羟基喜树碱液体栓塞剂的制备及体外栓塞效果评价  

Preparation and in vitro embolic efficiency evaluation of hydroxycamptothecine-loaded liquid embolic agent

作　　者：覃玲珍[1,2] 张晅[1] 吴琳娜[1] 张瑾[1] 潘昕[1] 李革 吴传斌[1,2] 

机构地区：[1]中山大学药学院,广东广州510006 [2]广东省创新药物制剂工程技术研究开发中心,广东广州510006 [3]广州新济药业科技有限公司,广东广州510006

出　　处：《药学学报》2014年第7期1069-1075,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81173002);广东省创新药物制剂工程技术研究开发中心资助项目(2011B080100019)

摘　　要：本文制备了羟基喜树碱立方液晶液体栓塞剂并对其体外栓塞性能进行评价。以植烷三醇为材料制备新型立方液晶液体栓塞剂,通过三元相图的绘制筛选最优处方;以偏光显微镜、差示扫描量热和小角衍射等手段对栓塞剂吸水后形成的立方液晶进行结构表征;通过液相检测和X射线衍射分析研究羟基喜树碱在制剂中的存在形式;初步评价了载药液体栓塞剂的体外溶出;建立了体外栓塞模型评价制剂体外栓塞性能,并考察了胶凝时间和凝胶黏附力。结果表明,制得的羟基喜树碱前体栓塞溶液黏度低,适于注射,能在水性环境中迅速形成有生物黏附性的高黏度立方液晶,内部结构为Pn3m型;具有较好的体外栓塞效果,且药物在形成凝胶后结构未发生改变,仍以闭环活性形式存在,药物能缓释30天以上,说明立方液晶液体栓塞剂具备用于栓塞治疗的特点,有用于肿瘤临床治疗的潜能。The purpose of this study is to investigate the preparation of hydroxycamptothecine（HCPT）-loaded cubic crystal liquid embolic precursor solution, and evaluate its in vitro embolic efficiency. Phytantriol was used as cubic crystal liquid embolic material, and the optimal formulation was selected according to ternary phase diagram. Polarized light microscopy, differential scanning calorimetry, and small angle X-ray scattering（SAXS） were used to characterize the cubic crystal structure. High performance liquid chromatography and X-ray diffraction analysis were used to investigate the lactone ring of HCPT. In vitro dissolution was preliminary evaluated, and the simulation embolic model was constructed to evaluate the embolic efficiency of precursor solution. Meanwhile, the gelation time and adhesion force were investigated. The results showed that HCPTloaded precursor solution for embolization had been successfully prepared with low viscosity which was injectable. The precursor solution could transform into Pn3m structure liquid crystal phase gel rapidly when contracting with excess water. The formed HPCT gel remained its lactone form as the same in precursor solution, and expressed the good ability to block the saline flow, and HCPT could keep sustained releasing drug over 30 days. The prepared drug-loaded embolic precursor solution showed a promising potential for vascular embolization and application in clinical treatment of tumor.

关 键 词：液体栓塞剂 立方液晶 植烷三醇 羟基喜树碱 

分 类 号：R943[医药卫生—药剂学]