Taguchi K, Fukushima S, Yamaoka Y, Takeuchi Y, Suzuki M
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Biol Pharm Bull. 1999 Apr;22(4):407-11. doi: 10.1248/bpb.22.407.
Enhancement of skin distribution of propylene glycol (PG) in the skin by high purity cis-unsaturated fatty acids with different alkyl chain lengths was studied in the rat using Fourier transform/attenuated total reflection (FT-IR/ATR) analysis. Two fatty acids with the double bond at the delta9 position, palmitoleic acid (omega7, delta9) and oleic acid (omega9, delta9), enhanced PG flux into the dermis and increased the dermal steady state level of PG. In contrast, myristoleic acid (omega5, delta9) was extremely weak in its action. A positional effect of the omega chain was observed. The rate of skin structural alteration increased in proportion to omega chain length. The application of three fatty acids with the double bond at the omega9 position, oleic acid (omega9, delta9), gondoic acid (omega9, delta11), erucic acid (omega9, delta13) enhanced PG distribution in the skin. While, nervonic acid (omega9, delta15) did not increase PG distribution in the skin. The relationship of the delta/omega ratio to parameters characterizing the action of enhancers (PG(peak area max), T(max alteration), and the slope) suggest that skin distribution increases as the position of the double bond is shifted toward the hydrophilic end. It is therefore likely that the ratio of the delta/omega chain length of the cis-unsaturated fatty acid determines the efficacy of these compounds as skin penetration enhancers. An adequate molecular volume may be required for cis-unsaturated fatty acids to act as enhancers.
利用傅里叶变换/衰减全反射（FT-IR/ATR）分析，在大鼠身上研究了不同烷基链长度的高纯度顺式不饱和脂肪酸对丙二醇（PG）在皮肤中分布的增强作用。两种双键位于δ9位的脂肪酸，棕榈油酸（ω7，δ9）和油酸（ω9，δ9），增强了PG向真皮的通量，并提高了PG在真皮中的稳态水平。相比之下，肉豆蔻油酸（ω5，δ9）的作用极其微弱。观察到了ω链的位置效应。皮肤结构改变的速率与ω链长度成正比。应用三种双键位于ω9位的脂肪酸，油酸（ω9，δ9）、山嵛酸（ω9，δ11）、芥酸（ω9，δ13），增强了PG在皮肤中的分布。然而，神经酸（ω9，δ15）并没有增加PG在皮肤中的分布。δ/ω比值与表征增强剂作用的参数（PG（最大峰面积）、T（最大改变）和斜率）之间的关系表明，随着双键位置向亲水端移动，皮肤分布增加。因此，顺式不饱和脂肪酸的δ/ω链长度比值可能决定了这些化合物作为皮肤渗透增强剂的功效。顺式不饱和脂肪酸作为增强剂可能需要足够的分子体积。
