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研究生: 邱佑寧
Chiou, You-ning
論文名稱: 基劑對外用皮質類固醇破壞皮膚障壁功能之研究
Effects of Vehicle Base on Topical Corticosteroid-induced Barrier Function Impairment
指導教授: 許漢銘
Sheu, Hamm-ming
蔡瑞真
Tsai, Jui-chen
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: 2007
畢業學年度: 95
語文別: 中文
論文頁數: 111
中文關鍵詞: 皮膚障壁功能外用皮質類固醇
外文關鍵詞: topical corticosteroids, skin barrier function
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  • 皮膚有防止水分散失、有毒物質、微生物入侵、防止UV等保護功能,統稱為皮膚障壁功能,而角質層是產生皮膚障壁功能的主要部位。
    過去研究已證實長期使用外用皮質類固醇,會造成皮膚障壁功能的破壞、皮膚萎縮症等副作用,研究也證實即使短期的使用強效外用皮質類固醇,雖然不致於破壞基礎狀態下的皮膚障壁功能,但是對於角質層的完整性、皮膚障壁功能的恒定仍然產生破壞,使皮膚更容易受到外力,如膠帶黏貼的破壞,以及皮膚障壁功能受到破壞後的回復能力減慢。
    本研究以小鼠為動物模式,以經皮水分散失基值,膠帶黏貼後的經皮水分散失增加量,及24小時內經皮水分散失回復率分別評估外用皮質類固醇clobetasol 17-propionate(CP)溶液及市售乳膏,對於基礎狀態下的皮膚障壁功能,角質層的完整性、皮膚障壁功能的恒定的影響。並以弱效外用皮質類固醇1% hydrocortiosone(HC)的市售乳膏作為對照組。之後並評估在每次給藥之後,給予不同基劑是否可以改善外用皮質類固醇對皮膚障壁功能的破壞。
    研究結果顯示給予3天0.05% CP溶液,相較於不給藥或給予vehicle組,在經皮水分散失與角質層完整度方面並無顯著差異,但在皮膚障壁功能回復方面有明顯減慢情形。給予0.05% CP市售乳膏,在連續給予3、5天後,顯著增加經皮水分散失基值,以5天給藥增加更為顯著,給予3、5天的CP乳膏同時也破壞角質層完整度,減慢皮膚障壁功能的回復。另外,連續給予5天HC乳膏不影響基礎狀態下的皮膚障壁功能,角質層完整度,與皮膚障壁功能的回復。給予1天CP乳膏則有稍微減慢皮膚障壁功能回復的作用。此結果顯示使用強效外用皮質類固醇CP乳膏3天後,會對皮膚障壁功能造成明顯的破壞,而持續給予5天之後會造成更嚴重的破壞。
    在給藥後同時給予不同基劑:petrolatum(凡士林)、palmitic acid,在本研究中並無顯著改善CP破壞皮膚障壁功能的作用。未來研究將可進一步探討給予其他基劑,延長基劑給予的時間,是否可以改善外用皮質類固醇對皮膚障壁功能的破壞,以及添加基劑是否影響皮質類固醇的藥物吸收及療效。

    The protective functions of skin include prevention from loss of body water, prevention from invasion of xenobiote and microorganism and UV-prevention, etc. These functions can be summarized as skin barrier function. Most of these protective functions reside in stratum corenum(SC).
    Previous studies have shown that long-term application of topical corticosteroids causes adverse effects such as disruption of skin barrier and skin atrophy. It has also shown that even short-term application of very potent topical corticosteroids casuses abonormal stratum corenum intergrity and barrier homeostasis, characterized by less resistance to injury, such as tape stripping and delayed barrier recovery after disruption of skin barrier.
    In the present study, we evaluated the effects of topical corticosteroids, clobetasol 17-propionate (CP), in solution and cream forms on barrier function in basal condition, barieir intergrity and barrier homeostasis with baseline transepidermal water loss (TEWL), rate of barrier disruption and barrier recovery in tape-stripped 24 hours of murine skin as animal model, respectively. In addition, we evaluated the effects of topically applied vehicle on CP-induced barrier function impairement.
    The results demonstrated that 3-day application of 0.05% CP solution, in propylene glycol/ethanol, compared to vehicle or no treatment, significantly delayed barrier recovery, but has no effect on baseline TEWL and barrier interigrity. Application of 0.05% CP cream for 3 and 5 days significantly increased baseline TEWL, decreased barrier interigrity, and delayed barrier recovery. 5-days treatment enhanced the increase in baseline TEWL. In addition, application of 1% HC cream for 5 days didn’t alter baseline TEWL, barrier interigrity and barrier recovery. Application of 0.05% CP cream for 1 day only caused slightly-delayed barrier recovery. These results indicated that 3 day treatment of CP cream caused barrier function impairment.
    Co-applicaation of petrolatum, palmitic acid after each CP cream treatment didn’t improve CP-induced impaired barrier function impairment. Further studies will be needed to show effects of co-application of other vehicle, extending exposure duration of vehicle on CP-induced impaired barrier function, and drug absorption.

    中文摘要 ................................................ i Abstract .............................................. iii 誌謝 .................................................... v 目錄 ................................................... vi 表目錄 ............................................... viii 圖目錄 .................................................. x 縮寫表 ................................................ xii 第一章 文獻回顧 ......................................... 1 第一節 皮膚障蔽功能 .............................. 1 第二節 調節皮膚障壁功能恒定的方法 ............... 23 第三節 皮質類固醇 ............................... 35 第二章 研究目的 ........................................ 54 第三章 研究材料及儀器 .................................. 55 第一節 研究材料 ................................. 55 第二節 儀器 ..................................... 56 第四章 研究方法及實驗設計 .............................. 58 第一節 動物模式的選擇 ........................... 58 第二節 TCS對皮膚障壁功能的影響 .................. 60 第三節 市售TCS乳膏對皮膚障壁功能的影響 .......... 62 第四節 添加不同基劑對TCS抑制皮膚障壁功能恆定的影響 ... 63 第五節 統計分析 ................................. 64 第五章 研究結果 ........................................ 65 第一節 動物模式的選擇 ........................... 65 第二節 TCS溶液對皮膚障壁功能的影響 .............. 68 第三節 TCS市售乳膏對皮膚障壁功能的影響 .......... 72 第四節 添加不同基劑對TCS抑制皮膚障壁功能恢復的影響 ... 79 第六章 討論 ............................................ 85 第一節 皮膚障壁功能的評估方式 ................... 85 第二節 皮質類固醇對皮膚障壁功能的影響 ........... 87 第三節 添加不同基劑對TCS抑制皮膚障壁功能恢復的影響 ... 89 第七章 結論 ............................................ 91 參考文獻 ............................................... 92

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