马钱子优化总生物碱复合磷脂传递体的制备与性质研究

The preparation and properties study of modified total alkaloids(MTA) from the seeds of Strychnou nux-vomica L

目的应用复合磷脂传递体技术以改善马钱子优化总生物碱的药剂学性质和透皮吸收效果。方法通过除去总生物碱中的大部分士的宁得到马钱子优化总生物碱。采用硫酸铵梯度法制备了马钱子优化总生物碱复合磷脂传递体,以包封率为指标确定了其最优磷脂组成。以相应的单一磷脂传递体为对照,比较了马钱子总生物碱复合磷脂传递体药剂学性质以及体外透皮吸收性质。采用DSC和分子模拟研究考察了复合磷脂的相互作用规律。结果优化后,马钱子总生物碱中马钱子碱与士的宁的比值从1:1.8改变为2.7:1,LD50比优化前提高了4.8倍。通过包封率考察确定SPC:DPPC=4:6为最佳复合磷脂组成。与单一磷脂传递体相比,马钱子优化总生物碱复合磷脂传递体的药剂学性质和体外透皮吸收效果显著提高。结论马钱子优化总生物碱复合磷脂传递体的药剂学性质与透皮吸收性能优于单一磷脂传递体。

Objective To improve the pharmaceutical properties and transdermal absorption ability of modified total alkaloids（MTA） from the seeds of Strychnou nux-vomica L.by transfersome technique.Methods To obtain the MTA,the content of strychnine was significantly reduced in the composition of total alkaloids.The novel transfersomes containing MTA was prepared by the ammonium sulfate gradient loading method.The optimal molar ratio of DPPC and SPC was determined by the evaluation of the encapsulation efficiency（EE）.The pharmaceutical properties and transderml absorption abilities of transfersomes with different lipid composition were compared.The mechanism accounted for the relationship between SPC and DPPC was further investigated by DSC and molecular modeling.Results The mass ratio of brucine to strychnine in the MTA was increased from 1：1.8 to 2.7：1.The LD50 value of MTA was increased about 4.8-fold compared with that of total alkaloids.The optimal molar ratio of DPPC and SPC was found to be 6：4.Compared with the corresponding DPPC or SPC transfersomes,the pharmaceutical properties and transderml absorption ability were significantly improved by the application of the novel transfersomes composed of both SPC and DPPC.Conclusions Compared with transfersomes composed of SPC or DPPC,novel transfersomes composed of both SPC and DPPC have been proved to be better carriers for the transdermal absorption of MTA.