臺灣博碩士論文加值系統

目錄
指導教授推薦書
口試委員會審定書
誌謝 iii
中文摘要 iv
英文摘要 v
目錄 vi
圖目錄 xi
表目錄 xvi
第一章 緒論 1
1.1研究動機與目的 1
第二章 文獻回顧 4
2.1類黃酮 4
2.1.1類黃酮的簡介 4
2.1.2類黃酮的藥理性質與生物活性 5
2.2檞皮素 6
2.2.1檞皮素的簡介 6
2.2.2檞皮素之物化性 7
2.2.3檞皮素之抗氧化潛力與機制 7
2.3自由基 10
2.3.1自由基的定義與分類 10
2.3.2自由基的傷害 12
2.3.3自由基對皮膚的影響 12
2.3.4自由基對眼睛的影響 13
2.4皮膚 14
2.4.1皮膚結構 14
2.4.2經皮藥物傳遞途徑 17
2.4.3自由基與皮膚間之氧化機制 18
2.5眼睛 20
2.5.1眼部結構與藥物傳遞途徑 20
2.5.2眼睛氧化之相關疾病 21
2.6微乳液 24
2.6.1微乳液簡介與型態 24
2.6.2微乳液於皮膚給藥之應用 26
2.6.3微乳液於眼部給藥之應用 29
2.7化學促進劑 30
2.7.1化學促進劑簡介 30
2.7.2帖烯類 32
第三章 實驗材料與方法 34
3.1 實驗材料 34
3.2 實驗儀器設備 36
3.3 實驗方法 37
3.3.1微乳液組成之成份篩選 39
3.3.2三相圖繪製 39
3.3.3不同比例之共溶劑與界面活性劑之微乳液製作 40
3.3.4物化性分析 41
3.3.5穿透式電子顯微鏡分析 42
3.3.6實驗動物製備 42
3.3.7穿透累積裝置及試驗方式 44
3.3.8高效能液態層析儀分析 45
3.3.9細胞培養與繼代 47
3.3.10細胞計數 48
3.3.11細胞存活率分析 48
3.3.12細胞抗過氧化氫能力分析 49
3.3.13檞皮素微乳液安定性分析 50
3.3.14清除自由基能力測試 50
3.3.15螯合亞鐵離子能力測試 52
3.3.16還原力測試 53
3.3.17組織切片和染色 54
3.3.18模擬淚液藥物釋放分析 54
3.3.18.1質傳公式簡化 55
3.3.19正立雷射掃描共軛焦顯微鏡分析 56
3.3.20統計分析 56
第四章 結果與討論 57
4.1微乳液組成成分篩選 57
4.1.1檞皮素之飽和溶解度 57
4.1.2不同油相之飽和檞皮素溶液體外經皮穿透累積試驗 58
4.2擬三相圖 64
4.3微乳液穿透累積及物化性試驗 72
4.3.1檞皮素微乳液之物化性質探討 72
4.3.2檞皮素微乳液之細胞存活率分析 76
4.3.3檞皮素微乳液之清除氧化傷害分析 84
4.3.4檞皮素微乳液接觸角與表面張力分析 91
4.3.5檞皮素微乳液之安定性測試 94
4.3.6穿透累積實驗結果分析 101
4.4微乳液之抗氧化能力探討 116
4.4.1微乳液之自由基清除率 116
4.4.2微乳液之螯合亞鐵離子能力 118
4.4.3微乳液之還原力 120
4.5組織切片染色 122
4.6檞皮素微乳液之藥物釋放分析 126
4.7檞皮素微乳液之組織螢光強度與累積深度分析 129
第五章 結論 133
參考文獻 135


圖目錄
圖一 實驗架構 3
圖二 檞皮素之化學結構 7
圖三 檞皮素之抗氧化機制[13] 9
圖四 皮膚結構[23] 16
圖五 藥物穿透角質層路徑[24] 18
圖六 ROS介導活化皮膚多種細胞信號之傳導途徑[27] 19
圖七 眼部結構與藥物傳遞途徑局部給藥[30] 21
圖八 微乳液之三種型態[37] 25
圖九 介面活性劑、油相與水之三相圖[38] 25
圖十 藥物穿透的疏水和親水路徑及促進劑作用模式[49] 31
圖十一 常見萜烯類結構[50] 33
圖十二 實驗流程 38
圖十三 (a)完整幼豬左耳、(b) 完整豬眼睛(組織處理前) 43
