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研究生: 葉力瑄
Yeh, Li-Hsuan
論文名稱: 含polypeptides接枝型共聚物之合成與其應用之研究
Synthesis of graft polypeptides copolymer and its application
指導教授: 陳志勇
Chen, Chuh-Yung
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年: 2009
畢業學年度: 97
語文別: 中文
論文頁數: 101
中文關鍵詞: 血液相容性接枝型共聚物聚胜肽巨單體甲基丙烯酸甲酯
外文關鍵詞: graft copolymer, polypeptide, macromonomer, MMA, blood compatibility
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  • 聚胜肽是一種具有結構類似於蛋白質螺旋狀的生物相容性材料,由於其可於製備時導入其它種高分子結構,擴大其應用範圍,使得聚胜肽成為近年來極受生醫界矚目的仿生材料。本研究以合成接枝型共聚物的方式將生物相容性佳的聚胜肽導入聚甲基丙烯酸甲酯(MMA)中,製得兼具高強度結構與高生物相容性的生醫材料。
    本研究首先將自行合成之α-amino acid N-carboxyanhydrides (NCA)單體以一級胺起始開環聚合反應,藉由單體與起始劑比例的控制,合成出不同聚合程度的poly(Z-L-lysine) (DP=7-21);接著在其尾端接上Glycidyl methacrylate (GMA),使其成為尾端帶有雙鍵的巨單體(macromonomer)。最後再以接枝聚合的方式與MMA進行共聚反應生成含有不同組成比例的接枝型共聚合物PMMA-graft-poly(Z-L-lysine),(其中poly(Z-L-lysine)含量由0%-100%)。本實驗以MALDI TOF鑑定確認PMMA-graft-poly(Z-L-lysine)的結構。另由FT-IR結果觀察,當側鏈長度相同,MMA含量愈高,其β摺板結構愈穩定;但若是MMA含量相同,側鏈長度愈長,其α螺旋結構相對含量愈高。最後,再以血漿再鈣化測試與血小板吸附實驗觀察此接枝型共聚合物在血液中對其的影響,結果顯示poly(Z-L-lysine)含量愈高,血小板吸附活化量愈少,血漿再鈣化時間愈短。

    Polypeptide (poly(L-lysine) derivatives) is a kinds of biomimetic material. Because it can be introduced into polymer structure, thus, polypeptides are highly interested and have been developed in pharmaceutical and biomedical sciences in recent years. In this study, the poly(L-lysine) was synthesized and introduced into the poly(methyl methacrylate) by using grafting polymerization to prepare a high performance biomaterial.
    Poly(Z-L-lysine) was firstly prepared by α-amino acid N-carboxyanhydrides (NCAs) with primary amine via the nucleophilic ring-opening polymerization. A series of poly(Z-L-lysine)(DP=7-21) could be obtained when the different amount of primary amine was used. Then, poly(Z-L-lysine) was further reacted with glycidyl methacrylate (GMA) to manufacture the poly(Z-L-lysine)-GMA macromonomer. Finally, the grafted copolymer was synthesized by using the poly(Z-L-lysine)-GMA macromonomer and MMA via grafting through method. MALDI TOF spectroscopy was used to identified the repeating units and chain end group of poly(Z-L-lysine) and macromonomer. FT-IR spectra show that the β-sheet structure is becoming more stable when MMA monomer ratio are increased. However, α-helix structure would be appeared when MMA monomer ratio was fixed. Moreover, the result of the plasma recalcification and plasma adhesion experiment shows that the plasma recalcification time were longer and the plasma adhere were fewer when more poly(Z-L-lysine) was existed.

    中文摘要 I 英文摘要 III 總目錄 IV 表目錄 VIII 圖目錄 IX 第一章 緒論 1 1-1生物醫用材料 1 1-2 醫用高分子材料 2 1-3骨科替代材料 5 1-4 生物醫用材料安全性評估 8 第二章 文獻回顧 12 2-1 聚胜肽(polypeptide)概述 12 2-2 聚胜肽之二級結構 17 2-2-1 α螺旋(α-helix) 17 2-2-2 β板摺(β-sheet) 18 2-2-3 自組裝(self-assembling) 19 2-3 含聚胜肽之共聚物的應用 20 2-4 凝血機制與排斥作用 28 2-4-1 血液的組成 28 2-4-2 血小板機能 30 2-4-3 凝血機制 35 2-4-4 排斥作用 38 2-5 研究動機 41 第三章 實驗 43 3-1 實驗藥品 43 3-2 實驗儀器 45 3-3 實驗步驟 47 3-3-1 製備Z-L-lysine NCA 單體 47 3-3-2 開環聚合反應(Ring-opening Polymerization)製備poly(Z-L-lysine) 48 3-3-3 以poly(Z-L-lysine)末端之氨基與GMA之環氧基反應,得末端具碳碳雙鍵且poly(Z-L-lysine)為側鏈聚單體(Macromonomer) 49 3-3-4 將末端具碳碳雙鍵且poly(Z-L-lysine)為側鏈之巨單體與MMA反應得接枝型共聚物PMMA-graft-poly(Z-L-lysine) 50 3-3-5 含聚胜肽之接枝型共聚物去保護PMMA-graft-poly(L-lysine) 51 3-3-6 血漿凝固時間(clotting time)之量測 52 3-3-7血小板吸附性質之測試 54 第四章 結果與討論 57 4-1 Z-L-(lysine) NCA monomer的合成與鑑定 57 4-2 poly(Z-L-lysine)的合成與鑑定 57 4-3 poly(Z-L-lysine)-GMA巨單體的合成與鑑定 61 4-4 PMMA-graft-poly(Z-L-lysine)的合成與鑑定 66 4-5 PMMA-graft-poly(L-lysine)共聚物去保護的合成與鑑定 74 4-6 FT-IR鑑定 77 4-6-1 相同長度側鏈(Z-L-lysine)之PMMA-graft-Poly (L-lysine)共聚物,改變共單體MMA含量對側鏈(Z-L-lysine)二級結構的影響 78 4-6-2 MMA含量相同,改變PMMA-graft-Poly (L-lysine)共聚物中側鏈poly(Z-L-lysine)長度,探討其對側鏈二級結構的影響 79 4-7 血漿再鈣化測試 84 4-8 血小板吸附實驗 86 第五章 結論 96 參考文獻 98

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