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研究生:陳嘉文
研究生(外文):Chia-Wen Chen
論文名稱:生物相容性共聚物之製備及其在皮質固醇包覆上應用之探討
論文名稱(外文):A study on the preparation of biocompatible copolymer and its application in carrying hydrocortisone
指導教授:許梅娟許梅娟引用關係
指導教授(外文):Mei-Chuan Hsu
學位類別:碩士
校院名稱:國立成功大學
系所名稱:化學工程學系碩博士班
學門:工程學門
學類:化學工程學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:87
中文關鍵詞:乳酸甘胺酸共聚物多孔膜藥物包覆皮質固醇
外文關鍵詞:foamcopolymerhydrocortisone
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乳酸甘胺酸共聚物 (PLGA) 由於具備生物相容性 (biocompatible) 與生物可劣解 (biodegradable) 等特性,因此能廣泛地應用在手術縫線、骨折癒合、組織工程及藥物釋放控制等方面。本研究中針對合成之乳酸甘胺酸共聚物的製備、物理性質與合成條件進行了一系列的探討,並將此合成製備之產物應用在多孔膜 (foam) 的製備與藥物的包覆上。

本研究中主要探討的主題有三方面:一為乳酸甘胺酸共聚物的製備及其性質之鑑定,合成之產物具有高純度且重量產率介於88-94% 之間,再者為在不同操作條件下以合成之共聚物製備多孔膜並歸納出最佳的製備條件,產物的形狀完整且表面孔洞均勻分散,其三則為包覆皮質固醇 (hydrocortisone) 之PLGA microspheres的製備,並對其製備程序、產物特性及藥物包覆的能力一一進行探討,包覆皮質固醇之PLGA microspheres最高可達50% 藥物含量。
PLGA can be widely used in sutures, fracture fixation, tissue engineering, and drug control/release because of its compatibility and biodegradation.
In this work, PLGA is successfully synthesized. PLGA of very high purity can be obtained with the yield of 88-94%. Its physical properties as well as the synthesis condition are discussed. The copolymer formed is applied to the preparation of porous foams and hydrocortisone-contained microspheres. The optimum condition for pre- paring porous foams is determined and an uniform foam of good shape is produced. For hydrocortisone-carried PLGA microspheres the preparation process, characteristic of the microspheres, and amount of drug being carried are all investigated. The maximum drug content of 50% can be achieved.
目錄
表目錄 I
圖目錄 II
第一章 緒論 1
1-1 生物可劣解 (Biodegradable) 聚合物之定義 1
1-2 乳酸 (Lactic acid) 及甘胺酸 (glycolic acid) 聚合物的定義與沿革 1
1-2-1 乳酸及甘胺酸的單體與聚合物的合成及應用 2
1-2-2 乳酸及甘胺酸聚合物的合成 6
1-2-3 乳酸及甘胺酸聚合物的生物劣解 (biodegradation) 方式 8
1-2-4 乳酸及甘胺酸聚合物生物劣解產物的生化去除 (bioelimination) 途徑 10
1-2-5 乳酸及甘胺酸聚合物的塑造技術 10
1-2-6 乳酸及甘胺酸聚合物的應用 11
1-3 骨架 (Scaffold) 的應用與發展 16
第二章 實驗方法 18
2-1 PLGA 的合成 18
2-2 多孔膜 (Foam) 的製備 18
2-3 Hydrocortisone-loaded PLGA microspheres的製備 18
2-4 皮質固醇 (Hydrocortisone) 含量的測定 19
2-5 實驗藥品 22
2-6 實驗儀器 23
第三章 結果與討論 24
3-1 合成的共聚物 (PLGA) 24
3-1-1 共聚物的分子結構 24
3-1-2 共聚物的熱學性質 36
3-1-3 共聚物的分子量與polydispersity 39
3-1-4 共聚物的結晶性 (crystallinity) 44
3-2 多孔膜 (Foam) 的製備 51
3-3 Hydrocortisone-loaded PLGA microspheres 54
3-3-1 製備drug-loaded microspheres 57
3-3-2 藥物含量的測定 66
第四章 結論 73
參考文獻 74

表目錄
表1-1 被認定為生物可劣解 (biodegradable) 的聚合物 1
表1-2 聚合物生物劣解方式的比較 9
表1-3 乳酸及甘胺酸聚合物生物劣解速率之比較 10
表1-4 商業上常用的手術縫線材料 12
表1-5 乳酸及甘胺酸聚合物在藥物釋放上的應用 16
表3-1-1 不同單體比例之聚合反應實驗結果 31
表3-1-2 不同反應溫度之聚合反應實驗結果 32
表3-1-3 聚合條件與文獻之比較 33
表3-1-4 聚合實驗結果與文獻之比較 34
表3-1-5 殘餘不純物的鑑定 35
表3-2-1 凝膠滲透層析法的實驗參數與實驗結果 40
表3-2-2 不同鏈長控制劑 (tetraphenyltin) 加量的聚合實驗結果 41
表3-3-1 X射線繞射儀XRD (X-ray diffraction) 分析所得之 值 50
表3-3-2 繞射晶格平面間的距離 (d,A) 的計算結果 50
表3-5 比較兩種microspheres製備程序的差異 58
表3-6 Hydrocortisone在不同溫度下的空白測試 58
表3-7-1 Hydrocortisone-loaded microsphere A組實驗結果 67
表3-7-2 Hydrocortisone-loaded microsphere B組實驗結果 68
表3-7-3 Hydrocortisone-loaded microsphere C組實驗結果 69
表3-7-4 Hydrocortisone-loaded microsphere D組實驗結果 70
表3-7-5 Hydrocortisone-loaded microsphere E組實驗結果 71
表3-7-6 Hydrocortisone-loaded microspheres與文獻之比較 72

圖目錄
圖1-1 甘胺酸交酯 (glycolide) 與乳酸交酯 (lactide) 的結構式 3
圖1-2 合成甘胺酸交酯 (glycolide) 的化學反應 3
圖1-3 L-、D-、D,L-乳酸交酯的結構式 4
圖1-4 合成L-乳酸交酯的化學反應 5
圖1-5 合成低分子量的乳酸及甘胺酸聚合物的化學反應式 7
圖1-6 合成高分子量乳酸及甘胺酸聚合物的化學反應式 7
圖1-7 乳酸及甘胺酸聚合物生物劣解產物的新陳代謝及排出途徑 11
圖2-1 Hydrocortisone溶液於240 nm下濃度對吸光值之檢量線 20
圖2-2 不同濃度之hydrocortisone溶液對HPLC積分面積之檢量線 21
圖3-1-1 1H-NMR spectrum of PLGA (with molar ratio LA/GA 67/33) 27
圖3-1-2 13C-NMR spectrum of PLGA (with molar ratio LA/GA 67/33) 28
圖3-1-3 13C-NMR spectrum of PLGA (with molar ratio LA/GA 67/33) 29
圖3-2 FT-IR spectrum of PLGA (with molar ratio LA/GA 67/33) 30
圖3-3 PLGA之化學結構式 26
圖3-4 TGA trace of PLGA (with molar ratio LA/GA 67/33) 37
圖3-5 DSC thermogram of PLGA (with molar ratio LA/GA 67/33) 38
圖3-6-1 GPC elution profiles of PLGA (with molar ratio LA/GA 67/33) 42
圖3-6-2 GPC elution profiles of cumulative weight fraction of PLGA (with molar ratio LA/GA 67/33) 43
圖3-8-1 X-ray diffraction (XRD) spectra of PLGA (with molar ratio LA/GA 88/12) 45
圖3-8-2 X-ray diffraction (XRD) spectra of PLGA (with molar ratio LA/GA 82/18) 46
圖3-8-3 X-ray diffraction (XRD) spectra of PLGA (with molar ratio LA/GA 67/33) 47
圖3-8-4 X-ray diffraction (XRD) spectra of PLGA (with molar ratio LA/GA 63/37) 48
圖3-8-5 X-ray diffraction (XRD) spectra of PLGA (with molar ratio LA/GA 45/55) 49
圖3-9-1 Photo of PLGA (with molar ratio LA/GA 67/33) foam 52
圖3-9-2 Scanning electron micrographs of PLGA (with molar ratio LA/GA 67/33) foam 53
圖3-10 Chemical structure of hydrocortisone (C21H30O5) 54
圖3-11-1 FT-IR spectrum of hydrocortisone 55
圖3-11-2 X-ray diffraction (XRD) spectra of hydrocortisone 56
圖3-12-1 FT-IR spectrum of hydrocortisone-loaded PLGA (with molar ratio
LA/GA 67/33) microspheres 60
圖3-12-2 FT-IR spectrum of (a) PLGA,(b) hydrocortisone (c) hydrocortisone-
loaded PLGA (with molar ratio LA/GA 67/33) microspheres 61
圖3-13 X-ray diffraction (XRD) spectra of hydrocortisone-loaded PLGA (with molar ratio LA/GA 67/33) microspheres 62
圖3-14-1 Scanning electron micrograph of hydrocortisone-loaded microspheres 63
圖3-14-2 Scanning electron micrograph of hydrocortisone-loaded microspheres 64
圖3-14-3 Scanning electron micrograph of drug-free microspheres 65
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