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研究生：	劉子瑜 Liu, Zih-Yu
論文名稱：	經皮輸送可撓式晶片傳遞傳明酸探討血清藥物濃度之研究 Study of Transdermal Delivery Flexible Chip to Transfer Tranexamic Acid for Drug Concentration of Serum
指導教授：	林裕城 Lin, Yu-Cheng
學位類別：	碩士 Master
系所名稱：	工學院 - 工程科學系 Department of Engineering Science
論文出版年：	2011
畢業學年度：	100
語文別：	中文
論文頁數：	91
中文關鍵詞：	經皮輸送、可撓式、微機電製程、電穿孔滲透
外文關鍵詞：	Transdermal Delivery, Flexible Chip, MEMS, Electroporation
相關次數：	點閱：64 下載：0
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本研究開發經皮輸送可撓式晶片系統並以傳明酸(Tranexamic acid, TA)乳液藥物經由鼠皮膚(Rat skin)傳輸至血液內，再以液相層析串聯質譜儀(Liquid chromatograph-Mass spectrometer, LC-MS)分析實驗動物血清，藉此作為藥物傳遞效果的依據。此可撓式晶片系統乃是使用微機電(Micro electro mechanical systems, MEMS) 與化鎳浸金(Electroless nickel/immersion gold, ENIG) 製程製作晶片，並利用電穿孔滲透法(Electroporation)作為實驗機制。當在晶片上施加脈衝電壓之後，電極與皮膚之間會產生一穿膜電場，使皮膚產生微小孔洞，讓藥物能順利穿透皮膚到血液內。本型經皮輸送可撓式晶片系統有別於一般電穿孔法，使用1 V、3 V、5 V、7 V 的低脈衝電壓下，即能得到經皮輸送的效果。並探討在不同脈衝頻率(1 Hz、10 Hz、100 Hz、1 kHz、10 kHz)下，對於經皮輸送效果的影響。實驗結果顯示在7 V 脈衝電壓及高頻率(10 kHz)下可以得到最好的藥物經皮輸送效果，為自然滲透的9.8 倍。因此，由實驗結果可以得到，利用此可撓式電穿孔晶片系統能有效地增加藥物的經皮輸送效果。

This study was developed transdermal delivery flexible chip system for delivering tranexamic acid into rat blood through skin. The chip system was used Micro-Electro-Mechanical-Systems (MEMS) and Electroless Nickel Immersion Gold (EN/IG) technology to fabricate as experimental mechanism.
The electrode would generate cell-penetrating electric field in the skin between electrodes when voltage was applied in chip. It could make the skin produce some tiny pores and delivery drug into it. This chip system is different to electroporation that it could gain transdermal delivery effect as using low voltage (1 V, 3 V, 5V, and 7 V). Moreover it was discussed the effect of transdermal delivery under different frequency (1 Hz, 10 Hz, 100 Hz, 1 kHz, and 10k Hz). It could gain excellent transdermal delivery effect when it was used voltage (7 V) and frequency (10k Hz), and it’s 9.8 times than passive transport. Therefore, this flexible chip system could enhance the transdermal delivery effectively from the experimental results.

中文摘要 .............................................. I
Abstract................................................ II
誌謝 ................................................. III
目錄 ................ ................................... IV
表目錄 ................. ........................... VIII
圖目錄 ................... ............................. IX
縮寫表 ......................... ...................... XII
第一章 緒論 ......................... ................ 1
1-1 前言 ......................................... 1
1-2 藥物經皮輸送路徑 ................... 4
1-2-1 皮膚結構與功能 ..................... 4
1-2-2 皮膚輸送路徑 ........................ 7
1-3 經皮輸送方式 ...................... 11
1-4 液相層析串聯質譜儀 ................... 18
1-4-1 液相層析串聯質譜儀原理 ........... 18
1-4-2 液相層析串聯質譜儀應用 .......... 19
1-5 研究動機與目的 .................. 23
1-6 研究架構 .............................. 24
第二章 可撓式晶片之設計與製作 ........... 26
2-1 晶片之結構設計 ...................... 26
2-2 可撓式晶片之製程 .................. 28
2-2-1 可撓式晶片基板之製程 ............. 28
2-2-2 可撓式晶片電極之製程 ............. 30
第三章 實驗與研究方法 .................. 32
3-1 實驗儀器與設備 ................... 32
3-1-1 脈衝電源供應系統 ................... 32
3-1-2 液相層析串聯質譜儀 .............. 35
3-1-3 高速離心機 .......................... 36
3-1-4 正立式顯微鏡 ...................... 37
3-2 實驗藥品 .............................. 38
3-2-1 經皮輸送藥物 ...................... 38
3-2-2 麻醉藥物 .............................. 40
3-3 實驗動物 ............................. 41
3-4 藥物自然滲透實驗方法 ............. 42
3-5 藥物經皮輸送之電穿孔方法 ............................. 43
3-5-1 電穿孔法之經皮輸送實驗 .............................. 43
3-6 皮膚損傷觀察方法 ............................ 45
3-6-1 皮膚觀察方法 .................... 45
3-6-2 色階分析方法 ....................... 45
3-7 血清檢體取樣方法 ................... 46
3-7-1 血清檢體取樣方法 .................. 46
3-8 液相層析串聯質譜儀分析方法 ............................. 47
3-8-1 液相層析串聯質譜儀分析條件 ...................... 47
3-9 統計分析方法 .................................... 48
3-9-1 統計分析 .......................... 48
第四章 結果與討論 ........................ 49
4-1 皮膚損傷程度 ..................... 49
4-1-1 皮膚表面損傷程度 ................ 50
4-1-2 鼠皮膚灰階化分析結果 ................. 54
4-2 藥物自然滲透之代謝效果 ............. 58
4-3 經皮輸送實驗結果 .................. 62
4-3-1 時間對藥物滲透效果之影響 ............ 62
4-3-2 脈衝電壓與脈衝頻率之影響 .................... 64
4-3-2-1 頻率對藥物滲透效果之影響 ......................... 65
4-3-2-2 電壓對藥物滲透效果之影響 ........................ 67
4-4 統計分析結果 .................... 69
4-4-1 不同脈衝電壓及脈衝頻率下的顯著性分析結果 ........... 69
第五章 結論與建議 ........................... 74
5-1 結論 .................................... 74
5-2 建議 ..................................... 76
參考文獻 ........................................... 77
附錄 ................................................. 86
自述 .................................................. 91
                                    

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