摘要：
背景:环丝氨酸肝毒性小,与现有抗结核药物无交叉耐药性,目前多用于耐药结核菌的治疗,但其口服和注射均有一定的神经毒性.目的:为克服该药的神经毒性,同时提高结核病灶局部位药物浓度,制备聚乳酸羟基乙酸-环丝氨酸缓释微球植入剂,观察其体外释药性能.方法:应用复乳溶剂挥发法制备聚乳酸羟基乙酸-环丝氨酸缓释微球,将微球经白芨多糖提取物黏结成海绵体植入剂,观察植入剂中乳酸羟基乙酸-环丝氨酸缓释微球的形态、粒径、载药量、包封率及体外实验性能.将聚乳酸羟基乙酸-环丝氨酸缓释微球植入剂分别置于室温(25°C)、高温(60°C)、高湿(93％)条件下放置,于0,1,2个月取样,考察微球的载药量、突释量、外观形态和分散性.结果与结论:聚乳酸羟基乙酸-环丝氨酸缓释微球球体圆整,平均粒径为(143±38) μm,植入剂微球载药量和包封率分别为38.38％和67.54％;植入剂中聚乳酸羟基乙酸-环丝氨酸缓释微球无明显突释现象,50 d药物累计释放65.62％;在室温、高温、高湿放置1,2个月后,聚乳酸羟基乙酸-环丝氨酸缓释植入剂微球的外观形态完整,载药量和突释量均无明显变化,质量稳定.结果表明,聚乳酸羟基乙酸-环丝氨酸缓释微球植入剂降解时间和药物释放结果符合骨恢复生长生物学要求.%BACKGROUND:Cycloserine with low hepatotoxicity exhibits no cross-resistance with the existing anti-tuberculosis drugs,and has been commonly used for the treatment of drug-resistant tuberculosis.However,its oral administration or injection leads to a certain degree of neurotoxicity.OBJECTIVE:To prepare poly(lactic-co-glycolic acid) (PLGA)-cycloserine sustained-release microspheres which are expected to reduce the neurotoxicity and adverse reactions,and maintain the drug concentration in the bone tuberculosis region for a long time,and to observe the in vitro drug release of the microspheresMETHODS:Double emulsion solvent evaporation method was used to prepare PLGA-cycloserine microspheres that were bonded into sponge implant by Bletilla striata polysaccharide extract.Then,morphology,particle size,encapsulation efficiency and in vitro performance of the microspheres were observed.The drug loading,burst release,appearance and dispersion of the microspheres were observed at 0,1,2 months after the microspheres were placed in room temperature (25 °C),high temperature (60 °C) and high humidity (93％),respectively.RESULTS AND CONCLUSION:The PLGA-cycloserine microspheres that were round and spherical presented with the mean particle size of (143±38) μm,the drug loading of 38.38％ and the encapsulation efficiency of 67.54％.No burst release occurred,and the cumulative release of drug within 50 days was 65.62％ After being stored at room temperature,high temperature and high humidity for 1 and 2 months,the microspheres were intact in the appearance and morphology,and showed insignificant changes in drug loading and burst release.To conclude,the time of degradation and the release of drug accord with the biological requirements of bone restoration.
