Sugibayashi K, Nakayama S, Seki T, Hosoya K, Morimoto Y
Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
J Pharm Sci. 1992 Jan;81(1):58-64. doi: 10.1002/jps.2600810112.
In order to clarify the mechanism of action of laurocapram (Azone) on the skin permeation of drugs, the following experiments were done. First, the effect of Azone on the skin components was compared with that of other penetration enhancers. Azone markedly fluidized liposomal lipids (as a model lipid system) compared with other enhancers. Ethanol extracted large amounts of the stratum corneum lipids, whereas Azone did not. These results suggest that the effect of Azone on the lipids in the stratum corneum is not the same as that of ethanol. In addition, ethanol increased the amount of free sulfhydryl (SH) group of keratin in the stratum corneum, whereas Azone did not directly affect the stratum corneum protein. Azone increased water content in the stratum corneum, as measured by skin conductance. This effect might be a reason for the action of Azone. For further understanding, the enhancing effects of Azone on the skin permeation of several model compounds (alcohols, sugars, and inorganic ions) were compared with the effects of pretreatment with distilled water, which was thought to increase water-holding capacity, and pretreatment with ethanol, which was thought to affect the lipids and protein in the skin barrier (i.e., stratum corneum). Pretreatment with water or ethanol enhanced skin permeation of hydrophilic compounds, whereas they decreased that of octanol, a hydrophobic compound. The tendency of Azone to increase or decrease the skin permeation rate of most compounds was similar to that of pretreatment with water or ethanol. However, the effect of Azone on the skin permeation of inorganic ions was relatively low, whereas that of pretreatment with water or ethanol was high.(ABSTRACT TRUNCATED AT 250 WORDS)
为阐明月桂氮䓬酮（氮酮）对药物经皮渗透的作用机制，进行了以下实验。首先，将氮酮对皮肤成分的作用与其他渗透促进剂进行比较。与其他促进剂相比，氮酮能显著使脂质体脂质（作为一种模型脂质体系）流化。乙醇能提取大量角质层脂质，而氮酮则不能。这些结果表明，氮酮对角质层脂质的作用与乙醇不同。此外，乙醇能增加角质层中角蛋白的游离巯基（SH）含量，而氮酮不直接影响角质层蛋白。通过皮肤电导率测量发现，氮酮能增加角质层中的含水量。这种作用可能是氮酮发挥作用的一个原因。为进一步了解，将氮酮对几种模型化合物（醇类、糖类和无机离子）经皮渗透的促进作用与用蒸馏水预处理（认为可增加持水能力）以及用乙醇预处理（认为可影响皮肤屏障即角质层中的脂质和蛋白质）的效果进行了比较。用水或乙醇预处理可增强亲水性化合物的经皮渗透，而降低疏水性化合物辛醇的经皮渗透。氮酮对大多数化合物经皮渗透率增加或降低的趋势与用水或乙醇预处理相似。然而，氮酮对无机离子经皮渗透的作用相对较低，而用水或乙醇预处理的作用较高。（摘要截选至250词）
