Study On Preparation And Pharmacodynamic Of Prolonged-release Ceftiofur Injecta

Objective:The objective of this study is to prepare a kind of Prolonged-Release Ceftiofur injecta ,through the study on its quality,security,pharmacokinetics and pharmacodynamics, provide the scientific theory for the use of Prolonged-Release Ceftiofur injecta in veterinary clinic.Method:1.Use the soybean oil for injection as the oil phase,through its HLB value to choose the suitable surfactant,use the orthogonal design to determine the optimal proportion of each constituent in injecta.To realize the quality evaluation of Prolonged-Release Ceftiofur injecta,its filling dispersion,sedimentation volume ratio,viscosity,syringeability,content and size distribution were detected.Besides Light accelerated test and United accelerated temperature and humidity test also was did.2.with the acute toxicity experience,muscle excitant test and pyrogen test as Measurement Indicators to detect the safety of Prolonged-Release Ceftiofur injecta.3.Part three:Use rabbits as the experimental animal to study the pharmacokinetics of Prolonged-Release Ceftiofur injecta. ,use the HPLC to test the plasma concentration,established the method to assay the content of Ceftiofur in plasma.4.Study the pesticide effect of Prolonged-Release Ceftiofur injecta to chicken infected escherichia coli experimently,In this test the experimental animal was divide into six groups:Prolonged-Release Ceftiofur injecta High dose,Medium dose,Low dose,Infected control,Control Con and Ceftiofur sodium powder-injection control group,use Protection ratio and RWG as the index to appraise its pesticide effect.Result:1.Obtaine the Prolonged-Release Ceftiofur injecta useing the suspension emulsionas as its carrier, the results of each quality evaluation were all comply with relevant provisions,and the injecta was stable to the light,temperature and humidity.2.The acute toxicity experience measured that the LD₅₀ of Prolonged-Release Ceftiofur injecta was 2532.27mg/kg,95%confidence interval was 2364mg/kg -2721mg/kg,the result indicated that this injecta was in the range of Low-toxic(500-5000mg/kg).Among the muscle excitant test,muscle of injection site had no obvious difference compared with the normal muscle tissue,it turned out that inject has no thrill to muscle.The result of pyrogen test was also comply with relevant provisions.3.The result turn out that this method has the advantages of specificity and high sensitivity,the recovery rate of Ceftiofur in plasma is high.Pharmacokinetic parameters were: AUC=319.1751,K_α=1.3998,C_max=27.8512μg/mL,T_max=1.9441 h,T_1/2β=16.1941 h,as the related articles(boda WU 2008)reported,Pharmacokinetic parameters was calculated after the rabbit was injected the common Ceftiofur injecta were: AUC=217.9502,K_α=3.4791,C_max=20.6072μg/mL,T_max=0.6947 h,T_1/2β=10.2988 h,compare the two groups data, we find that the time to peak of Prolonged-Release Ceftiofur injecta delayed 1.25h,the half life of elimination of Prolonged-Release Ceftiofur injecta extended 5.89h,illustrate that it was absorbed smoothly,clear up slowly in tissue,effective plasma concentration could keep a long time,had the obvious Prolonged-Release effect.4.the result of pesticide effect turned out that the of Prolonged-Release Ceftiofur injecta High dose,Medium dose,Low dose,Infected control,Control Con and Ceftiofur sodium powder-injection control group were 100%,80%,73%,53% and 27%,RWG were 95.02%,96.12%,93.01%,88.17% and 89.45%。Compare with the Infected control,the Protection ratio of High dose,Medium dose,Low dose group and Ceftiofur sodium powder-injection control group has increased in the different degree(High dose,Medium dose,Low dose groupP<0.01;Ceftiofur sodium powder-injection control group P<0.05);but the increase of the Protection ratio of High dose,Medium dose was obvious even more,Compare with the Ceftiofur sodium powder-injection control group High dose group has the extremely significant(P<0.01),Medium dose group has the significant increase (P<0.05),the Protection ratio of the low dose group and the Ceftiofur sodium powder-injection control group has no significant difference(P>0.05) .The Protection ratio of High dose,Medium dose,Low dose group reduced successively,High dose group and Medium dose group has the significant difference(P<0.05), High dose group and Low dose group has the extremely significant difference(P<0.01),Medium dose group and Low dose group has no significant difference(P>0.05),.The RWG of each group had no significant difference(P>0.05).5.Conclusion:In this study prepared a kind of Prolonged-Release Ceftiofur injecta,its craft was simple and stability was well.This injecta was safety,had no thrill to muscle,Compared with the common injecta,its hold up time of effective serum concentration extended 2 days, and its Protection ratio to colibacillosis increased 47%.