| OBJECTIVE: Lig Lactone shows very strong activity in cure Acute Renal Failure without correlated medicine report in the world.It's raw material was extracting from plant.The intravenous emulsion was prepared with pressure homogenizing technology(HE).The preparation is belong to the first species new medicine of traditional Chinese medicine.We extract ed Lig Lactone raw material. The Reverse-phase HPLC method was established to control the emulsion's quality.The stability was studied to develop a useful method for it's preservation.The pharmacodynamics was investigated to provide the bases for clinical application. Plasma protein binding ratio was determine to know the drug is binding-sensitive. METHODS The intravenous emulsion was preparation with high pressure homogenizing technology(HE). The Reverse-phase HPLC method with ultraviolet detection was used to determine the content of Lig Lactone and the variety of the content when lighted and heated and accelerated. After the injection of the intravenous emulsion of LIG within rats caudal vein and dog forelimb vein, we assay the concentration of Lig Lactone in blood vs time and use software 3p87 calculate the data of concentration ,so that we can make sure the rudiment procedure and the pharmacokinetics of Lig Lactone in vivo. After the injection of the intravenous emulsion of LIG within mouse caudal vein,we assay the concentration of Lig Lactone in different organs and blood at different time. After the injection of the intravenous emulsion of LIG, we assay the concentration of Lig Lactone in stool and urine and bile to calculate the total excretion amount of it. Through the test that liver homogenization and blood metabolize Lig Lacton in vitro. ,we may deduce the possible metabolism route of the Lig Lactone. Use ultrafiltration determine the plasma protein binding ratio RESULTS (1)The established reversed HPLC method is reliable. The stability and precision and accuracy specificity and reproducibility and toleration of the method are qualified.The regression equation is y=18.931x-3.2601,r2=0.9999(relation betweent he peak area of Lig Lactone and the sample size by HPLC-UV method) (2)The results of accelerated tsetse showed that the colur and the content of Lig Lactone and the mean diameter and PH were kept still under 25℃ after 9 months ,but the content droped slightly after 12 month . The results of accelerated tsetse showed that the content of Lig Lactone droped gradually under 40℃ in 1 to 6 months. .The influential factors proved that the light can affect remarkably the content of Lig Lactone of the emulsion and the content of Lig Lactone dropped 60% under 4700Lx after 10 days.The long-term tests proved that the contentand the colur and the mean diameter and PH are stabile under 6℃ in commercially available back. The intravenous emulsion shoud be stored under 6℃±2℃. (3)The results that the c-t date that the intravenous emulsion was injected within rats caudal vein (the dose is 50mg/kg,20mg/kgand5mg/kg) analyzed by 3p87 computing program showed that the pharmacokinetic behavior of the intravenous emulsion of lig fitted a three-compartment open pharmacokinetic model. The distribution phase half-life,t1/2pi(50mg/kg,20mg/kgand5mg/kg) is respectively 8min,2 min and 4min .t1/2α(50mg/kg,20mg/kg and 5mg/kg )is respectively 27min,23 min and20 min.The elimination phase half-life, t1/2β(50mg/kg,20mg/kg and 5mg/kg)is respectively 330min,421min and 618 min .AUC of these doses (50mg/kg,20mg/kg and 5mg/kg) which were caculated by statistic moment algorithm are respectively 2811.5and1695.2and 755.7(μg/ml )(min). (4) The results that the c-t date that the intravenous emulsion was injected within rats caudal vein (the dose is 10mg/kg) in multiple-dosage showed that the pharmacokinetic behavior of the intravenous emulsion of lig fitted three –conpartment model. The distribution phase half-life of the first dosage and the last dosage,t1/2pi is respectively 3.6min,8.6 min,t1/2αis respectively 25min,13min and20min. (5) The results that the c...
|
PDF Full Text Request