Pharmacokinetics And Tissue Distribution Of Hydroxypropyl Cyclodextrin Inclusion Complex Of Zedoary Turmeric Oil

Zedoary has thousands of years in using history,the main active part of volatile oil is extracted from the rhizome,and having antitumor,antiviral,antibacterial,anti-inflammatory and other physiological activities.In clinical dosage form,Zedoary turmeric oil is mainly used by Twain-80 for injection solubilizer.Because Zedoary oil is not stable under high temperature conditions and the adverse reactions caused by the use of Twain-80,which reduced the stability,efficacy and safety of zedoary turmeric oil injection.The 2010 edition of Pharmacopoeia of Zedoary turmeric oil injection has been canceled and stop production.But the pharmacological effect of zedoary turmeric oil is clear and has a high development value,urgently need of research and development of a new type of safe and stable dosage form for clinical.We have preparated zedoary turmeric oil and hydroxypropyl cyclodextrin(ZTO-HPCD),This study is to establish a method for determination of zedoary turmeric oil and HPLC in biological samples,After administration of ZTO-HPCD,through the determination of the concentration of the index components of germacrone of vivo concentration in rat in and the concentration of main organs in mice,to study the ZTO-HPCD dynamic feature and in vivo distribution in animal,to provide an experimental basis for the research and development of oral ZTO-HPCD drug dosage forms.The main research contents and results are as follows:1 To establish a method for the determination of germacrone in biological samples of HPLCChromatographic condition:chromatographic column:Symmetry C18(5?m,4.6×250 mm);the mobile phase of acetonitrile water,acetonitrile:water=70:30(V/V);column temperature was 30?;flow rate was 1ml/min;detection wavelength was 210 nm;sample size was 20?l.By using acetonitrile as the solvent of protein in plasma and tissues of precipitated protein,germacrone in rat plasma from 0.04?1.67?g/ml concentration range,in different tissues of mice heart,liver,spleen,lung,kidney and brain in 0.13?5.33?g/g concentration all showed a good linear relationship(r>0.998).This method has good specificity,precision,stability and recovery rate are in accordance with the relevant requirements,can be used for the determination of germacrone in biological samples.2 Pharmacokinetics of ZTO-HPCD in ratsThe effective constituents of germacrone in zedoary oil as index components,Determination of rat blood drug concentration to study the pharmacokinetics of ZTO-HPCD in rats,the rats were administered with three doses(1g/kg,2g/kg,4g/kg),the data were processed by two compartment model,and the pharmacokinetic parameters were determined.The peak blood concentration as follows(0.527±0.035).(0.752±0.068)?(1.320±0.166)?g/ml;the peak time of the three groups were(5.667±0.816)?(5.333±1.033)?(5.000±1.095)h;the half-life of drug absorption t1/2k? in rat plasma was(1.041±0.866)?(1.361 ±1.045)?(1.705±1.033)h;the distribution half lives ti/2? were(2.324±0.678)?(2.487±1.205)?(2.779±1.809)h;the elimination half lives ti/2? were(3.433±0.806)?(4.847±0.956)?(5.178±1.202)h;The elimination rates CL/F were(175.619±9.438)?(213.521±9.351)?(233.79±10.232)ml/h/kg;the area of time-blood drug concentration under the curve AUCo-24 were(5.588±0.253)?(8.589±0.285)?(15.314±0.802)?g·h/ml?3 Study on the tissue distribution of ZTO-HPCD in miceMice were administered ZTO-HPCD by 2g/kg,HPLC determination of germacrone concentration in mice(heart,liver,spleen,lung,kidney and brain)in 1,3,6,12,24h.Comparison of drug distribution in different tissues,and the use of multiple components in zedoary oil with fluorescence characteristics,frozen sections of mouse tissues after administration of the same dose,observated of a large number of fresh tissue sections of mice by fluorescence microscopy,Comparative analysis of the statistics of zedoary oil in the organization general distribution trend.The results is same as the germacrone in zedoary turmeric oil components in various tissue distribution of quantitative analysis by HPLC.There were significant differences in the distribution of different time points in each tissue after administration.The distribution of drug in each tissue changed with time.and reached the maximum value at 6h,the distribution amount of germacrone in various tissues:were the liver>spleen>kidney>heart>lung>brain.In this study,we reported the distribution characteristics of pharmacokinetics and tissue distribution of ZTO-HPCD after oral administration.For the further development of zedoary turmeric oil and hydroxypropyl cyclodextrin inclusion complexes to lay the foundation for the pharmacodynamic study,to provide experimental basis for clinical application of hydroxypropyl cyclodextrin inclusion compound oral preparation.