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研究生:李怡潔
研究生(外文):Yi-Chieh Lee
論文名稱:聚氰基丙烯酸乙酯藥物載體系統製備之研究
論文名稱(外文):Studies on the Synthesis of Poly(ethyl cyanoacrylate) Nanoparticles as Drug Carrier Systems
指導教授:王勝仕
口試委員:邱文英賴進此侯劭毅王孟菊林達顯
口試日期:2014-07-08
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:化學工程學研究所
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:2014
畢業學年度:102
語文別:中文
論文頁數:109
中文關鍵詞:阿茲海默症血腦屏障Clioquinol聚氰基丙烯酸乙酯
外文關鍵詞:Alzheimer’s diseaseblood brain barrierClioquinolpoly ethyl cyanoacrylate
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在台灣已逐漸步入高齡化的社會,台灣失智症協會(Taiwan Alzheimer’s Disease Association)已估計台灣的失智人口到2060年時將逼近80萬人,而失智症中阿茲海默症之病患又佔其多數,如何有效地預防及治療阿茲海默症將會是一個相當重要之課題。

Clioquinol (CQ)為一種金屬螯合劑,已經在文獻中證實可以用以治療阿茲海默症(AD),但由於CQ本身之特性導致其無法順利地通過血腦屏障(Blood brain barrier);研究人員發現若使用奈米顆粒作為藥物載體,可利用其藥物載體之標靶性,可以使藥物通過血腦屏障並發揮其功效。

因已有許多文獻指出聚氰基丙烯酸烷基酯(Poly alkyl cyanoacrylate,PACA)及聚氰基丙烯酸丁酯(Poly butyl cyanoacrylate, PBCA)等具有具有生物相容性(Biocompatibility)及生物可降解性(Biodegradability),可以作為藥物載體幫助藥物順利地送達目的地。此論文中主要是利用聚氰基丙烯酸乙酯(Poly ethyl cyanoacrylate,PECA)作為藥物載體,利用調整其起始條件,得到吾人所需之大小以通過血腦屏障,並測量其性質、藥物釋放速率等,以了解其特性,以便日後實際運用於治療阿茲海默症上。


In Taiwan, we are entering aging society. Taiwan Alzheimer’s Disease Association estimates that the population of dementia in Taiwan will be near to 800000 in 2060. Alzheimer’s disease makes up the greatest number of cases among all causes of dementia. Therefore, how to prevent and cure Alzheimer’s disease effectively is becoming an important issue.

Clioquinol is one of the metal chelating agent and has been found to be beneficial in the treatment for Alzheimer''s disease. While clioquinol itself cannot easily pass through the blood brain barrier, the research showed that, with nanoparticles used as the drug carriers, the targeting property/feature of the drug carriers would aid in the passage of clioquinol across the blood brain barrier and thus exerting its effects.

Many studies have demonstrated that, due to their biocompatibility and biodegradability, poly alkyl cyanoacrylates (PACA), and poly butyl cyanoacrylate (PBCA) can be used as the drug carriers and help the drugs reach the destination. In this thesis, the poly ethyl cyanoacrylate (PECA) was used as a drug carrier system. In order to obtain the proper size of PECA nanoparticle drug carrier to pass the blood brain barrier, several key parameters of the synthesis of PECA nanoparticle drug carriers were examined. The important properties/features along with the drug release rates of the PECA nanoparticle drug carrier were also determined. We believe the outcome from this research may contribute to the treatment for Alzheimer’s disease.


摘要 I
ABSTRACT II
目錄 IV
表目錄 VII
圖目錄 VIII
第一章 序論 1
1.1前言 1
1.2 研究目的 2
第二章 文獻回顧 3
2.1阿茲海默症 3
2.1.1阿茲海默症簡介 3
2.1.2阿茲海默症現今治療方法 7
2.1.3血腦屏障[84] 17
2.1.4 乙型類澱粉蛋白 (β-Amyloid Protein) 23
2.1.5 Clioquinol (CQ) 27
2.2乳化聚合(EMULSION POLYMERIZATION) 28
2.2.1乳化聚合簡介 28
2.2.2乳化聚合成核機制 31
2.2.3 迷你乳化聚合[136] 33
2.3高分子顆粒之性質 36
2.3.1高分子簡介 36
2.3.2高分子聚合方式 37
2.3.3離子聚合(Ionic polymerization) 38
2.3.4奧士瓦爾多併吞效應(Ostwald ripening effect) 39
2.3.5冷凍乾燥(Freeze drying) 40
2.4奈米顆粒藥物載體的標靶性[177] 44
2.5奈米顆粒特性之測量 45
2.5.1奈米顆粒大小與界面電位(Zeta potential) 45
2.5.2穿透式電子顯微鏡(Transmission Electron Microscopy,TEM) 47
第三章 實驗方法 49
3.1實驗藥品 49
3.2實驗儀器 50
3.3實驗流程 51
3.3.1製作奈米顆粒 51
3.3.2高分子轉化率(Conversion) 53
3.3.3高分子產率(Yield) 55
3.3.4藥物包覆率(Loading capacity(LC) and Encapsulation efficiency(EE)) 57
3.3.5藥物釋放速率(Release rate) 58
第四章 結果與討論 60
4.1 PECA奈米顆粒之尺寸 60
4.1.1單體濃度之影響 67
4.1.2界面活性劑濃度之影響 68
4.1.3界面活性劑種類之影響 69
4.1.4反應過程中轉速之影響 74
4.1.4反應過程中均質時間之影響 78
4.2 PECA之化率轉 80
4.3 PECA之產率 81
4.4藥物包覆率LOADING CAPACITY(LC)及ENCAPSULATION EFFICIENCY(EE) 82
4.5藥物釋放速率 84
第五章 結論及未來發展 88
附錄 89
參考文獻 94


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