皮質類固醇類藥品對於發炎性皮膚疾病是相當有效的治療，然而長期使用皮質類固醇類藥品可能導致局部副作用，而其中以皮膚萎縮為最常見的副作用。研究顯示皮質類固醇類藥品會抑制皮膚角質層脂肪的生合成和減少角質細胞橋小體的數目，而影響皮膚障壁的恆定和角質層的完整性。目前臨床上皮膚科醫師多建議在使用外用皮質類固醇療法時並用保濕劑來緩解局部的副作用。在開發中國家植物油常被用來按摩新生兒以改善其皮膚障壁功能，而動物研究顯示高linoleic acid 含量的植物油，如葵花油，對皮膚障壁有最大的好處，不僅由於linoleic acid 是體內的必須脂肪酸，也是相當強的PPARα activator，可刺激使角質功能成熟的酵素β-Glucocerebrosidase活化，使得角質層及顆粒層的層狀結構完整，進而促進胚胎鼠表皮障壁的形成。
另外，當皮膚角質層酸化的過程遭到破壞時，皮膚表面pH值會變得較中性，皮膚障壁功能逐漸異常。研究顯示將遭到破壞的皮膚暴露在酸性的pH值(5.5)下，可以達到正常障壁功能的回復；反之，在中性或鹼性pH值(7.4)下，則會延緩障壁功能的回復。
本研究之目的在應用調節與修復皮膚障壁功能恆定之方法，開發以植物油為油相之外用皮質類固醇乳劑。選用的藥品為超強效價的clobetasol propionate (CP)，首先製備不同種類及不同比例之植物油乳劑，並分別配製成pH5.5、pH7.4，及不同比例CP含量之乳劑，篩選其CP穿皮速率與市售品Dermovate®乳膏相近者，進行人體試驗確認其血管收縮反應與市售品Dermovate®相近，且藉由皮膚障壁功能恆定試驗與市售品Dermovate®作比較，評估處方製劑對皮膚障壁功能恆定之影響。開發之處方製劑期望能造福皮膚疾病患者，避免因長期使用外用皮質類固醇製劑引起之局部不良反應。
研究結果顯示，以植物油為油相之外用CP乳劑之穿皮速率與血管收縮反應無相關性。隨著製劑中油相比例的減少，血管收縮反應亦無顯著上升之現象。中性之處方製劑，相對於較低pH值之處方製劑並未造成皮膚障壁功能恆定之惡化。此外，內含30 % 葵花油，10 % propylene glycol，乳化劑glycerol monostearate及polyethylene glycol monostearate分別為10.5 % 及4.5 %之pH 5.5處方製劑不僅在藥效上與Dermovate®相當，並有助於皮膚障壁功能之恆定。故未來可針對此處方組成，進一步加以改善，降低因長期使用外用皮質類固醇製劑引起之局部不良反應。

Glucocortiocoids(GCs) are highly effective for the topical treatment of inflammatory skin diseases. Their long-term use, however, is often accomparied by severe and partially irreversible adverse effects, with skin atrophy being the most prominent limitation, where a major function of the skin, the formation of a permeability barrier is compromised. Studies have demonstrated that topical GC therapy display adverse effects on permeability barrier homeostasis and stratum corneum integrity and cohesion, attributable to a profound global inhibition of lipid synthesis and a diminution the density of corneodesmosomes in the lower stratum corneum. Vegetable oils have been applied topically to enhance epidermal barrier function in neonates.
In mouse skin acutely disrupted by tape-stripping, it appears that vegetable oils with high linoleic acid content, for example, the sunflower seed oil, provide the most potential benefit to the skin barrier. Recently, the essential fatty acid－linoleic acid has been shown to be one of the most potent activators of PPARα, and its application to fetal rat skin explants at physiologic concentrations increased the activity of β-Glucocerebrosidase and improved SC integrity, which was correlated with an increase in corneodesmosome density and desmoglein-1 content, and then accelerated epidermal barrier development. The skin surface pH value will be elevated through disrupting the mechanisms of stratum corneum acidification, which result in abnormal skin barrier function. Exposure of intact murine stratum corneum to a neutral pH produced abnormalities in stratum corneum integrity and cohesion.
The objectives of the studies were to apply the strategies to modulate and improve skin barrier homeostasis, to develop topical GC formulations based on different kinds of vegetable oils at different pH value. The super-potent clobetasol propionate (CP) was selected as drug candidate. The vegetable oil creams containing 0.05-0.1 % CP were prepared and their drug delivery through skin was compared with Dermovate cream. Studies on healthy human volunteers were conducted to verify the vasoconstriction responses of formulations and the influences on skin barrier homeostasis. The studies were aimed to develope formulations which would prevent the long-term GC therapy-induced skin atrophy in diseased-skin patients.
The results demonstrated that there was no correlation between the in vitro skin flux and the in vivo vasoconstriction responses of the prepared formulations. The vasoconstriction responses have not been enhanced as the oil content of formulation was decreased. In comparison with formulations at acidic pH, there was no apparent deterioration on skin barrier homeostasis following application of formulations at neutral pH. The formulation based on 30 % sunflower oil, 10.5 % glycerol monostearate, 4.5 % polyethylene glycol monostearate and 10 % propylene glycol, adjusted at pH 5.5, demonstrated some improvement in skin barrier homeostasis. Further investigation will be needed to develop effective and safe formulations.

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