黄癸素平衡溶解度和表观油水分配系数的测定
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摘要
目的:研究黄癸素(berberineα-hydroxyβ-decanoylethyl sulfonate,HB)在不同pH磷酸盐缓冲液(PBS)中的平衡溶解度以及在正辛醇-水/PBS中的表观油水分配系数,为开发新型的HB制剂提供依据。方法:采用高效液相色谱法(HPLC)测定HB在不同pH的PBS中的平衡溶解度;采用摇瓶法测定HB在正辛醇-水/PBS中的表观油水分配系数。结果:37℃时HB在水中的平衡溶解度为378.5μg·m L~(-1),pH为5时溶解度最小;HB的表观油水分配系数Papp为0.096,pH>5时,Papp<1,pH<5时,Papp>1。结论:HB的平衡溶解度与表观油水分配系数与介质的pH有关,推测其进入胃肠道后不易被吸收。
Objective: To determine the equilibrium solubility and apparent partition coefficient( Papp) of berberine α-hydroxy β-decanoylethyl sulfonate( HB) in a series of phosphate buffer solutions( PBS) of different pHs to provide a theoretical basis for the exploitation of HB preparations. Methods: A high performance liquid chromatography( HPLC) method was established and used to detect the concentration of HB in water and buffer solutions; the partition coefficients of HB in n-octanol-water/buffer solution systems were determined by shaking flask method. Results: The equilibrium solubility of HB in water was 378. 5 μg·m L~(-1) at 37 ℃ and the solubility was the lowest at pH 5. The Pappof HB was 0. 096,and it was < 1 at pH of > 5 and > 1 at pH of < 5.Conclusion: The equilibrium solubility of HB and the apparent oil-water partition coefficient are related to the pH of the medium,suggesting that it is not easily absorbed after entering the gastrointestinal tract.
Objective: To determine the equilibrium solubility and apparent partition coefficient( Papp) of berberine α-hydroxy β-decanoylethyl sulfonate( HB) in a series of phosphate buffer solutions( PBS) of different pHs to provide a theoretical basis for the exploitation of HB preparations. Methods: A high performance liquid chromatography( HPLC) method was established and used to detect the concentration of HB in water and buffer solutions; the partition coefficients of HB in n-octanol-water/buffer solution systems were determined by shaking flask method. Results: The equilibrium solubility of HB in water was 378. 5 μg·m L~(-1) at 37 ℃ and the solubility was the lowest at pH 5. The Pappof HB was 0. 096,and it was < 1 at pH of > 5 and > 1 at pH of < 5.Conclusion: The equilibrium solubility of HB and the apparent oil-water partition coefficient are related to the pH of the medium,suggesting that it is not easily absorbed after entering the gastrointestinal tract.
引文
[1]林菁,彭华毅,王希,等.黄癸素对肿瘤细胞增殖的抑制作用[J].中药药理与临床,2011,27(1):20-23.
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[3]王希,林菁,彭华毅.黄癸素对人口腔上皮样癌KB细胞株及化学诱导性仓鼠颊癌作用的研究[J].福建医科大学学报,2012,46(2):100-103.
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[6]曾佳,黄婷,李芳,等.RP-HPLC测定左炔诺孕酮与孕二烯酮表观油水分配系数及平衡溶解度[J].中国新药杂志,2014,23(14):1703-1707.
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[9]孙永强,严益民,屠永锐,等.甲磺酸雷沙吉兰油水分配系数的测定[J].中国新药杂志,2014,23(13):1562-1564.
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[11]康伟松,程辟,曾建国.血根碱、白屈菜红碱离子对化合物的体外菌活性研究[J].中南药学,2014,12(5):406-410.
[12]贾本真.小檗碱离子对化合物的抗肿瘤作用用途:CN102309483 B[P].2013.
[13]黄嗣航,龙晓英,袁飞,等.盐酸小檗碱的溶解度及油水分配系数与大鼠在体肠吸收之间的相关性研究[J].中国现代应用药学,2012,29(3):233-238.
[14]张双庆.介绍物理化学方法研究药物吸收、分布、代谢和排泄[J].中国药事,2012,26(6):641-645.
[2]林菁,王希.黄癸素对拓扑异构酶的影响及联合羟喜树碱的抗肿瘤作用[J].药学学报,2011,46(4):390-394.
[3]王希,林菁,彭华毅.黄癸素对人口腔上皮样癌KB细胞株及化学诱导性仓鼠颊癌作用的研究[J].福建医科大学学报,2012,46(2):100-103.
[4]郁丹红,贾晓斌.相似性分析用于丹参二萜醌组分平衡溶解度和油水分配系数的研究[J].中国中药杂志,2013,38(12):1860-1864.
[5]杨滨,马攀勤,孙进,等.HPLC法测定盐酸普拉克索平衡溶解度和表观油水分配系数[J].中国药剂学杂志:网络版,2016,14(1):26-32.
[6]曾佳,黄婷,李芳,等.RP-HPLC测定左炔诺孕酮与孕二烯酮表观油水分配系数及平衡溶解度[J].中国新药杂志,2014,23(14):1703-1707.
[7]FAIYAZ S,NAZRUL H,FARS KC,et al.Solubility and thermodynamics of apremilast in different mono solvents:determination,correlation and molecular interactions[J].Int J Pharm,2017,523(1):410-417.
[8]袁礼,钟思雨,周容,等.HPLC法测定斑蝥素的平衡溶解度和表观油水分配系数[J].中国新药杂志,2017,26(10):1185-1188.
[9]孙永强,严益民,屠永锐,等.甲磺酸雷沙吉兰油水分配系数的测定[J].中国新药杂志,2014,23(13):1562-1564.
[10]袁礼,钟思雨,周容,等.HPLC法测定斑蝥素的平衡溶解度和表观油水分配系数[J].中国新药杂志,2017,6(10):1185-1188.
[11]康伟松,程辟,曾建国.血根碱、白屈菜红碱离子对化合物的体外菌活性研究[J].中南药学,2014,12(5):406-410.
[12]贾本真.小檗碱离子对化合物的抗肿瘤作用用途:CN102309483 B[P].2013.
[13]黄嗣航,龙晓英,袁飞,等.盐酸小檗碱的溶解度及油水分配系数与大鼠在体肠吸收之间的相关性研究[J].中国现代应用药学,2012,29(3):233-238.
[14]张双庆.介绍物理化学方法研究药物吸收、分布、代谢和排泄[J].中国药事,2012,26(6):641-645.