Inhibition of COX-2 and/or 5-LOX activity by fractions isolated or derived from hops

• US 20090118373A1
• Filed: 06/10/2004
• Published: 05/07/2009
• Est. Priority Date: 06/20/2001
• Status: Active Grant

• Current Assignee: MetaProteomics, LLC
• Original Assignee: MetaProteomics, LLC
• Inventors: Fuller, Mark, Tripp, Matthew L., Babish, John G., Darland, Gary K., Bland, Jeffrey S.
• Granted Patent: US 7,901,713 B2
• Time in Patent Office: Days
• US Class Current: 514/573
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A natural formulation of compounds isolated or derived from hops which inhibit the activity of cyclooxygenase-2 (COX-2) and/or 5-lipoxygenase (5-LOX) is disclosed. The hops formulations may be administered to a mammal to treat or inhibit a pathological condition associated with the activity of COX-2 and/or 5-LOX in such a mammal.

Claims

1. A method of treating or inhibiting a pathological condition in a mammal involving inhibiting inducibility or activity of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), the method comprising administering to the mammal a composition comprising a compound selected from the group consisting of reduced isoalpha acids, tetra-hydroisoalpha acids, and hexa-hydroisoalpha acids.

2. The method of claim 1, wherein the compound selected from the group consisting of reduced isoalpha acids, tetra-hydroisoalpha acids, and hexa-hydroisoalpha acids is derived from hops.

3. The method of claim 1, wherein the compound selected from the group consisting of reduced isoalpha acids, tetra-hydroisoalpha acids, and hexa-hydroisoalpha acids comprises a member of a supragenus having the formula:

wherein R′

is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl;

wherein R″

is selected from the group consisting of CH(CH₃)₂, CH₂CH(CH₃)₂, and CH(CH₃)CH₂CH₃;

and wherein R, T, X, and Z are independently selected from the group consisting of H, F, Cl, Br, I, and π

orbital, with the proviso that if one of R, T, X, or Z is a π

orbital, then the adjacent R, T, X, or Z is also a π

orbital, thereby forming a double bond.

4. The method of claim 1, wherein the compound selected from the group consisting of reduced isoalpha acids, tetra-hydroisoalpha acids, and hexa-hydroisoalpha acids comprises a member of Genus A having the formula:

wherein R′

is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R″

is alkyl; and

wherein R″

is selected from the group consisting of CH(CH₃)₂, CH₂CH(CH₃)₂, and CH(CH₃)CH₂CH₃.

5. The method of claim 1, wherein the compound selected from the group consisting of reduced isoalpha acids, tetra-hydroisoalpha acids, and hexa-hydroisoalpha acids comprises a member of Genus B having the formula:

wherein R′

is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl;

and wherein R″

is selected from the group consisting of CH(CH₃)₂, CH₂CH(CH₃)₂, and CH(CH₃)CH₂CH₃.

6. The method of claim 1, wherein said compound selected from the group consisting of reduced isoalpha acids, tetra-hydroisoalpha acids, and hexa-hydroisoalpha acids comprises a member selected from the group consisting of dihydro-isohumulone, dihydro-isocohumulone, dihydro-adhumulone, tetrahydro-isohumulone, tetrahydro-isocohumulone, tetrahydro-adhumulone, hexahydro-isohumulone, hexahydro-isocohumulone, and hexahydro-adhumulone.

