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研究生:邱文昱
研究生(外文):Wen-YuChiu
論文名稱:陰陽離子液胞包覆油/水溶性藥物之行為探討
論文名稱(外文):Simultaneous Encapsulation of Oil-soluble and Water-soluble Drugs in Catanionic Vesicles
指導教授:楊毓民楊毓民引用關係
指導教授(外文):Yu-Min Yang
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:2012
畢業學年度:100
語文別:中文
論文頁數:132
中文關鍵詞:陰陽離子界面活性劑陰陽體雙重包覆物理穩定性流動性包覆效率釋放速率
外文關鍵詞:catanionic surfactantcatansomesimultaneous encapsulationphysical stabilityfluidityencapsulation efficiencyrelease rate
相關次數:
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三種陰陽離子界面活性劑(DeTMA-DS、DeTMA-TS、DTMA-DS)可經由沉澱法製備出,藉由乙醇當共溶劑的半自發製程,以純水水合製備陰陽體(catansomes)。本實驗探討膽固醇的濃度對陰陽體粒徑、界面電位、分散係數與物理穩定性的影響以及以親油性藥物(維他命E醋酸酯)與親水性藥物(熊果素)作為被包覆物,探討單一包覆以及雙重包覆藥物液胞的油溶性/水溶性藥物包覆行為、雙層膜流動性和水溶性藥物的釋放行為。此外,因維他命E醋酸酯結構與膽固醇類似,所以更進一步地探討維他命E醋酸酯是否具有膽固醇使液胞穩定之效果。
實驗結果顯示,膽固醇可以提升液胞的穩定性,由其是6mM濃度下。對於包覆藥物的液胞系統來說,維他命E醋酸酯似乎可以扮演膽固醇的角色使液胞穩定性提升。不過,熊果素的添加可能會破壞液胞頭基間的作用力使液胞穩定性下降。油溶性藥物包覆方面,液胞雙層膜的流動性越低,疏水程度越高越能包覆住油溶性藥物。水溶性藥物包覆方面,液胞粒徑越大,包覆水溶性藥物的體積也越大。此外,液胞雙層膜流動性、滲透性越低也能包覆住越多的水溶性藥物。釋放方面,液胞雙層膜的流動性越低越能抑制水溶性藥物的釋放。
本實驗所選用的油溶性藥物-維他命E醋酸酯。其結構與膽固醇類似,由實驗結果得知,維他命E醋酸酯不僅僅是被包覆物,同時還具有膽固醇般膜內穩定性的角色。不過,相較於膽固醇,維他命E醋酸酯對於雙層膜的交互作用力影響程度較小。

Three catanionic surfactants (DeTMA-TS , DeTMA-DS and DTMA-DS) can be made by precipitation . Catanionic vesicles can be prepared with 20v/v% ethanol by the semi-spontaneous process. A study can be tested the effects of cholesterol concentrations on the size, zeta-potential, PDI ,and physical stability in 20v/v% ethanol solution. The catansomes were used to solubilize oil-soluble drug such as vitamin E acetate and encapsulate water-soluble drug such as arbutin to test oil-soluble drug , water-soluble drug and simultaneous encapsulation on encapsulation behavior , membrane rigidity and release behavior . In addition, because structure of vitamin E acetate is similar to cholesterol , a study if vitamin E acetate act as stabilizer as cholesterol is deserved to research.
The experimental results reveal cholesterol can stabilize the vesicle, especially for 6mM. For drugs encapsulated catansome system, vitamin E acetate seems to act as stabilizer as cholesterol to let vesicle stable. On the contrary, arbutin can damage the stability of vesicle because it damage the attration force between head groups. As for encapsulation of oil-soluble drug , encapsulation efficiency of oil-soluble drug increased with the decrease of membrane fluidity because membrane is more hydrophobic. As for encapsulation of water-soluble drug , encapsulation efficiency of water-soluble drug increased with the increase of vesicle size due to the core volume. In addition, encapsulation efficiency of water-soluble drug increased with the decrease of membrane fluidity due to membrane permeability. Release rate of water-soluble drugs decreased with the decrease of membrane fluidity. What’s more, vitamin E acetate can stabilize vesicles without cholesterol. Therefore, vitamin E acetate can be not only encapsulater drug , but also the stabilizer.

