人参皂苷Re-β-环糊精包合物的制备及其体内药动学研究

Preparation and in vivo pharmacokinetics of ginsenoside Re-β-cyclodextrin inclusion complex

目的制备人参皂苷Re-β-环糊精包合物,并考察其体内药动学。方法溶液搅拌-冷冻干燥法制备β-环糊精包合物,测定溶解度、溶出度,FT-IR、XRD、DSC、SEM进行表征。大鼠随机分为2组,分别灌胃给予人参皂苷Re及其β-环糊精包合物的混悬液(100 mg/kg),于0.083、0.25、0.5、1、2、3、4、6、9、10、12、24 h采血,HPLC-MS/MS法测定人参皂苷Re血药浓度,计算主要药动学参数。结果环糊精包合物溶解度、溶出度分别为原料药的10.11、4.26倍。人参皂苷Re与β-环糊精以非共价键形式结合,并且前者以无定形状态存在,生成了新物相。与原料药比较,β-环糊精包合物C_(max)、AUC_(0~24h)、AUC_(0~∞)升高(P<0.05),CLt、Vdss降低(P<0.05),T_(1/2)、MRT延长(P<0.05),T_(max)缩短(P<0.05),相对生物利用度为191.01%。结论环糊精包合物可明显提高人参皂苷Re溶出度、体内生物利用度。

AIM To prepare ginsenoside Re-β-cyclodextrin inclusion complex and to investigate its in vivo pharmacokinetics.METHODS Theβ-cyclodextrin inclusion complex was prepared by solution stirring-freeze drying method,then the solubility and dissolution rate were determined,and the characterization was performed by FT-IR,XRD,DSC and SEM.Rats were randomly assigned into two groups and given intragastric administration of the suspensions of ginsenoside Re and itsβ-cyclodextrin inclusion complex(100 mg/kg),respectively,after which blood collection was made at 0.083,0.25,0.5,1,2,3,4,6,9,10,12,24 h,HPLC was adopted in the plasma concentration determination of ginsenoside Re,and main pharmacokinetic parameters were calculated.RESULTS The solubility and dissolution rate ofβ-cyclodextrin inclusion complex were 10.11 and 4.26 times as high as those of raw medicine,respectively.Ginsenoside Re andβ-cyclodextrin were combined in a non-covalent bond form,and the former existed in an amorphous state with the generation of new phase.Compared with raw medicine,theβ-cyclodextrin inclusion complex displayed increased C_(max),AUC_(0-24h) and AUC _(0~∞)(P<0.05),decreased CLt and Vdss(P<0.05),prolonged T_(1/2) and MRT(P<0.05),and shortened T_(max)(P<0.05),the relative bioavailabiliy was 191.01%.CONCLUSIONβ-Cyclodextrin inclusion complex can obviously improve the dissolution rate and in vivo bioavailability of ginsenoside Re.