Okabe H, Obata Y, Takayama K, Nagai T
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Drug Des Deliv. 1990 Sep;6(3):229-38.
The percutaneous absorption promoting effect and skin irritancy of cyclic monoterpenes were investigated in rats and with rabbits, respectively. Ketoprofen (KPF) was applied to rat skin in gel ointments containing various cyclic monoterpenes. Plasma concentrations of KPF markedly increased with the addition of the hydrocarbons of cyclic monoterpenes such as trans-p-menthane and d-limonene, whereas no significant enhancing effect was observed in the cases of other terpenes such as l-menthol, l-menthone and 1,8-cineole. The lipophilicity of the enhancers seems the important factor in promoting penetration of KPF through the skin. The enhancing activity of d-limonene was found to be much higher than that of Azone. Irritancy of the hydrocarbons of cyclic monoterpenes and Azone to the skin was evaluated using a Draize scoring method with rabbits. No change was observed on the skin surface when ethanol containing 2% of the hydrocarbons was applied to the dorsal skin, though a slight edema and erythema were observed in the case of Azone. In particular, an obvious difference was observed in the erythema formation between Azone and the hydrocarbons of cyclic monoterpenes.
分别在大鼠和家兔身上研究了环状单萜的经皮吸收促进作用和皮肤刺激性。将酮洛芬（KPF）应用于含有各种环状单萜的凝胶软膏中的大鼠皮肤。随着环状单萜烃类如反式薄荷烷和d-柠檬烯的添加，KPF的血浆浓度显著增加，而在其他萜类如l-薄荷醇、l-薄荷酮和1,8-桉叶素的情况下未观察到显著的增强作用。增强剂的亲脂性似乎是促进KPF经皮渗透的重要因素。发现d-柠檬烯的增强活性远高于氮酮。使用家兔的Draize评分法评估环状单萜烃类和氮酮对皮肤的刺激性。当将含有2%烃类的乙醇应用于背部皮肤时，皮肤表面未观察到变化，而在氮酮的情况下观察到轻微的水肿和红斑。特别是，在氮酮和环状单萜烃类之间的红斑形成方面观察到明显差异。
