一种新型的溶石药物控释金属支架治疗难治性胆总管结石的实验研究

发布时间：2018-06-13 21:03

本文选题：金属支架 + 覆膜　；参考：《东华大学》2017年硕士论文

【摘要】：胆结石疾病是一种常见的胆道疾病,给病人的工作生活带来极大痛。药物控释支架携带药物溶解胆总管结石被认为是最佳给药途径之一,且支架对结石的磨损破坏作用可增加溶石效果,此外支架还可提供引流胆汁,保持胆管通常的作用。因此,药物控释支架在胆结石的临床治疗中有着良好的应用前景。本研究中通过不同的制备方法制备出两种溶石药物控释金属支架,静电纺丝载药纳米纤维覆膜金属支架和浸涂覆膜药物洗脱金属支架。静电纺丝载药纳米纤维覆膜金属支架通过同轴静电纺丝法制备载药覆膜,纳米纤维覆膜最高的含药率可达37.5%。通过扫描电子显微镜、透射电子显微镜、红外光谱、热解重量分析、力学测试等方式对纳米纤维膜的相关特理化性进行分析。在体外实验中,体外药物释放实验和体外降解实验来评价药物的释放行为及药物的释放对载药纳米纤维的降解影响,体外溶石实验则用来评价静电纺丝载药纳米纤维覆膜金属支架的体外溶石效果。用细胞毒性实验评价制备的静电纺丝载药纳米纤维覆膜金属支架生物相容性。研究结果显示,制备得到的载药纳米纤维形貌良好,具有壳-芯结构,胆酸钠(SC)和乙二胺四乙酸(EDTA)两种药物成功载入纳米纤维内部。载药纳米纤维中EDTASC含量越大,EDTASC的释放量越多,且溶石效果越好。制备的载有EDTASC的纳米纤维无明显细胞毒性,不会抑制细胞的增殖生长。浸涂覆膜药物洗脱金属支架通过浸涂覆膜的方法制备,载药覆膜中含药率为50%。通过光学显微镜、扫描电子显微镜、X射线衍射、热解重量分析及支架的径向力学性能测试等技术对载药涂层中的载药形式和浸涂覆膜药物洗脱金属支架力学进行分析。通过体外药物释放实验和体外溶石实验评价药物的持续释放时间和胆结石的溶石效果。研究结果显示,EDTA和SC成功载入浸涂覆膜药物洗脱金属支架的覆膜中,EDTA在载药涂层中以晶体颗粒形式存在,而SC则是以非晶体的形式存在。制备的支架径向压缩力学性能良好。浸涂覆膜药物洗脱金属支架在体外的药物释放时间可达28天,且溶石效果明显,胆结石的最终质量损失可达可达33.3%。对比实验结果显示,浸涂覆膜药物洗脱金属支架溶石效果好于静电纺丝载药纳米纤维覆膜金属支架。
[Abstract]:Gallstone disease is a common biliary disease, which brings great pain to patients' working life. Drug controlled release stent carrying drugs to dissolve common bile duct stones is considered to be one of the best ways of administration, and the wear and tear of stent can increase the effect of dissolution of stones, in addition, the stent can also provide drainage of bile to maintain the common role of bile duct. Therefore, drug controlled release stent has a good prospect in the clinical treatment of gallstones. In this study, two kinds of controlled release metal stents were prepared by different preparation methods, such as electrospinning drug-loaded nano-fiber coated metal scaffolds and impregnated coated drug-eluting metal stents. The drug-loaded nano-fiber coated metal scaffold was prepared by coaxial electrospinning. The highest drug content of nano-fiber film was 37.5%. Through scanning electron microscope, transmission electron microscope, infrared spectrum, pyrolysis gravimetric analysis, mechanical test and other methods to analyze the properties of nanofiber film. In vitro, drug release experiments and in vitro degradation tests were used to evaluate the drug release behavior and the effect of drug release on the degradation of drug-loaded nanofibers. In vitro litholysis test was used to evaluate the in vitro dissolution effect of nano-fiber coated metal scaffolds. The biocompatibility of nanofiber coated metal scaffolds prepared by electrostatic spinning was evaluated by cytotoxicity test. The results show that the prepared drug-loaded nanofibers have a good morphology, with a chitosan core structure, sodium cholate (SCT) and ethylenediamine tetraacetic acid (EDTA) loaded into the nanofibers successfully. The larger the EDTASC content in the drug-loaded nanofibers, the more the release of EDTASC and the better the litholytic effect. The prepared nanofibers containing EDTASC have no cytotoxicity and do not inhibit the proliferation and growth of cells. The drug-eluting metal stent was prepared by the method of impregnation and coating, and the drug content in the coated film was 50%. By means of optical microscope, scanning electron microscope, X-ray diffraction, pyrolysis gravimetric analysis and radial mechanical properties test of the drug-loaded coating, the forms of drug loading and the mechanics of drug-eluting metal scaffold coated with impregnated film were analyzed. The sustained release time and the litholytic effect of gallstones were evaluated by in vitro drug release test and in vitro litholysis experiment. The results showed that EDTA and SC were successfully loaded into the coated metal scaffolds coated with film, and EDTA existed in the form of crystal particles in the coating, while the SC existed in the form of amorphous. The mechanical properties of the prepared scaffolds are good in radial compression. The drug release time of drug-eluting metal stent in vitro was up to 28 days, and the litholysis effect was obvious, and the final mass loss of gallstone could reach 33.3%. The results show that the litholytic effect of drug-eluting metal stent is better than that of electrospinning drug-loaded nano-fiber coated metal stent.
【学位授予单位】：东华大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R657.4;R318.08

【参考文献】