[1] ZHOU BinSONG XuanfeiXIE HuanWANG YunZHANG Yongping,.Determination of Equilibrium Solubility and Apparent Oil-Water Distribution Coefficient of Danshen Extract [J]. Modern Traditional Chinese Medicine, 2024, (02): 79-86. [doi: 10.13424/j.cnki.mtcm.2024.02.015]
Determination of Equilibrium Solubility and Apparent Oil-Water Distribution Coefficient of Danshen Extract
- Article number:
- 1672-0571(2024)02-0079-08
- Keywords:
- Key words:Equilibrium solubility; Apparent oil-water distribution coefficient; Danshen extract; Ultra high performance liquid chromatography
- ZTFLH:
- R284
- Code:
- A
- Abstract:
- Abstract：Objective To determine the equilibrium solubility of the “water lipid” binary component index components in different solvents and the apparent oil-water distribution coefficient at different pH values in Danshen extract，and to explore the solubility performance of Danshen extract.Methods Ultra high performance liquid chromatography (UPLC) combined with mass weighting coefficient method was used to characterize the overall solubility of six indicator components，including rosmarinic acid，purpuric acid，salvianolic acid B，salvianolic acid A，cryptotanshinone，and salvianone IIA，in solutions of different polarities and pH values，as well as the overall oil-water distribution coefficient in a saturated n-octanol water system in Danshen extract.Results At 37 ℃，the overall solubility of the extract in eight solvents including water，methanol，ethanol，acetonitrile，n-butanol，acetone，trichloromethane，and ethyl acetate ranged from 0.62 to 11.58 mg·mL-1，and the equilibrium solubility in water was relatively high；The equilibrium solubility in the buffer solution shows a trend of first increasing，then decreasing，and finally stabilizing；The overall oil-water distribution coefficient Kapp in the saturated n-octanol water system ranges from -1.12 to -0.16，and the lgP reaches its maximum at pH 4.97.Conclusion The solubility and permeability of Danshen extract are both poor.When designing the dosage form，it is possible to consider adding an appropriate amount of alcohols to the prescription to improve solubility，adjust pH value，and use permeation promoting methods to promote drug transdermal absorption.
References:
［1］杨贵雅,薛紫鲸,张丹,等.基于指纹图谱和多成分含量测定的丹参药材皮部和木部化学成分比较研究［J］.中草药,2019,50(21):5328-5335.
［2］李园园,刘佳,梁悦,等.丹参水溶性成分的抗炎作用［J］.黑龙江畜牧兽医,2020(13):132-134,137.
［3］高燕,杨龙飞,丁晓彦,等.丹参水溶性成分对尾动脉血管狭窄斑马鱼血管舒张作用的研究［J］.中华中医药杂志,2019,34(11):5384-5387.
［4］杨龙飞,赵渤年,丁晓彦,等.基于斑马鱼模型的丹参促血管生成及心脏损伤保护作用的研究［J］.中华中医药杂志,2018,33(6):2620-2624.
［5］高秀容,许小红,杨恒博,等.丹参提取物中脂溶性成分检测及体外溶出行为考察［J］.医药导报,2019,38(1):79-83.
［6］赵梅,郭振丰,李天时,等.丹参酮ⅡA对大鼠实验性心肌梗死心律失常机制研究［J］.中国医院药学杂志,2016,36(17):1452-1455.
［7］Wang YF,Duo DL,Yan YJ,et al.Extract of Salvia przewalskii repair tissue damage in chronic hypoxia maybe through the RhoA-ROCK signalling pathway［J］.Biological & Pharmaceutical Bulletin,2020,43(3):432-439.
［8］王平,高燕,殷洁,等.丹参脂溶性成分对心肌细胞缺氧缺糖损伤的保护作用［J］.中华中医药杂志,2015,30(1):38-41.
［9］张涛,张娟红,徐丽婷.中药丹参类制剂临床研究及应用进展［J］.实用药物与临床,2015,18(3):330-334.
［10］谢凯.丹参药效部位提取及其缓释制剂中释药模式研究［D］.广州:广东药学院,2008.
