紫杉醇新剂型的开发及临床研究进展  

Advances in clinical research and development of new form of paclitaxel

作　　者：张晓静[1] 张频[1] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤医院内科,北京100021

出　　处：《癌症进展》2007年第1期66-72,98,共8页Oncology Progress

摘　　要：紫杉醇广泛用于卵巢癌、乳腺癌、肺癌等多种肿瘤的治疗。但由于其难溶于水，需溶于聚氧乙烯蓖麻油（cremophor EL）与无水乙醇混合溶媒中增加水溶性，而cremophor EL在体内降解时释放组胺，导致不同程度的过敏反应，亦可引起神经细胞内颗粒释放及脱髓鞘改变而加重紫杉醇的外周神经毒性。为降低毒性，提高其疗效，近年来临床上陆续开发了紫杉醇的新剂型，其中不含聚氧乙烯蓖麻油注射紫杉醇白蛋白纳米混悬液（ABI-007）已在欧美上市，具有不用抗过敏预处理、疗效较好、毒性较低等特点；现正在国内进行临床研究我国研发的紫杉醇脂质体已开始在临床应用而紫杉醇的前体药物（DHA—PTX）和聚合物剂型genexol—PM及xyotax也正在临床前和临床Ⅰ-Ⅲ期研究中，显示了良好的前景。本文就紫杉醇的作用机制，不良反应及新制剂的开发和应用进行回顾和综述。Over the past two decades, paclitaxel has played a significant role in the treatment of various malignancies. However, intravenous administration of paclitaxel is hindered by poor water solubility of the drug. Currently, paclitaxel is dissolved in a mixture of ethanol and Cremophor EL, and this formulation is associated with significant side effects, which are considered to be related to the pharmaceutical vehicle, ternative including clinically relevant acute hypersensitivity reactions and peripheral neuropathy, etc. Alformulations of paclitaxel were developed in order to improve its aqueous solubility, and decrease the side effects, which include albumin nanoparticles （ABI -007 ）, taxane polyglutamates （Genexol -PM and Xyotax）, prodrugs （ DHA - PTX）, and lipsomes, etc. An overview of these novel formulations of paclitaxel, their mechanisms of action, adverse effects, and clinical administration will be discussed.

关 键 词：紫杉醇剂型 白蛋白溶剂型纳米紫杉醇 紫杉醇脂质体 前体药物 聚合物剂型 

分 类 号：R73-361[医药卫生—肿瘤]