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一種新型的溶石藥物控釋金屬支架治療難治性膽總管結(jié)石的實(shí)驗(yàn)研究

發(fā)布時(shí)間:2018-06-13 21:03

  本文選題:金屬支架 + 覆膜。 參考:《東華大學(xué)》2017年碩士論文


【摘要】:膽結(jié)石疾病是一種常見(jiàn)的膽道疾病,給病人的工作生活帶來(lái)極大痛。藥物控釋支架攜帶藥物溶解膽總管結(jié)石被認(rèn)為是最佳給藥途徑之一,且支架對(duì)結(jié)石的磨損破壞作用可增加溶石效果,此外支架還可提供引流膽汁,保持膽管通常的作用。因此,藥物控釋支架在膽結(jié)石的臨床治療中有著良好的應(yīng)用前景。本研究中通過(guò)不同的制備方法制備出兩種溶石藥物控釋金屬支架,靜電紡絲載藥納米纖維覆膜金屬支架和浸涂覆膜藥物洗脫金屬支架。靜電紡絲載藥納米纖維覆膜金屬支架通過(guò)同軸靜電紡絲法制備載藥覆膜,納米纖維覆膜最高的含藥率可達(dá)37.5%。通過(guò)掃描電子顯微鏡、透射電子顯微鏡、紅外光譜、熱解重量分析、力學(xué)測(cè)試等方式對(duì)納米纖維膜的相關(guān)特理化性進(jìn)行分析。在體外實(shí)驗(yàn)中,體外藥物釋放實(shí)驗(yàn)和體外降解實(shí)驗(yàn)來(lái)評(píng)價(jià)藥物的釋放行為及藥物的釋放對(duì)載藥納米纖維的降解影響,體外溶石實(shí)驗(yàn)則用來(lái)評(píng)價(jià)靜電紡絲載藥納米纖維覆膜金屬支架的體外溶石效果。用細(xì)胞毒性實(shí)驗(yàn)評(píng)價(jià)制備的靜電紡絲載藥納米纖維覆膜金屬支架生物相容性。研究結(jié)果顯示,制備得到的載藥納米纖維形貌良好,具有殼-芯結(jié)構(gòu),膽酸鈉(SC)和乙二胺四乙酸(EDTA)兩種藥物成功載入納米纖維內(nèi)部。載藥納米纖維中EDTASC含量越大,EDTASC的釋放量越多,且溶石效果越好。制備的載有EDTASC的納米纖維無(wú)明顯細(xì)胞毒性,不會(huì)抑制細(xì)胞的增殖生長(zhǎng)。浸涂覆膜藥物洗脫金屬支架通過(guò)浸涂覆膜的方法制備,載藥覆膜中含藥率為50%。通過(guò)光學(xué)顯微鏡、掃描電子顯微鏡、X射線衍射、熱解重量分析及支架的徑向力學(xué)性能測(cè)試等技術(shù)對(duì)載藥涂層中的載藥形式和浸涂覆膜藥物洗脫金屬支架力學(xué)進(jìn)行分析。通過(guò)體外藥物釋放實(shí)驗(yàn)和體外溶石實(shí)驗(yàn)評(píng)價(jià)藥物的持續(xù)釋放時(shí)間和膽結(jié)石的溶石效果。研究結(jié)果顯示,EDTA和SC成功載入浸涂覆膜藥物洗脫金屬支架的覆膜中,EDTA在載藥涂層中以晶體顆粒形式存在,而SC則是以非晶體的形式存在。制備的支架徑向壓縮力學(xué)性能良好。浸涂覆膜藥物洗脫金屬支架在體外的藥物釋放時(shí)間可達(dá)28天,且溶石效果明顯,膽結(jié)石的最終質(zhì)量損失可達(dá)可達(dá)33.3%。對(duì)比實(shí)驗(yàn)結(jié)果顯示,浸涂覆膜藥物洗脫金屬支架溶石效果好于靜電紡絲載藥納米纖維覆膜金屬支架。
[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.
【學(xué)位授予單位】:東華大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R657.4;R318.08

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