7. The method of claim 1, wherein the pathologic condition is an allergic disorder.

8. The method of claim 1, wherein the pathologic condition is cancer.

9. The method of claim 8, wherein the cancer is breast cancer.

10. The method of claim 8, wherein the cancer is prostate cancer.

11. The method of claim 8, wherein the cancer is colon cancer.

12. The method of claim 8, wherein the cancer is pancreatic cancer.

13. The method of claim 1, wherein the pathologic condition is an inflammatory disease.

14. The method of claim 13, wherein the inflammatory disease is asthma.

15. The method of claim 13, wherein the inflammatory disease is Alzheimer Disease.

16. The method of claim 13, wherein the inflammatory disease is arthritis.

17. The method of claim 13, wherein the inflammatory disease is Crohn'"'"'s Disease.

18. The method of claim 13, wherein the inflammatory disease is eczema.

19. The method of claim 13, wherein the inflammatory disease is Inflammatory Bowel Disease.

20. The method of claim 13, wherein the inflammatory disease is osteoarthritis.

21. The method of claim 13, wherein the inflammatory disease is psoriasis.

22. A method of treating or inhibiting a pathological condition in a mammal involving inhibiting inducibility or activity of 5-lipoxygenase (5-LOX), the method comprising administering to the mammal a composition comprising a compound selected from the group consisting of reduced isoalpha acids, tetra-hydroisoalpha acids, and hexa-hydroisoalpha acids.

23. The method of claim 22, wherein the compound selected from the group consisting of reduced isoalpha acids, tetra-hydroisoalpha acids, and hexa-hydroisoalpha acids is derived from hops.

24. The method of claim 22, wherein the compound selected from the group consisting of reduced isoalpha acids, tetra-hydroisoalpha acids, and hexa-hydroisoalpha acids comprises a member of a supragenus having the formula:

wherein R′

is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R″

is alkyl;

wherein R″

is selected from the group consisting of CH(CH₃)₂, CH₂CH(CH₃)₂, and CH(CH₃)CH₂CH₃;

and wherein R, T, X, and Z are independently selected from the group consisting of H, F, Cl, Br, I, and π

orbital, with the proviso that if one of R, T, X, or Z is a π

T orbital, then the adjacent R, T, X, or Z is also a π

orbital, thereby forming a double bond.

25. The method of claim 22, wherein the compound selected from the group consisting of reduced isoalpha acids, tetra-hydroisoalpha acids, and hexa-hydroisoalpha acids comprises a member of Genus A having the formula:

wherein R′

is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl; and

wherein R″

is selected from the group consisting of CH(CH₃)₂, CH₂CH(CH₃)₂, and CH(CH₃)CH₂CH₃.

26. The method of claim 22, wherein the compound selected from the group consisting of reduced isoalpha acids, tetra-hydroisoalpha acids, and hexa-hydroisoalpha acids comprises a member of Genus B having the formula:

wherein R′

is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl;

and wherein R″

is selected from the group consisting of CH(CH₃)₂, CH₂CH(CH₃)₂, and CH(CH₃)CH₂CH₃.

27. The method of claim 22, wherein said compound selected from the group consisting of reduced isoalpha acids, tetra-hydroisoalpha acids, and hexa-hydroisoalpha acids comprises a member selected from the group consisting of dihydro-isohumulone, dihydro-isocohumulone, -dihydro-adhumulone, tetrahydro-isohumulone, tetrahydro-isocohumulone, tetrahydro-adhumulone, hexahydro-isohumulone, hexahydro-isocohumulone, and hexahydro-adhumulone.

28. The method of claim 22, wherein the pathologic condition is an allergic disorder.

29. The method of claim 22, wherein the pathologic condition is cancer.

30. The method of claim 29, wherein the cancer is breast cancer.

31. The method of claim 29, wherein the cancer is prostate cancer.

32. The method of claim 29, wherein the cancer is colon cancer.

33. The method of claim 29, wherein the cancer is pancreatic cancer.

34. The method of claim 22, wherein the pathologic condition is an inflammatory disease.

35. The method of claim 34, wherein the inflammatory disease is asthma.

36. The method of claim 34, wherein the inflammatory disease is Alzheimer Disease.

37. The method of claim 34, wherein the inflammatory disease is arthritis.

38. The method of claim 34, wherein the inflammatory disease is Crohn'"'"'s Disease.

39. The method of claim 34, wherein the inflammatory disease is eczema.

40. The method of claim 34, wherein the inflammatory disease is Inflammatory Bowel Disease.

41. The method of claim 34, wherein the inflammatory disease is osteoarthritis.

42. The method of claim 34, wherein the inflammatory disease is psoriasis.