Compositions containing prodrugs of florfenicol and methods of use

Abstract

The present invention provides compositions and methods for administering florfenicol to mammals. The compositions contain a prodrug of florfenicol in a pharmaceutically acceptable carrier. In one embodiment the prodrug is an esterized form of florfenicol. Examples of suitable prodrugs include one or a combination of one or a combination of the following: florfenicol acetate, florfenicol propionate, florfenicol butyrate, florfenicol pentanoate, florfenicol hexanoate, florfenicol heptanoate, florfenicol octanoate, florfenicol nanoate, florfenicol decanoate, florfenicol undecanoate, florfenicol dodecanoate, and florfenicol phthalate. In another embodiment the prodrug is converted into the florfenicol in vivo by the action of one or more endogenous esterases. The invention also provides new compounds, pharmaceutical compositions containing the compounds, and methods for their administration.

1 - 24 . (canceled) 
     
     
         25 . A composition comprising a first ester prodrug of florfenicol, a second ester prodrug of florfenicol, and a pharmaceutically acceptable carrier, wherein the composition is formulated as a composition for administration to a mammal by injection. 
     
     
         26 . The composition of  claim 25 , wherein the concentration of the prodrugs of florfenicol in the composition is at least about 200 mg/mL. 
     
     
         27 . The composition of  claim 25 , wherein at least one of the ester prodrugs of florfenicol is an ester formed between florfenicol and a carboxylic acid. 
     
     
         28 . The composition of  claim 25 , wherein both the first ester prodrug of florfenicol and the second ester prodrug of florfenicol are an ester formed between florfenicol and a carboxylic acid. 
     
     
         29 . The composition of  claim 25 , wherein the first ester prodrug of florfenicol and the second ester prodrug of florfenicol are selected from the group consisting of florfenicol acetate, florfenicol propionate, florfenicol butyrate, florfenicol pentanoate, florfenicol hexanoate, florfenicol heptanoate, florfenicol octanoate, florfenicol nanoate, florfenicol decanoate, florfenicol undecanoate, florfenicol dodecanoate, and florfenicol phthalate. 
     
     
         30 . The composition of  claim 29 , wherein the first ester prodrug of florfenicol and the second ester prodrug of florfenicol are selected from the group consisting of florfenicol acetate, florfenicol propionate, florfenicol butyrate, florfenicol hexanoate, florfenicol phthalate 
     
     
         31 . The composition of  claim 25 , wherein the composition forms a drug depot when injected into a mammal. 
     
     
         32 . The composition of  claim 25 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of N-methyl pyrrolidone, pyrrolidone, polyethylene glycol, propylene glycol, glycerol formal, isosorbid dimethyl ether, ethanol, dimethyl sulfoxide, tetrahydrofurfuryl alcohol, triacetin, and combinations thereof. 
     
     
         33 . The composition of  claim 32 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of propylene glycol, glycerol formal, and combinations thereof. 
     
     
         34 . A method of treating a bacterial infection in a feline comprising injecting the feline with the pharmaceutical composition of  claim 25 . 
     
     
         35 . A method of treating a bacterial infection in a feline comprising injecting the feline with the pharmaceutical composition of  claim 26 . 
     
     
         36 . A method of treating a bacterial infection in a feline comprising injecting the feline with the pharmaceutical composition of  claim 27 . 
     
     
         37 . A method of treating a bacterial infection in a feline comprising injecting the feline with the pharmaceutical composition of  claim 28 . 
     
     
         38 . A method of treating a bacterial infection in a feline comprising injecting the feline with the pharmaceutical composition of  claim 29 . 
     
     
         39 . A method of treating a bacterial infection in a feline comprising injecting the feline with the pharmaceutical composition of  claim 30 . 
     
     
         40 . A method of treating a bacterial infection in a feline comprising injecting the feline with the pharmaceutical composition of  claim 31 . 
     
     
         41 . A method of treating a bacterial infection in a feline comprising injecting the feline with the pharmaceutical composition of  claim 32 . 
     
     
         42 . A composition comprising (i) a first ester prodrug of florfenicol having a first release rate, (ii) a second ester prodrug of florfenicol have a second release rate, and (iii) a pharmaceutically acceptable carrier, wherein the composition is formulated for administration to a mammal by injection, the composition forms a drug depot when injected into the mammal, and the first release rate is different from the second release rate. 
     
     
         43 . The composition of claim  1 , wherein the first ester prodrug of florfenicol is florfenicol butyrate and the second ester prodrug of florfenicol is florfenicol hexanoate.