葛根素、黄芩苷、小檗碱及其在葛根芩连制剂(汤剂及微丸)中溶解度及油水分配系数的比较

Solubility and oil-water partition coefficient of puerarin,baicalin and berberine hydrochloride in Gegenqinlian formula

目的 比较37℃下葛根素、黄芩苷、小檗碱及其在葛根芩连制剂（汤剂及微丸）中不同pH缓冲液中的溶解度及油水分配系数,为其口服吸收研究提供依据.方法 采用摇瓶-高效液相法测定葛根素、黄芩苷、小檗碱及其在葛根芩连制剂（汤剂及微丸）在不同pH缓冲液中的溶解度,及在正辛醇-缓冲液体系中的油水分配系数.结果 在pH1.2、4.5、6.8条件下,葛根素、黄芩苷、小檗碱单一成分的溶解度分别是27.088～ 30.805、0.007～ 11.694、0.181～2.169 mg·mL^-1,3种成分在葛根芩连汤剂及微丸中溶解度范围分别是57.518～68.450、11.652～12.416、4.402～5.688 mg·mLL^-1和2.545～2.922、0.287～0.548、0.332～0.522 mg· mLL^-1;相应条件下,葛根素、黄芩苷、小檗碱单一成分的表观油水分配系数范围分别是0.081～0.136、0.689～3.706、0.244～0.579,3种成分在汤剂及微丸中的油水分配系数范围分别是0.290 ～0.603、3.032～10.019、1.110～3.952和0.150～0.217、0.486～8.305、0.440 ～0.838.结论 受到多种成分的相互影响及提取、制剂工艺的影响,制剂中有效成分的溶解度及油水分配系数与单一成分相比差异较大.与葛根芩连微丸相比,葛根芩连汤对复方中难溶性成分具有显著的增溶作用,可能有利于药物体内吸收,为中药剂改工艺研究提供参考.通过测定制剂中难溶性成分的溶解度及油水分配系数为研究中药复方有效成分的口服提供一定依据.

Objective To compare solubility （S） and oil/water partition coefficient （Po/w） of puerarin （PUE）,baicalin （BA） and berberine hydrochloride （BH） in Gegenqinlian pills （GQP） and Gegenqinlian decoction （GQD） in buffer with different pH value at 37 ℃.Methods The solubility and oil/water partition coefficient of puerarin,baicalin and berberine hydrochloride was determined with a shake flaskHPLC method.Results The ranges of S of PUE,BA,BH at pH 1.2,4.5 and 6.8 were from 27.088 to 30.805,0.007 to 11.694,0.181 to 2.169 mg · mLL^-1,respectively,and which in GQD and GQP were from 57.518 to 68.450,11.652 to 12.416,4.402 to 5.688 mg · mLL^-1 and 2.545 to 2.922,0.287 to 0.548,0.332 to 0.522 mg · mL^L-1,respectively.Similarly,under the corresponding conditions,the ranges of Po/w of PUE,BA,BH were from 0.081 to 0.136、0.689 to 3.706、0.244 to 0.579 and which in GQD and GQP were from 0.290 to 0.603,3.032 to 10.019,1.110 to 3.952 and 0.150 to 0.217,0.486 to 8.305,0.440 to 0.838,respectively.Conclusion Affected by multifarious ingredient,extracting process or preparation technology,S and Po/w of all insoluble active ingredients in Chinese herbal compound prescription were significant different with monomer.Compared with GQP,insoluble components were significantly solubilized in GQD,which might be beneficial for active ingredients absorption in vivo and provide a reference for improvement of Chinese medicine formulations.It is important to determine S and Po/w of insoluble active ingredients existed in Chinese herbal compound,which can be applied to provide some reference to study their absorbability of oral administration.