本文選題：阿維菌素納米脂質(zhì)體 + 制備　； 參考：《西北農(nóng)林科技大學(xué)》2015年碩士論文

【摘要】：本研究旨在研制出包封率高、穩(wěn)定性好、安全高效的阿維菌素納米脂質(zhì)體(AVMNL),并對(duì)其在山羊體內(nèi)的藥物代謝動(dòng)力學(xué)過(guò)程、急性毒性試驗(yàn)和臨床治療效果進(jìn)行研究。1.阿維菌素納米脂質(zhì)體制備方法篩選本試驗(yàn)以包封率為指標(biāo),根據(jù)阿維菌素的性質(zhì),從薄膜分散法和改良薄膜分散法中篩選制備AVMNL的最佳方法。改良薄膜分散法制備的納米脂質(zhì)體包封率為90.36%,與薄膜分散法的差異性顯著(P0.05)。改良薄膜分散法是制備AVMNL的最佳方法。2.阿維菌素納米脂質(zhì)體制備及理化性質(zhì)考察本試驗(yàn)采用改良薄膜分散法制備AVMNL,通過(guò)正交試驗(yàn)設(shè)計(jì)優(yōu)化處方和制備工藝,最終得到的最佳配方為:藥物與磷脂質(zhì)量比為1:10,磷脂與膽固醇質(zhì)量比為9:1,PBS緩沖液pH為7.0;最佳工藝條件為超聲5 min,蒸發(fā)溫度為40℃,凍融3次。得到的AVMNL外觀呈均一牛奶狀液體,電鏡下呈球形且分布均勻,平均粒徑大小為198.2 nm。3阿維菌素納米脂質(zhì)體穩(wěn)定性試驗(yàn)用紫外可見(jiàn)分光光度法測(cè)定阿維菌素納米脂質(zhì)體中阿維菌素的含量,并通過(guò)熱穩(wěn)定性試驗(yàn)和光穩(wěn)定性試驗(yàn)考察其穩(wěn)定性。試驗(yàn)結(jié)果表明,阿維菌素在254 nm處有最大吸收,在2μg/mL-32μg/mL范圍內(nèi)線性關(guān)系良好,其平均回收率為(96.51±4.21)%,RSD為0.04%,說(shuō)明此方法測(cè)定結(jié)果準(zhǔn)確可靠。阿維菌素納米脂質(zhì)體對(duì)熱不敏感,但在光照條件下包封率降低,說(shuō)明應(yīng)避光保存。4阿維菌素納米脂質(zhì)體的藥動(dòng)學(xué)試驗(yàn)皮下注射阿維菌素納米脂質(zhì)體,研究阿維菌素納米脂質(zhì)體在山羊體內(nèi)的藥代動(dòng)力學(xué)過(guò)程。用乙酸乙酯多次萃取血清中的藥物后氮?dú)饬鲹]干,HPLC測(cè)定阿維菌素含量。藥動(dòng)學(xué)結(jié)果采用經(jīng)典的房室模型進(jìn)行曲線擬合。5只山羊的藥動(dòng)學(xué)過(guò)程均符合有吸收因素的一室模型,主要藥動(dòng)學(xué)參數(shù):吸收半衰期t1/2Ka=0.24±0.03 d,消除半衰期t1/2Ke=6.74±0.80 d,最高藥物濃度Cm=60.76±5.62ng/mL,藥-時(shí)曲線下面積AUC=664.35±28.14 ng/mL)·d,達(dá)峰時(shí)間tp=1.20±0.08 d,藥效可維持30 d以上。結(jié)果表明阿維菌素納米脂質(zhì)體緩釋效果確定,可作為阿維菌素長(zhǎng)效制劑進(jìn)行更深入的研究。5阿維菌素納米脂質(zhì)體的急性毒性試驗(yàn)預(yù)試驗(yàn)皮下注射阿維菌納米素脂質(zhì)體后,死亡率100%的劑量為153.68 mg/kg,死亡率0%的劑量為57.97 mg/kg。LD50為98.36mg/kg,LD50的95%的可信限(FL)范圍為:83.39mg/kg-116.01 mg/kg。6阿維菌素納米脂質(zhì)的臨床治療試驗(yàn)在山羊體內(nèi)通過(guò)皮下注射阿維菌素納米脂質(zhì)體三個(gè)不同治療劑量(0.2 mg/kg、0.5 mg/kg、1.0 mg/kg)進(jìn)行驅(qū)蟲(chóng),與阿維菌素普通注射劑(0.2 mg/kg)相比發(fā)現(xiàn)阿維菌素納米脂質(zhì)體具有良好的緩釋作用,且以1.0 mg/kg劑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，

本文編號(hào)：1791643