吴永秋,万君晗,杨健峰,黄传利,黄蓓,张彩凤,龙晓英
WU Yongqiu,WAN Junhan,YANG Jianfeng,HUANG Chuanli,HUANG Bei,ZHANG Caifeng,LONG Xiaoying

• 1:广东药科大学

摘要(Abstract)：

目的以盐酸小檗碱为原料,制备游离小檗碱,增加小檗碱在油和水中的溶解度。方法通过加入NaOH中和盐酸形成游离小檗碱,以乙醚为溶剂进行萃取;测定游离小檗碱在不同油相和不同pH缓冲液中的溶解度,并测定其油水分配系数。结果萃取体系中,盐酸小檗碱最佳浓度为2 mg·mL~(-1),NaOH浓度为0.108 mol·L~(-1)(NaOH与盐酸小檗碱的摩尔比为87.81:1),最佳萃取溶剂为乙醚;盐酸小檗碱在几种油相中基本不溶,游离小檗碱在油酸乙酯、柠檬油、大豆油、橄榄油、肉豆蔻酸异丙酯的溶解度分别为(4.39±0.30)、(3.85±0.17)、(3.84±0.06)、(2.17±0.10)、(0.63±0.02)mg·mL~(-1),在水、pH1.2盐酸溶液、pH5.0、pH6.8和pH7.4缓冲液中的溶解度比盐酸小檗碱分别提高了6,13,12,10,9倍;在模拟胃肠液pH1.2、pH6.8和pH7.4磷酸盐缓冲液中游离小檗碱的油水分配系数P比盐酸小檗碱分别提高了2,3,4倍。结论游离小檗碱的脂溶性、水溶性及油水分配系数与盐酸小檗碱相比均有增加,为后期促进其口服吸收的研究奠定基础。
OBJECTIVE To prepare the free berberine in order to increase the solubility of berberine in oils and water.METHODS The hydrochloric acid of berberine hydrochloride was neutralized by adding Na OH,and then extracted with ether. The solubility and oil-water partition coefficient of free berberine at different oils and different pH buffers were measured. RESULTS In the extraction system,the optimum concentration of berberine hydrochloride and Na OH was 2 mg·mL~(-1)and 0.108 mol·L~(-1)( the molar ratio of Na OH to berberine hydrochloride was 87. 81 : 1),respectively. The optimum extraction solvent was ether. Berberine hydrochloride was insoluble in several kinds of oils. The solubility of free berberine was( 4.39±0.30) 、( 3.85±0.17) 、( 3.84±0.06) 、( 2.17±0.10) and( 0.63±0.02) mg·mL~(-1)in ethyl oleate,lemon oil,soybean oil,olive oil and isopropyl myristate,respectively. The solubility of free berberine was 6,13,12,10 and 9 times higher than that of berberine hydrochloride in water,pH1.2,pH5.0,pH6.8 and pH7.4 phosphate buffers,respectively.The water-oil partition coefficients of free berberine in the simulate gastrointestinal fluids( pH1.2,pH6.8 and pH7.4) were improved by 2,3 and 4 times compared with berberine hydrochloride in similar condition. CONCLUSION The oil solubility,water solubility and oilwater partition coefficient of free berberine are increased compared with that of berberine hydrochlorided. Our results provide a base for further study of berberine oral absorption in future.

关键词(KeyWords)： 盐酸小檗碱;溶解度;油水分配系数;萃取
berberine hydrochloride;solubility;oil-water partition coefficient;extraction

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(81573353)

作者(Author): 吴永秋,万君晗,杨健峰,黄传利,黄蓓,张彩凤,龙晓英
WU Yongqiu,WAN Junhan,YANG Jianfeng,HUANG Chuanli,HUANG Bei,ZHANG Caifeng,LONG Xiaoying

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