叶黄素酯冻干亚微乳的制备及体内外评价  

Preparation,in vitro and in vivo Evaluation of Lutein Ester Freeze-dried Submicron Emulsion

作　　者：马晴 金美熹 王晓丽 甘勇 MA Qing;JIN Meixi;WANG Xiaoli;GAN Yong(School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023;School of Pharmacy,China Pharmaceutical University,Nanjing 211198;State Key Lab.of Drug Research and Center of Pharmaceutics,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203;University of Chinese Academy of Sciences,Beijing 100049)

机构地区：[1]南京中医药大学新中药学院,江苏南京210023 [2]中国药科大学药学院,江苏南京211198 [3]中国科学院上海药物研究所,新药研究国家重点实验室药物制剂研究中心,上海201203 [4]中国科学院大学,北京100049

出　　处：《中国医药工业杂志》2023年第10期1450-1458,共9页Chinese Journal of Pharmaceuticals

摘　　要：采用高速剪切-高压均质法制备了叶黄素酯(1)亚微乳,再进一步冷冻干燥制成1冻干亚微乳(F-1-SME)。所得F-1-SME复溶后均匀性良好,平均粒径为(181.33±1.29)nm,包封率为(97.17±0.79)%;在高温、高湿和强光试验中均保持着良好的稳定性(10 d内1含量下降≤5%),在模拟胃肠液中至少可稳定24 h。并且,F-1-SME经体外模拟消化后,仍有(72.95±0.05)%的1溶于水相中,说明亚微乳暴露于胃肠液后,对1仍具有一定的增溶作用,有利于其口服递送。大鼠药动学试验结果显示,按同等剂量灌胃给药后,1冻干乳剂组大鼠血浆中的c_(max)和AUC_(0→24 h)分别为1市售片剂组的2.7和2.8倍,提示F-1-SME的口服生物利用度显著提高。在大鼠视网膜蓝光损伤模型中,口服F-1-SME可有效保护视网膜细胞,说明1冻干乳剂在缓解视网膜蓝光损伤方面具有良好的应用前景。Lutein ester(1) submicron emulsion was prepared via high-speed shear high-pressure homogenization method,and further combined with freeze-drying method to prepare 1 freeze-dried submicron emulsion.The freezedried submicron emulsion of 1(F-1-SME) demonstrated good uniformity,with a particle size of(181.33±1.29)nm and an encapsulation efficiency of(97.17±0.79)%.The F-1-SME maintained good stability(with a content decrease no more than 5% within 10 days) under high temperature,high humidity,and strong light conditions,and it was stable in simulated gastrointestinal fluid for at least 24 hours.After being treated with simulated gastrointestinal fluid,(72.95±0.05)% of 1 was detected dissolving in the aqueous phase,indicating that the submicron emulsion still had a certain solubilizing effect on 1 after exposure to gastrointestinal fluid,which was conducive to enhancing oral absorption.Furthermore,pharmacokinetic test results of F-1-SME in rats showed that the c_(max) in rat plasma and AUC_(0→24 h) of F-1-SME group were 2.7-and 2.8-times higher than those of the commercially available tablets group after gavage administration of the same dose,indicating a significant increase in the oral bioavailability of F-1-SME.Finally,in a rat model of retinal blue lightinduced damage,oral administration of the F-1-SME demonstrated effective protection of retinal cells,indicating its potential for protecting retinal from blue light damage.

关 键 词：叶黄素酯 亚微乳 冷冻干燥 口服生物利用度 稳定性 蓝光防护 

分 类 号：R944.9[医药卫生—药剂学]