阿维菌素纳米脂质体的制备及质量控制

发布时间：2018-04-23 10:52

  本文选题：阿维菌素纳米脂质体 + 制备　； 参考：《西北农林科技大学》2015年硕士论文

【摘要】：本研究旨在研制出包封率高、稳定性好、安全高效的阿维菌素纳米脂质体(AVMNL),并对其在山羊体内的药物代谢动力学过程、急性毒性试验和临床治疗效果进行研究。1.阿维菌素纳米脂质体制备方法筛选本试验以包封率为指标,根据阿维菌素的性质,从薄膜分散法和改良薄膜分散法中筛选制备AVMNL的最佳方法。改良薄膜分散法制备的纳米脂质体包封率为90.36%,与薄膜分散法的差异性显著(P0.05)。改良薄膜分散法是制备AVMNL的最佳方法。2.阿维菌素纳米脂质体制备及理化性质考察本试验采用改良薄膜分散法制备AVMNL,通过正交试验设计优化处方和制备工艺,最终得到的最佳配方为:药物与磷脂质量比为1:10,磷脂与胆固醇质量比为9:1,PBS缓冲液pH为7.0;最佳工艺条件为超声5 min,蒸发温度为40℃,冻融3次。得到的AVMNL外观呈均一牛奶状液体,电镜下呈球形且分布均匀,平均粒径大小为198.2 nm。3阿维菌素纳米脂质体稳定性试验用紫外可见分光光度法测定阿维菌素纳米脂质体中阿维菌素的含量,并通过热稳定性试验和光稳定性试验考察其稳定性。试验结果表明,阿维菌素在254 nm处有最大吸收,在2μg/mL-32μg/mL范围内线性关系良好,其平均回收率为(96.51±4.21)%,RSD为0.04%,说明此方法测定结果准确可靠。阿维菌素纳米脂质体对热不敏感,但在光照条件下包封率降低,说明应避光保存。4阿维菌素纳米脂质体的药动学试验皮下注射阿维菌素纳米脂质体,研究阿维菌素纳米脂质体在山羊体内的药代动力学过程。用乙酸乙酯多次萃取血清中的药物后氮气流挥干,HPLC测定阿维菌素含量。药动学结果采用经典的房室模型进行曲线拟合。5只山羊的药动学过程均符合有吸收因素的一室模型,主要药动学参数:吸收半衰期t1/2Ka=0.24±0.03 d,消除半衰期t1/2Ke=6.74±0.80 d,最高药物浓度Cm=60.76±5.62ng/mL,药-时曲线下面积AUC=664.35±28.14 ng/mL)·d,达峰时间tp=1.20±0.08 d,药效可维持30 d以上。结果表明阿维菌素纳米脂质体缓释效果确定,可作为阿维菌素长效制剂进行更深入的研究。5阿维菌素纳米脂质体的急性毒性试验预试验皮下注射阿维菌纳米素脂质体后,死亡率100%的剂量为153.68 mg/kg,死亡率0%的剂量为57.97 mg/kg。LD50为98.36mg/kg,LD50的95%的可信限(FL)范围为:83.39mg/kg-116.01 mg/kg。6阿维菌素纳米脂质的临床治疗试验在山羊体内通过皮下注射阿维菌素纳米脂质体三个不同治疗剂量(0.2 mg/kg、0.5 mg/kg、1.0 mg/kg)进行驱虫,与阿维菌素普通注射剂(0.2 mg/kg)相比发现阿维菌素纳米脂质体具有良好的缓释作用,且以1.0 mg/kg剂量皮下注射效果最好。
[Abstract]:The aim of this study was to develop a high encapsulation rate, good stability, high safety and high efficiency abamectin nano-liposome AVMNLX, and to study the pharmacokinetics, acute toxicity test and clinical therapeutic effect of AVMNLX in goats. Screening method for preparation of avermectin nanoliposomes the best method for preparing AVMNL was selected from the film dispersion method and the modified membrane dispersion method according to the properties of abamectin. The encapsulation efficiency of nano-liposomes prepared by the modified film dispersion method was 90.36, which was significantly different from that of the thin-film dispersion method (P 0.05). The improved film dispersion method is the best method for preparing AVMNL. Preparation and Physicochemical Properties of avermectin Nanoliposomes in this study AVMNLs were prepared by modified membrane dispersion method. The formulation and preparation process of AVMNLs were optimized by orthogonal design. The optimum formulation is as follows: the mass ratio of drug to phospholipid is 1: 10, the mass ratio of phospholipid to cholesterol is 9: 1, the pH of PBS buffer solution is 7.0, the optimum technological conditions are ultrasonic 5 min, evaporation temperature 40 鈩，

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