in vitro release test showed that GM-CSF-CS-NPS released fast in 1 hour and became slower after 7 hour.更多还原