Identification of free-b-ring flavonoids as poten cox-2 inhibitors

• US 20040092458A1
• Filed: 08/27/2003
• