Studies On The Synthesis Process Optimization And Pharmacologic Of Florfenicol Succinate

This topic selecting DMAP as a new catalyst and solvent acetone synthesized florfenicol succinic based on others’ resarech,at the same time,optimize the synthetic process through the single factor experiment and orthogonal design experiment.Also studies on antibacterial activity,local toxicity, pharmacokinetic and organization distribution in rats of florfenicol succinic.Under the condition of useing DMAP as catalyst and acetone as solvent,synthesis florfenicol succinic.Through melting point,TLC and HPLC analysis shows that the compounds with high purity. Under the same conditions for its Rf and retention time are at equal with the standard of florfenicol succinic.The result of melting point is the same with Yangpeng’s rearech,Infrared spectrometry showes products and standard atlas of florfenicol succinic is identical.Therefore it can be obtained by those methods of comprehensive analysis that synthesis of products are florfenicol succinic.The optimized synthesis process and the traditional comparative analysis shows that reaction temperature by original 80℃decrease to 60℃,mild reaction conditions making the selective raise and the side reaction reduce,so that the work of purification become very easy.Reaction time is shortened by the original 15h above to 4h,Yield increase by 70%up to 88.1%.The traditional method of separation and purification by dilute acids and deionized water repeated washing,after repeated crystallization with organic solvent can be highly purified products;a new method of separation and purification,reduced the process trival,wash with water instead of organic solvents as solvent solution can be a crystallization of crystallization of the product,the same purity purity 97%above. Using organic solvents have been recoved than 80%in the synthetic process.Synthetic raw material cost have been reducted too.Later the synthetic amplification experiments showed that the process of product quality and yield stable,process conditions simple,easy to operate and controllable,While the preliminary evaluation process conditions of synthesis florfenicol succinic’s profit will be so large,so that the process of industrialization of further research has good economic value and broad application prospect.We have reseach antibacterial effect of florfenicol and florfenicol sodium succinic on escherichia coli,staphylococcus aureus,bacillus subtilis and Bacillus proteus by using the microorganism method.Contrast research shows that,with the produrg and florfenicol administration after from 0～3h inside this paragraph of time the bacteriostatic circle diameter are the same,and the statistical analysis shows that,also had no significant difference(P＜0.05),and that produrg and florfenicol of four kinds of bacteria have good antibacterial activity,and the result is quite.Through i.m 30mg/kg(by florfenicol) florfenicol sodium succinic,in rats florfenicol sodium succinic can quickly into florfenicol,and which exist in rats mainly with three forms FF,Fs,FFa. The pharmacokintie characcteriatis was conformed to one-coparment open model with first-absorption tare.The primary parameters were as following;FF Tmax was 1 h,Cmax was 6.28u g/mL,Vd,AUC,CL/F(s) respectively was 0.77 mg/L,37.03μg/mL and 0.258 L/h,show in vivo FF,eliminate distributed widely in slow,maintain effective blood concentrations of for a long time.After discontinuation FF mainly concentrated in the lung,liver and kidney,but through statistical analysis showed no significant differences.The highest total residual of FF and FFa in the liver and kidneys organization,and we can know that liver and kidneys are the main target organs in rats of FE This series of dynamic parameters and organization for the distribution of clinical medicine of further research provides corresponding theoretical basis.Local toxicity test of skin irritation test and dosing parts excitant experiments show that fiorfenicol sodium succinic is no stimulation or low excitant in its clinical dosing and range.In the test,hemolytic test shows that the concentration of different doses florfenicol sodium succinic in its observation period of time were found to show no hemolysis phenomenon,and according to the standard method of Health Department,are far smaller than the rate of hemolysis of 5%,so it can be use intravenous injection administration.Therefore local toxicity in clinical drug experiments showed that the compound was toxicity and safe within the dose.