聚己內酯於抗粘黏之應用

Abstract

聚己內酯於抗粘黏之應用 術後粘黏是傷口癒合不可避免的過程，但隨之而來會造成許多問題，包括慢性腹部不適疼痛、小腸阻塞、婦女不孕症、二度手術的困難。 爲了預防粘黏，曾有很多方法被使用。在減少手術傷害方面，可經由腹腔鏡手術、使用沒有滑石粉的外科手套、精細輕巧的操作、細心止血等，但即使如此，成功率仍然很低。而使用纖維溶解酵素、非類固醇抗發炎藥物、類固醇藥物等，都有某種程度的危險。 抗粘黏薄膜使用在手術後受傷的漿膜上，形成保護層。聚己內酯是個醫學工程上常用、易獲取、便宜、無毒、生物相容性高的物質，因此被選為抗粘黏的材料。 本研究包括三個部分，以聚己內酯為對象，首先確定其是否適合作為抗粘黏材料，再加上布洛芬(ibuprofen)，觀察是否增加其黏附力，最後利用超音波造成表面孔洞化，以研究表面粗糙度，及是否增加生物黏附力。 聚己內酯先製備成薄膜，接觸角約為97度，其表面具有一些微小孔洞。在布洛芬加入後，電子顯微鏡檢查顯示表面變得較粗糙，接觸角下降到56度，其生物黏附力從12N增加到18N。另外聚己內酯薄膜經超音波處理後，電子顯微鏡觀察發現孔洞變大，所占面積由1.5%增加到46%。以原子力顯微鏡檢測的粗糙度 由8.6 nm增加至25.2 nm。接觸角在140分鐘處理後的薄膜為52度，生物黏附力也一樣達到18N。 在細胞毒性方面，Seprafilm、聚己內酯薄膜、聚己內酯─布洛芬(10)薄膜都沒有不良的細胞毒性。聚己內酯─布洛芬(10)薄膜的藥物釋放測驗，顯示半小時釋出50%，到4小時釋出69.4%，此時達到高原期，整個釋出量在168小時是76.1%。 在動物試驗方面，粘黏積分評估得到結果是Seprafilm、聚己內酯薄膜與控制組相比，均有統計學上差異。另一實驗也顯示Seprafilm、聚己內酯薄膜(無縫線)、聚己內酯─布洛芬(10)薄膜與控制組相比，有統計學上差異，但各組間差異沒有達到統計學上差異。在粘黏面積的定量試驗方面，Seprafilm、聚己內酯薄膜、聚己內酯─布洛芬(10)薄膜與控制組相比，有統計學上差異，但各組間差異沒有達到統計學上差異。不過加入布洛芬，有比Seprafilm及聚己內酯薄膜更好的傾向。超音波處理後的聚己內酯薄膜沒有老化(aging)的現象。 因此，以聚己內酯為基礎的抗粘黏薄膜，可以達到不錯的效果，

Polycaprolactone in prevention of post-surgical adhesion Abstract Adhesions are unavoidable consequences of surgery and other trauma. Although adhesion is a physiologically inevitable and important part of wound healing, undesirable postsurgical adhesions can cause serious complications including: pain, functional obstruction, and harder second surgeries. To reduce postsurgical adhesion formation, fibrinolytic agents, anticoagulants, anti-inflammatory agents, and antibiotics have been used . However, these agents alone cannot prevent adhesion formation effectively because clearance occurs too rapidly. Recently, a variety of bioresorbable anti-adhesion barriers have been developed. Polycaprolactone (PCL) is a biodegradable polyester with a low melting point of around 60°C and a glass transition temperature of about -60°C. PCL holds certain advantages over other polymers such as polylactic acid. These advantages are that: (i) it is more stable in ambient conditions; (ii) it is significantly less expensive; and (iii) it is readily available in large quantities. Firstly, this study was based on polycaprolactone to evaluate the efficacy of its anti-adhesion, and the anti-adhesion result was promising. Additionally, ibuprofen was loaded to polycaprolactone and fabricated to films in different fraction. This novel film had rougher surface, lower contact angle, more bioadhesive strength and better anti-adhesion ability than control group. Thirdly, polycaprolactone was ultrasound treated at different period, and resulted in many more micropores, the roughness of film surface enhanced under atomic force microscopy, and bioadhesive strength increased as well. No aging phenomenon was found for ultrasound treated PCL film.