超氧化物歧化酶明胶微球的制备与表面化学修饰研究

【作者】 梁荣才；

【导师】 莫凤奎；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2003， 硕士

【摘要】 超氧化物歧化酶(SOD)是重要的氧自由基清除剂，可以用于治疗和预防与自由基损伤有关的一些疾病。目前，SOD在临床应用上主要以注射方式给药，而口服给药方式研究较少。本工作将SOD制成微球，以提高SOD稳定性和口服相对生物利用度，且在微球制备条件方面作了进一步研究。 以连苯三酚自氧化法作为SOD的活力分析方法，并对该方法的精密度，回收率及线性范围进行了考察。结果表明，该方法可行。 从理化性质的角度，考察了不同高分子材料对SOD活力的影响，结果表明天然高分子材料更有助于保持SOD的活力。 本工作采用乳化凝聚法制备明胶微球。对制备条件先进行了单因素考察，然后利用正交设计进行了优选。最佳制备条件为：水相油相体积比为3：40，温度为60℃，时间为5min，转速为400rpm；所得微球载药量为23200u／g，包封率为88％，粒径分布集中在25～75um。 本工作考察了海藻酸钠的流变性，与明胶的相容性，以及与明胶的界面张力，并测定了壳聚糖的脱乙酰度和分子量。在此基础上制备了明胶海藻酸钠复合微粒及表面修饰的明胶微球，对它们的各种性质，包括含药量，稳定性，释放性及表面性质进行了研究。 在药效学方面，首先考察了SOD抗小鼠耳肿胀作用的量效关系，然后考察了SOD溶液和不同形式微球抗炎作用的时效关系。结果表明，几种微球均可显著延长SOD抗炎作用的时间。更多还原

【Abstract】 Superoxide dismutase (SOD) is an important scanvenger of reactive oxygen radicals, which can be used to treat or prevent radical-related diseases. Nowadays, SOD is used mainly as injection clinically, while oral formulation for SOD is less investigated. In this work, SOD gelatin microspheres were made with the aim to improve its stability, oral relative bioavailability, and to study the preparation conditions of microspheres.First, the auto-oxidization of pyrogallol was used as the analysis method to determine SOD activity, and the precision , recovery and linear range of the method were investigated. The results showed that the method was feasible.In physical and chemical property tests, different macromolecular materials were tried to protect SOD activity, and the results showed that natural polymers, such as gelatin and alginate, were more effective in SOD activity protection than synthesized ones.In this study, SOD gelatin microspheres were prepared by emultion coagulation procedure. After single factor tests, the orthogonal design were performed to opitimize the conditions for the process. The best condition was W/O,3: 40, temperature, 60 C, time, 5 min, agitation rate, 400rpm. The microspheres thus derived had an embedding rate of 88%, a drug loading of 23200u/g, and a size mainly around 25-75 urn.We studied the rheology of alginate, its compatability with gelatin and the interfacial tension between alginate and gelatin, the molecular weight and degree of deacylation of chitosan were determined as well. On the basis of the work above,the alginate gelatin complex microparticle and the surface modified microsphereswere prepared, and the SOD embedding rate ,SOD stability and release behavior of the product were determined . The surface property of the modified microsphere were studied, too.In pharmacodynamics, the dose-response relationship of SOD in antiinflammation was studied, then the time-response property of different microspheres were investigated. The results showed that all of the microspheres could prolong the antiinflammation time in mouse.更多还原