圖十四 Franz擴散槽裝置 45
圖十五 20μg/ml榭皮素的高效能液態層析儀層析圖譜、榭皮素檢量線 46
圖十六 Geraniol、Linalool、1,8-Cineole、α- Terpineol之豬皮穿透曲線 60
圖十七 Geraniol、Linalool、1,8-Cineole、α-Terpineol之豬皮累積量 61
圖十八 介面活性劑Tween 80、共溶劑 Glycerol、水之豬皮穿透曲線 62
圖十九 介面活性劑Tween 80、共溶劑 Glycerol、水之豬皮累積量 63
圖二十 微乳液外觀 65
圖二十一 1.8-Cineole之擬三相圖(Tween 80/Glycerol=1/1) 66
圖二十二 1.8-Cineole之擬三相圖(Tween 80/Glycerol=1/2) 67
圖二十三 1.8-Cineole之擬三相圖(Tween 80/Glycerol=1/3) 68
圖二十四 Linalool之擬三相圖(Tween 80/Glycerol=1/1) 69
圖二十五 Linalool之擬三相圖(Tween 80/Glycerol=1/2) 70
圖二十六 Linalool之擬三相圖(Tween 80/Glycerol=1/3) 71
圖二十七 榭皮素微乳液載體的穿透式電子顯微鏡影像 75
圖二十八 Cineole微乳液於RGC-5細胞之細胞活性 78
圖二十九 Linalool微乳液於RGC-5細胞之細胞活性 79
圖三十 Cineole微乳液於HACAT細胞之細胞活性 80
圖三十一 Linalool微乳液於HACAT細胞之細胞活性 81
圖三十二 Cineole微乳液於SIRC細胞之細胞活性 82
圖三十三 Linalool微乳液於SIRC細胞之細胞活性 83
圖三十四 檞皮素微乳液於RGC-5細胞之抗氧化傷害能力 86
圖三十五 檞皮素微乳液於HACAT細胞之抗氧化傷害能力 87
圖三十六 檞皮素微乳液於SIRC細胞之抗氧化傷害能力 88
圖三十七 檞皮素微乳液於RGC-5、HACAT、SIRC細胞之EC50 90
圖三十八 Cineole微乳液之表面張力(成分參考表7) 92
圖三十九 Linalool微乳液之表面張力(成分參考表8) 93
圖四十 Cineole微乳液之接觸角(成分參考表7) 93
圖四十一 Linalool微乳液之接觸角(成分參考表8) 94
圖四十二 Cineole微乳液之粒徑變化(室溫下儲存八週) 97
圖四十三Linalool微乳液之粒徑變化(室溫下儲存八週) 97
圖四十四 Cineole微乳液之分散係數變化(室溫下儲存八週) 98
圖四十五 Linalool微乳液之分散係數變化(室溫下儲存八週) 98
圖四十六 Cineole微乳液之表面電位變化(室溫下儲存八週) 99
圖四十七 Linalool微乳液之表面電位變化(室溫下儲存八週) 99
圖四十八 Cineole微乳液之包覆率變化(室溫下儲存八週) 100
圖四十九 Linalool微乳液之包覆率變化(室溫下儲存八週) 100
圖五十 Cineole微乳液之豬皮穿透曲線(成分參考表7) 104
圖五十一 Cineole微乳液之豬皮累積量 (成分參考表7) 105
圖五十二 Linalool微乳液之豬皮穿透曲線(成分參考表8) 106
圖五十三 Linalool微乳液之豬皮累積量(成分參考表8) 107
圖五十四 Cineole微乳液之鞏膜穿透曲線(成分參考表7) 108
圖五十五 Cineole微乳液之鞏膜累積量(成分參考表7) 109
圖五十六 Linalool微乳液之鞏膜穿透曲線(成分參考表8) 110
圖五十七 Linalool微乳液之鞏膜累積量(成分參考表8) 111
圖五十八 Cineole微乳液之角膜穿透曲線(成分參考表7) 112
