Pharmaceutical compositions, methods of making pharmaceutical compositions, and kits comprising 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}4-chlorophenyl dihydrogen phosphate

1. A pharmaceutical composition comprising 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate (Formula I)

and one or more Bronsted bases, wherein the one or more Bronsted bases is a solid, and wherein the pharmaceutical composition has <2% N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide after one week at room temperature, and the pharmaceutical composition is suitable for dissolution with an aqueous solution to form an injection.

2. A method of making the pharmaceutical composition of claim 1 comprising admixing 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate and one or more Bronsted bases.

3. A kit, wherein the kit comprises one or more containers comprising 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate (Formula I)

and one or more Bronsted bases, wherein the kit has <5% N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide after one week at room temperature.

4. The kit of claim 3 , wherein a conjugate acid of the one or more Bronsted bases has a pKa between 6 and 11.

5. The kit of claim 3 , wherein a conjugate acid of the one or more Bronsted bases has a pKa between 8 and 10.

6. The kit of claim 3 , wherein the one or more Bronsted bases are selected from the group consisting of a C 1-8 -alkyl mono-, di-, or tri-carboxylic acid salt, a phosphate salt, an amine, an amine salt, an acetate salt, a hydroxide salt, an alkoxide salt, a carbonate salt, a bicarbonate salt, and a metal borate salt.

7. The kit of claim 3 , wherein the one or more Bronsted bases are an amine and/or a salt thereof.

8. The kit of claim 7 , wherein the one or more Bronsted bases are (HO) n R 8 NH 2 , [(HO) n R 8 ] 2 NH, [(HO) n R 8 ] 3 N, and/or a salt thereof, wherein each R 8 is independently C 1-8 alkyl and n is 0 or C 1-8 -alkylene and each n is independently 1-8.

9. The kit of claim 3 , wherein the one or more Bronsted bases are tris(hydroxymethyl)aminomethane, meglumine, ethanolamine and/or a tris(hydroxymethyl)aminomethane salt.

10. The kit of claim 3 , wherein the one or more Bronsted bases are an alkali carbonate salt and/or a sodium phosphate.

11. The kit of claim 3 , wherein Formula I is lyophilized.

12. The kit of claim 3 , wherein Formula I is amorphous.

13. The kit of claim 3 , wherein Formula I and the one or more Bronsted bases are in the same container.

14. The kit of claim 3 , wherein the one or more Bronsted bases is a solid.

15. The kit of claim 3 , wherein the kit further comprises an aqueous solution for mixture with Formula I to form an injection.

16. The kit of claim 15 , wherein the aqueous solution is sterile water for injection, a sterile solution comprising dextrose, a sterile solution comprising sodium chloride, a sterile solution comprising benzyl alcohol, or Lactated Ringer's.

17. The kit of claim 16 , wherein the aqueous solution is sterile water for injection or 0.9% sodium chloride injection.

18. The kit of claim 15 , wherein Formula I is in a first container and the one or more Bronsted bases are dissolved in the aqueous solution in a second container.

19. The kit of claim 3 , wherein the kit has <2% N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide after one week at room temperature.

20. The kit of claim 18 , wherein the kit has <2% N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide after one week at room temperature.

21. The kit of claim 3 , wherein the kit comprises instructions for administering Formula I to a patient in need thereof.

22. The kit of claim 21 , wherein the kit comprises instructions for administering Formula I to a patient in need thereof to treat edema.

23. The kit of claim 22 , wherein the edema is cerebral edema.

24. The kit of claim 23 , wherein the cerebral edema is consequent to an ischemic stroke, traumatic brain injury, or closed head trauma.

25. The kit of claim 23 , wherein the cerebral edema is consequent to an ischemic stroke.

26. The kit of claim 24 , wherein the cerebral edema is cytotoxic cerebral edema.

27. The kit of claim 25 , wherein the cerebral edema is cytotoxic cerebral edema.

28. A method of administering a pharmaceutically acceptable salt of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate (Formula I)

by injection to a human, wherein the method comprises mixing Formula I, one or more Bronsted bases, and an aqueous solution to form a composition and administering the composition thus obtained 24 hours or less after mixture with the aqueous solution to the human.

29. The method of claim 28 , wherein the human has cerebral edema.

30. The method of claim 29 , wherein the cerebral edema is consequent to a stroke, traumatic brain injury, closed head trauma, or hypoxia.

31. The method of claim 29 , wherein the cerebral edema is consequent to an ischemic stroke.

32. The method of claim 30 , wherein the hypoxia is caused by cardiac arrest, stroke, or other interruption of blood perfusion to the brain.

33. The method of claim 30 , wherein the cerebral edema is cytotoxic cerebral edema.

34. The method of 31 , wherein the cerebral edema is cytotoxic cerebral edema.