Flow Characteristics Of Single-phase And Two-phase Fluids In Tight Oil Reservoir

Background and objective:Dehydroeffusol is a phenanthrene compound,which was isolated from Junsus effusus L.of traditional Chinese medicine.It has an anxiolytic effect was confirmed through the elevated plus-maze test and hole-board test in mice,which was one of the active constituents of restlessness and insomnia in Junsus effusus L,in our previous experiments.The pharmacokinetics and in vivo processes of dehydro effusol in mice were studied,and the elimination half-life of about 200～260 min,the target organ for anxiolytic effect may be brain tissue,and no muscle relaxation side effect under anxiolytic dose.Based on the previous studies,this project intends to prepare dehydroeffusol sustained-release tablets for in-vitro studies in vitro,providing a basis for the clinical application of a new class of drugs for the dehydroeffusol.Method:1 The dried medulla common rush was used as the raw material,and silica gel column chromatography was combined with thin layer chromatography(TLC)to prepare and purify the dehydroeffusol.Qualitative analysis was performed by nuclear magnetic resonance spectroscopy(NMR)and the purity was determined by high performance liquid chromatography(HPLC).2 HPMC as a backbone material was used to prepare a dehydroeffusol hydrophilic gel matrix sustained-release tablet.The release of dehydroeffusol was used as an in vitro release index,using the ultraviolet and visible spectrophotometry(UV)to determine the cumulative release of the drug,the effects of prescribing factors such as HPMC,fillers and lubricants on the release of dehydroeffusol were investigated.The orthogonal test was designed to optimize prescription and verify.3 The dehydroeffusol was used as an in vitro release indicator,the influence of the release medium,temperature,volume,and the the dissolution apparatus,rotation speed,and instrumentation on the release of the drug were investigated.Dehydroeffusol sustained-release tablets for drug release curve were fitted and release mechanism was elucided.4 A HPLC method was used for the determination of the concentration of dehydroeffusol in blood.The self-made dehydroeffusol tablet was used as a reference preparation,the dehydroeffusol sustained release tablet was used as a test preparation to study the pharmacokinetics in rabbits and in vitro correlation assessment.Result:1 Obtained>90%purity of dehydroeffusol monomer 20 g.2 The optimal formulation of the dehydroeffusol sustained-release tablets was:HPMC K4M 35%,MCC 15%,lactose 44%,and magnesium stearate 1%and prepared by whole powder was directly tableted.The cumulative release rate of the sustained-release tablets at 2 h,6 h,and 12 h was 30%,60%,and 90%,and the reproducibility and homogeneity were good.3 The established in vitro release assay conditions were:0.5%Tween-80 solution 900 mL as release medium,temperature at 37±0.5℃,paddle method,speed at 100 rpm.The pH of the release medium,the dissolution apparatus,etc.have no effect on the release of dehydroeffusol.The release profile of dehydroeffusol can be fitted by the first-order kinetic equation.The drug release mechanism is synergistic between drug diffusion and gel erosion.4 The rabbits oral administrationed self-made dehydroeffusol sustained-release tablets and ordinary tablets,the blood drug concentration by pharmacokinetic processing software DAS2.0 for pharmacokinetic parameter fitting,the result showed that the absorbtion of dehydroeffusol in rabbits conforms two-bedroom model.The Cmax of the two was 3.99 and 12.16 ng·mL-1,respectively;the tmax was 3 and 2 h,and the AUC0-∞ was 17.692 and 15.164 ng·h·mL-1,respectively.The Loo-Riegelman method was good in in vitro and in vivo.Conclusion:By combining silica gel column chromatography with thin layer chromatography(TLC),dehydroeffusol monomers can be extracted and separated from dried medulla common rush with a yield of approximately 0.1%.The prepared dehydroeffusol sustained-release tablets have no burst release in the early stage,stable release in the middle stage,complete release of the drug in the later stage,reaching a sustained release effect of 12 hours,and good reproducibility and uniformity.The in vitro release profile of dehydroeffusol sustained-release tablets is a first-order kinetic equation.The mechanism of drug release is the synergy between diffusion and dissolution.Compared with ordinary tablets,the amount of Cmax in dehydroeffusol sustained release tablets decreased and tmax extended,which showed obvious release effect,used the Loo-Riegelman method to do correlation between in vivo evaluation and found that the Sustained release tablets in vivo correlation is more significant.