马钱子总碱中2种成分的平衡溶解度、油水分配系数、体外透皮特性  

Equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of two constituents in total alkaloids from Strychni Semen

作　　者：王艳宏[1] 齐笑 关枫[1] 冯宇飞[1] 李永吉[1] 陈大忠[2] 

机构地区：[1]黑龙江中医药大学药学院,黑龙江哈尔滨150040 [2]黑龙江中医药大学中医药研究院,黑龙江哈尔滨150040

出　　处：《中成药》2017年第10期2034-2038,共5页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金项目(81473359);黑龙江省科技厅青年基金项目(QC07C107);黑龙江省教育厅科学技术研究项目(11531357)

摘　　要：目的考察马钱子Strychni Semen总碱中马钱子碱和士的宁的平衡溶解度、油水分配系数、体外透皮特性。方法饱和溶解法测定2种成分在乙醇(10%、20%、30%、60%、90%、无水乙醇)、三氯甲烷、正辛醇、表面活性剂(0.5%吐温、0.5%去氧胆酸钠、0.5%油酸)中的平衡溶解度;摇瓶法测定两者在PBS(pH 2.5、4.0、5.0、5.8、6.8、7.0、7.4、9.0)中的油水分配系数;改良Franz扩散池法评价其在PBS、20%乙醇、无水乙醇中的体外透皮特性。结果马钱子碱、士的宁均在三氯甲烷中的平衡溶解度最高,表面活性剂中最低;在体积分数大于20%的乙醇或pH小于8.0的PBS中,士的宁平衡溶解度高于马钱子碱,并分别在60%乙醇和pH 2.5 PBS中达到最高。2种成分油水分配系数相近,均随pH增加而升高,在pH9.0时最高。两者分别在无水乙醇、pH9.0 PBS中的累计透皮吸收率最高。结论溶剂种类对马钱子碱和士的宁的平衡溶解度、油水分配系数、透皮吸收均有明显影响。本研究可为马钱子总碱经皮给药生物利用度的改善及相关制剂的开发提供参考。AIM To investigate the equilibrium solubilities, oil-water partition coefficients and in vitro skin permeation features of brucine and strychnine in total alkaloids from Strychni Semen. METHODS Saturated dis- solution method was applied to determining the equilibrium solubilities of two constituents in ethanol （ 10% , 20% , 30% , 60% , 90% , anhydrous ethanol）, trichloromethane, n-octanol and surfactants （0. 5% tween, 0. 5% sodi- um deoxycholate, 0.5% oleic acid）. Shake-flask method was adopted in detecting their oil-water partition coeffi- cients in PBS （ pH 2.5, 4.0, 5.0, 5.8, 6.8, 7.0, 7.4, 9.0）. Modified Franz diffusion cell method was used for evaluating their in vitro skin permeation features in PBS, 20% ethanol and anhydrous ethanol. RESULTS Both brucine and strychnine showed the highest equilibrium solubilities in trichloromethane and the lowest equilibrium solubilities in surfactants. The equilibrium solubility of strychnine was higher than that of brucine in ethanol （〉20%） orPBS （pH similar oil-water partitio 〈 8.0）, which reached the highest in 60% ethanol and pH 2.5 PBS, respectively. The n coefficients of two constituents, proportional to pH value, reached the highest at pH 9.0.And they exhibited the highest accumulated transdermal absorptivities in anhydrous ethanol and pH 9.0 PBS, re- spectively. CONCLUSION Solvent type has obvious effects on the equilibrium solubilities, oil-water partition coefficients and in vitro skin permeation features of both brucine and strychnine. This study can provide a reference for the bioavailability improvement of transdermal drug delivery and development of related preparations.

关 键 词：马钱子总碱 马钱子碱 士的宁 平衡溶解度 油水分配系数 体外透皮特性 

分 类 号：R969.1[医药卫生—药理学]