Objectives:To investigate the pharmacokinetics (PK) and pharmacodynamics (PD)of index components of Zisu Fang preparations and additionally analysis the anti-dementia drug system characteristics.Methods:A PK-PD-drug i...Objectives:To investigate the pharmacokinetics (PK) and pharmacodynamics (PD)of index components of Zisu Fang preparations and additionally analysis the anti-dementia drug system characteristics.Methods:A PK-PD-drug interaction (DI) method was applied to determine the characteristics of index components of Zisu Fong preparations in vivo.Results:In the PK study,maximum plasma concentration,area under the plasma concentration-time curve,and mean residence time of index components of Zisu Fang preparations were higher in the memory-deficit model group than in the control group.This suggested that the index components of Zisu Fang preparations had an affinity for the state of dementia in this model.In the PD study,at the peak time points of anti-dementia efficacy (0.17 h and 1 h),the plasma concentrations of index components of Zisu Fang preparations reached the first or second largest plasma concentration peak or were close to the plasma concentration peak,and showed positive correlation between these two peaks,indicating that the index components of Zisu Fang synergistically exerted an anti-dementia effect.According to the association analysis of PK-PD-DI,baicalin,rosmarinic acid,salvianolic acid B,matrine,and tanshinone ⅡA were the main active ingredients of the anti-dementia drug system of Zisu Fang preparations in vivo,but were only efficacious against dementia when all five components were present at a specific concentration and proportion.Conclusions:Based on the PK and PD correlation analysis,baicalin,rosmarinic acid,salvianolic acid B,matrine,and tanshinone ⅡA are the main active ingredients of Zisu Fang preparations with regard to its anti-dementia effects,and represent the basic characteristics of drug system:natures,synergy,and affinity.展开更多
目的探讨奥拉西坦联合丁苯酞对非痴呆型血管性认知障碍(vascular cognitive impairment of non-dementia,VCIND)患者的临床疗效。方法将64例VCIND患者随机分为对照组与联合组,每组32例。2组均接受常规治疗,对照组给予奥拉西坦治疗,联合...目的探讨奥拉西坦联合丁苯酞对非痴呆型血管性认知障碍(vascular cognitive impairment of non-dementia,VCIND)患者的临床疗效。方法将64例VCIND患者随机分为对照组与联合组,每组32例。2组均接受常规治疗,对照组给予奥拉西坦治疗,联合组给予奥拉西坦联合丁苯酞治疗,疗程为3个月。比较2组患者治疗前后蒙特利尔认知评估量表(Montreal cognitive assessment scale,MoCA)评分、简易精神状态评价量表(mini mental state evaluation scale,MMSE)、美国国立卫生院卒中量表(national institutes of health stroke scale,NIHSS)评分和日常生活活动能力量表(activity of daily living scale,ADL)评分,检测血清转化生长因子-β(transforming growth factor-β,TGF-β)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、抗凋亡因子(anti-apoptotic factor,Livin)、神经元特异性烯醇化酶(neuron-specific enolase,NSE)和神经生长因子(nerve growth factor,NGF)水平的变化,检测脑血管平均血流速度(mean velocity,V_(m))、动脉搏动指数(pulsatility index,PI)与阻力指数(resistance index,RI)。结果治疗后,2组MoCA、MMSE和ADL评分均升高,NIHSS评分均降低,且联合组MoCA、MMSE和ADL评分显著高于对照组(P<0.05)。2组脑血管V_(m)均升高,PI和RI均降低,且联合组显著优于对照组(P<0.05);2组血清MMP-9NSE均降低,TGF-β、Livin和NGF水平均升高,且联合组显著优于对照组(P<0.05)。结论奥拉西坦联合丁苯酞治疗VCIND可有效改善患者的脑血管功能,保护神经功能及认知功能,其机制可能与纠正血清TGF-β、MMP-9、Livin、NSE及NGF水平有关。展开更多
文摘Objectives:To investigate the pharmacokinetics (PK) and pharmacodynamics (PD)of index components of Zisu Fang preparations and additionally analysis the anti-dementia drug system characteristics.Methods:A PK-PD-drug interaction (DI) method was applied to determine the characteristics of index components of Zisu Fong preparations in vivo.Results:In the PK study,maximum plasma concentration,area under the plasma concentration-time curve,and mean residence time of index components of Zisu Fang preparations were higher in the memory-deficit model group than in the control group.This suggested that the index components of Zisu Fang preparations had an affinity for the state of dementia in this model.In the PD study,at the peak time points of anti-dementia efficacy (0.17 h and 1 h),the plasma concentrations of index components of Zisu Fang preparations reached the first or second largest plasma concentration peak or were close to the plasma concentration peak,and showed positive correlation between these two peaks,indicating that the index components of Zisu Fang synergistically exerted an anti-dementia effect.According to the association analysis of PK-PD-DI,baicalin,rosmarinic acid,salvianolic acid B,matrine,and tanshinone ⅡA were the main active ingredients of the anti-dementia drug system of Zisu Fang preparations in vivo,but were only efficacious against dementia when all five components were present at a specific concentration and proportion.Conclusions:Based on the PK and PD correlation analysis,baicalin,rosmarinic acid,salvianolic acid B,matrine,and tanshinone ⅡA are the main active ingredients of Zisu Fang preparations with regard to its anti-dementia effects,and represent the basic characteristics of drug system:natures,synergy,and affinity.
