Yoneto K, Li S K, Higuchi W I, Shimabayashi S
Sekisui Chemical Co., Ltd., Medicated Patch Department, Amagasaki, Hyogo, Japan.
J Pharm Sci. 1998 Feb;87(2):209-14. doi: 10.1021/js970190k.
In a previous study, the enhancing effects of a series of 1-alkyl-2-pyrrolidones (APs; 1-ethyl, 1-butyl, 1-hexyl, and 1-octyl-2-pyrrolidone) on the transport of steroidal permeants across hairless mouse skin were investigated via a parallel pathway skin model. Isoenhancement concentration conditions were deduced under which different APs induce essentially the same transport enhancement for the lipoidal pathway of the stratum corneum (s.c.). As a continuing effort to understand the mechanism of action of permeation enhancers, the influence of the APs on permeant partitioning into hairless mouse s.c. was investigated under the isoenhancement concentration conditions using beta-estradiol (E2 beta) as the model permeant. The amount of E2 beta uptake into s.c. was found to be essentially the same for all the APs under these isoenhancement conditions. This result suggests that inducing a higher partitioning tendency for E2 beta into the lipoidal pathway of hairless mouse s.c. is a principal mechanism of action of the APs in enhancing transdermal transport. The uptake of the APs into s.c. lipoidal domains was also determined, and the results show only a modest (approximately 2-fold) increase in the uptake of the APs in going from 1-ethyl-to 1-octyl-2-pyrrolidone under isoenhancement conditions. This indicates the potency of the APs as permeation enhancers is only very modestly dependent upon the alkyl chain length in this chain length region when compared at concentrations in the microenvironment where the action occurs in the lipid domains.
在之前的一项研究中，通过平行途径皮肤模型研究了一系列1-烷基-2-吡咯烷酮（APs；1-乙基、1-丁基、1-己基和1-辛基-2-吡咯烷酮）对甾体渗透剂透过无毛小鼠皮肤转运的增强作用。推导了等增强浓度条件，在此条件下不同的APs对角质层脂质途径诱导基本相同的转运增强。作为理解渗透促进剂作用机制的持续努力，在等增强浓度条件下，以β-雌二醇（E2β）作为模型渗透剂，研究了APs对渗透剂在无毛小鼠角质层中分配的影响。发现在这些等增强条件下，所有APs使E2β进入角质层的量基本相同。该结果表明，诱导E2β在无毛小鼠角质层脂质途径中具有更高的分配倾向是APs增强透皮转运的主要作用机制。还测定了APs进入角质层脂质区域的量，结果显示在等增强条件下，从1-乙基-2-吡咯烷酮到1-辛基-2-吡咯烷酮，APs的摄取仅适度增加（约2倍）。这表明，当在脂质区域发生作用的微环境中以浓度进行比较时，APs作为渗透促进剂的效力仅非常适度地依赖于该链长区域中的烷基链长度。
