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研究生:鍾文梅
研究生(外文):Wen-Mei Chung
論文名稱:以EDC交聯之聚半乳糖醛酸薄膜在生醫應用方面可行性的評估
論文名稱(外文):Study of EDC-crosslinked polygalacturonic acid membrane for the feasibility of
指導教授:王盈錦
指導教授(外文):Yng-Jinn Wang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:醫學工程研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:63
中文關鍵詞:聚半乳糖醛酸1-(3-二甲氨基丙基)-3-乙基碳二亞胺鹽酸鹽高分子薄膜
外文關鍵詞:polygalacturonic acid1-ethyl-3-(3-dimethylaminopropyl)-carbodiimidepolymeric membrane
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我們曾以1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) 交聯處理polygalacturonic acid (PGA) 作為手術後抗沾粘膜,目前持續致力於探索PGA在生醫應用方面的潛力,我們製作出四種不同特性的高分子膜,分別在80% 乙醇及80% 丙酮中以15mM、50mM EDC交聯處理PGA。
由IR分析中,在1800 cm-1產生新的吸收峰,推測可能是anhydride中的C=O鍵結。除此之外,相對於交聯前PGA的吸收峰範圍 (3000-3500cm-1),經交聯後則變得較窄 (3200-3400cm-1),可以知道PGA上有部份的hydroxy基團在交聯反應中被消耗掉了。所有EDC交聯的PGA膜,在可見光區的穿透率約50%-70%。
此四種不同條件的交聯膜植入老鼠皮下並在14天後取出組織觀察結果;無論是乙醇溶劑或是丙酮溶劑的系統,植入後發現,以15mM EDC交聯之PGA膜皆碎裂,而50mM EDC交聯之PGA膜仍維持植入前的形態。此外,所有PGA交聯膜都可有效地避免手術後的腹腔沾黏現象;在乙醇溶劑系統下,15mM EDC交聯之PGA膜在植入後的14天後會完全地降解;然而其他三種交聯膜仍完整地存在;植入部位的週邊組織也可觀察到發炎現象與血管新生。因此需進一步進行長時間植入體內 (in vivo) 的實驗,來探討這幾種PGA交聯膜的生物相容性。
We have previously developed a postsurgical anti-adhesion membrane by crosslinking polygalacturonic acid (PGA) with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). As a continuous effort to explore the potential biomedical application of PGA, we have fabricated and characterized four different types of polymeric membranes by crosslinking PGA with 15 mM or 50 mM EDC in the aqueous solutions of 80% ethanol and 80% acetone, separately.
The crosslink was confirmed by a new C=O absorption appeared near 1800 cm-1, probably by anhydride bonding. In addition, a narrower absorption peak (3200-3400 cm-1) was observed for the crosslinked membrane as compared with the wider range of 3000-3500 cm-1 found in the PGA membrane before EDC treatment, indicating a portion of the PGA hydroxy groups was consumed by the crosslinking reaction. All of the EDC-crosslinked PGA membranes had a transmission efficiency of 50% - 70% to visible light. The four different crosslinked PGA membranes were implanted subcutaneous in mice and retrieved for histological examination 14 days after implantation. The PGA membranes crosslinked with 15 mM EDC in both aqueous solutions of ethanol and acetone appeared to be more fragile as compared with those crosslinked at 50 mM EDC, which maintained integrity of the implanted membranes. All PGA membranes effectively prevented the post-surgical adhesion in the abdominal cavity. PGA membrane of 15 mM EDC treatment in ethanol was completely degraded in 14 days after implantation, whereas all other three PGA membranes remained intact. Inflammation and angiogenesis were also observed around the implanted sites. Long-term in vivo implant study is suggested to further study the biocompatibility of these PGA membranes.
中文摘要 II
ABSTRACT IV
圖目錄 IX
表目錄 XI
第一章:背景介紹 1
1-1 生物性可降解高分子材料 1
1-2 薄膜製備與成膜機制 3
1-3聚半乳糖醛酸 (Polygalacturonic acid,PGA) 4
1-3-1聚半乳糖醛酸的介紹 4
1-3-2 聚半乳糖醛酸的應用 5
1-4 高分子薄膜之交聯反應 7
1-4-1 交聯之目的與方法 7
1-4-2 交聯劑 1-ethyl-3-(dimethylaminopropyl)-carbodiimide 8
1-4-3 交聯劑N-hydroxysuccinimide 9
1-5 眼部方面的應用 12
1-6 皮膚方面的應用 14
1-6-1 皮膚構造 14
1-6-2 皮膚傷口的癒合 16
1-7 腹腔方面的應用 20
1-7-1 腹膜結構 20
1-7-2 腹腔壁傷口癒合 20
1-8 研究動機 22
第二章:實驗藥品與儀器 23
2-1 實驗藥品 23
2-2 實驗儀器 24
第三章:材料與方法 24
3-1 Polygalacturonic acid 薄膜的製備與分析 25
3-1-1 Polygalacturonic acid 的純化 25
3-1-2 Polygalacturonic acid 純化後分子量分析 25
3-1-3 Polygalacturonic acid 薄膜的製備 26
3-1-4 Polygalacturonic acid 薄膜的透光性 26
3-2 Polygalacturonic acid 薄膜以EDC 交聯 27
3-2-1 以乙醇作為EDC/NHS之交聯溶劑 27
3-2-2 以丙酮作為 EDC/NHS 之交聯溶劑 27
3-3 薄膜之物性及化性分析 28
3-3-1 膨潤率(swelling ratio,Q)測試 28
3-3-2 Micro FTIR 光譜分析 28
3-3-3 ESCA (Electron Spectroscopy for Chemical Analysis) 分析 28
3-4 薄膜體內測試 29
3-4-1 體內降解動物模式建立 29
3-4-2 高分子與動物組織界面之組織學觀察 29
第四章:結果與討論 31
4-1 Polygalacturonic acid 純化後分子量分析 31
4-2 PGA薄膜的透光性 34
4-3 PGA交聯膜的溶解性測試 36
4-4膨潤率(swelling ratio,Q)測試 38
4-5 Micro FTIR 光譜分析 39
4-6 ESCA (Electron Spectroscopy for Chemical Analysis) 分析 42
4-7 高分子與動物組織界面之組織學觀察 45
第五章:結論 59
參考文獻: 62
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