［11］朱建辉,王超超,张明磊.丹参注射液临床及实验研究现状［J］.海峡药学,2019,31(12):104-107.
［12］闫佳怡,阮盼盼,张卓,等.复方丹参滴丸对急性高原病大鼠作用及机制［J］.中国临床药理学杂志,2022,38(22):2736-2740.
［13］米热阿依·木太力甫,克徳尔阿依·木太力甫,米尔斯曼古力·米吉提.超微加味丹参饮对氯化钴诱导损伤的大鼠冠状动脉血管内皮细胞的影响［J］.中医药导报,2022,28(9):19-24.
［14］周慧慧,杜少兵,高速,等.丹参-红花配方颗粒制备工艺的优化、TLC鉴别及含量测定［J］.华西药学杂志,2022,37(3):292-296.
［15］成冯镜茗,吕健,谢雁鸣.复方丹参喷雾剂/气雾剂治疗冠心病心绞痛有效性与安全性的Meta分析［J］.中国药物警戒,2023,20(5):536-543.
［16］张涛,张娟红,徐丽婷.中药丹参类制剂临床研究及应用进展［J］.实用药物与临床,2015,18(3):330-334.
［17］潘素静,龙晓英,林婉婷,等.复方丹参制剂口服吸收研究新进展［J］.中成药,2013,35(7):1526-1530.
［18］刘丹,贾晓斌,萧伟.质量分数权重系数法表征银杏内酯组分溶解性及表观油水分配系数的探讨［J］.中国中药杂志,2013,38(12):1865-1870.
［19］张敏敏,刘冲,陈文.金合欢素平衡溶解度、油水分配系数和解离常数的测定［J］.时珍国医国药,2020,31(5):1084-1087.
［20］侯迪旭,吴学萍,李树英,等.基于体外释放的半固体制剂透皮吸收及其影响因素探讨［J］.中国新药杂志,2018,27(15):1807-1812.
［21］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.
［22］毛美玲,谢丽钰,罗文宽，等.丹参及其有效成分对心血管系统的药理机制研究进展［J/OL］.中华中医药学刊:1-12［2023-09-18］.http://kns.cnki.net/kcms/detail/21.1546.R.20230915.1809.094.html.
［23］佟煜,张萌,王安琪，等.丹参及其相关制剂有效成分稳定性的研究进展［J/OL］.中成药:1-7［2023-05-08］.http://kns.cnki.net/kcms/detail/31.1368.R.20230119.1635.001.html.
［24］李占鹰,贾林,袁丽君,等.丹参素药理作用的研究进展［J］.华西药学杂志,2021,36(5):600-603.
［25］王景雁,兰颐,林红梅,等.薄荷醇对不同logP值中药有效成分经皮吸收的促透研究［J］.中国新药杂志,2016,25(2):202-209.
［26］王景雁,兰颐,茹庆国,等.氮酮对不同亲脂性中药有效成分的经皮促透作用研究［J］.北京中医药大学学报,2016,39(2):155-161.
［27］朱溶月,常道潇,隋宏,等.HPLC法测定叶黄素的平衡溶解度及表观油水分配系数［J］.药学研究,2018,37(7):388-390,412.
［28］靳佳慧,马静,刘征辉,等.氧化白藜芦醇溶解性、油水分配系数和胶束制备及其透皮性能的研究［J］.时珍国医国药,2019,30(7):1615-1618.
［29］李国锋,权英淑,神山文男,等.皮肤不同层对脂溶性药物经皮渗透的影响［J］.中国药学杂志,2002,37(11):33-36.
［30］郭静一,何群,郭瑜,等.双烟酸姜黄素酯平衡溶解度及表观油水分配系数的测定［J］.中国药师,2018,21(2):197-200,214.
［31］滕巧巧,朱信辉,华佳,等.脂溶性小檗碱衍生物的合成及其表观油水分配系数测定［J］.常州大学学报(自然科学版),2019,31(6):23-30.
Memo
基金项目：国家自然科学基金面上项目（81873020）；贵州省高等学校中药民族药（苗药）新剂型新制剂工程研究中心（黔教技［2022］022）