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研究生(外文):Tzu-Ping Jao
論文名稱(外文):The Preparation of Artificial Skin with Collagen Extracted from Fish Scale and The Quantitative Research of Its Transdermal Drug Delivery Application
指導教授(外文):Hou-Chien Chang
口試委員(外文):Wen-Tung ChengChih-Hsin Shih
外文關鍵詞:fish scalecollagenpermeability
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膠原蛋白是一種纖維蛋白,可分為28型,主要分佈於細胞外之外基質,穩定器官以及結締組織以維持原本結構之完整性。膠原蛋白之提取,已經廣泛運用於醫藥以及化妝品等領域。由於一直有動物疫情產生,源自於陸生動物之膠原蛋白安全性受到質疑,而水生動物之膠原蛋白逐漸作為替代。而近期發生塵暴事件,人工皮使用量大增而有不足的情況,計畫以魚鱗中的膠原蛋白製膜以取代人工皮。本研究主要分為兩個部分—實驗及模擬,實驗部分,將魚鱗中之膠原蛋白萃取出來並且製成膜,於體外模式進行藥物分子滲透膠原蛋白膜的實驗,實驗結果以累積滲透量對時間作圖,觀察藥物分子累積滲透情形。模擬部分,加入數值模型量化滲透膜的表觀滲透係數,量化維生素C經皮滲透模式以及膜之滲透係數。實驗結果以維生素C累積滲透量對實驗時間作圖,觀察維生素C累積滲透量的情形,再加入數值模型量化維生素C滲透豬皮、CA膜以及膠原蛋白膜的表觀滲透係數,結果分別為2.5×10-7 cm/s、5.6×10-6 cm/s以及9.8×10-6 cm/s,與相關研究文獻進行比對與討論,除了不同藥物分子的莫爾體積會影響滲透係數,仍有許多原因影響藥物分子對皮膚的滲透係數,都是未來必須進行研究與確認維生素C經皮膚滲透的模式與皮膚的滲透係數。

There are 28 different types of collagen, which vary considerably in their complexity and diversity of their structure. Collagen has been widely used in fields including medicines and cosmetics due to its excellent biocompatibility. However, stock diseases pose threat to collagen products due to their limited sources including porcine skin and bovine skin currently. As a consequence, the alternative source of collagen, especially from aquatic animals finds it advantage in biomedical industry. The tragedy of dust storm in 2015 inspires the research on artificial skin alternative, here an efficient process of manufacturing artificial skin with minimum cost is proposed. The work is composed of the experimental and simulative parts. In experimental part, the collagen is extracted form fish scale and made into membrane with cellulose acetate. In the in vitro experiment the real time concentration of the sample solution is recorded and analyzed by High Performance Liquid Chromatography. While in simulative part, a diffusion model is developed, attempting to describe this mass transport process with diffusion theories mathematically. Output of the comparison between model data and experimental results generates the permeability of the whole skin, cellulose acetate membrane and collagen membrane. Results are 2.5×10-7 cm/s, 5.6×10-6 cm/s, and 9.8×10-6 cm/s for diffusions in vertical cells respectively. The former is validated against literature data(2.5×10-7 cm/s) and discussed from molecular viewpoint theoretically.

第一章 緒論......1
第二章 文獻回顧...2
2-1 藥物經皮輸送系統......2
2-2 藥物經皮滲透原理......3
2-3 皮膚結構.....5
(1) 表皮層.......5
(2) 真皮層.......6
(3) 皮下組織.....6
2-4 經皮滲透途徑..7
(1) 角質細胞間路徑........7
(2) 直接穿透角質細胞路徑...7
(3) 附屬器路徑....8
(4) 其他滲透路徑..8
2-5 皮膚屏障功能..8
2-6 促進經皮吸收方法......8
(1) 化學性方法....9
(2) 物理性方法....10
2-7 化學性促滲劑..11
2-8 膠原蛋白特性..14
2-9 高分子材料....15
2-10 定量與定性分析.......18
第三章 實驗材料與方法......19
3-1 實驗方法.....19
3-2 皮膚樣本前處理........21
3-3 膠原蛋白萃取..21
3-4 膠原蛋白膜製備程序.....21
3-5 體外經皮滲透實驗步驟...22
(1) 垂直式Franz Diffusion Cell (FDC).....22
(2) 取樣..22
3-6 HPLC分析方法..23
(1) HPLC系統配備..23
(2) 分離條件......23
(3) 校正曲線之建立.....24
(4) 操作步驟.....24
(5) 維生素C分析條件.......24
3-7 數值模型分析擬合流程...25
3-8 實驗藥品.....28
3-9 實驗儀器.....29
第四章 實驗結果與討論......30
4-1 標準曲線.....30
4-2 維生素C累積滲透量.....31
4-3 數值模型模擬結果......35
4-4 量化維生素C滲透係數....36
4-5 滲透係數與時間關係.....44
4-6 研究結果與文獻比較.....46
第五章 結論與未來展望......51
第六章 參考文獻...52

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