| Erigeron breviscapus is the Asteraceae Erigeron genus of hand dry grass (Erigeron breviscapus (vant.)). Located in the southwest provinces, it is a conventional medicine in Miao,Yi,Tibetan,Dai and other 10 ethnic groups. It was firstly recorded in the "Yunnan Materia Medica", in Ming Dynasty. Lanmao said "Erigeron breviscapus......The left and right side paralysis, rheumatism pain.. Dengzhanxixin injection is contained in Chinese Pharmacopoeia (2015 edition). It is Erigeron breviscapus of dry grass by extracting phenolic components, made of sterile water solution. The main components are scutellarin and total caffeic acid ester,etc. Scutellarin and caffeates substances boast of functions such as expanding blood vessels, accelerating blood flow, reducing blood viscosity, peripheral resistance, and platelet count and inhibited platelet aggregation. A good curative effect has been found in the Clinical application for the treatment of stroke sequelae and rheumatic joint pain. Today, the study of Dengzhan Xixin is concentrated on the composition of scutellarin. But, there is no simultaneous study on the pharmacokinetics of multiple components. The study of pharmacokinetic is rarely based on animal models, not to mention the study on the relationship between PK-PD (pharmacokinetics and pharmacodynamics).Objective:To study the relationships of PK-PD for Dengzhanxixin Injection in the treatment of the cerebral ischemia-reperfusion injury, therefore aiming to deduce the quantity-effect relationship to provide reference for clinical optimization.Methods:After the MCAO was produced, Dengzhanxixin Injection was injected 5 mL/kg/d. Meanwhile, study of pharmacodynamics (PD) to treat the model of MACO rats and the pharmacokinetics (PK) for 7 chemical compositions was carried out. PD was compared with PK, and the relationship between the blood concentration of the 7 chemical components and the rate of cerebral infarction was analyzed, and the parameter was calculated.Results:During the time of 5min-50h after cerebral ischemia, Dengzhanxixin Injection can reduce the rate of cerebral infarction on MCAO rats. The onset of time is 5 min after cerebral ischemia, the last of time is 48 h, the Tmax is 24h; T1/2 is 21.84 h, Emax is 11.71%.The time dose relationship of the 7 chemical components was negatively correlated, and the main parameters are as follows: ? Scutellarin of Tmax is 5min, Cmax is 45.47?g/mL, T1/2 is 1.04h, Tmin is 6h and Cmin is 0.47?g/mL.? 4-Caffeoylquinic acid of Tmax is 5min, Cmax is 2.68?g/mL, T1/2 is 28.44h, Tmin is 2h and Cmin is 0.15?g/mL.? 5-Caffeoylquinic acid of Tmax is 5min, Cmax is 1.86?g/mL, T1/2 for the 42.51h, Tmin is 3h and Cmin is 0.10?g/mLmax is 10min, Cmax is 1.14?g/mL, Emax is 0.0061, EC50 is 0.67?g/mL.? 3,5-Dicaffeoylquinic acid of Tmax is 5min,, Cmax is 6.93?g/mL, T1/2 for the 28.98h, Tmin is 2h and Cmin is 0.42?g/mL.? 4,5-Dicaffeoylquinic acid of Tmax is 5min, Cmax is 6.96?g/mL, T1/2 for the 39.12h, Tmin is 3h and Cmin is 0.17?g/mL.? Chlorogenic acid of Tmax is 5min, Cmax is 2.38?g/mL, T1/2 for the 40.01h, Tmin is 2h and Cmin is 0.17?g/mL.? Isochlorogenic acid B of Tmax is 5min, Cmax is 14.45?g/mL, T1/2 for the 56.84h, Tmin is 6h and Cmin is 0.14?g/mL.The main parameters of the dose effect relationship between the 7 chemical components and the rate of cerebral infarction are as follows: ? Effective blood drug concentration of Scutellarin is in the range of 0.47-45.47?g/mL,Tmax is 10min, Cmax is 36.33?g/mL, Emax is 0.61%,EC50 is 17.35?g/mL.? Effective blood drug concentration of 4-caffeoylquinic acid is in the range of 1.35-2.68?g/mL,Tmax is 10min, Cmax is 1.97?g/mL, Emax is 0.61%, EC50 is 1.13?g/mL.? Effective blood drug concentration of 5-caffeoylquinic acid is in the range of 0.97-1.86?g/mL,Tmax is 10min, Cmax is 1.14?g/mL, Emax is 0.61%, EC50 is 0.67?g/mL.? Effective blood drug concentration of 3,5-dicaffeoylquinic acid is in the range of 2.52-6.93?g/mL,Tmax is 10min,Cmax is 5.62?g/mL,Emax is 0.61%,EC50 is 3.19?g/mL.? Effective blood drug concentration of 4,5-dicaffeoylquinic acid is in the range of 2.60-6.96?g/mL,Tmax is 10min,Cmax is 2.39?g/mL,Emax is 0.61%,EC50 is 2.77?g/mL.? Effective blood drug concentration of chlorogenic acid is in the range of 1.22-2.38?g/mL,Tmax is 10min, Cmax is 1.95?g/mL, Emax is 0.61%,EC50 is 0.97?g/mL.? Effective blood drug concentration of isochlorogenic acid B is in the range of 0.13-14.45?g/mL,Tmaxis 10min, Cmax is 9.11?g/mL, Emax is 0.61%, ECso is 4.87?g/mL.Conclusion:Dengzhan Xixin injection can reduce the infarction rate of MCAO rats. It has the characteristics of quick effect, long half-life and main long time, and the strongest effect occurred at 24h. The effection peak of Dengzhanxixin Injection is laging of the value of blood drug concentration, which shows that its effect ventricular is not in the blood. It reduces the effect of cerebral infarction rate and the average blood concentrations of 7 chemical composition,in brain ischemia 5-10 min was negatively correlated,in 10 min-6 h was positively correlated. |
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