圖五十九 Cineole微乳液之角膜累積量(成分參考表7) 113
圖六十 Linalool微乳液之角膜穿透曲線(成分參考表8) 114
圖六十一 Linalool微乳液之角膜累積量(成分參考表8) 115
圖六十二 (a) Cineole、(b) Linalool微乳液之自由基清除率 117
圖六十三 (a) Cineole、(b) Linalool微乳液之螯合亞鐵離子能力 119
圖六十四 Cineole、Linalool微乳液之螯合亞鐵離子能力 120
圖六十五 (a) Cineole、(b) Linalool微乳液之還原力測試 121
圖六十六 Cineole、Linalool微乳液之還原力測試 122
圖六十七 皮膚之組織切片染色 123
圖六十八 鞏膜之組織切片染色 124
圖六十九 角膜之組織切片染色 125
圖七十 Cineole、Linalool微乳液之藥物釋放率 127
圖七十一 Cineole、Linalool微乳液之藥物累積量 128
圖七十二 Cineole微乳液於皮膚、角膜及鞏膜之累積分布 130
圖七十三 Cineole微乳液之累積深度與螢光強度 132


 
表目錄
表1 類黃酮的基本結構、分類與膳食來源[4] 5
表2 活性氮與活性氧的種類[16] 11
表3 微乳液與不同動物之皮膚及不同保存條件下，其穿透量及穿透係數[39] 27
表4 不同檞皮素乳液型態作用於皮膚之穿透累積比較 28
表5 奈米乳液包覆藥物用於眼部之傳遞[45] 29
表6 眼部藥物傳遞之方式 30
表7 不同Tween 80/ Glycerol比例之1,8-Cineole微乳液組成 40
表8 不同Tween 80/ Glycerol比例之Linalool微乳液組成 40
表9 模擬淚液配方[56] 55
表10 藥物釋放模式與擴散係數之關係[57] 55
表11 檞皮素於不同油相及微乳液成分中之飽和溶解度 58
表12 不同油相及微乳液成分中之豬皮分配係數Ks/w 64
表13 Cineole微乳液之物化性結果分析(成分參考表7、8) 74
表14 Linalool微乳液之物化性結果分析(成分參考表7、8) 74
表15 Cineole與Linalool微乳液之半致死濃度(RGC-5) 79
表16 Cineole與Linalool微乳液之半致死濃度(HACAT) 81
表17 Cineole與Linalool微乳液之半致死濃度(SIRC) 83
表18 Cineole、Linalool微乳液之抗氧化傷害模式分析(RGC-5) 89
表19 Cineole、Linalool微乳液之抗氧化傷害模式分析(HACAT) 89
表20 Cineole、Linalool微乳液之抗氧化傷害模式分析(SIRC) 90
表21 Cineole微乳液之豬皮穿透分配特性分析(成分參考表7) 105
表22 Linalool微乳液之豬皮穿透分配特性分析(成分參考表8) 107
表23 Cineole微乳液之鞏膜穿透分配特性分析(成分參考表7) 109
表24 Linalool微乳液之鞏膜穿透分配特性分析(成分參考表8) 111
表25 Cineole微乳液之角膜穿透分配特性分析(成分參考表7) 113
表26 Linalool微乳液之角膜穿透分配特性分析(成分參考表8) 115
表27 Cineole、Linalool微乳液之清除自由基模式分析 118
表28 Cineole、Linalool微乳液於PVDF膜之穿透特性分析 127
表29 根據Peppas所回歸出之參數 128
表30 Cineole與Linalool微乳液在PVDF膜之分配係數Ks/w (12hr) 129

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