缓释利福平微球释药性质及兔脊柱结核模型建立的初步实验研究

发布时间：2018-07-16 21:15

【摘要】：目的：通过缓释利福平微球体外和体内脊柱旁局部给药释药实验，研究该微球在体外和体内脊柱旁释药特点；在兔腰椎上钻孔植入标准结核菌株H37Rv建立兔脊柱结核模型，为将来进行同类实验奠定实验基础。方法：(1) 用优化O／W乳化—溶剂挥发法制备PLGA—利福平缓释微球，常规冻干保存。(2) 采用扫描电镜对该微球进行形态学观察，并用粒度分析仪测定其分布。(3) 采用高效色谱仪实验建立用于利福平含量测定的标准曲线和回归方程，测定其载药量和包封率。(4) 以PBS液为体外降解和释药介质，初步研究利福平微球体外释药性质。(5) 将利福平微球植入兔脊柱旁，初步研究其在体内的释药性质。(6) 通过兔腰椎椎体钻孔植入结核标准菌株H37Rv，，建立兔脊柱结核模型。结果：(1) PLGA—利福平缓释微球表面光滑圆整，球体均匀度好，无粘连现象。(2) 粒度分析仪检测，微球大小较均匀，平均粒径为68.699μm。(3) 利福平微球的载药量为33.16±1.33(％)，包封率为54.79±1.37(％)。(4) 利福平微球体外释药结果显示：微球体外释药过程较为稳定，突释期内微球体外释放度为14.56％，42d后累计释放度达到92.14％，微球体外释药规律符合Higuchi方程：F(t)=15.404t~(1／2)-8.8915(r=0.9984)。(5) 体内实验结果显示，将利福平微球按含利福平75mg·kg~(-1)的剂量植入椎
[Abstract]:Objective: to study the drug release characteristics of rifampicin microspheres in vitro and in vivo by local administration of rifampicin microspheres in vitro and in vivo, and to establish a rabbit spinal tuberculosis model by implanting standard tuberculosis strain H37Rv into the lumbar vertebrae of rabbits. To lay the experimental foundation for the similar experiment in the future. Methods: (1) PLGA-rifampicin sustained-release microspheres were prepared by optimized O / W emulsification-solvent volatilization method and were preserved by freeze-drying. (2) the morphology of PLGA-rifampicin microspheres was observed by scanning electron microscope (SEM). The distribution of rifampicin was determined by particle size analyzer. (3) the standard curve and regression equation for the determination of rifampicin were established by high performance chromatograph. (4) PBS solution was used as in vitro degradation medium and drug release medium. The in vitro drug release properties of rifampicin microspheres were studied. (5) rifampicin microspheres were implanted beside the spinal column of rabbits and their release properties in vivo were preliminarily studied. (6) the rabbit spinal tuberculosis model was established by implanting the standard tuberculosis strain H37Rvthrough the rabbit lumbar vertebrae. Results: (1) PLGA-rifampicin sustained-release microspheres had smooth surface, good spherical uniformity and no adhesion. (2) Particle size analysis showed that the size of microspheres was uniform. The average diameter of rifampicin microspheres was 68.699 渭 m. (3) the drug loading of rifampicin microspheres was 33.16 卤1.33 (%), and the entrapment efficiency was 54.79 卤1.37 (%). (_ 4). The results showed that the release process of rifampin microspheres in vitro was relatively stable. The in vitro release rate of microspheres reached 92.14 after 42 days of sudden release, and the in vitro release pattern of microspheres was in accordance with Higuchi equation: F (t) 15.404t-1 ~ (1 / 2) -8.8915 (r 0.9984). (5). The results showed that rifampicin microspheres were implanted into vertebrae at the dose of rifampin 75mg kg ~ (-1).
【学位授予单位】：四川大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R529.2;R-332

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