Kitagawa S, Kasamaki M, Ikarashi A
Niigata College of Pharmacy, Japan.
Chem Pharm Bull (Tokyo). 2000 Nov;48(11):1698-701. doi: 10.1248/cpb.48.1698.
Effects of cetyltrimethylammonium and two other n-alkyltrimethylammoniums on the permeation of benzoic acid through excised guinea pig dorsal skin were examined. Cetyltrimethylammonium markedly increased both the flux and permeability coefficient in the concentration range of 0.5 and 5 mm. However, 50mM cetyltrimethylammonium decreased them. The presence of 2 mm cetyltrimethylammonium, which induced a maximal enhancement effect, also increased the fluxes of 4-methyl, 4-ethyl and 4-n-propyl substituents of benzoic acid, but the enhancement effects were less. Analysis of the free energy of transfer of the methylene group of the substituents from the aqueous phase to skin suggested that cetyltrimethylammonium made the skin relatively more hydrophilic. Electron spin resonance spectra analysis by a long-chain quaternary alkylammonium analog, 4-(N,N-dimethyl-N-pentadecyl)ammonium-2,2,6,6-tetramethylpiperidine-1-ox yl iodide (CAT-15), showed that the spin label was present in a nearly solid state in both excised skin and its stratum corneum. This finding suggested the high affinity of the long-chain alkylammoniums to proteins in the stratum corneum and the involvement of the interaction between the cationic surfactants and the proteins in their improvement of the hydrophilic property of the skin, as well as their marked enhancement effects on the skin permeation of relatively hydrophilic drugs.
研究了十六烷基三甲基铵及其他两种正烷基三甲基铵对苯甲酸透过豚鼠背部离体皮肤渗透的影响。在0.5至5毫米的浓度范围内，十六烷基三甲基铵显著增加了通量和渗透系数。然而，50毫摩尔的十六烷基三甲基铵使其降低。存在2毫米可诱导最大增强效应的十六烷基三甲基铵时，也增加了苯甲酸4 - 甲基、4 - 乙基和4 - 正丙基取代物的通量，但增强效果较小。对取代基亚甲基从水相转移至皮肤的自由能分析表明，十六烷基三甲基铵使皮肤相对更具亲水性。通过长链季铵烷基铵类似物4 -（N，N - 二甲基 - N - 十五烷基）铵 - 2,2,6,6 - 四甲基哌啶 - 1 - 氧基碘化物（CAT - 15）进行的电子自旋共振光谱分析表明，自旋标记物在离体皮肤及其角质层中均以近乎固态存在。这一发现表明长链烷基铵与角质层中的蛋白质具有高亲和力，阳离子表面活性剂与蛋白质之间的相互作用参与了它们对皮肤亲水性的改善，以及它们对相对亲水性药物皮肤渗透的显著增强作用。
