左金方与黄连中小檗碱型生物碱提取动力学差异性的研究

Extraction kinetical deviations of berberine alkaloids in Rhizoma Coptidis and Zuojin Formulae

目的:利用已建立的中药提取动力学数学模型研究单复方中药成分溶出差异规律。方法:运用中药复方成分提取动力学数学模型研究黄连及左金方中小檗碱类生物碱的提取动力学行为;运用HPLC指纹图谱法同时测定黄连或复方中小檗碱类生物碱的含量及ρ2、w0参数,运用吸水法测定V0、V1、V2参数;并用SPSS软件非线性拟合各成分提取动力学的M、α、N、β、L参数,用EXCEL依公式计算各成分K、k1′、k2′、ρ1、ρ2、tmax、cmax、AUC、P、D参数及偏差。结果:黄连的V0、V1、V2分别为47.02、6.75、446.23 mL;盐酸小檗碱、盐酸蛇根碱、盐酸巴马亭的ρ2分为0.720 8、0.564 7、0.625 7;w0分别为7.561%、1.220%、1.450%;单味黄连及左金方中盐酸小檗碱、盐酸蛇根碱、盐酸巴马亭药时曲线呈三室模型(R2>0.95),主要提取动力学参数tmax分别为251.6、249.3、343.9、172.8、287.63、175.4 min;cmax分别为4.958、0.7382、1.217、4.252、0.6055、0.9185 mg/mL;P分别为65.02%、60.00%、83.25%;55.77%、49.22%、62.81%;D分别为0.043 04%、0.052 62%、0.017 13%、0.018 25%、0.003 024%、0.012 89%。单味黄连与左金方提取动力学参数偏差以盐酸蛇根碱的AUC最大,为-1613%,以盐酸蛇根碱k1′最小,为-12.40%。k1′、k2′、ρ1均为负数,说明复方配伍溶出效果差于单味黄连,cmax、P、D均为正数,说明单味黄连溶出效果优于左金方配伍。其偏差值越大,效果越明显。结论:中药提取动力学数学模型能客观地描述中药及复方中有效成分的提取行为,能定量表达其溶出差异,是研究中药复方溶解规律和提取工艺的有效工具。

AIM ： To study the extraction kinetical deviation rules of muhicomponents in single and formula for the traditional Chinese materials medica. METHODS： By the established kinetics model of the components extracted form the Chinese medicine compound prescription（KMCECMCP） , the kinetical profile deviations of berberine alkaloids in Rhizoma Coptidis and Zuojin formulae were carried out, with analyses of berberine alkaloids,ρ2 and w0 by HPLC chromatographic fingerprint, with deterimation of V0, V1, V2 by water absorbing, with fited M,α,N,β,L by SPSS 16 edition, with calculation of parameters and their differences of K, k1＇, k2＇, ρ1, tmax, Cmax, AUC, P, D by EXCEL software on bases of kinetical expressions. RESULTS ： The V0, V1 , V2 for Rhizoma Coptidis were 47. 02 mL, 6.75 mL,446.23 mL respectively; The ρ2 for the berberine hydrochloride, serpentine hydroehloride, pal- marine hydrochloride in Rhizoma Coptidis and ZuoJin formulae were 0. 720 8,0. 564 7,0. 625 7 ; and the w0 as 7. 561% ,1. 220% ,1. 450% respectively; The extraction kinrtical profiles for the tri-constituents were fitted three compartment model （R2 〉 0.95 ） ; The main kinetical parameters such as tmax for the tri-constituents in single and formula materials were respectively 251.6 rain, 249.3 rnin, 343.9 min, 172.8 min, 287.63min, 175.4 min; as Cmax as 4 425 mg · mL^-1 , 658.8mg · mL^-1, 1 086 mg · mL^-1, 3 795 mg · mL^-1 , 540.4 mg · mL^-1 , 819.7 mg · mL^-1 ;as P as 65.02%, 60.00%, 83.25%, 55.77%, 49.22%, 62.81% ;as D as 0.04304%, 0. 05262%, 0.0171 3%, 0.018 25%, 0.003 024%, 0. 012 89%. The extraction kinetical deviations for the single and formula were at maximum of AUC as-1 613% , whereas at minimum of k1 ＇as -12.40% for serpentine hydrochloride; k1＇, k2 t, ρ1 were negative meant the effects of dissolution for formulae were better than that for single Rhizorna Coptidis ; cmax P, D were positive, vice versa. The more the deviation values were, the more effects of dissolution were. CONCLUSION ： It is suggested that for the single and formula materials, the KMCECMCP was decribed objectively the extraction kinetical profiles expressed quantitatively the deviations of dissolution, was a useful tool to study their solubility rules and extraction technique.