Preliminary Study On Preparation And Pharmacology And Toxicology Of Annalgin In Situ Gel Injection

In order to improve the incidence of rebound and high frequency of drug administration,we should increase the bioavailability and efficacy of the drug.In this study,the intramuscular injection of an in situ gel was prepared,and the preparation,in vitro release,in vitro dissolution,acute toxicity,muscle irritation,preliminary pharmacodynamics,and pharmacokinetics were investigated in order to lay the foundation for the clinical application of an in situ gel injection.1.The gelation temperature of three kinds of near in situ gels,which are21%P407+2%P188+0.2%SS+0.01%Na₂-EDTA+30%annalgin,22%P407+2%P188+0.2%SS+0.01%Na₂-EDTA+30%annalgin,and23%P407+4%P188+0.2%SS+0.01%Na₂-EDTA+30%annalgin,respectively.The gelation temperature is suitable for gelation under hypothermia,and the gelation temperature was 36.1±0.3°C,35.9±0.2,36.3±0.4°C,respectively.2.Through the in vitro dissolution and in vitro release experiments of three kinds of hydrogels,it was found that the dissolution rate of the in situ gel at 6h and the release rate in vitro could reach about 90%.The cumulative dissolution rate（X）of the three in situ gel was illustrated by the cumulative dissolution rate（η）,and the regression equation wasη=1.0274X+0.9653,respectively.（R²=0.9985）,η=1.0326X+1.3096（R²=0.9977）,η=1.0296 X+1.4511（R²=0.9975）,and its linear relationship is good,indicating that the dissolution of the gel is the main factor controlling the release of the in situ gel.3.In the acute toxicity test,the LD₅₀=2199.355 mg/kg was injected into the abdominal cavity of the mice by the injection of an in situ gel injection.The 95%confidence limit was 2127.501.675 mg/kg-2273.021 mg/kg;the mice were injected with LD50=1913.329 mg/kg in the aqueous solution of the aqueous solution,and the95%confidence limit was 1626.702mg/kg-2250.460 mg/kg,indicating that the injections of the in situ gel were reduced.The toxic effect of annalgin near.The results of muscle stimulation test showed that the stimulation of in situ gel injection was small and suitable for intramuscular injection.4.The antipyretic experiment showed that the antipyretic effect of the high dose group（168mg/kg）,the medium dose group（126mg/kg）and the low dose group（84mg/kg）on the rats could maintain 7h,6h and 4h respectively,while the antipyretic effect of the antipyretic solution group（126mg/kg）could only maintain the 3.5h,and the antipyretic injection of the antipyretic solution group（126mg/kg）was injected into the in situ gel injection.The agent prolongs the time of the action of annalgin.5.The pharmacokinetics of anagaric in situ gel injection and anagaric aqueous solution were compared with rats as model animals.The results showed that the pharmacokinetic data of the two agents were in accordance with the first order absorption model,and the pharmacokinetic parameters of ananin in situ gel:the half-life(t_1/2)of the gel group was significantly higher than that of the solution.Group（P<0.05）;the apparent scavenging rate（V1/F）of the solution group was significantly higher than that in the in situ gel group;the absorption half life(t_1/2Ka)in the in situ gel group was significantly lower than that in the solution group（P<0.05）,which was in accordance with the results of the half-life elimination.The mean residence time（MRT）in situ gel group was significantly higher than that in solution group（P<0.01）.The Tmax in the in situ gel group was 60+0min,which was significantly greater than that in the solution group（17.5+6.124min）（P<0.01）,and the maximum blood concentration（Cmax）in the in situ gel group was not quite different from that in the solution group.The area under the curve of the in situ gel group（AUC（0-t））was significantly higher than that in the solution group（P<0.01）,indicating that the relative bioavailability of the InaI near in situ gel injection was higher than that in the aqueous solution.In this experiment,the preparation of the preparation is simple and reliable,and the quality is controlled.The drug release experiment,acute toxicity study,preliminary pharmacodynamic study and pharmacokinetics experiment showed that the injection of the near in situ gel injection was slow compared with the aqueous solution in vivo and in vitro.It could reduce the number of drugs and had better clinical application value.