纳他霉素纳米乳的制备及其体外抑菌效果研究

Preparation of natamycin nanoemulsion and its antifungal effect in vitro

【目的】制备纳他霉素纳米乳(NATA-NE),测定其对白色念珠菌(Candida albicans)、青霉菌(Peni-cillium)和酿酒酵母菌(Saccharomyces cerevisiae)的最小抑菌浓度(MIC)和最小杀菌浓度(MFC),以指导临床合理用药。【方法】综合纳米乳和纳他霉素的优势,将纳他霉素制成水包油型NATA-NE,以酮康唑和特比萘芬作为阳性药物对照,根据美国临床实验室标准化委员会(NCCLS)制定的真菌体外药敏试验方法M-27A和M-38P,测定药物对3种受试菌株的MIC,并研究了NATA-NE的杀菌效果。【结果】NATA-NE对青霉菌、白色念珠菌和酿酒酵母菌的MIC值为1,0.5,0.5μg/mL;NATA原料药、酮康唑和特比萘芬对上述3种菌的MIC值分别为2,1,1μg/mL;4,8,8μg/mL和1,8,16μg/mL,NATA-NE的MIC值均小于或等于其他3种药物。3种菌在2μg/mL NATA-NE的作用下1.5h后,均未见生长;NATA原料药则需要4μg/mL、2h才能达到同样效果,而酮康唑和特比萘芬分别需要16μg/mL、4h和32μg/mL、4h才能达到同样效果。【结论】临床使用NATA-NE治疗动物真菌病时,可适当降低给药剂量和用药次数,以降低成本和对动物不可预期的副作用。

[Objective] Natamycin nanoemulsion was prepared,and clinical therapy was investigated by natamycin nanoemulsion（NATA-NE） on Candida albicans, Penicillium and Saccharomyces cerevisiae the minimum inhibitory concentration （MIC） and minimum fungicidal concentration （MFC） determination. [Method] Taking advantages of nanoemulsion and natamycin, which was made of the oill-in-water nanoe- mulsion natamycin, with ketoconazole and terbinafine as a positive drug control, three kinds of strains were measured by Fungi in vitro susceptibility with testing method M-27A,M-38P. According to the clinical la- boratory standards（NCCLS） established by national committee, NATA-NE fungicide performance was in- vestigated. [Result] The MIC values of NATA-NE for Penicillium, C. albicans and S. cerevisiae were 1, 0.5,0.5 Ftg/mL; natamycin API, ketoconazole and terbinafine, respectively, for the MIC value of the three fungi were 2,1,1 /ug/mL, 4,8,8/ug/mL and 1,8,16/ug/mL. NATA-NE of the MIC values were less than or equal to the other three drugs. Three kinds of fungi in 2 /lg/mL NATA-NE for more than 1.5 h showed no growth. Natamycin solution needed 4 ptg/mL, 2 h in order to achieve the same effect. The ketoconazole and terbinafine,respectively,needed 16/ug/mL,4 h and 32/ug/mL,4 h. [Conclusion] In clinical treatment of an-imal mycosis with NATA-NE,it is appropriate to reduce the dosage so as to reduce costs and unanticipated side effects on animals.