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目的:研究舒胸片(三七、红花、川芎复方制剂)的组分配伍药动学,为新的组方配伍提供依据。方法:6组大鼠分别口服给予5 mL.kg-1川芎红花共提物(CHE);羟基红花黄色素A(HSYA)与阿魏酸(FA)混合溶液(HFM);三七总皂苷(PNS)溶液;PNS与川芎红花共提物混合溶液(PCHE);PNS,HSYA与FA的混合溶液(PHFM);川芎挥发油(CVO)与PHFM混合乳液(CVO-PHFM)。采用HPLC测定大鼠血浆中HSYA,FA,人参皂苷Rg1和Rb1的浓度,通过模型拟合计算药动学参数Ka,Kel,Cm ax,Tm ax和AUC,并进行统计学检验,比较不同混合物给药后,4种活性成分的药动学差异。结果:大鼠口服给予6种给药溶液后,HSYA和Rg1符合单室模型,而FA和Rb1符合双室模型。与口服HFM相比,口服CHE后,FA的Kel显著性减小,Cm ax显著性降低,K12显著性提高,其他药动学参数无明显差异。在CHE和HFM中分别加入PNS(即PCHE和PHFM)对HSYA的影响相似,HSYA的Ka值显著性的增加,Tm ax显著性的降低,其他参数均无统计学显著差异;PNS与HFM合用后,Rg1的Ka值显著性的提高,Tm ax显著性的缩短;而对FA与Rb1的药动学几乎无影响。川芎挥发油与活性成分的组合(CVO-PHFM)给药后,增加了Rb1的Cm ax,减小了其分布常数K12,并提高了HSYA,FA与Rg1的口服生物利用度,分别是口服PHFM的6.056,2.854和2.055倍。结论:舒胸片组分的不同配伍口服给药后,其活性成分的药动学参数有一定的变化,但只有在川芎挥发油存在时,才有明显的促吸收或提高生物利用度的作用。
OBJECTIVE: To study the pharmacokinetics of the combination of ShuChian tablets (Panax ginseng, Safflower, and Chuanxiong) and to provide basis for the compatibility of new groups. METHODS: Six groups of rats were orally administered with 5 mL.kg-1 of common extract of chuanxiong saffron (CHE); hydroxysafflor yellow A (HSYA) and ferulic acid (FA) mixed solution (HFM); Saponin (PNS) solution; PNS and Chuanxiong safflower extract mixture solution (PCHE); PNS, HSYA and FA mixed solution (PHFM); Chuanxiong volatile oil (CVO) and PHFM mixed emulsion (CVO-PHFM). The concentrations of HSYA, FA, and ginsenosides Rg1 and Rb1 in rat plasma were determined by HPLC. The pharmacokinetic parameters Ka, Kel, Cm ax, Tm ax, and AUC were calculated by model fitting, and statistical tests were performed to compare different mixtures. After the drug, the pharmacokinetics of the four active ingredients were different. RESULTS: After oral administration of 6 dosing solutions in rats, HSYA and Rg1 conformed to a single-chamber model, while FA and Rb1 met a two-compartment model. Compared with oral HFM, after oral administration of CHE, the Kel of FA significantly decreased, the Cm ax significantly decreased, the K12 significant increased, and there was no significant difference in other pharmacokinetic parameters. The addition of PNS (ie, PCHE and PHFM) to CHE and HFM, respectively, had similar effects on HSYA. The Ka value of HSYA increased significantly, the Tm ax decreased significantly, and there was no statistically significant difference in other parameters. After PNS and HFM were used together, The increase of the Ka-value of Rg1 and the decrease of Tm ax were significant, while it had little effect on the pharmacokinetics of FA and Rb1. After administration of CVO-PHFM, the combination of volatile oil and active ingredients of Rhizoma Chuanxiong increased the Cm ax of Rb1, decreased its distribution constant K12, and increased the oral bioavailability of HSYA, FA, and Rg1, respectively. 6.056, 2.854 and 2.055 times. CONCLUSION: The pharmacokinetic parameters of the active ingredients of the Shu Xiong Tablets were changed after oral administration. However, only when the volatile oil of Rhizoma Chuanxiong was present, could the absorption or bioavailability be significantly improved.