| 研究生: |
林銘楷 Lin, Ming-Kai |
|---|---|
| 論文名稱: |
人體皮脂對藥物角質層滲透性之影響 Effect of Sebum on Drug Transport Across Human Stratum Corneum in Vivo |
| 指導教授: |
蔡瑞真
Tsai, Jui-Chen 許漢銘 Sheu, Hamm-Ming |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 臨床藥學研究所 Institute of Clinical Pharmacy |
| 論文出版年: | 2004 |
| 畢業學年度: | 92 |
| 語文別: | 中文 |
| 論文頁數: | 102 |
| 中文關鍵詞: | 人體皮脂 、藥物滲透性 、角質層 |
| 外文關鍵詞: | Sebum, Drug transport, Stratum corneum |
| 相關次數: | 點閱:117 下載:2 |
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皮脂為一複雜的脂肪混合物,由哺乳動物之皮脂腺所分泌,覆蓋在皮膚表面形成一層非定形的脂肪薄膜。皮脂的功能包括潤滑皮膚、防止水分散失、抑制革蘭氏陽性菌的生長,及防止外來物質的侵入。皮脂成分包括triglycerides、wax esters、squalene、cholesterol esters,皮脂經由毛囊的輸送過程中,細菌會分解部分的triglycerides,形成free fatty acids。皮脂含量在身體不同部位差異很大,可能超過100倍以上,例如:前額、臉頰屬於高皮脂含量的部位,而手臂、大腿等的皮脂分泌則較低。
文獻上對於皮脂在皮膚障壁功能上扮演的角色鮮有記載,曾有報告指出皮脂會增加皮膚的滲透性,研究上亦顯示不飽和脂肪酸可作為經皮吸收促進劑,與角質層作用時,使角質層中脂質亂度增加,而改變藥物經由角質層的滲透性。而最近電子繞射的研究則進一步顯示:皮脂會與人體角質層中的脂質作用而改變角質層的晶型排列,使其由斜方晶型變化為六角晶型,增加長鏈脂質的活動性,而影響其滲透性。
本研究的目的在以活體方式,以角質層層撕技術輔以衰減式全反射之傅立葉轉換紅外光譜分析或高效能液相層析儀之分析,探討皮脂對藥品穿透人體角質層之影響。我們以兩種不同親脂性和分子大小的模式藥物,4-cyanophenol (CP)和cimetidine (CM),探討在前額部位去除皮脂和在前臂內側部位添加皮脂對角質層滲透性之影響,同時利用傅立葉轉換紅外光譜分析來觀察皮脂對角質層脂質結構的改變。
研究結果顯示,當補充皮脂於前臂內側時,親水性藥物(CM)穿透角質層的滲透性增加約3.5倍,主要來自擴散係數的改變,但是對於親脂性的藥物(CP),則沒有影響。而額頭部位在去除皮脂後,亦造成CM滲透性小幅但有意義的下降(-25 %)。進ㄧ步利用ATR-FTIR技術則觀察到前臂內側補充皮脂後,角質層紅外線光譜中代表脂肪acyl chain的CH2 asymmetric和symmetric stretching bands之波峰皆往高波數移動,表示其亂度增加,而將額頭的皮脂去除之後其亂度也稍微降低。
總括,額頭、手臂去除或添加皮脂前後CM角質層滲透性之變化與人體角質層紅外線光譜中CH2 asymmetric和symmetric stretching bands之波數有良好的線性關係,推論皮脂造成角質層障壁功能及親水性藥物滲透性之改變主要是由於細胞間隙脂肪分子結構亂度增加所致。
Sebum, which is secreted by mammalian sebaceous glands, is a complex mixture of lipids and forms a fluid film over the skin surface. The functions of sebum have been known to soften the skin, to regulate the water content of the epidermis, to inhibit the growth of gram-positive bacteria and to prevent an invasion of external organisms. Sebum content varies greatly from one anatomical site to another, with a more than 100-fold difference among regions. Human sebum is primarily composed of triglycerides, wax esters, squalene and small amounts of cholesterol esters. Triglycerides are partially hydrolyzed during its passage through the hair canal with the release of free fatty acid.
Studies on the role of sebum in the barrier function have been scarce. It has been suggested that sebum may increase skin permeability. Studies have demonstrated that fatty acids may alter the barrier function of stratum corneum by disordering structures of the lipid molecules and that skin permeability of some drugs have increased in the presence of fatty acids. Recent studies using electron diffraction techniques revealed that the sebaceous lipids may interact with human SC lipids resulting in a shift in lattice packing pattern from orthorhombic to hexagonal. As a result of this phase transition, the mobility of the alkyl chains of the endogenous lipid increases. Base on the findings of these studies, it has been concluded that sebaceous lipids may increase skin permeability. However, direct evidence on the effect of sebum on drug transport in vivo has never been provided.
The purposes of this study were to investigate the effect of sebum on drug transport across human stratum corneum in vivo of two model compounds of different lipophilicity and molecular size, 4-cyanophenol (CP) and cimetidine (CM) and the effect of sebum on morphology of stratum corneum lipids.
The results demonstrated that sebum supplement increased the SC permeability of CM at the forearm for more than three fold, but not that of CP. The increase in SC permeability of CM was mainly attributed to the enhanced SC diffusivity. Sebum removal at the forehead has small, but significant(-25 %)effect on the SC permeability of CM. Sebum supplement at forearm produced a marked shift of the CH2 asymmetric/symmetric stretching frequency in comparison with the control, and sebum removal at forehead decreased the frequency of the CH2 asymmetric/symmetric stretching.
In conclusion, SC permeability of CM was linearly correlated to the frequency shift of CH2 asymmetric/symmetric stretching due to sebum treatment. Sebum treatment increased the SC permeability of relatively hydrophilic drug and altered the barrier function of stratum corneum by disordering structures of the intercellular lipid molecules.
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