高效皮肤渗透促进剂-氮酮对角膜内皮的影响

Azone-induced changes on corneal endothelium in rabbits

目的观察低浓度氮酮对眼组织尤其对角膜内皮的影响，以确定这种高效皮肤渗透促进剂在眼科的应用价值。方法将２５只白兔随机分为５组。Ⅰ、Ⅱ、Ⅲ组双眼分别滴０．３％、０．６％及０．９％氮酮乳剂；第Ⅳ组双眼滴空白乳剂作溶媒对照；第Ⅴ组不滴药做正常对照。各组每日滴眼３次，持续４周。结果裂隙灯检查及石蜡切片显示，全部实验眼及对照眼的结膜、角膜均无损害，虹膜、晶体、睫状体、脉络膜及视网膜均正常。锥蓝、茜素红双重染色及扫描电镜观察显示，全部实验眼及对照眼角膜内皮细胞形态无异常。组织化学酶染色显示，角膜内皮细胞活性正常。结论氮酮有望用于滴眼液配方，增加多种滴眼液的角膜透性及生物利用度，增强疗效，避免毒性，有较大的临床应用价值。

Objective To investigate ocular toxic effect of azone at low concentrations in rabbits to determine whether this penetration enhancer has any value for ocular use. Methods 0.3%, 0.6%, 0.9% concentrations of azone in an ocular emulsion vehicle were studied. Rabbits in three experimental groups received topical 30 μl of 0.3%, 0.6%, 0.9% azone respectively three times daily for 4 weeks. Rabbits in control group 1 received 30 μl of vehicle without azone as negative control and rabbits in control group 2 received nothing as normal control. Clinical and histopathological examinations of rabbit cornea endothelial cells were made by slit lamp biomicroscopy, light microscopy and scanning electron microscopy. Results No clinical and histopathological evidence of ocular toxicity occurred in all treated and control eyes. The concentration of azone used in this study was 3 9 times higher than that (at 0.1% ) at which corneal penetration of hydrophilic compounds can be enhanced enormously. Conclusion Azone has value for incorporation into ocular formulations to increase therapeutic action of many hydrophilic drugs.