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研究生:邱雪瑩
研究生(外文):Xue-Ying Khew
論文名稱:以氫氧基磷灰石作為藥物載體應用於預防阿茲海默症之研究
論文名稱(外文):The study of hydroxyapatite as drug carrier for Alzheimer’s disease prevention
指導教授:林峯輝
指導教授(外文):Feng-Huei Lin
口試委員:楊禎明陳克紹張國基
口試委員(外文):Jen-Ming YangKo-Shao Chen
口試日期:2016-07-15
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:醫學工程學研究所
學門:工程學門
學類:綜合工程學類
論文種類:學術論文
論文出版年:2016
畢業學年度:105
語文別:中文
論文頁數:45
中文關鍵詞:阿茲海默症氫氧基磷灰石多奈哌齊藥物載體老年化
外文關鍵詞:Alzheimer’s diseasehydroxyapatitedonepezildrug carrieraging
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阿茲海默症是現代老年化社會普及的一種神經退化疾病,會嚴重影響患者的日常生活以及為身邊的人帶來諸多不便。目前阿茲海默症無法完全根治,只能透過藥物改善或是減緩病情的惡化。預防醫學對於老年化社會是一項重要的議題,也是目前醫學上的重點發展。因此,希望藉由預防注射來代替口服的給藥方式,讓患者免於每日服藥的不便性,也減輕照護者的負擔。
本研究以氫氧基磷灰石/多奈哌齊 (donepezil) 材料作為實驗主要的藥物載體,並探討氫氧基磷灰石作為多奈哌齊載體材料之特性及載藥量。本研究主要分為材料分析、載藥量分析、藥物釋放分析、體外細胞實驗與初步之動物實驗。
透過 XRD、FTIR、SEM 觀察氫氧基磷灰石/多奈哌齊之分析,證實多奈哌齊確實被氫氧基磷灰石所包覆。以 TGA 分析得到其載藥量約為 12 %。藥物釋放測試顯示氫氧基磷灰石/多奈哌齊於酸性環境下多奈哌齊很快就被大量釋放出來。藉由體外細胞試驗 WST-1 與 LDH ,結果顯示氫氧基磷灰石/多奈哌齊並不會對細胞的增生或存活造成影響,同時也不會對細胞造成毒性。
由研究結果顯示,氫氧基磷灰石/多奈哌齊對於阿茲海默症的預防具有潛在的臨床運用價值。
Alzheimer’s disease (AD) is the most common type of neurodegenerative disease in aging society, which will reducing life quality of patients, and inconvenience to the caregivers. However, Alzheimer’s disease is currently that is no drug can successfully treat it. Current approaches focus on slowly or delay the symptoms of Alzheimer’s disease. Hence, researchers hope to develop therapies that the actual underlying cause of the disease can be prevented.
The purpose of study is to develop hydroxyapatite/donepezil which could carry drugs. The material synthesis, drug loading test, drug release test, in vitro study and in vivo study were evaluated.
In material synthesis study, donepezil is indeed into hydroxyapatite was confirmed by XRD analysis, FTIR, and SEM observations. TGA analysis showed the drug loading of hydroxyapatite/donepezil is about 12 %. The drug release tests showed hydroxyapatite/donepezil a great number of donepezil release in the acidic environment in a short time. In in vitro study, WST-1 test showed there is no negative effect on cell viability and cell proliferation. LDH test showed no cytotoxicity on cell.
The results suggest that hydroxyapatite/donepezil would be a potential candidate for prevention Alzheimer’s disease.
口試委員會審定書 i
誌謝 ii
中文摘要 iii
ABSTRACT iv
目錄 v
圖目錄 ix
表目錄 xi
名詞縮寫 xii
第1章 緒論 1
1.1 前言 1
1.2 阿茲海默症簡介 1
1.3 阿茲海默症之病程 2
1.4 阿茲海默症之類型 3
1.5 阿茲海默症之成因 3
1.6 阿茲海默症之藥物治療 5
1.7 臨床上之給藥途徑 6
1.8 研究動機 7
1.9 研究目的 8
第2章 理論基礎 9
2.1 材料介紹 9
2.1.1 氫氧基磷灰石之簡介 9
2.1.2 氫氧基磷灰石之製備 10
2.2 多奈哌齊之簡介 10
2.2.1 多奈哌齊之治療效果 11
2.2.2 多奈哌齊之預防效果 11
2.3 含有多奈哌齊之氫氧基磷灰石之給藥途徑 12
2.4 阿茲海默症之動物誘導模式 14
第3章 實驗方法 16
3.1 實驗儀器 16
3.2 實驗藥品 17
3.3 實驗流程 18
3.4 材料製備 18
3.4.1 HAP/ DPZ製備 18
3.5 材料性質分析 19
3.5.1 形貌表徵 19
3.5.2 成份結構 19
3.5.3 材料載藥量分析 21
3.6 藥物釋放試驗 21
3.6.1 可見光紫外光分光光譜儀 21
3.7 細胞培養 22
3.7.1 3T3 細胞株培養 22
3.7.2 培養基製備 22
3.7.3 磷酸鹽緩衝溶液製備 22
3.7.4 解凍細胞 23
3.7.5 繼代培養 23
3.7.6 細胞計數 23
3.8 材料生物相容性測試 24
3.8.1 WST-1增生及活性測試 24
3.8.2 LDH細胞毒性測試 25
3.9 動物實驗 26
3.9.1 實驗動物來源 26
3.9.2 動物實驗之分組 27
3.9.3 動物實驗之時程 27
3.9.4 莫氏水迷宮 28
3.9.5 舉臂式十字迷宮 30
第4章 結果與討論 32
4.1 材料性質分析 32
4.1.1 X 光繞射分析結果 32
4.1.2 紅外線光譜儀 33
4.2 掃描式電子顯微鏡觀察 34
4.2.1 掃描電子顯微鏡結果 34
4.2.2 能量色散X-射線分析結果 34
4.2.3 粒徑大小分析結果 35
4.3 材料載藥量分析 35
4.3.1 熱重分析測試結果 35
4.4 藥物釋放分析 36
4.5 材料生物相容性測試 37
4.5.1 WST-1 測試結果 37
4.5.2 LDH 測試結果 37
4.6 動物實驗 38
4.6.1 舉臂式十字迷宮結果 38
4.6.2 莫氏水迷宮結果 39
第5章 結論 41
第6章 參考文獻 42
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