Comparative Of Integrated Pharmacokinetics Of Huang-lian-jie-du-tang And Couplet Medicines In This Prescription

Chinese herbal compound with a characteristic of complex and can affect in a wide range.Study on pharmacodynamic characteristics of Chinese herbal compound can guide clinical application and make reasonable dosage regimen.Huang-lian-jie-du-tang(HLJDT)which has been used in traditional medicine for two thousand years.Its clinical application is very rich involving a variety of diseases,and the clinical research background is mature.This article takes HLJDT as the research object,which compares the integrated pharmacodynamic differences among HLJDT and its couplet medicines huanglian-huangqin(LQ),huanglian-huangbai(LB),huanglian-zhizi(LZ).To supplied the theoretical basis on curing stroke using HLJDT in clinic.Purposes:Comparative of pharmacodynamic process about HLJDT and LQ,LB,LZ on rats with cerebral ischemia,discussed the actions of each herb in the prescription;Classified integration of indicative constituents in HLJDT and LQ,LB,LZ,investigated the interactionamong each durg;Total integration of indicative constituents in HLJDT and LQ,LB,LZ combined the data of anti-oxidative free radical,then curves of concentration-time-effect were built,which can verify result of pharmacodynamic preliminary.Contents:1.Compared the contents of water extraction fluid system of HLJDT and LQ,LB,LZ in vitro;2.Compared the pharmacokinetic characteristics of main ingredients in HLJDT and LQ,LB,LZ in vivo using rats with cerebral ischemia.Meanwhile,figured out the different pharmacokinetic characteristic between rats-MCAO and rats-normal after being administered;3.Classified integration of indicative constituents in HLJDT and LQ,LB,LZ;4.Comprehensive analysis of PK/PD data sets,and established PK/PD model.Methods:1.Prepared dried powder of HLJDT and LQ,LB,LZ.After administration,draw blood at a predetermined different time points.2.Established content detection methods of gardenia acid,geniposide,baicalin,coptisine,palmatine,berberine,baicalein in the plasma;examined pharmacodynamic influence law of the main component of the different groups of drugs at pathological state and normal state;3.Classified integration of iridoid,flavonoids,alkaloids in HLJDT and LQ,LB,LZ using user-defined weight coefficient based on AUC,studying the function of each herb in prescription,and the interaction between them;4.Conducted the pharmacodynamic study of the anti-free radical oxidation and measured SOD and MDA contents of plasma at different time points;combined total integration of indicative constituents in HLJDT and LQ,LB,LZ,which can verify result of pharmacodynamic preliminary.Results and Conclusions:According the results of content in vivo,the contents of gardenia acid and geniposide in LZ were 1.948?11.478 mg/g which were lower than that of HLJDT(2.188?13.322 mg/g),respectively;the contents of baicalin,baicalein were 13.677?1.400 mg/g in LQ which were lower than that of HLJDT(17.514,1.945 mg/g),respectively;the contents of coptisine palmatine,berberine in LB were 1.498?1.288?8.586 mg/g which were lower than that of HLJDT(3.646?3.773?22.681 mg/g),LQ(2.645?2.716?10.506 mg/g),LZ(2.965?3.201?17.984 mg/g),respectively.The results of pharmacodynamics in vivo:1)after being administered,the rats-MACO had better absorptions than rats-normal,which can be seen from the shorter Tmax,higher Cmax and so on;2)after being classified integration,the flavonoids in LQ and HLJDT had a high similarity in concentration-time curve and pharmacokinetic parameters,the values of AUC(0-t)?AUC(0-?)?Tmax?Cmax were 39.06 mg/L*h?45.47 mg/L*h?0.63 h?2.26 mg/L of LQ,while them were 47.09 mg/L*h?53.26 mg/L*h?0.5 h?3.65 mg/L of HLJDT;the iridoid in LZ and HLJDT had a high similarity in concentration-time curve and pharmacokinetic parameters,the values of AUC(0-t)?AUC(0-?)Tmax?Cmax were 85.67 mg/L*h?127.66 mg/L*h?0.54 h?8.21 mg/L of LZ,while them were 145.46 mg/L*h?217.03 mg/L*h?0.417 h?10.17 mg/L of HLJDT;however,the alkaloid in LQ,LB,LZ very different from HLJDT whatever in oncentration-time curve and pharmacokinetic parameters.Results of anti-free radical oxidation showed that cerebral ischemia cause to hypoxic injury occurred on rats,after being administered,the contents of SOD had an ascending trend in 72h and the levels of MDA decreased significantly.It resulted from HLJDT,LQ,LB,LZ can improve the hypoxic injury caused by cerebral ischemia.The effect of HLJDT was the best which followed by LZ;curves of SOD showed a certain dose-effect relationship,but the curves of MDA showed no significant dose-effect relationship from the PK/PD model.This experiment compared HLJDT,LQ,LB,and LZ using integrated pharmacodynamic theory.After being administered,the rats-MACO had better absorptions than rats-normal,the flavonoids in LQ and HLJDT had a high similarity in concentration-time curve and pharmacokinetic parameters,the iridoid in LZ and HLJDT had a high similarity in concentration-time curve and pharmacokinetic parameters,however,the alkaloid in LQ,LB,LZ very different from HLJDT whatever in oncentration-time curve and pharmacokinetic parameters.Finally,the data of anti-oxidative free radical were used to verify the results of pharmacodynamic preliminary.This study can guide clinical application and make reasonable dosage regimen.