Study On Screening Of Active Components In Different Extractions Of Platycodon Grandiflorum With The Effect Of Tylosin Tartrate Pharmacokinetic In Mice After Oral Administration

Objective:A study was performed under the guidance of the "Tying in"theory and use d the similar method of pervious relevant laboratory studies.we extracted chemical compo nents of Platycodon grandiflorum and used Tylosin tartrate as the target drug, determined by high-performance liquid chromastographic method to investigate the influence of these different extractions of Platycodon grandiflorum roots on the pharmacokinetics and tissue distribution character of Tylosin tartrate in mice, after oral administration.Main purpose of this laboratory study is try to screen the active contents.Method:288 healthy kunming mice were randomly divided into5 groups-control gro up;the mices in group I were orally given with single dose of tylsoin tartrate at 600mg/k g·b·w, mices in group Ⅱ were orally given with single dose of tylsoin tartrate and petroleum ether extraction simultaneously. Group Ⅲ gave a single dose of tylosin tartrate and ethyl ac etate extraction simultaneously, group Ⅳ gave the single dose of tylosin tartrate and Chlor oform extraction simultaneously,and group Ⅴ gave the single dose of tylosin tartrate and n-b utyl alcohol extraction simultaneously, mices in the last group were given single dose of tylo sin tartrate and the water extraction of Platycodon grandiflorum. The concentrations of tylso nsin tartrate in plasma and tissues were determined by high performance liquid chromatogra phy.and the The pharmacokinetic parameters were calculated by using Pk-solver pharmacoki netics software.After sceening the effective extract that the Platycodon grandiflorum do the job to direct tylosin tartrate into the lungs, we used TLC method to make a preliminary test on the proba bly exsited monomers of this extraction, then mixed the selected monomers with tylosin tartr ate to do the oral administrattion on mice, and the concentrations of tylosin tartrate were also determined by HPLC.Results:Concentration-time cruve of each group showed the multi peak phenomenons, so the pharmacokinetics data were best described by Non compartmental model,The main Ph armacokinetics parameters were as follows,respectively.Group I:half-life time(t1/2)=51.94± 0.71min; peak concentration (Tmax)=80min; peak concentration (Cmax)=42.12±2.19μg/mL; area under the curved (AUC)=3620±99.34μg/mL;numerical value of apparent volume of distr ibution(Vz)=12.09±0.28 L·kg-1;clearance(Cl)=0.16±0.0047L·kg-1·min-1. GroupⅡ:compa red with contrast group, t1/2 became shorter, peak concentration and peak time were decreased, as well as the AUC, however Vz and Cl were increased. Group Ⅲ:t1/2become shorter; whil e Cmax and AUC were increased. Group IV:half-life time became longer than group I; the peak concentration and peak time were increased; while the Vz and Cl were decreased. Gro up V:t1/2 become shorter; the peak concentration increased; yet the area under the curve decr eased. Group VI:half-life time became longer, while Cmax and AUC were decreased.The ethyl acetate extraction of Platycodon grandiflorum contained daucosterol, betulin, a-spinach sterols, and we found a-spinach sterols can improve the peak concentration of lu ng tissue.(83±0.60μg/mL) by HPLC.Conclusions: ① Tylosin tartrate in healthy mices was quickly absorbed with high concentration in plasma, distributed comparative wide, eliminated fast a. ② the petroleum ether extraction of Platycodon grandiflorum could influence the pharmacokinetic parameters of tylosin tartrate in mice significantly:accelerated the speed of drug absorption, yet reduced the absorption extent, speed up the drug distribution from plasma to the tissues compared with the contrast group. ③The ethyl acetate extraction can not only accelerate the drug absorption speed, also increase the degree of absorption, but narrow the distribution range. ④ The Chloroform extraction can promote drug absorption, and increase the absorption rate, and the residence time in the body became longer which means it can slow down the drug metabolism⑤The n-butyl alcohol extraction also can increase the absorption rate, however reduced the absorption extent.and the drug distribution scope in the body became wider. ⑥The water extraction increased the drug absorption rate and reduced the absorption extent. ⑦ Different extractions of Platycodon grandiflorum roots made a great influence on the drug distribution in tissues, each group made the drug concentration in heart higher than contrast group, especially the petroleum ether extraction, only the ethyl acetate extraction increased the lung drug concentration,which suggests this extraction may contain the active components to make the Platycodon grandiflorum roots have a drug-lung targeting effect. ⑧The monomer of Platycodon grandiflorum α-spinach sterols can accelerate drug absorption rate, reducing its extent of absorption, and can significantly promote the drug transportation to the lung tissue.