Morimoto K, Tojima H, Haruta T, Suzuki M, Kakemi M
Department of Pharmaceutics, Osaka University of Pharmaceutical Sciences, Japan.
J Pharm Pharmacol. 1996 Nov;48(11):1133-7. doi: 10.1111/j.2042-7158.1996.tb03908.x.
Effects of straight-chain, cis-type, unsaturated fatty acids with various structures (alkyl chain lengths, numbers of double bonds, position of double bonds, and cis- and trans-positional isomers) on the skin permeation of indomethacin were examined by using rat skins in-vitro. Furthermore, the disordering degrees of the intercellular lipid domain in the stratum corneum, which were treated with preparations of unsaturated fatty acids, were measured by the Fourier transform infrared (FT-IR) method using excised rabbit ear skins. Unsaturated fatty acids enhanced the permeation of indomethacin through rat skins. These permeation-enhancing effects by unsaturated fatty acids were affected by changes of their alkyl chain length from C14 to C22. The lag-times on the permeation of indomethacin were shortened by unsaturated fatty acids in the following order: C20 = C18 = C22 < C16 < C14. These fluxes were increased by unsaturated fatty acids in the following order: C20 > C22 = C18 = C16 > C14. Therefore, gondoic acid (cis-11-eicosenoic acid; C20H38O2) mostly enhanced the skin permeation of indomethacin. However, the enhancing effects of unsaturated fatty acids (C18 chain) were not affected by their differences of position and numbers of double bonds. These permeation-enhancing effects which were evaluated by flux were related to the degrees of wave-number shift in the frequency of the antisymmetric CH bond stretching absorbance (near 2920 cm-1) on FT-IR spectra of the fatty acid-treated stratum corneum. Therefore, the perturbation increase of lipid domain in the stratum corneum by these fatty acids probably was the cause of the enhancing effects of permeation of indomethacin.
利用大鼠皮肤体外实验，研究了具有不同结构（烷基链长度、双键数目、双键位置以及顺反位置异构体）的直链、顺式不饱和脂肪酸对吲哚美辛经皮渗透的影响。此外，使用切除的兔耳皮肤，通过傅里叶变换红外（FT-IR）法测量了用不饱和脂肪酸制剂处理后的角质层细胞间脂质域的无序程度。不饱和脂肪酸可增强吲哚美辛透过大鼠皮肤的渗透作用。这些不饱和脂肪酸的渗透增强作用受其烷基链长度从C14变为C22的影响。不饱和脂肪酸使吲哚美辛渗透的滞后时间缩短，顺序如下：C20 = C18 = C22 < C16 < C14。这些通量增加的顺序如下：C20 > C22 = C18 = C16 > C14。因此，二十碳烯酸（顺式-11-二十碳烯酸；C20H38O2）对吲哚美辛的皮肤渗透增强作用最为显著。然而，不饱和脂肪酸（C18链）的增强作用不受双键位置和数目的差异影响。通过通量评估的这些渗透增强作用与脂肪酸处理后的角质层FT-IR光谱中反对称CH键拉伸吸收频率（接近2920 cm-1）的波数位移程度相关。因此，这些脂肪酸对角质层脂质域的扰动增加可能是吲哚美辛渗透增强作用的原因。
