复合三联抗结核药聚乳酸-羟基乙酸缓释微球的制备及体外释药特性

发布时间：2018-06-25 20:28

本文选题：抗结核药 + 异烟肼　；参考：《中国脊柱脊髓杂志》2015年05期

【摘要】：目的 :制备复合异烟肼(H)、利福平(R)、吡嗪酰胺(Z)的聚乳酸-羟基乙酸(HRZ/PLGA)缓释微球,观察其理化性质和体外缓释特性。方法:以PLGA(450mg)为载体,避光条件下称取H(40mg)、R(60mg)、Z(125mg),采用复乳-溶剂挥发法制备HRZ/PLGA缓释微球,应用扫描电镜观察微球的形态特征;应用高效液相色谱法(HPLC)测定其载药量、包封率;采用溶出法、HPLC于3h、6h、12h、1d、2d、3d、6d、9d、12d、15d、20d、25d、30d、40d、50d测定H、R、Z三种药物的浓度,观察其是否均大于10倍最低抑菌浓度(MIC),计算其日均释药率、累计释药率。结果:HRZ/PLGA微球在电镜下观察呈圆球形,平均粒径为10.3±4.7μm;H、R、Z三种药物的载药量分别为(18.02±0.36)%、(22.46±0.24)%、(21.68±0.37)%,包封率分别为(54.79±1.13)%、(72.35±0.39)%、(67.21±0.68)%;体外缓释试验显示微球缓释前12d左右,三种药物的累计缓释度均超过了50%,日均释药率分别为5.05%、4.89%、6.86%;第12天后三药的缓释基本趋于稳定,日均释药率分别为0.17%、0.26%、0.16%;三种药物缓释到50d时均大于10倍MIC。结论:HRZ/PLGA微球具有优良的载药及药物缓释效果,是一种理想的复合抗结核药物缓释系统。
[Abstract]:Aim: to prepare composite isoniazid (H), rifampicin (R) and pyrazinamide (Z) polylactic acid-glycolic acid (HRZ / PLGA) sustained release microspheres and observe their physicochemical properties and in vitro sustained release properties. Methods: using 450mg as carrier, H (40mg) R (60mg) Z (125mg) was used to prepare HRZ / PLGA sustained-release microspheres by means of compound emulsion and solvent volatilization. The morphological characteristics of the microspheres were observed by scanning electron microscope (SEM), and the drug loading and encapsulation efficiency were determined by high performance liquid chromatography (HPLC). HPLC was used to determine the concentrations of three drugs, HG RZ, at 3h, 6h, 12h, 12h, 1d, 3d, 3d, 6d, 9d, 12d, 15d, 20d, 25d, 30d, 30d, 40d, 50d, to observe whether they were all more than 10 times the minimum inhibitory concentration (MIC), to calculate their daily average release rate, and to calculate the cumulative drug release rate. Results the microspheres of HRZ / PLGA microspheres were spherical under electron microscope, with an average particle size of 10.3 卤4.7 渭 m, and the drug loading amounts of the three drugs were (18.02 卤0.36), (22.46 卤0.24), (21.68 卤0.37), respectively, and the entrapment rates were (54.79 卤1.13), (72.35 卤0.39), (67.21 卤0.68), respectively. The accumulative sustained-release degree of the three drugs exceeded 50 and the daily average drug release rate was 5.05 and 4.896.86 respectively. After the 12th day, the sustained release rate of the three drugs tended to be stable, the daily average drug release rate was 0.17 ~ 0.26 and 0.16, respectively, and the three drugs were more than 10 times at 50 days. Conclusion the microspheres of w HRZ / P PLGA have excellent drug delivery and drug delivery effect, and are an ideal drug delivery system for antituberculotic drugs.
【作者单位】：宁夏医科大学研究生院;美国南佛罗里达大学药学院;宁夏医科大学总医院脊柱骨科;宁夏医科大学总医院创伤骨科;宁夏医科大学药学院;
【基金】：国家自然科学基金项目(代码:81360275) 宁夏自然科学基金项目(代码:NZ13131) 宁夏医科大学基金项目(代码:XT20)
【分类号】：R943

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