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標題: | 以泊洛沙姆(poloxamer 407)及玻尿酸共同組成之新型態水膠以達到尿激酶之長效釋放 Achieving sustain release of urokinase with a novel hydrogel system composed by poloxamer 407 and hyaluronic acid |
作者: | Wei-Yang Lin 林威揚 |
指導教授: | 楊台鴻 |
關鍵字: | 高分子水膠,泊洛沙姆,玻尿酸,尿激?,緩效釋放, hydrogel,poloxamer 407,hyaluronic acid,urokinase,sustain release, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 在肺部感染後因細菌進入肋膜腔後產生的膿胸,在臨床上是一種常見的狀況。在肋膜腔內之感染因啟動身體之免疫系統並引起發炎反應,若無妥善治療常造成肋膜腔內之纖維組織增生(fibrin formation),而使胸水無法完全引流及肺部擴張受限。臨床處置包括靜脈注射抗生素、早期胸腔穿刺抽出感染性胸水、胸腔引流管置入、或胸腔鏡手術進入肋膜腔中進行清創剝除因感染而增厚的肋膜。另外,為了使堆積在胸腔內之感染性胸水不至於因為纖維組織增生造成的分隔化(loculation)而無法妥善引流,臨床上亦經常使用尿激酶經胸腔引流管灌注至胸腔內,已達到纖維溶解(fibrinolysis)之效果。然而由於灌注之水溶性尿激酶容易經由引流管流出,無法均勻分布整個胸腔,且停留在胸腔內時間短,因此效果相當有限,並且需單日多次數且多日之療程。本實驗將尿激酶載入由泊洛沙姆(poloxamer)及玻尿酸共同構成之高分子水膠中,並且經由活體外試驗(in vitro study)證明其可以達到24小時以上之長效釋放。同時並深入研究此種高分子水膠之成膠性質、溫度引發之相變化、電顯下之顯微構造,並找出能達到最佳尿激酶釋放效果之泊洛沙姆(poloxamer)及玻尿酸之組成比例。 Pleural empyema is an inflammatory condition characterized by pus accumulation inside pleural cavity, which is usually followed by bacterial pneumonia. During the disease process, the pro-inflammatory and pro-fibrotic cytokines in the purulent pleural effusion cause fibroblasts proliferation and deposition of extracellular matrix, which will finally lead to fibrin deposition and fibrothorax. Urokinase instillation therapy through chest drainage tube are frequently used for fibrinolysis in empyema patients. However, urokinase treatment requires multiple instillation (2~3 times per day, for 4~8 days) and is easily flowed out from the chest drainage tube due to its high water solubility. In this in vitro study, we develop a thermo-responsive hydrogel based on poloxamer 407 (P407) combined with hyaluronic acid (HA) and investigate into different combinations of P407 and HA for the optimal effect of urokinase loading and release. The micellization and gelation behavior, gel dissolution, drug release, gel microstructure and fourier transform infrared spectroscopy (FT-IR) of the P407-HA hydrogel are also studied. The addition of HA decrease the critical micellization temperature (CMT) without affecting the micellization intensity and critical gelation temperature (CGT). The P407-HA hydrogel also has better hydrogel property and a more compact microstructure comparing to the P407 alone. The thermo-responsive P407-HA hydrogel may have a promising potential in hydrophilic drugs loading and delivery. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71834 |
DOI: | 10.6342/NTU201804246 |
全文授權: | 有償授權 |
顯示於系所單位: | 醫學工程學研究所 |
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