Florfenicol prodrug having improved water solubility

1. A method of treating a subject that has a bacterial infection or that is susceptible to infection by a pathogenic bacterium comprising administering to the subject a therapeutically- or prophylactically-effective amount of a pharmaceutical composition comprising a florfenicol phosphate ester having the chemical structure

or a salt thereof, and a pharmaceutically acceptable carrier; wherein said administering of the prophylactically-effective amount of the pharmaceutical composition to the subject animal results in a sufficient plasma concentration of florfenicol to prohibit bacteria from accumulating in sufficient quantity to cause an infection.

2. The method of claim 1 , wherein the florfenicol phosphate ester is a florfenicol prodrug having the chemical structure:

wherein M 1 + and M 2 + are H + or a pharmaceutically-acceptable mono-cation, or taken together, are a pharmaceutically-acceptable di-cation.

3. The method of claim 2 , wherein M 1 + and M 2 + are independently selected from the group consisting of H + , Na + , NH 4 + , and K + .

4. The method of claim 3 , wherein M 1 + or M 2 + is H + and M 2 + or M 1 + , which is not H + , is Na + .

5. The method of claim 3 , wherein M 1 + and M 2 + are both Na + .

6. The method of claim 2 , wherein M 1 + and M 2 + are independently selected from the group consisting of H + and a protonated amine.

7. The method of claim 6 , wherein the protonated amine is NR 1 R 2 R 3 H + , and

wherein R 1, R 2, and R 3 are independently selected to be either H, methyl, ethyl, propyl, isopropyl, —CH 2 CH 2 OH and —CH 2 C(CH 2 OH) 3 .

8. The method of claim 7 , wherein the protonated amine is selected from the group consisting of:

9. The method of claim 8 , wherein the protonated amine is:

10. The method of claim 7 ,

wherein R 1 is either H, methyl, ethyl, propyl, isopropyl, —CH 2 CH 2 OH and —CH 2 C(CH 2 OH) 3 ; and

wherein R 2 and R 3 are linked to form a five or six membered ring.

11. The method of claim 10 , wherein the five or six membered ring are selected from the group consisting of pirolidine, piperidine, or morpholine.

12. The method of claim 2 , wherein M 1 + and M 2 + comprise respectively, H + and a mono-cationic form of a dibasic amino acid.

13. The method of claim 2 , wherein M 1 + and M 2 + are independently selected to be either H + , meglumine, benzocaine, or procaine.

14. The method of claim 2 , wherein M 1 + and M 2 + are taken together, and selected from the group consisting of Ca +2 , Mg +2 , a bis-protonated diamine, and a di-cationic form of a dibasic amino acid.

15. The method of claim 2 , wherein the pharmaceutically acceptable carrier is an aqueous solution.

16. The method of claim 15 , wherein the pH of the aqueous solution is between pH 3.5 and pH 6.5.

17. The method of claim 16 , wherein the pH of the aqueous solution is between pH 4.0 and pH 6.

18. The method of claim 17 , wherein the pH of the aqueous solution is between pH 4.5 and pH 5.5.

19. The method of claim 2 , wherein the pharmaceutical composition comprises a mixture of two or more salts of the florfenicol prodrug.

20. The method of claim 2 , wherein the florfenicol phosphate ester is a mixture of a salt form of the florfenicol phosphate ester and an acid form of the florfenicol phosphate ester; and wherein a molar ratio of the base that is combined with the acid form of the florfenicol phosphate ester is in the range of 0.6-1.4.

21. The method of claim 20 , wherein the molar ratio is in the range of 0.8-1.2.

22. The method of claim 21 , wherein the molar ratio is in the range of 0.9-1.1.

23. The method of claim 1 , wherein the pharmaceutical composition is administered orally or parenterally.

24. The method of claim 2 , wherein the pharmaceutical composition is administered orally or parenterally.