蟾酥总内酯聚乳酸微球的制备、缓释性能及其临床药效评价  

Preparation of polylactic acid microspheres containing lactones from Venenum Bufonis,its slow-release characteristics and therapeutic effects on mycoplasmal pneumonia of swine

作　　者：陈秀秀[1] 王文佳[1] 吴倩倩[1] 沈祥广[1] 邱电 董斌 梁梓森[1] 方炳虎[1] 曾振灵[1] 陈建新[1] 

机构地区：[1]华南农业大学兽医学院广东省兽药研制与安全评价重点实验室,广东广州510642 [2]广东惠华药业有限公司,广东广州511300

出　　处：《中国兽医学报》2015年第12期2014-2020,共7页Chinese Journal of Veterinary Science

基　　金：国家自然科学基金资助项目(30972217);广州市科技计划资助项目(201300000201);广东大华农动物保健品股份有限公司资助项目(012A201105-2)

摘　　要：为获得具有缓释性能的蟾酥总内酯微球，以75％乙醇及二氯甲烷提取蟾酥粉，获得蟾酥总内酯；以聚乳酸（PLA）为包材，采用乳化-溶剂挥发法制备了蟾酥总内酯PLA微球。以扫描电子显微镜观察微球的形貌及颗粒大小，采用分光光度法测定该微球的包封率及载药量，采用动态透析法考察该微球的体外药物释放过程。采用高效液相色谱-质谱／质谱分析方法，获得了蟾酥总内酯溶液剂及PLA微球皮下注射大鼠后蟾毒灵的药代动力学参数。采用蟾酥总内酯PLA微球分别与泰乐菌素及氟苯尼考配伍，肌肉注射治疗临床猪喘气病，考察微球的协同疗效。结果显示，蟾酥总内酯在蟾酥中的含量为30．1％；制得的蟾酥总内酯PLA微球呈完整的圆球型，大部分微球粒径在1-10μm，微球平均载药量为23．4％，平均包封率为31．5％。在体外微球中蟾酥总内酯24h释放30％，10d释放67％，具有明显的药物缓释效果。大鼠皮下注射蟾酥总内酯PLA微球后，蟾毒灵的达峰时间（Tmax）、消除半衰期（t1/2）和平均滞留时间（MRT）分别是皮下注射蟾酥总内酯溶液剂的4．0，18．5，2．5倍，微球给药后蟾毒灵的血浆峰浓度值只有溶液剂的23．9％，表明PLA微球具有明显的药物缓释效果，可延长药效作用时间并减少药物毒性。蟾酥总内酯PLA微球与泰乐菌素及氟苯尼考联用治疗临床猪喘气病具有良好的协同作用。The purpose of this study was to obtain microspheres containing lactones from Venenurn Bufonis with drug controlled-release property, and evaluate therapeutic effects of the microspheres on mycoplasma pneumoniae of swine clinically. Total lactones were extracted from Venenurn Bulbhis with 75% ethanol and methylene dichloride. Using polylactic acid （PLA） as encapsulating materials,PLA microspheres containing lactones from Venenurn Bufonis were prepared by the emul- sion-solvent evaporation method. The obtained microspheres was observed with a scanning electron microscopy to survey their morphological structure and size. The drug loading capacity and encapsulating efficiency of the microspheres was determined with a ultraviolet visible spectropho- tometry. The dynamic dialysis method was used to investigate the drug release in vitro of the microspheres. A high-performance liquid chromatograpgy linked with tandem mass spectrometry analysis method for determining bufalin in rat plasm was established to obtain pharmacokinetics parameters of subcutaneously injection of liquors and microspheres of Venenum Bufonis lactones. The therapeutic effect of intramuscular injection of the microspheres combined with tylosin and florfenicol, respectively, on myeoplasma pneumoniae of swine clinically was surveyed. Results showed that the content of total lactones in Venenum Bufonis was 30. 1%. The obtained micro- spheres were round and easy to disperse. Particle size of most microspheres ranged from 1 to 10/2m. The mean drug-loading capacity and drug-encapsulating rate of the microspheres was 23.4% and 31.5% ,respectively. A obvious slow-release effect of lactones from the microspheres was observed with a 30% drug release rate during 24 h and a 67% drug release rate during 10 d. The peak-reaching time （Tmax）,eliminated half life time （t1/2） and mean residence time （MRT） of bufalin in a subcutaneously injection of the microspheres in rats was 4.0,18.5 and 2.5 times of that of the liquors,respectively. The plasm peak c

关 键 词：蟾酥总内酯 聚乳酸 微球 药物代谢动力学 缓释 

分 类 号：S853.7[农业科学—临床兽医学]