雷帕霉素-多聚丙交酯乙交酯药膜洗脱支架结构设计和体外药代动力学研究  

The design and pharmacokinetics in vivo of Rapamycin-PLGA membrane eluting stent

作　　者：徐克[1] 夏永辉[1] 冯博[1] 黄莹莹[2] 齐民[2] 杨大智[2] 

机构地区：[1]中国医科大学附属第一医院放射科,辽宁沈阳110001 [2]大连理工大学材料科学与工程学院,辽宁大连116024

出　　处：《中国介入影像与治疗学》2007年第6期473-477,共5页Chinese Journal of Interventional Imaging and Therapy

基　　金：国家自然科学基金资助项目(30470521)

摘　　要：目的设计适合外周血管的药物洗脱支架可降解多聚物载体药膜,明确所设计药膜的药物释放规律。方法将抗增殖药物雷帕霉素(Rapamycin)加入可降解聚乳酸类多聚物聚丙交酯-乙交酯(PLGA)中制成雷帕霉素PLGA复合物,再将该复合物采用浸涂法均匀涂至镍钛合金外周血管支架表面,制成药物洗脱支架7枚,分为1枚及6枚两组置入人体血液环境模拟系统中进行腐蚀,以高效液相色谱仪分别检测第1、2、3、4、5、6、7、8、9、10天药物释放量(以百分比表示),描记药物释放曲线,用最小二乘法进行回归分析,总结药膜体外药代动力学释放曲线方程,明确药物释放时间和药物累计释放量之间的关系。结果单枚支架药物随时间累计释放量(百分比):第1、2、3、4、5、6、7、8、9、10天分别为14.09,16.71,22.39,29.72,32.98,34.93,37.01,39.55,41.60,43.74,释放曲线符合Higuchi方程:Mt/M∞(%)=2.9605×t1/2(h)-1.315(r=0.9906,n=10);6枚支架组药物随时间累积释放量(百分比):第1、3、5、7、9天分别为11.02,19.01,29.62,35.66,41.23,释放曲线符合Higuchi方程:Mt/M∞(%)=3.1722×t1/2(h)-5.682(r=0.9944,n=5)。结论聚乳酸类多聚物PLGA可以承载和控释抗增殖药物雷帕霉素,PLGA-雷帕霉素复合物可以用来涂敷镍钛合金外周血管支架,药物释放可持续50天以上,药物的释放规律能够和血管内膜增生的时间窗相适应。因此,聚乳酸类多聚物PLGA是外周血管药物洗脱支架较为理想的药物载体,PLGA-雷帕霉素药膜的药代动力学规律在预防支架内再狭窄方面将具有较高的临床应用价值。Objective To design a scientific mode of drug-eluting stent membrane fit for peripheral artery and to identify the drug releasing rule of the membrane. Methods Mix Rapamycin and PLGA to gain the compounds; aplly the NiTi alloy human peripheral artery stents with the compounds using dipping coating technique to achieve 7 drug-eluting stents. Put 1 and 6 stents in the human body fluid environment simulation system to erode and detect the daily accumulative dose of the drug release with high performance liquid chromatogram （HPLC） with 10 days, tracing the drug releasing curve. Analyze the results with least square method and summarize the time-dose curve equation of the drug membrane releasing. Results The accumulative release of single stent： 14.09, 16.71, 22.39, 29.72, 32.98, 34.93, 37.01, 39.55, 41.60, 43.74 in 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 days respectively, the releasing curve follow the Higuchi equation： Mt/M∞（% ）= 2. 9605 × t1/2 （h） - 1.315 （r= 0.9906, n = 10）, while the six stents group 11.02, 19.01, 29. 62, 35.66, 41.23 in 1, 3, 5, 7, 9 days. The releasing curve follow the Higuchi equation： Mt/M∞（% ） = 3. 1722 × t1/2 （h） - 5. 682 （ r= 0. 9944, n = 5）. Conclusion PLGA can carry and control the release of Rapamycin, PLGA-Rapamycin compounds can be coated the NiTi alloy human peripheral artery stents, the drug releasing can last more than 50 days, the rule of the drug-release can fit the intima proliferation. Therefore, PLGA is the satisfactory drug carrier of drug-eluting stent,and the pharmacokinetics of PLGA-Rapamycin membrane have potential clinical value in preventing the in-stent stenosis.

关 键 词：支架 多聚丙交酯-乙交酯 雷帕霉素 药代动力学 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]