臺灣博碩士論文加值系統

本研究以開環聚合反應（ring-opening polymerization）合成兩性的雙團聯共聚物(A-B type diblock copolymers)，研究分兩部分進行：第一部分以三亞甲基碳酸酯(TMC)為A段單體，聚己內酯（ε-CL）為B段單體，合成含有不同ε-CL比例之PTMC-b-PCL 共聚物，並以膠體滲透層析儀、核磁共振儀與示差掃描熱卡計鑑定之，鑑定結果發現，當ε-CL比例增加時，共聚物熔點溫度隨之增加，但玻璃轉移溫度隨之下降。研究之第二部分是合成具有不同支鏈取代基的雙團聯共聚物，並經由氫化作用，改變共聚物上的支鏈取代基性質，利用高分子自組裝(self-assembly)特性，以油/水乳化劑法(O/W emulsion method)，將共聚物製備成微胞形態，再以螢光光譜、紫外光/可見光光譜、穿透式電子顯微鏡與動態光散射儀，探討其微胞特性差異。此部分結果顯示，樣品之臨界微胞濃度介於2.23-14.6 mgL-1，微胞形態則可呈現圓形、核與殼形，藥物包覆效率介於11.6~54.6%。此外，氫化後的共聚物所形成之微胞由於其親/疏水性差異增加，提升其臨界微胞濃度(CMC)與藥物包覆效率(EE)。

A series of amphiphilic diblock PTMC-block-PCL copolymers were synthesized by ring-opening polymerization from trimethylene carbonate (TMC) and ε-caprolactone (ε-CL) in the presence of SnOct2 catalyst. The prepared samples were characterized by DSC、1H NMR and GPC techniques. According to DSC results, when the ε-CL content of diblock copolymer increased, the melting temperature (Tm) increased, but the glass-transition temperature (Tg) decreased .The Oil/Water emulsion method was employed to prepare the micelles from the copolymers. The characteristics of the micelles in an aqueous phase were investigated by fluorescence spectrum、ultraviolet/visible spectrum、transmission electron microscope and dynamic light scattering technique. The diblock copolymers with various pendant groups formed micelles in the aqueous phase with critical micelle concentrations（CMCs）in the range from 2.23 mgL-1 to 14.6 mgL-1. The efficiency of drug entrapment for the micelles was 11.6% ~ 54.6%. The micelles basically exhibited spherical or core-and-shell texture. After hydrogenation, the critical micelle concentrations and drug entrapment efficiency of the micelles increased.

