Safety Evaluation And Pharmacodynamic Study Of Florfenicol Double-suspension Emulsion Oral Liquid

Purpose:To evaluate the safety of florfenicol double-suspension emulsion oral solution in mice and target animals,and to study the in vitro antibacterial effect of florfenicol double-suspension emulsion oral solution on chicken E.coli and Salmonella pullorum,and the clinical therapeutic effect of artificially infected chicken E.coli and Salmonella pullorum on target animal chickens provides data support and theoretical guidance for the clinical use of the drug.Method:1.Acute toxicity test of florfenicol double-suspension emulsion oral liquid:in two steps,the first step was to carry out the minimum total lethal dose experiment,with normal saline as the control group,and a single dose of 0.4ml/10g for mice.According to the reference standard,the florfenicol double-suspension emulsion oral liquid was administered once according to different concentrations.After administration for 7 days,the mice in each group showed signs of poisoning or death.The second part was subjected to the maximum tolerated dose test.The saline was used as the control group,and the mice were administered with florfenicol double-suspension emulsion oral solution 2.4ml/30g,which is 0.24g/kg,based on the standard of more than 5000 mg/kg.body weight?calculated as florfenicol?,observed for7 days after administration,and showed signs of poisoning or death in each group of mice.2.Safety test of florfenicol double-suspension emulsion oral solution on target animal chicken:The healthy chicken was used as the control group,and the test drugs were administered at the doses of 1,3,and 5 times of the recommended dose of the florfenicol solution for the control,and the drugs were continuously administered for15 days.After the test,the test chickens were observed for signs of poisoning;All groups of chickens received appropriate amount of whole blood,and blood physiology and biochemical indicators were detected.The chickens in each group were randomly examined for necropsy,the weight of each group was weighed,the organ index was calculated,and some organs were taken for histopathological examination.Observe whether there is pathological change;the weight and consumption of feed of each group of chickens were weighed before and after the test,and the relative weight gain rate and feed-to-meat ratio were calculated.3.Florfenicol double-suspension emulsion oral liquid bacteriostatic test:florfenicol solution as a control group,using test tube 10 times dilution method to detect florfenicol double-suspension emulsion oral liquid on chicken E.coli.The minimum inhibitory concentration?MIC?of Salmonella typhimurium was determined by plate counting method.The minimum bactericidal concentration?MBC?of florfenicol double-suspension emulsion oral solution against chicken E.coli and Salmonella pullorum was determined.4.Florfenicol double-suspension emulsion oral liquid for artificial infection of chicken E.coli,Salmonella pullorum clinical treatment test:florfenicol double-suspension emulsion oral liquid high?1.5ml/L?,medium?1.0ml/L?,low?0.5ml/L?dose group and florfenicol solution drug control group?1.0ml/L?,negative control group?no drug administration?,healthy control group?no challenge administration?The chickens artificially infected with chicken E.coli and Salmonella pullorum were treated by mixed drink administration.After 3 days of administration,the observation was continued for 15 days.Pathological necropsy and pathogenic bacteria were isolated and cultured during the test to determine the cause of death.Before and after the test,the weight of each group of chickens and the consumption of feed were weighed,and the relative weight gain rate and material were calculated.Meat ratio;the number of chickens born,the number of dead chickens,the number of improved chickens and the number of cured chickens during the statistical test,the incidence,mortality,cure rate,and efficiency were calculated.Result:1.The results of acute toxicity test data show that the LD₅₀ of florfenicol double-suspension emulsion oral liquid is more than 5000mg/kg.The range is classified according to the chemical acute toxicity dose classification table,which is an actual non-toxic substance.2.The results of the safety test data show that the tested drug groups were in good mental condition compared with the blank control group,and the feeding and drinking water were normal.Before and after the test,the body weight of each test group and the blank control group were different.3.In vitro antibacterial test data showed that the MIC values of fenfluramine double-suspension emulsion oral solution and florfenicol solution against chicken E.coli were 0.048?g/ml,and the MIC values of the two drugs against Salmonella typhimurium were also 0.048?g/ml;the flufenicol double-suspension emulsion oral solution and florfenicol solution have a MBC value of 12.5?g/ml for chicken E.coli,and the MBC values of both drugs against Salmonella typhimurium are0.195?g/ml.4.The clinical trials of artificially infected chickens with Salmonella pullorum showed that the incidence rates of florfenicol double-suspension emulsion oral liquid were 100%in the high,medium and low dose groups,and the mortality rates were80%,80%,95%,respectively.The effective rates were 20%,20%,and 5%,respectively.The cure rates were 15%,20%,and 5%,respectively.The relative weight gain rates were 66.30%,103.59%,and 75%,respectively.The feed-to-meat ratio was 2.99 and2.20,respectively.5.46,the incidence of florfenicol solution was 100%,the mortality rate was 95%,the effective rate was 5%,the cure rate was 5%,the relative weight gain rate was 58.40%,and the feed-to-meat ratio was 3.28.Clinical trials of artificially infected E.coli chickens showed that the incidence rates of florfenicol double-suspension emulsion oral liquid in the high,medium and low dose groups were 100%,and the mortality rates were 65%,55%,70%,respectively.The efficiencies were 35%,45%,and 30%,respectively.The cure rates were 30%,35%,and 25%,respectively.The relative weight gain rates were 81.24%,66.52%,and80.84%,respectively.The feed-to-meat ratios were 3.64,3.43,and 4.39,respectively.The incidence of florfenicol solution was 100%,the mortality rate was80%,the effective rate was 20%,the cure rate was 20%,the relative weight gain rate was 73.82%,and the feed-to-meat ratio was 3.24.Conclusions:The florfenicol double-suspension emulsion oral liquid is an actual non-toxic substance,and it is safe and reliable to use 5 times higher than the clinical recommended dose;the in vitro antibacterial test of florfenicol double-suspension emulsion oral liquid and fluorobenzene nico solution is quite effective;medium dose?1.0ml/L?florfenicol double-suspension emulsion oral liquid can effectively treat chicken colibacillosis and chicken chalk salmonellosis.