Dolezal P, Hrabálek A, Semecký V
Faculty of Pharmacy, Charles University, Hradec Králové, Czechoslovakia.
Pharm Res. 1993 Jul;10(7):1015-9. doi: 10.1023/a:1018914806761.
The synthesis of epsilon-aminocaproic acid esters is described. Two representative members from a group of five of the 1-alkyl homologues synthetized as flexible analogues of 1-alkylazacyclohepatanone derivatives were evaluated in vitro for their effectiveness on the transport of theophylline through the excised human cadaver skin in comparison with Azone. The 1-octyl- and 1-dodecyl-epsilon-aminocaproic acid esters (OCEAC and DDEAC) show excellent penetration enhancement. Donor samples contained 2.5% theophylline and 1% enhancers tested in three different vehicles. Fluxes of theophylline were increased with OCEAC about 19 times from olive oil, 45 times from water, and about 38 times from water-propylene glycol (3:2) vehicle toward controls (with DDEAC about 17, 39, and 35 times, respectively) and they were markedly higher than Azone under the given conditions. Acute LD50's (i.p. in mice) of OCEAC (DDEAC) were 245 mg/kg (352 mg/kg), with a slightly lower toxicity than Azone. OCEAC and DDEAC did not exhibit acute dermal irritation in vivo on rabbits at a 5% concentration in white petrolatum.
本文描述了ε-氨基己酸酯的合成。作为1-烷基氮杂环庚烷酮衍生物的柔性类似物合成的一组五个1-烷基同系物中的两个代表性成员，与氮酮相比，在体外评估了它们对茶碱透过离体人尸体皮肤转运的有效性。1-辛基-和1-十二烷基-ε-氨基己酸酯（OCEAC和DDEAC）显示出优异的渗透增强效果。供体样品含有2.5%的茶碱和1%在三种不同载体中测试的增强剂。与对照相比，OCEAC使茶碱从橄榄油中的通量增加约19倍，从水中增加45倍，从水-丙二醇（3:2）载体中增加约38倍（DDEAC分别约为17、39和35倍），并且在给定条件下它们明显高于氮酮。OCEAC（DDEAC）的急性半数致死量（小鼠腹腔注射）为245mg/kg（352mg/kg），毒性略低于氮酮。OCEAC和DDEAC在白色凡士林5%浓度下对家兔未表现出急性皮肤刺激性。
