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研究生:卓柔孜
研究生(外文):Rou Zi Zhuoa
論文名稱:鉺雅鉻雷射促進經皮傳遞之研究:以胜肽、疫苗及抗乾癬藥物為例
論文名稱(外文):Enhancement of Transdermal Drug Delivery by Erbium:YAG Laser: Peptides, Vaccine, and Anti-psoriatic Drug
指導教授:方嘉佑
指導教授(外文):J. Y. Fanga
學位類別:碩士
校院名稱:長庚大學
系所名稱:天然藥物研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
論文頁數:107
中文關鍵詞:鉺雅鉻雷射電破法胜肽甲氨蝶呤溶菌酶經皮吸收
外文關鍵詞:Er:YAG laserelectroporationpeptidemethotrexatelysozymetransdermal delivery
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鉺雅鉻雷射是目前醫學美容上廣泛使用的非侵入性手術。本研究之目的在於運用鉺雅鉻雷射促進及控制胜肽與甲氨蝶呤 (MTX) 的經皮穿透,並藉由體外擴散裝置來觀察胜肽與 MTX 在裸鼠皮的穿透情形,由於鉺雅鉻雷射可促使部分角質層產生剝離現象,進而提高胜肽及 MTX 的經皮穿透效果,且透過電子顯微鏡中觀察到角質層的確有變薄及間斷的情形。在胜肽的部份,其穿透效果經投與不同能量雷射後,比未經處理組高出 3~140 倍不等之促進效果。同時發現不同分子量、親脂性質及序列的胜肽都是影響穿透的重要因素,此部分確實也由雷射共軛焦顯微鏡拍出的影像顯示出雷射處理過後之皮膚,其胜肽的經皮穿透效果有顯著性增加。在體內試驗研究中,則使用雷射處理老鼠皮膚並施予溶菌酶此抗原作為皮膚免疫模式。實驗結果顯示經雷射處理後,可提高了 3 倍的血清抗體。在 MTX 的部份,主要是使用鉺雅鉻雷射及電破法這兩種物理性促進方式,來幫助提高此類用來治療乾癬之藥物的經皮穿透效果。結果顯示經雷射處理後其促進效果是較為明顯的。且在投與不同能量的雷射於皮膚後,有高出 3~80 倍的促進效果。而電破法方面則在施予 10 個脈衝後,顯示 MTX 的 flux 有提高 2 倍的促進。當雷射處理後再與電破法合併使用 10 分鐘,則發現其經皮穿透的效果較單獨使用的高。然而,此結果僅於低能量 1.4 J/cm2 的雷射中觀察出協同效應。另外,本實驗為模擬乾癬的皮膚,以膠帶反覆撕除角質層,使過度剝離的皮膚出現表皮增生之情況,並由此發現增生皮膚不僅個體差異大,且於 MTX 的促進效果也較低。依本實驗結果證明,雷射以及電破法不論是在單獨使用上或是結合使用上均可促進藥物的經皮傳遞。
Erbium:yttrium-aluminum-garnet (Er:YAG) laser is a non-invasive surgery to various dermal diseases and has been widely applied in skin regeneration operations. The aim of this study was to enhance and control skin permeation of peptides and methotrexate (MTX) by an Er:YAG laser. The peptides and MTX transported through nude mouse skin were measured using a diffusion assembly. The stratum corneum (SC) layer was partly ablated by an Er:YAG laser, resulting in an enhancing effect on peptides and MTX delivery. A thinning and discontinuous SC layer was observed after laser exposure by electron microscopy. The flux of peptides across laser-treated skin with various fluences was 3~140-fold higher than that across intact skin. The molecular size, lipophilicity, and sequence of the peptides were found to play an important role to modulate the enhancing activity. The result of confocal laser scanning microscopy (CLSM) indicates a significant increase in skin deposition of peptides into laser-treated skin. In an in vivo study, mouse skin was treated with the laser followed by skin vaccination with lysozyme antigen. The result indicated that the levels of IgG in serum were significantly increased by a 3-fold after the laser treatment. In MTX, physical enhancement methods by using both of Er:YAG laser and electroporation to enhance the transdermal delivery of psoriasis drugs. The enhancing effect was more pronounced after applying the laser. Er:YAG laser pretreatment on the skin produced a 3~80-fold enhancement depended on the magnitude of laser fluence. Using electroporation, treatment with 10 pulses resulted in a 2-fold increase in MTX flux. A combination of laser pretreatment and subsequent electroporation for 10 min resulted in a higher drug permeation than either technique alone. However, this synergistic effect was only observed when the lower laser fluence 1.4 J/cm2 was applied. The model of skin where epidermal hyperproliferation was reproduced by a tape-stripping technique. The hyperproliferative skin generally showed a greater variability and lower permeation on MTX flux. The results shown in the present study encourages further investigation about the laser and electroporation either alone or in combination could significantly increase drug delivery via the skin.
中文摘要 ............................................v
英文摘要 ............................................vi
總目錄 ..............................................viii
圖目錄 ..............................................xii
表目錄 ..............................................xiv
第一章 ..............................................1
第二章 ..............................................26
第三章 ..............................................42
第四章 ..............................................82
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