增效酮康唑滴眼液抗眼科丝状真菌活性研究

Experimental study of ketaconazole eye drops in the inhibition of pathogenic filamentous fungi

目的评价两种自制的增效酮康唑滴眼液及酮康唑混悬滴眼液体外抗眼科丝状真菌活性。方法用微量液基稀释法测定两种增效酮康唑滴眼液及酮康唑混悬滴眼液对4株眼科常见致病丝状真菌(串珠镰刀菌、烟曲霉菌、黄曲霉菌及黑曲霉菌)的最低抑菌浓度(MIC),用二甲基亚砜(DMSO)溶解的酮康唑液做对照。结果增效酮康唑滴眼液Ⅰ、增效酮康唑滴眼液Ⅱ、酮康唑混悬滴眼液及DMSO溶解的酮康唑液对串珠镰刀菌的MIC分别为2、1、16、2μg/mL;对烟曲霉菌的MIC分别为0.5、0.5、2、0.5μg/mL;对黄曲霉菌的MIC分别为16、16、128、16μg/mL;对黑曲霉菌的MIC分别为0.25、0.25、4、0.25μg/mL。上述结果显示3种酮康唑滴眼液及DMSO溶解的酮康唑液对黑曲霉菌的作用最强,对烟曲霉菌、串珠镰刀菌的作用依次递减,对黄曲霉菌的作用较弱。两种增效酮康唑滴眼液的作用强度与DMSO溶解的酮康唑液的相似,三者的抗真菌活性均明显强于酮康唑混悬滴眼液。结论两种增效酮康唑滴眼液对4株眼科常见致病丝状真菌的体外抗真菌活性较酮康唑混悬滴眼液的明显增强,说明增加酮康唑的溶解度可明显增加其抗真菌活性。

Objective T o evaluat e antifungal activities of three kinds of ketaconazole eye drops against pathogeni c filamentous fungi in vitro.Methods The minimum inhibitory concentration(MIC )of three kinds of ketaconazole eye drops against4strains of ocular pathogenic filamentous fungi(Fusarium moniliforme,Aspergillus fumigatus,Aspergillus fla vus,and Aspergillus niger)were determined by modified NCCLS M38-P broth mic rodilution method.Ketaconazole solution in dimethy sulforxide(DMSO)was served as contol.Results MICs of ketaconazole eye drops I,ketaconazole eye drops II ,ketaconazole eye suspension and ketaconazole solution in DMSO were2,1,16 and2μg/ml against Fusarium monilifore,0.5,0.5,2and0.5μg/ml ag ainst Aspergillus fumigatus,16,16,128and16μg/ml against Aspergill us flavus,0.25,0.25,4and0.25μg/ml against Aspergillus niger, respectively.The three kinds of ketaconazole eye drops and ketaconazole solutio n in DMSO proved to be highly active against Aspergillus niger,and also exerted good activities against Aspergillus fumigatus and Fusarium monilifore.The anti fungal activities of ketaconazole eye drops I and ketaconazole eye drops II were similar to that of ketaconazole solution in DMSO.The antifungal activities of ketaconazole eye drops I,ketaconazole eye drops II and ketaconazole solution in DMSO were much higher than that of ketaconazole eye suspension.Conclusion Thes e results suggest that increasing solvability of ketaconazole can significantly enhance its antifungal activity.