米托蒽醌肝动脉栓塞羧甲基淀粉微球的研究

STUDY ON THE MITOXANTRONE CARBOXYMETHYL STARCH MICROSPHERES FOR HEPATIC ARTERY CHEMOEMBOLIZATION

为进一步研究栓塞微球的制备工艺、体外释药规律及药动学与药效学之间的关系，以米托蒽醌为模型药物、羧甲基淀粉钠为载体材料、对苯二甲酰氯为交联剂，经均匀设计法优化了制备空白羧甲基淀粉微球的工艺，用吸附法制备了米托蒽醌载药羧甲基淀粉微球。对载药微球的理化性质进行了研究。并以家兔为模型动物研究了载药微球经肝动脉栓塞给药后的药代动力学情况。结果表明：载药微球的平均算术粒径为７５７１μｍ，含药量为１３２１％，吸水膨胀率为７１９４％，体外释药符合单指数模型。药动学研究表明，米托蒽醌制成微球经肝动脉栓塞给药后可延长药物驻留于靶位的时间，提示有利于肝癌的治疗。

In this paper, the technology for the preparation of plain carboxymethyl starch microsphere (CMS MS) was optimized by the uniform design method with CMS Na as carrier material and p phthaloyl chloride as acrosslinker. The carboxymethyl starch microsphere loaded mitoxantrone (DHAQ CMS MS) was prepared by absorption method. Then, its morphology, size and size distribution, characteristics of drug loading, drug release in vitro , preparation for clinical application and its stability were studied. The pharmacokinetics of DHAQ CMS MS in rabbit was also studied. The results showed that the average diameter of the DHAQ CMS MS was 75 71 μm, drug loading was 13 21%, expansion ratio in water was 71 94%. The release of DHAQ in vitro from the microspheres was found to fit the model of single exponential function. The suspension prepared in this paper is not only convenient for clinical use, but also favorable for the improvement of the drug stability. The pharmacokinetic parameters obtained from the hepatic atery chemoembolization showed that the DHAQ CMS MS group, when compared with the solution group, exhibited a higher blood drug concentration in hepatic vein, its MRT was 1 96 times that of the solution group. As for the result of the peripheral vein, the MRT of the DHAQ CMS MS group was 1 95 times that of the solution group. This means that the drug when loaded in microsphere will be concentrated in its targeted site for a longer period, which is favorable for the treatment of hepatic cancer.