Compositions and method for treating infection in cattle and swine

Abstract

Novel formulations combining a non-steroidal anti-inflammatory drug (NSAID) such as flunixin, with a fluorinated chloramphenicol or thiamphenicol derivative antibiotic such as florfenicol are disclosed. Methods for using such formulations in the treatment and prevention of infectious diseases of bovines and swine, including bovine respiratory disease and swine respiratory disease, are also disclosed.

We claim:  
     
         1 . A composition for the treatment of microbial infection in an animal comprising flunixin or one of its pharmaceutically acceptable salts and a compound of Formula I:  
       
         
           
           
               
               
           
         
       
       wherein R is a member selected from the group consisting of methyl or ethyl or a halogenated derivative thereof, dihalogenodeuteriomethyl, 1-halogeno-1-deuterioethyl, 1,2-dihalogeno-1-deuterioethyl, azidomethyl and methylsulfonylmethyl; 
 each of X and X′ is a member independently selected from the group consisting of NO 2 , SO 2 R 1 , SOR 1 , SR 1 , SONH 2 , SO 2 NH 2 , SONHR 1 , SO 2 NHR 1 , COR 1 , OR 1 , R 1 , CN, halogen, hydrogen, phenyl, and phenyl substituted by halogen, NO 2 , R 1 , PO 2 R 1 , CONHR 1 , NHR 1 , NR 1 R 2 , CONR 1 R 2 , OCOR 1 , or OR 1 , wherein each of R 1 . and R 2  is a member independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl butyl, t-butyl, isobutyl and phenyl;  
 and Z is hydrogen or an acyl group of a hydrocarboncarboxylic acid having up to 16 carbon atoms or an acyl group of an aminohydrocarboncarboxylic acid having up to 12 carbon atoms; and the pharmaceutically acceptable salts of said acyl groups.  
 
     
     
         2 . The composition of  claim 1 , wherein R is a halogenated derivative of methyl or ethyl.  
     
     
         3 . The composition of  claim 2 , wherein R is CHCl 2  or CHF 2 .  
     
     
         4 . The composition of  claim 3 , wherein Z is hydrogen, X is SO 2 R 1  or phenyl, and X′ is hydrogen.  
     
     
         5 . The composition of  claim 4 , wherein R 1  is methyl.  
     
     
         6 . The composition of  claim 1 , further comprising an aprotic polar solvent.  
     
     
         7 . The composition of  claim 6 , wherein the aprotic polar solvent is selected from the group consisting of a pyrrolidone solvent, N,N-dimethylacetamide, N,N-dimethylformamide, DMSO, acetone and glycerol formal.  
     
     
         8 . The composition of  claim 7 , wherein the aprotic polar solvent is a pyrrolidone solvent and the pyrrolidone solvent is N-methyl-2-pyrrolidone or 2-pyrrolidone.  
     
     
         9 . A composition for the treatment of microbial infection in an animal comprising: 
 a) florfenicol;    b) flunixin or one of its pharmaceutically acceptable salts; and    c) from about 5% to about 80% of an aprotic polar solvent.    
     
     
         10 . The composition of  claim 9  wherein the aprotic polar solvent is selected from the group consisting of N,N-dimethylacetamide, N-methyl-2-pyrrolidone, 2-pyrrolidone, glycerol formal, and combinations thereof.  
     
     
         11 . The composition of  claim 10  comprising: 
 a) from about 10% to about 50% w/v florfenicol;  
 b) from about 1% to about 10% w/v flunixin meglumine;  
 c) from about 25% to about 60% of the aprotic solvent.  
 
     
     
         12 . The composition of  claim 11 , wherein the aprotic solvent is N-methyl-2-pyrrolidone.  
     
     
         13 . The composition of  claim 11 , wherein the aprotic solvent is 2-pyrrolidone.  
     
     
         14 . The composition of  claim 11 , wherein the aprotic solvent is N,N-dimethylacetamide.  
     
     
         15 . The composition of  claim 11 , wherein the aprotic solvent is glycerol formal.  
     
     
         16 . The composition of  claim 11 , further comprising a second solvent.  
     
     
         17 . The composition of  claim 11 , further comprising a stabilizer.  
     
     
         18 . The composition of  claim 17 , wherein the stabilizer is citric acid.  
     
     
         19 . The composition of  claim 16 , wherein the second solvent is selected from the group consisting of water, propylene glycol, polyethylene glycol, triacetin, dimethyl-isosorbide, ethanol, isopropanol, glycerin, 1,2-propanediol, glycol ethers, benzyl alcohol, and combinations thereof.  
     
     
         20 . The composition of  claim 19 , wherein the second solvent is selected from the group consisting of polyethylene glycol having an average molecular weight between 200 and 400, propylene glycol, ethanol, water, and combinations thereof.  
     
     
         21 . A method of treating bovine respiratory disease in an animal comprising the step of subcutaneously administering to an animal in need of such treatment a therapeutically effective amount of the composition of  claim 1 .  
     
     
         22 . A method of treating swine respiratory disease in an animal comprising the step of administering to an animal in need of such treatment a therapeutically effective amount of the composition of  claim 1 .  
     
     
         23 . A method of treating footrot in an animal comprising the step of subcutaneously administering to an animal in need of such treatment a therapeutically effective amount of the composition of  claim 1 .  
     
     
         24 . A method of treating acute mastitis in an animal comprising the step of subcutaneously administering to an animal in need of such treatment a therapeutically effective amount of the composition of  claim 1 .  
     
     
         25 . A method of treating pinkeye in an animal comprising the step of subcutaneously administering to an animal in need of such treatment a therapeutically effective amount of the composition of  claim 1 .  
     
     
         26 . A method of treating metritis in an animal comprising the step of subcutaneously administering to an animal in need of such treatment a therapeutically effective amount of the composition of  claim 1 .  
     
     
         27 . A method of treating enteritis in an animal comprising the step of subcutaneously administering to an animal in need of such treatment a therapeutically effective amount of the composition of  claim 1 .  
     
     
         28 . A method of a microbial infection in an animal comprising the step of subcutaneously administering to an animal susceptible to such a microbial infection a prophylactic amount of the composition  claim 1 .  
     
     
         29 . The method of  claim 28  wherein the microbial infection is bovine respiratory disease.