Compositions and methods relating to ionic salts of peptides
The present invention relates to compounds of Formula I, compositions containing same, and methods of use.
1. A compound of Formula I, or an enantiomer, polymorph, solvate, or hydrate thereof, which is a salt of an amino acid moiety and one or two fatty acids, A and B:
wherein
A and B are the same or different, and each of A and B is independently selected from the group consisting of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA),
either A or B, but not both, may be absent,
X 1 and X 2 are each independently selected from (CH 2 ) 3 —R 1 , and (CH 2 ) 4 —R 2 , where R 1 and R 2 are each a basic function which may be the same or different, the basic function being selected from the group consisting of a primary amine, a secondary amine, a tertiary amine, and a guanidine, and
X 3 is H.
2. The compound of claim 1 , wherein X 1 and X 2 are both (CH 2 ) 4 —R 2 and R 2 is NH 3 +.
3. The compound of claim 2 , wherein A or B is absent and the remainder is EPA.
4. The compound of claim 2 , wherein A and B are both present and are each EPA.
5. The compound of claim 2 , wherein A or B is absent and the remainder is DHA.
6. The compound of claim 2 , wherein A and B are both present and are each DHA.
7. The compound of claim 2 , wherein A or B is absent and the remainder is DPA.
8. The compound of claim 2 , wherein A and B are both present and are each DPA.
9. The compound of claim 1 , wherein X 1 and X 2 are both (CH 2 ) 3 —R 1 and R 1 is NHC(NH 2 +)NH 2 .
10. The compound of claim 9 , wherein A or B is absent and the remainder is EPA.
11. The compound of claim 9 , wherein A and B are both present and are each EPA.
12. The compound of claim 9 , wherein A or B is absent and the remainder is DHA.
13. The compound of claim 9 , wherein A and B are both present and are each DHA.
14. The compound of claim 9 , wherein A or B is absent and the remainder is DPA.
15. The compound of claim 9 , wherein A and B are both present and are each DPA.
16. The compound of claim 1 , wherein X 1 is (CH 2 ) 3 —R 1 , R 1 is NHC(NH 2 +)NH 2 , X 2 is (CH 2 ) 4 —R 2 and R 2 is NH 3 +.
17. The compound of claim 16 , wherein A or B is absent and the remainder is EPA.
18. The compound of claim 16 , wherein A and B are both present and are each EPA.
19. The compound of claim 16 , wherein A or B is absent and the remainder is DHA.
20. The compound of claim 16 , wherein A and B are both present and are each DHA.
21. The compound of claim 16 , wherein A or B is absent and the remainder is DPA.
22. The compound of claim 16 , wherein A and B are both present and are each DPA.
23. The compound of claim 1 , wherein X 1 is (CH 2 ) 4 —R 2 , R 2 is NH 3 +, X 2 is (CH 2 ) 3 —R 1 , and R 1 is NHC(NH 2 +)NH 2 .
24. The compound of claim 23 , wherein A or B is absent and the remainder is EPA.
25. The compound of claim 23 , wherein A and B are both present and are each EPA.
26. The compound of claim 23 , wherein A or B is absent and the remainder is DHA.
27. The compound of claim 23 , wherein A and B are both present and are each DHA.
28. The compound of claim 23 , wherein A or B is absent and the remainder is DPA.
29. The compound of claim 23 , wherein A and B are both present and are each DPA.
30. A pharmaceutical composition comprising the compound of claim 1 , and a carrier.
31. The pharmaceutical composition of claim 30 , wherein the composition is a solid oral dosage form.
32. The pharmaceutical composition of claim 30 , wherein the composition is an intravenous dosage form.
33. The pharmaceutical composition of claim 30 , wherein the composition is an ophthalmic formulation.
34. A package or kit comprising a unit dosage form of the pharmaceutical composition of claim 30 , at least one container for holding the unit dosage forms, and instructions for use.
35. The pharmaceutical composition of claim 30 , wherein the composition is a parenteral dosage form.
36. A method for treating a metabolic disease or disorder in a subject, the method comprising administering to the subject a pharmaceutical composition comprising the compound of claim 1 , wherein the metabolic disease or disorder is selected from the group consisting of hypertriglyceridemia, severe hypertriglyceridemia, hypercholesterolemia, pre-diabetes, fatty liver disease, and obesity.
37. The method of claim 36 , wherein the subject is human.
38. A method for treating a cardiovascular disease or disorder in a subject, the method comprising administering to the subject a pharmaceutical composition comprising the compound of claim 1 , wherein the cardiovascular disease or disorder is selected from the group consisting of atrial fibrillation, myocardial infarction, and congestive heart failure.
39. The method of claim 38 , wherein the subject is human.
40. A method for treating an inflammatory disease or disorder in a subject, the method comprising administering to the subject a pharmaceutical composition comprising the compound of claim 1 , wherein the inflammatory disease or disorder is selected from the group consisting of arthritis, irritable bowel syndrome, ophthalmic inflammation disorders, and dry eye syndrome.
41. The method of claim 40 , wherein the subject is human.
42. A method for treating a gastrointestinal disorder or complication thereof in a subject, the method comprising administering to the subject a pharmaceutical composition comprising the compound of claim 1 , wherein the gastrointestinal disorder or complication thereof is selected from the group consisting of bowel obstruction, short bowel syndrome, Gastroschisis, prolonged diarrhea, high-output fistula, Crohn's disease, ulcerative colitis, colon cancer, familial adenomatous polyposis, parenteral nutrition-associated liver disease, essential fatty acid deficiency, a congenital gastrointestinal anomaly, and necrotizing enterocolitis.
43. The method of claim 42 , wherein the gastrointestinal disorder or complication is bowel obstruction.
44. The method of claim 42 , wherein the subject is human.
45. A method for treating a neurological disorder in a subject, the method comprising administering to the subject a pharmaceutical composition comprising the compound of claim 1 , wherein the neurological disorder is selected from the group consisting of Alzheimer's disease, attention deficit hyperactivity disorder (ADHD), depression, traumatic brain injury, spinal cord injury, ischemic stroke, and concussion.
46. The method of claim 45 , wherein the subject is human.