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研究生:邱林聰
研究生(外文):Lin-Tsung Chiou
論文名稱:經皮輸送晶片傳遞模式藥物探討皮膚滲透率之研究
論文名稱(外文):Study of Transdermal Delivery Chip to Transfer Model Drug for Skin Permeation
指導教授:林裕城林裕城引用關係
指導教授(外文):Yu-Cheng Lin
學位類別:碩士
校院名稱:國立成功大學
系所名稱:工程科學系碩博士班
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:2009
畢業學年度:97
語文別:中文
論文頁數:118
中文關鍵詞:微機電製程拉曼光譜經皮輸送電穿孔滲透法
外文關鍵詞:Transdermal DeliveryElectroporationMEMSMicroscope Raman Spectrometer
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本研究開發經皮輸送晶片系統以傳輸凝膠藥物(磺胺嘧啶銀,Silver Sulfadiazine)至鼠皮膚(Rat Skin)內,此晶片系統乃是使用微機電製程(Micro-Electro-Mechanical-Systems,MEMS)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,讓藥物能順利傳遞進去皮膚內。本型經皮輸送晶片系統有別於一般電穿孔法,使用10 V、20 V、30 V的脈衝電壓下,即能得到經皮輸送的效果。並探討在不同脈衝頻率(0.01 Hz、1 Hz、10 Hz、1 kHz)下,對於經皮輸送效果的影響。本研究使用共軛焦顯微拉曼光譜儀(Microscope Raman Spectrometer)分析在皮膚內藥物的光譜強度,藉此作為藥物傳遞效果的依據。並以晶片電場模擬與實驗結果相互佐證,當電壓增加時,藥物傳遞深度也隨著增加。在30 V脈衝電壓下,藥物可以傳遞到200 um深度下,並在低頻率(0.01 Hz)下可以得到較好的經皮輸送效果。因此,由實驗結果可以得到,利用此電穿孔晶片系統能有效地增加藥物的經皮輸送效果,並增加藥物傳遞的最大深度。
This study was developed transdermal delivery chip system for delivering Silver Sulfadiazine into rat skin. The chip system was used Micro-Electro-Mechanical-Systems (MEMS) technology to fabricate and electroporation 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 voltage (10 V、20 V、30 V). Moreover it was discussed the effect of transdermal delivery under different frequency (0.01 Hz、1 Hz、10 Hz、1 kHz). It was used microscope Raman spectrometer to analyze spectral strength of drug as drug delivery effect. The results of simulation could prove experimental results that delivery depth was increased with voltage. It could gain excellent transdermal delivery and delivery into 200 um depth when it was used voltage (30 V) and frequency (0.01 Hz). Therefore, this chip system could enhance the transdermal delivery effectively and delivery depth from the experimental results.
中文摘要 I
Abstract II
誌謝 III
目錄 IV
圖目錄 VII
第一章 緒論 1
1-1 前言 1
1-2 藥物之經皮輸送路徑 4
1-2-1 皮膚的結構與功能 4
1-2-2 皮膚輸送路徑 7
1-3 經皮輸送方式 10
1-4 拉曼散射 16
1-4-1 拉曼散射原理 16
1-4-2 拉曼散射應用 17
1-5 研究動機與目的 22
1-6 研究架構 23
第二章 材料與方法 25
2-1 實驗儀器 25
2-1-1 脈衝電源供應系統 25
2-1-2 共軛焦拉曼光譜儀 27
2-2 實驗藥品 29
2-2-1 經皮傳遞藥物介紹(燙膚舒凝膠) 29
2-3 實驗鼠皮膚之處理方法 31
2-3-1 實驗鼠皮膚之取皮與保存 31
2-4 晶片之結構設計與數值模擬分析 33
2-4-1 晶片之結構設計 33
2-4-2 晶片之數值模擬分析 35
2-4-3 建立晶片結構之數值模型 37
2-4-4 晶片結構之離散化 39
2-4-5 晶片之邊界條件的設定與運算 40
2-4-6 晶片結構之網格密度分析 42
2-4-7 模擬後處理 45
2-5 晶片之製程 46
2-5-1 晶片之製程 46
2-6 藥物經皮輸送方法與拉曼光譜分析法 51
2-6-1 電穿孔法之經皮輸送實驗 51
2-6-2 共軛焦拉曼光譜儀操作流程 53
2-6-3 拉曼光譜定性分析法 56
2-6-4 拉曼光譜分析與前處理 57
第三章 結果與討論 61
3-1 晶片結構之模擬結果分析 61
3-1-1 晶片電場分佈之模擬結果分析 61
3-1-2 晶片電場強度之模擬結果分析 64
3-2 經皮輸送實驗結果 70
3-2-1 經皮輸送晶片系統對凝膠滲透效果之影響 70
3-2-2 經皮輸送實驗之拉曼光譜掃描結果 73
3-2-3 經皮輸送晶片系統 - 頻率對藥物滲透效果之影響 87
3-2-4 經皮輸送晶片系統 - 電壓對藥物滲透深度之影響 89
第四章 結論與建議 92
4-1 結論 92
4-2 建議 94
參考文獻 96
附錄 106
自述 118
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