肝动脉栓塞米托蒽醌乙基纤维素微球的研究

利用正交实验设计法,优选适用于肝动脉栓塞的米托蒽醌乙基纤维素微球制备条件和工艺;采用动态透析法研究了该微球的体外释药规律;根据混悬液的稳定性理论,优选并制备了适于临床肝动脉介导栓塞使用的米托蒽醌乙基纤维素微球混悬注射液。结果表明∶在优化工艺条件下制得的米托蒽醌乙基纤维素微球外形圆整,球径在40～200μm范围内的占总数的91.9%,平均球径为110.24±38.19μm;包封率为55.6%;载药量为12.5%;体外释药符合单指数模型,释药方程为lg(Y_∞-Y)=-0.116t-1.198×10^-3(γ=0.9992,t₅₀=2.6h);其混悬液适于临床应用。用狗进行的实验表明肝血药浓度高,平均驻留时间比注射剂长2.45倍。

STUDY ON THE MITOXANTRONE ETHYLCELLULOSE MICROSPHERES FOR LIVER ARTERY EMBOLIZATION

In this paper, orthogonal test was used to optimize the preparation conditions and technique of mitoxantrone ethylcellulose microspheres (DHAQ-EC-MS) for liver embolization. The dynamic osmosis method was used to study the drug release characteristics of DHAQ-EC-MS. DHAQ-EC-MS suspension for clinical liver artery embolization was prepared. The result showed that the DHAQ EC MS is regular in its morphology with a mean diameter of 110.24±38.19 μm. The drug loading was 12.5% and embedding ratio was 55.6%. The release characteristics was in accord with single exponential model. The drug release equation is lg(Y_∞-Y)=-0.116t-1.198×10^-3 (γ=0.9992, t₅₀=2.6 h). The DHAQ EC MS was shown to be physically and chemically stable and its suspension is suitable for clinical use. Experiments in dogs indicate that drug concentration of DHAQ-EC-MS in hepatic vein blood was higher than DHAQ solution, and the MRT_0～72 was 2.45 times higher than DHAQ solution.