目錄
指導教授推薦書
口試委員會審定書
授權書
誌謝
中文摘要...................................................................................................vi
英文摘要..................................................................................................vii
第1章 緒論.............................................................................................1
第2章 文獻回顧.....................................................................................4
第3章 實驗設計與方法
3.1 實驗流程...................................................................................10
3.2 實驗藥品...................................................................................11
3.3 實驗步驟
3.3.1 雙團聯共聚物PTMC-b-PCL與含取代基共聚物合成步驟...........................................................................................13
3.3.1.1 PTMC與含取代基PTMC巨起始劑合成..........................13
3.3.1.2 雙團聯共聚物合成..............................................................13
3.3.1.3 含取代基之雙團聯共聚物合成..........................................13
3.3.2 雙團聯共聚物氫化步驟.......................................................13
3.3.3 體外水解樣品製備...............................................................14
3.3.4 螢光光譜樣品製備...............................................................14
3.3.5 微胞樣品製備.......................................................................14
3.3.6 藥物包覆樣品製備...............................................................15
3.3.7 藥物釋放製備與實驗...........................................................16
3.4 分析儀器...................................................................................17
第4章 結果與討論
4.1 共聚合物合成結果與鑑定.......................................................20
4.2 共聚合物氫化檢測...................................................................21
4.3 共聚合物熱學性質...................................................................22
4.4 共聚物水解速率……....……………………………………...23
4.5 共聚物臨界微胞濃度...............................................................24
4.6 共聚物微胞相形態...................................................................25
4.7 共聚物微胞粒徑分析...............................................................26
4.8 共聚物微胞其藥物包覆效率...................................................27
4.9 共聚物微胞其藥物釋放速率…....……………………….......27
第5章 結論...........................................................................................28
參考文獻
表目錄
表1-1 生醫材料於人體上的應用產品............................................... 31
表1-2 生物可分解性高分子須具備之特性....................................... 32
表2-1 微胞形成與藥物包覆作用力................................................... 33
表2-2 團聯共聚物其微胞之熱力學與動力學穩定度之影響因素... 34
表4-1 巨起始劑3a合成結果…….....…............................................ 35
表4-2 雙團聯共聚物合成結果…….....….......................................... 36
表4-3 雙團聯共聚物之微胞粒徑分析............................................... 37
表4-4 不同官能基共聚物其微胞之藥物包覆效率比較…….…...... 38
圖目錄
Scheme 1 雙團聯共聚物合成示意圖................................................ 39
圖1-1 典型藥物於血液中濃度與時間關係圖............................ 40
圖2-1 高分子微胞core-shell球形結構....................................... 41
圖2-2 微胞形成機制圖................................................................ 42
圖2-3 微胞製備方式(1) .............................................................. 43
圖2-4 微胞製備方式(2) .............................................................. 44
圖2-5 理想微胞系統特性............................................................ 45
圖2-6 高分子微胞含ADR藥物系統結構圖.............................. 46
圖2-7 功能性高分子微胞藥物載體系統.................................... 47
圖4-1 巨起始劑3a之氫譜核磁共振鑑定圖譜........................... 48
圖4-2 PTMC1-b-PCL100(5a)之氫譜核磁共振鑑定.................. 49
圖4-3 紅外線光譜圖PTMC2-b-PCL100 (a)氫化前 (b)氫化後(PMMC-b-PCL100)........................................................... 50
圖4-4 氫化前後GPC比較圖(a) PTMC2-b-PCL100 (氫化前)
(b) PMMC- b-PCL(氫化後).............................................. 51
圖4-5 PTMC1-b-PCL之DSC圖(macroinitiator/ε-CL molar ratio (a) 1/30 (b) 1/60 (c) 1/80 (d) 1/100) ......................... 52
圖4-6 PTMC1-b-PCL(■)；PTMC2-b-PCL(●)；PTMC3-b-PCL (▲) 水解分子量與分布變化圖.......................................
53
圖4-7 不同濃度的PTMC1-b-PCL 100(Entry 5) 去離子水溶液其pyrene溶液螢光激發光譜(λem=390nm) ............... 54
圖4-8 不同濃度的PTMC2-b-PCL 100(Entry 7)去離子水溶液其pyrene溶液螢光激發光譜(λem=390nm) ................... 55
圖4-9 不同濃度的PTMC3-b-PCL 100(Entry 9)去離子水溶液其pyrene溶液螢光激發光譜(λem=390nm) ................... 56
圖4-10 不同濃度的PTMC1-b-PBCL100 (Entry 10)去離子水溶液其pyrene溶液螢光激發光譜(λem=390nm) ............... 57
圖4-11 不同濃度的PMMC-b-PCL 100(Entry 11)去離子水溶液其pyrene溶液螢光激發光譜(λem=390nm) ................... 58
圖4-12 不同濃度的PTMC1-b-PHCL 100(Entry 12)去離子水溶液其pyrene溶液螢光激發光譜(λem=390nm) ............... 59
圖4-13 雙團聯共聚物之pyrene 溶液激發光譜Imax/Imin vs. Log C 60
圖4-14 雙團聯共聚物之pyrene 溶液激發光譜Imax/Imin vs. Log C (氫化前後比較) 61
圖4-15 PTMC1-b-PCL100微胞相形態........................................ 62
圖4-16 PTMC2-b-PCL100微胞相形態........................................ 62
圖4-17 PTMC3-b-PCL100微胞相形態........................................ 63
圖4-18 PTMC1-b-PBCL100微胞相形態..................................... 63
圖4-19 PMMC-b-PCL100微胞相形態......................................... 64
圖4-20 PTMC1-b-PHCL100微胞相形態..................................... 64
圖4-21 共聚物之微胞包覆藥物AM之藥物釋放速率圖(■，PTMC2-b-PCL100；●，PMMC-b-PCL100)....................... 65

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