复方头孢泊肟酯纳米乳的研制及其药效与安全性研究  

Preparation,Efficacy and Safety Evaluation of Compound Nanoemulsion of Cefpodoxime Proxetil

作　　者：刘岳[1] 李梦云[1] 郑寅[1] 高娴[1] 欧阳五庆[1] 杨鸣琦[1] 

机构地区：[1]西北农林科技大学动物医学院,杨凌712100

出　　处：《畜牧兽医学报》2015年第6期1026-1036,共11页ACTA VETERINARIA ET ZOOTECHNICA SINICA

基　　金：农业科技成果转化资金项目(2013GB2G000475)

摘　　要：为研究头孢泊肟酯与牛至油在纳米水平的联合药效,首次制备复方头孢泊肟酯纳米乳并进行体外抑菌试验及急性毒性研究。在传统纳米乳制备方法筛选初步处方基础上,采用多指标正交试验法确定最优处方。以L9(34)正交表设计试验,以抑菌圈直径和纳米乳稳定常数Ke为考察指标,选择头孢泊肟酯和牛至油质量分数比(A)、纳米乳水相pH(B)、乳化温度(C)作为考察因素;体外抑菌试验采用微量肉汤稀释法;急性毒性试验采用最大耐受剂量法并进行了组织病理学检查。结果显示:针对致病性大肠杆菌、沙门菌最优处方为头孢泊肟酯0.33%、牛至油2.67%、1,2-丙二醇1.13%、EL-40 22.51%、蒸馏水73.36%,纳米乳pH值为6.17;与原料药相比,受试药物的最低抑菌浓度和最低杀菌浓度差异显著(P<0.05);小鼠经口急性毒性最大耐受剂量大于1 800mg·kg-1,为低毒级药物,无肾、肠毒性,但可引起肝轻微病理损伤。结果表明,牛至油在纳米水平提高了致病性大肠杆菌、沙门菌、奇异变形杆菌、巴氏杆菌、痢疾杆菌、金黄色葡萄球菌、无乳链球菌对头孢泊肟酯敏感性。To study the efficacy of combined application of cefpodoxime proxetil and Origanum oil in nanoscale level,compound nanoemulsion of cefpodoxime proxetil was innovatively prepared.Furthermore,antibacterial activity tests in vitro and acute toxicity tests were conducted.Preliminary prescription was sieved on the base of traditional method of preparation of nanoemulsion.Then the multi-index orthogonal experiment was proceeded with L9(34)orthogonal test table,regarding bacteriostatic circle diameter and nanoemulsion stability constant Ke as examining index.Three elements,ratio of the mass fraction of cefpodoxime proxetil and Origanum oil,pH of aqueous phase and emulsifying temperature are selected as factors.Antibacterial activity tests in vitro and acute toxicity tests were done through trace broth dilution method and maximal tolerance dose test.Then histopathological examination was measured.The optimal prescription is composed of 0.33% of cefpodoxime proxetil,2.67% of Origanum oil,1.13% of 1,2-propylene glycol,22.51% of EL-40,73.36% of distilled water for enteropathogenic E.coli and Salmonellaand pH value of nanoemulsion is 6.17.Compared with the active pharmaceutical ingredients,both of the minimum inhibitory concentrations and minimum bactericidal concentrations of test drug were significantly different(P<0.05);the maximum tolerated dose of the oral acute toxicity of mice is higher than 1 800mg·kg-1,showing low toxicity.Histopathological examinations show no toxic-ity of kidney and small intestine,but can do pathological damage to the liver.When in the presence of Origanum oil,enteropathogenic E.coli,Salmonella,Proteus mirabilis,Pasteurella,Shigella dysenteriae,Staphylococcus,Streptococcus agalactiae are more sensitive to CFP-OR-NE than cefpodoxime proxetil.

关 键 词：头孢泊肟酯 牛至油 纳米乳 

分 类 号：S859.5[农业科学—临床兽医学]