注射用大黄素脂质体的制备及质量评价
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摘要
建立大黄素脂质体包封率的测定方法,制备包封率高的注射用大黄素脂质体,并对其进行质量评价。采用离心沉淀-微孔滤膜挤压法分离游离大黄素和大黄素脂质体,高效液相色谱法测定大黄素脂质体的包封率;采用薄膜分散-冷冻干燥法制备注射用大黄素脂质体,以包封率为评价指标,建立制备工艺;考察注射用大黄素脂质体的包封率、表面形态、平均粒径、zeta电位及贮存稳定性。结果表明:在磷脂、胆固醇、大黄素的质量比为70∶2∶3,水为水化液,预冻温度-10℃,蔗糖为冻干保护剂,蔗糖与水质量比为1∶10,5%葡萄糖注射液为再水化液的条件下,制得的注射用大黄素脂质体包封率在80%以上,形态呈规则球形,平均粒径(206.3±17.5) nm,zeta电位(-31.6±0.8) mV,4℃密封环境下可贮存3个月以上。
To establish the entrapment efficiency determination of emodin liposomes, emodin liposome for injection with high entrapment efficiency was prepared and its quality was evaluated. Non encapsulated drugs were expected by centrifugal settling-micromembrane extruding method. The entrapment efficiency was determined by HPLC. The preparation of emodin liposome for injection was conducted by thin film dispersion-freeze drying method. The entrapment efficiency was taken as the evaluation index,and the preparation technology was established. The entrapment efficiency, the surface morphology, the mean particle diameter, the zeta potential and the storage stability were studied. The optimized preparation conditions were as follows: the ratio of lecithin-cholesterol-emodin was 70∶2∶3, double-distilled water was hydrated fluid, pre-freezing temperature was 10 ℃, sucrose was the protective agent, the ratio of sucrose-water was 1∶10, and 5% glucose injection was rehydrated fluid. The entrapment efficiency was above 80%, the surface morphology was regular sphere, the mean particle diameter was(206.3±17.5) nm, the zeta potential was(-31.6±0.8) mV and the storage time was longer than 3 months in 4 ℃ sealed environment.
To establish the entrapment efficiency determination of emodin liposomes, emodin liposome for injection with high entrapment efficiency was prepared and its quality was evaluated. Non encapsulated drugs were expected by centrifugal settling-micromembrane extruding method. The entrapment efficiency was determined by HPLC. The preparation of emodin liposome for injection was conducted by thin film dispersion-freeze drying method. The entrapment efficiency was taken as the evaluation index,and the preparation technology was established. The entrapment efficiency, the surface morphology, the mean particle diameter, the zeta potential and the storage stability were studied. The optimized preparation conditions were as follows: the ratio of lecithin-cholesterol-emodin was 70∶2∶3, double-distilled water was hydrated fluid, pre-freezing temperature was 10 ℃, sucrose was the protective agent, the ratio of sucrose-water was 1∶10, and 5% glucose injection was rehydrated fluid. The entrapment efficiency was above 80%, the surface morphology was regular sphere, the mean particle diameter was(206.3±17.5) nm, the zeta potential was(-31.6±0.8) mV and the storage time was longer than 3 months in 4 ℃ sealed environment.
引文
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[9] Desai M P,Labhasetwar V, Amidon G L, et al. Gastrointestinal uptake of biodegradable microparticles: effect of particle size[J]. Pharm Res, 1996, 13: 1838-1845.
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[2] 张永强,龙婷,牛亚军,等.天然蒽醌化合物口服吸收及代谢研究进展[J].海峡药学,2014,26(7):1-5.
[3] 张彦,杜永平,王文勇,等.蒽醌类中药导致结肠黑变病的机制研究[J].现代生物医学进展,2013,13(3):408-415.
[4] 姜华,高原,杨景明.中药脂质体的研究进展[J].当代医学,2009,15(28):12-13.
[5] Torchilin V P,Weissig V.Liposomes:A Practial Approach[M].Englanel:Oxford University Press,2003.
[6] 严建业,王元清,黄丹,等.HPLC-DAD测定虎杖苷、白藜芦醇、大黄素的平衡溶解度及表观油水分配系数[J].中成药,2015,37(12):2628-2632.
[7] 李琅琅,王文喜,牛泱平.低速离心法测定荧光红GG脂质体包封率[J].浙江工业大学学报,2009,3(5):535-537.
[8] 顾宜,石玉,张三奇,等.大黄素纳米脂质体的制备及质量评价[J].第四军医大学学报,2003,24(5):479.
[9] Desai M P,Labhasetwar V, Amidon G L, et al. Gastrointestinal uptake of biodegradable microparticles: effect of particle size[J]. Pharm Res, 1996, 13: 1838-1845.
[10] Tang L, Zhang Y, Qian Z, et al.The mechanism of Fe2+-initiated lipid peroxidation in liposomes :the dual function of ferrousions, theroles of the pre-existing lipid peroxides and the lipidperoxyl radical[J].Biochem J, 2000, 352:27-36.