Compounds from an extract of Artemisia and methods for treating disorders

• US 20070224301A1
• Filed: 03/21/2006
• Published: 09/27/2007
• Est. Priority Date: 03/21/2006
• Status: Abandoned Application

• Current Assignee: Rutgers University
• Original Assignee: Rutgers University
• Inventors: Raskin, Ilya, Ribnicky, David, Cefalu, William, Poulev, Alexander, Logendra, Sithes
• Application Number:
  US11/385,524
• Publication Number:
  US 20070224301A1
• Time in Patent Office: Days
• US Class Current: 424/740
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 36/282 Artemisia, e.g. wormwood or sagebrush
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/48 of the pancreatic hormones

Abstract

This invention comprises an extract of Artemisia dracunculus that can be used for the treatment and prevention of diabetes, diabetic complications, metabolic syndrome and other comorbidities that share the underlying commonality of insulin resistance. The invention includes the identity of six compounds from the extract that contribute to the activity of the extract by inhibiting protein tyrosine phosphatase-1B (PTP-1B) activity, phosphoenolpyruvate carboxykinase (PEPCK) gene expression or aldose reductase activity (ALR2). The compounds include 4,5-Di-O-caffeoylquinic acid, davidigenin, 6-demethoxycapillarisin, 2′,4-dihydroxy-4′-methoxydihydrochalcone, 2′,4′-dihydroxy-4-methoxdihydrochalcone and sakuranetin.

Claims

1-28. -28. (canceled)

29. A pharmaceutical composition comprising one or more isolated compounds selected from the group consisting of 4,5-Di-O-caffeoylquinic acid, 2′

,4′

-dihydroxy-4-methoxydihydrochalcone, and 2′

,4-dihydroxy-4′

-methoxydihydrochalcone, wherein said composition is formulated for internal administration.

30. (canceled)

31. A purified composition comprising two or more isolated compounds selected from the group consisting of 4,5-Di-O-caffeoylquinic acid, davidigenin, 6-demethoxycapillarisin, 2′

,4′

-dihydroxy-4-methoxydihydrochalcone, 2′

,4-dihydroxy-4′

-methoxydihydrochalcone and sakuranetin wherein said one or more compounds are derived from a plant or plant extract of Artemisia dracunculus.

33. The composition of claim 31, further comprising at least one additive.

34. The composition of claim 33, wherein said additive is a pharmaceutically acceptable carrier, excipient, diluent or solvent

35. The composition of claim 33, wherein said composition is formulated as a capsule, tablet, syrup, concentrate, powder, granules, aerosol, or bead.

32. (canceled)

36. A composition for modulating enzyme aldose reductase (ALR2) activity in a mammal comprising isolated 4,5-Di-O-caffeoylquinic acid, and 2′

,4′

-dihydroxy-4-methoxydihydrochalcone.

44. The composition of claim 36, further comprising davidigenin.

45. The composition of claim 36, further comprising 6-demethoxycapillarisin.

37. A composition for modulating protein tyrosine phosphatase-1B (PTP-1B) activity in a mammal comprising two or more isolated compounds selected from 2′

,4′

-dihydroxy-4-methoxydihydrochalcone, 2′

,4-dihydroxy-4′

-methoxydihydrochalcone and sakuranetin.

38. A composition for modulating hepatic glucose output in a mammal comprising the isolated compounds 6-demethoxycapillarisin and 2′

,4′

-dihydroxy-4-methoxydihydrochalcone.

41. A pharmaceutical composition comprising three or more isolated compounds selected from the group consisting of 4,5-Di-O-caffeoylquinic acid, davidigenin, 6-demethoxycapillarisin, 2′

,4′

-dihydroxy-4-methoxydihydrochalcone, and 2′

,4-dihydroxy-4′

-methoxydihydrochalcone.

42. A pharmaceutical composition comprising two or more isolated compounds selected from the group consisting of 4,5-Di-O-caffeoylquinic acid, 6-demethoxycapillarisin, 2′

,4′

-dihydroxy-4-methoxydihydrochalcone, and 2′

,4-dihydroxy-4′

-methoxydihydrochalcone.

43. A pharmaceutical composition comprising two or more isolated compounds selected from the group consisting of 4,5-Di-O-caffeoylquinic acid, davidigenin, 2′

,4′

-dihydroxy-4-methoxydihydrochalcone, and 2′

,4-dihydroxy-4′

-methoxydihydrochalcone.