總目錄
摘 要 I
Abstract III
誌 謝 V
總目錄 VI
表目錄 XI
圖目錄 XIV
第一章 緒論 1
1-1 前言 1
1-2 研究動機與目的 5
第二章 文獻回顧 6
2-1陰陽離子液胞種類的定義 6
2-2共溶劑對陰陽離子液胞結構狀態的影響 8
2-3膽固醇對於液胞雙層膜的影響 10
2-4維他命E(醋酸酯)對液胞雙層膜的影響 12
2-5熊果素對液胞雙層膜的影響 13
2-6液胞雙層膜流動性對油溶性藥物包覆的影響 14
2-7液胞粒徑對水溶性藥物包覆的影響 18
2-8液胞雙層膜流動性對水溶性藥物包覆的影響 21
2-9液胞雙層膜流動性對水溶性藥物釋放的影響 25
第三章 實驗 28
3-1實驗藥品 30
3-2 實驗儀器及裝置 31
3-2-1均質機 31
3-2-2雷射光散射法粒徑/界面電位分析儀 32
3-2-3凝膠層析 33
3-2-4穿透式電子顯微鏡(TEM) 34
3-2-5熱掃描卡量計(DSC) 35
3-2-6螢光偏極化(FP) 36
3-2-7高效能液相層析儀(HPLC) 37
3-3 實驗方法 38
3-3-1陰陽離子界面活性劑的製備 38
3-3-2陰陽體的製備 39
3-3-3液胞粒徑、電位、穩定性的測量 40
3-3-4陰陽體包覆油/水溶性藥物的製備與液胞的包覆、釋放 41
3-3-5 DSC所需的液胞樣品的製備 43
3-3-6穿透式電子顯微鏡(TEM)的樣品製備 43
3-3-7偵測液胞雙層膜流動性之樣品製備 44
第四章 結果與討論 45
4-1未包覆藥物液胞的基本物理性質 45
4-1-1未包覆藥物陰陽體的TEM圖 47
4-1-2未包覆藥物陰陽體的粒徑 49
4-1-3未包覆藥物陰陽體的電位 50
4-1-4未包覆藥物陰陽體的穩定性 51
4-1-5未包覆藥物陰陽體雙層膜的相變行為與流動性 53
4-2單一包覆油溶性藥物液胞的基本物理性質 55
4-2-1單一包覆油溶性藥物陰陽體的TEM圖 56
4-2-2單一包覆油溶性藥物陰陽體的粒徑 58
4-2-3單一包覆油溶性藥物陰陽體的電位 60
4-2-4單一包覆油溶性藥物陰陽體的穩定性 62
4-2-5單一包覆油溶性藥物陰陽體雙層膜的流動性 65
4-2-6 凝膠層析的分離 68
4-2-7單一包覆油溶性藥物陰陽體的包覆效率 69
4-3單一包覆水溶性藥物液胞的基本物理性質 70
4-3-1單一包覆水溶性藥物陰陽體的TEM圖 71
4-3-2單一包覆水溶性藥物陰陽體的粒徑 73
4-3-3單一包覆水溶性藥物陰陽體的電位 76
4-3-4單一包覆水溶性藥物陰陽體的穩定性 78
4-3-5單一包覆水溶性藥物陰陽體雙層膜的流動性 81
4-3-6凝膠層析之建立與質量平衡 83
4-3-7單一包覆水溶性藥物陰陽體的包覆效率 85
4-3-8單一包覆水溶性藥物陰陽體的釋放行為 87
4-4雙重包覆油/水溶性藥物液胞的基本物理性質 90
4-4-1雙重包覆油/水溶性藥物陰陽體的TEM圖 92
4-4-2雙重包覆油/水溶性藥物陰陽體的粒徑 93
4-4-3雙重包覆油/水溶性藥物陰陽體的電位 95
4-4-4雙重包覆油/水溶性藥物陰陽體的穩定性 97
4-4-5雙重包覆油/水溶性藥物陰陽體的流動性 100
4-4-6 雙重包覆油/水溶性藥物陰陽體的包覆效率 104
4-4-7 雙重包覆油/水溶性藥物陰陽體的釋放行為 109
4-5 維他命E醋酸酯對於液胞雙層膜的影響 113
4-5-1維他命E醋酸酯是否具有膽固醇般穩定液胞的角色 113
4-5-2維他命E醋酸酯的濃度對於液胞雙層膜流動性與包覆效率的影響 116
第五章 結論與建議 118
5-1 結論 118
5-2 建議 121
參考文獻 122
自述 132

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