普通针毛蕨总黄酮包合物的制备及其生物利用度研究

Preparation of inclusion compound of total flavones of Macrothelypteris torresiana,and the study of its bioavailability

目的:了解普通针毛蕨总黄酮及其包合物的活性成分在人工胃、肠液中的稳定性及其生物利用度。方法:以人工胃、肠液将普通针毛蕨总黄酮0.5%CMC-Na混悬剂及HP-β-CD包合物制成高、中、低3个浓度样品,在温孵箱内37℃恒温、振荡50r.min-1,于0、4、8、12、20、24h取样品进行HPLC检测,检测其活性成分代表原芹菜素的峰面积进行比较;高、中、低3种相等剂量(按体质量分别以100,200,300mg.kg-1给药)的普通针毛蕨总黄酮混悬剂及其包合物进行动物灌胃血液吸收动力学实验,采用Das 2.0软件对各组血药浓度进行房室模型分析。结果:普通针毛蕨总黄酮及其包合物的所有样品在0～24h内,同一样品间所含的原芹菜素峰面积差异无显著性(P>0.05),相同浓度的样品组与阳性组、阴性组比较所含的原芹菜素峰面积无显著性差异(P>0.05),说明原芹菜素在胃肠液中比较稳定,不易破坏;普通针毛蕨总黄酮混悬剂及其包合物的大鼠灌胃血液吸收动力学试验,表现出明显的线性动力学特征,显示包合物延长了半衰期、血药浓度达峰时间变短,峰浓度有所提高,消除半衰期相对延长,AUC相对加大,说明包合处理可提高总黄酮口服吸收的生物利用度。结论:普通针毛蕨总黄酮中的活性成分在人工胃肠液稳定性强,不易破坏;包合物的生物利用度显著提高。

OBJECTIVE To investigate the stability of total flavones of Macrothelypteris torresiana in the artificial gastric juice （AGJ） and the artificial intestinal iuice （AIJ） and its bioavailability. METHODS 0. 5% CMCNa suspension and HP-β- CD inclusion compound of total flavones of Macrothelypteris torresiana were dissolved by AGJ and AIJ to obtain three concentrations samples at low, middle and high levels, respectively. The samples were incubated at 37 ℃, and vibrated at the rate of 50 r·min-1. Then, the peak areas of protoapigenone in all samples, which is the main flavone in Macrothelypteris torresiana, were detected by HPLC method after vibrated in the incubator for 0, 4, 8, 12, 16, 20 h, respectively. Three doses of suspension and inclusion compound （at the doses of 100, 200 mg.kg-1 , and 300 mg.kg -1 , respectively） were administrated by gastric gavage to rats for the blood absorption kinetics experiment, then the blood concentrations in each group were calculated by DAS 2. 0 program to analyze protoapigenone＇s compartmental model. RESULTS For all samples, in the time range of 0 - 24 h, the peak area of protoapigenone in one sample showed no significant difference （P〉0. 05）. For samples at the same concentration, the peak area of protoapigenone showed no significant difference when compared with the negative group and positive group （P〉0. 05）. The results of bioavailability study indicated that blood absorption of suspension and inclusion compound showed clear linear absorptive character, and the inclusion compound could improve the bioavailability compared with the suspension, which it could prolong the half time, shorten the peak plasma concentration time, increase the peak plasma concentration, prolong the elimination half time, and increase the AUC. CONCLUSION The active flavone compound in Macrothelypteris torresiana is stable in AGJ and AIJ, and the inclusion compound can significantly improve the bioavailability （P〈0. 05）.