Preparation And Pharmacodynamics Study Of Compound Gentamycin Injection

In this study,gentamicin and flunixin meglumine were used to match ratio to proceed screening and optimization of prescription,which adopt Orthogonal test.And finally we can develop compound gentamicin injection.After that quality control,antibacterial activity in vitro,acute toxicity and safety evaluation and other related items of of compound gentamicin injection should be investigated.All of these research were proceeded to provide some reference in the clinical application of compound gentamicin injection.1.The preparation and quality control of Compound gentamicin injectionFormula components and their approximate usage of compound gentamicin injection can be determined through pretest.Filter and development of prescription was used orthogonal test of L₉（3³）.In the aspect of quality control,compound gentamicin injection was inspected from the clarity,pH value and heat source.In the aspect of experiment of stability,compound gentamicin injection was studed by light stability test,Accelerated test and long-term test.The results are as follows.The optimal formula of compound gentamicin injection as follows:the quality of gentamicin is 1g,the quality of flunixin meglumine is 0.01g,N,N-Dimethylformamide has the content of 6%,Polyethylene glycol has the content of 3%,Anhydrous sodium sulfite has the content of 0.06%.And the rest part was injection water.In the aspect of quality control,injection is clear and does’t contain abnormal objects which are visible.The pH of injection is from the range of 7.0⁷.5.At the same time,there are not any heat source reaction for the injection.In the aspect of stability,the content of two ingredient in the injection mainly keep steady.And there was no significant change in the apparent characteristics of injection.Certainly,pH of injection also keeps steady.2.Establishment of Method for Determination of Compound Gentamicin InjectionThe content of gentamycin and flunixin meglumine in compound gentamicin injection was determined by ultraviolet spectrophotometry and high performance liquid chromatography,respectively.The purpose of this process is for effective quality control of compound gentamicin injection.The results shows that,the linear relationship of gentamicin is good from range of 10⁶0μg/mL,the average recovery rate of gentamicin is from range of99%¹00%and the RSD is below 1%.Meantime,the stability of this method is well.Average content of gentamycin in compound gentamicin injection is 19.75μg/mL and average content of gentamycin is 98.75%of the marked amount.This result meet veterinary pharmacopeia regulations.Similarly,the linear relationship of flunixin meglumine is good from range of31.25¹000μg/m L,the average recovery rate of flunixin meglumine is from range of102.71%¹08.33%and the RSD is below 3%,Average content of flunixin meglumine in compound gentamicin injection is 212.8μg/mL and average content of gentamycin is 106.4%of the marked amount.This result meet veterinary pharmacopeia regulations.3.Pharmacodynamic test of compound gentamicin injectionMilk which is from sows suffering from mastitis should be arranged for the following process:collection of milk,the isolation and culture of bacterial and identification test.The purpose of this process is to determine major pathogenic bacterias of milk which are called Staphylococcus aureus,Escherichia coli and S.galactiae.Antibacterial test in vitro of compound gentamicin injection and gentamicin injection main apply double dilution method in the experiment.The aim of this test is that Minimal inhibitory concentration（MIC）and minimum bactericidal concentration（MBC）of Staphylococcus aureus,Escherichia coli and S.galactiae should be mainly determined for two injection.Results are as follows.MIC of compound gentamicin injection on three bacterial are 1.18、2.35、4.70μg/m L,MBC on three bacterial are 2.35、4.70、9.39μg/mL,MIC of gentamicin injection on three bacterial are 2.35、4.70、9.39μg/m L,MBC on three bacterial are 4.70、18.78、18.78μg/mL.In the other hand,Results show that the antibacterial and bactericidal effects of compound gentamycin injection have been significantly improved.4.Safety evaluation of compound gentamicin injectionThe LD₅₀ of gentamicin group was 482.2 mg/kg,and the LD₅₀ of compound gentamicin injection group was 490.6 mg/kg.Compound gentamicin injection and gentamicin injection are both belong to moderately toxic drugs.And the main manifestation of them are nephrotoxicity.These results are similar to previous studies.Results of the test show that LD₅₀of compound gentamycin injection is slightly higher than LD₅₀0 of gentamicin injection.And Flunixin meglumine can reduce gentamicin toxicity.Compound gentamicin injection has no hemolytic reaction,no systemic allergy reaction and muscle irritation,which indicates that the injection is safe.