乙酰异戊酰泰乐菌素纳米乳的制备及其体外抑菌活性和急性毒性测定

【目的】制备乙酰异戊酰泰乐菌素纳米乳，并对其理化性质、体外药效和安全性进行评价。【方法】利用伪三元相图法，优选配方，制备乙酰异戊酰泰乐菌素纳米乳，用透射电镜、激光粒度分析仪对其形态和粒径分别进行考察；通过高速离心、留样观察试验检验其稳定性；通过抑菌试验考察其体外药效；通过急性毒性试验考察其安全性。【结果】乙酰异戊酰泰乐菌素纳米乳配方中各组分的质量分数为：吐温80 25%、无水乙醇15%、乙酸乙酯4.4%、乙酰异戊酰泰乐菌素1%、蒸馏水54.6%。制备的纳米乳为橘黄色澄清透明液体，流动性良好，在透射电镜下其形态为规则的圆球形，平均粒径为11.1 nm，分散性好；稳定性试验结果显示，其未有分层、絮凝、沉淀等现象发生，稳定性好。体外抑菌试验结果表明，乙酰异戊酰泰乐菌素纳米乳对畜禽常见病原菌致病性大肠杆菌、金黄色葡萄球菌、沙门氏菌、巴氏杆菌、无乳链球菌的最小抑菌质量浓度分别为16，2，8，4，8 μg/mL；该纳米乳的半数致死量（LD₅₀）为2 425 mg/kg，属于低毒药物，安全性好。【结论】成功研制了乙酰异戊酰泰乐菌素纳米乳，其稳定性好，体外药效明显增强，且低毒，有望应用于兽医临床。

Preparation of Acetylisovaleryltylosin nanoemulsion and determination of its bacteriostatic activity and acute toxicity in vitro

【Objective 】Acetylisovaleryltylosin nanoemulsion was prepared,and its quality,in vitro pharmacy and toxicity were evaluated.【Method】The preparation of the Acetylisovaleryltylosin Nanoemulsion was optimized by studying the pseudoternary phase diagram.Its configuration and partical size were measured by TEM and LPSA.Its pharmacy in vitro and toxicity were also evaluated.【Result】The mass fraction of the components in Acetylisovaleryltylosin nanoemulsion was Tween-80 25%,ethanol 15%,ethyl acetate 4.4%,Acetylisovalerylty losin 1%,and distilled water 54.6%.The shape of Acetylisovaleryltylosin nanoemulsion was spherical under TEM,with the average diameter of 11.1 nm.Acetylisovaleryltylosin nanoemulsion was stable after high speed centrifuge and reserving at-4 ℃,room temperature and 60 ℃.The MIC of Acetylisovaleryltylosin nanoemulsion on entero pathogenic E.coli,Staphylococcus,Salmonella,Pasteurella and Streptococcus agalactiae was respectively 16,2,8,4,8 μg/mL.Its LD50 was 2 425 mg/kg.【Conclusion】The Acetylisovaleryltylosin nanoemulsion was a kind of clarity solution with very good stability.The antibacterial effect of Acetylisovaleryltylosin Nanoemulsion on above bacteria in vitro was remarkable,and its toxicity was low.