Compositions and methods relating to salts of specialized pro-resolving mediators

1. A compound of Formula IV which contains a scaffold of two amino acid moieties coordinated around a divalent metal and one or two SPM molecules A, B, ionically bound to at least one basic function provided by the scaffold:

wherein

M is a divalent metal selected from magnesium (Mg 2+ ), calcium (Ca 2+ ), and zinc (Zn 2+ ),

A and B are each independently an SPM molecule selected from the group consisting of resolvins and their aspirin-triggered counterparts,

A and B may be the same or different,

either A or B, but not both, may be absent,

R 1 and R 2 are each independently —(CH 2 ) 3 —Y 1 , and —(CH 2 ) 4 —Y 2 ,

where Y 1 and Y 2 are each a basic function selected from a positively charged primary amine, a positively charged secondary amine, a positively charged tertiary amine, and a positively charged guanidine,

X 1 and X 2 are each independently H or CO—Z and Z is a peptide comprising 1 to 5 amino acids.

2. The compound of claim 1 , wherein M is selected from magnesium (Mg 2+ ) or calcium (Ca 2+ ).

3. The compound of claim 1 , wherein R 1 and R 2 are each —(CH 2 ) 4 —Y 2 and Y 2 is —NH 3 + .

4. The compound of claim 1 , wherein X 1 and X 2 are each H.

5. The compound of claim 1 , wherein A and B are the same and selected from the group consisting of RvD1, RvD2, RvE1, AT-RvD1, AT-RvD2, and AT-RvE1.

6. The compound of claim 5 , wherein A and B are RvE1.

7. The compound of claim 5 , wherein A and B are AT-RvE1.

8. The compound of claim 1 , which is selected from the group consisting of bis RvE1 magnesium di-lysinate (bis RvE1-Mg-lys-lys), bis RvE1 calcium di-lysinate (bis RvE1-Ca-lys-lys), bis RvE1 zinc di-lysinate (bis RvE1-Zn-lys-lys), bis AT RvE1 magnesium di-lysinate (bis AT(18S)-RvE1-Mg-lys-lys), bis AT RvE1 calcium di-lysinate (bis AT(18S)-RvE1-Ca-lys-lys), and bis AT RvE1 zinc di-lysinate (bis AT(18S)-RvE1-Zn-lys-lys).

9. A pharmaceutical composition comprising the compound of claim 1 , and a carrier or excipient.

10. The pharmaceutical composition of claim 9 , formulated as an oral or rectal dosage form.

11. A method for treating inflammation in a subject in need thereof, the method comprising administering to the subject the compound of claim 1 .

12. A method for treating a disease or disorder selected from ulcerative colitis, Crohn's disease, proctitis, pouchitis, Crohn's disease of the pouch, eosinophilic colitis, lymphocytic colitis, collagenous colitis, diversion colitis, chemical colitis, and ischemic colitis in a subject in need thereof, the method comprising administering to the subject the compound of claim 1 .

13. A method for treating a disease or disorder selected from eosinophilic esophagitis, Behcet's disease, irritable bowel syndrome, Celiac disease, intestinal mucositis, diverticulitis, and short bowel syndrome in a subject in need thereof, the method comprising administering to the subject the compound of claim 1 .

14. A method for treating ulcerative colitis, Crohn's disease, or pouchitis in a subject in need thereof, the method comprising administering to the subject the compound of claim 1 .

15. A method of making a compound of claim 1 , the method comprising contacting a solution of the SPM in a nonaqueous solvent with an amount of magnesium, calcium, or zinc di-lysinate, such that the molar amount of the SPM to the metal di-lysinate is about 2:1.

16. The method of claim 15 , wherein the solution further comprises an antioxidant, preferably tocopherol.

17. The method of claim 13 , wherein the disease or disorder is eosinophilic esophagitis.

18. The compound of claim 1 , wherein

A and B are both present and each is RvE1,

R 1 and R 2 are each —(CH 2 ) 4 —Y 2 ,

Y 2 is —NH 3 + , and

X 1 and X 2 are each H.

19. The compound of claim 18 , wherein M is magnesium and the compound is designated bis RvE1 magnesium di-lysinate (bis RvE1-Mg-lys-lys).

20. A pharmaceutical composition comprising the compound of claim 19 , and a carrier or excipient.

21. A method for treating ulcerative colitis in a subject in need thereof, the method comprising administering to the subject the compound of claim 19 , or the pharmaceutical composition of claim 20 .

22. A method for treating Crohn's disease in a subject in need thereof, the method comprising administering to the subject the compound of claim 19 , or the pharmaceutical composition of claim 20 .

23. A method for treating pouchitis in a subject in need thereof, the method comprising administering to the subject the compound of claim 19 , or the pharmaceutical composition of claim 20 .

24. A method for treating eosinophilic esophagitis in a subject in need thereof, the method comprising administering to the subject the compound of claim 19 , or the pharmaceutical composition of claim 20 .

25. The compound of claim 18 , wherein M is calcium or zinc.

26. A pharmaceutical composition comprising the compound of claim 25 , and a carrier or excipient.

27. A method for treating ulcerative colitis in a subject in need thereof, the method comprising administering to the subject the compound of claim 25 , or the pharmaceutical composition of claim 26 .

28. A method for treating Crohn's disease in a subject in need thereof, the method comprising administering to the subject the compound of claim 25 , or the pharmaceutical composition of claim 26 .

29. A method for treating pouchitis in a subject in need thereof, the method comprising administering to the subject the compound of claim 25 , or the pharmaceutical composition of claim 26 .

30. A method for treating eosinophilic esophagitis in a subject in need thereof, the method comprising administering to the subject the compound of claim 25 , or the pharmaceutical composition of claim 26 .