Büyüktimkin S, Büyüktimkin N, Rytting J H
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
Pharm Res. 1993 Nov;10(11):1632-7. doi: 10.1023/a:1018980905312.
The biodegradable transdermal penetration enhancer, dodecyl 2-(N,N-dimethylamino)propionate (II; DDAIP), was prepared by reacting dodecyl 2-bromopropionate (I), obtained by reaction of n-dodecanol with 2-bromopropionyl halogenide, with dimethylamine. The penetration enhancing effects of DDAIP on the transport of indomethacin, clonidine, and hydrocortisone across shed snake skin (Elaphe obsoleta) were evaluated. Azone and lauryl alcohol, a possible decomposition product of DDAIP, were used as standard enhancers for comparison. In terms of flux, DDAIP showed 4.7 and 7.5 times the promoting effect for indomethacin compared to azone and lauryl alcohol, respectively. With clonidine this effect was 1.7 and 3.1 times, whereas with hydrocortisone it was 2.4 and 2.8 times higher, respectively. In vitro biodegradability of DDAIP was demonstrated in the presence of porcine esterase. The results indicate that DDAIP increases markedly the transepidermal delivery of several types of drug substances.
可生物降解的透皮渗透促进剂2-（N，N-二甲基氨基）丙酸十二酯（II；DDAIP）是通过使正十二醇与2-溴丙酰卤反应得到的2-溴丙酸十二酯（I）与二甲胺反应制备而成。评估了DDAIP对吲哚美辛、可乐定和氢化可的松透过蛇蜕（锦蛇）皮肤转运的促进作用。将氮酮和DDAIP可能的分解产物月桂醇用作标准促进剂进行比较。就通量而言，与氮酮和月桂醇相比，DDAIP对吲哚美辛的促进作用分别高出4.7倍和7.5倍。对于可乐定，该作用分别为1.7倍和3.1倍，而对于氢化可的松，该作用分别高出2.4倍和2.8倍。在猪酯酶存在的情况下证明了DDAIP的体外生物降解性。结果表明，DDAIP显著提高了几种类型药物的经皮递送量。
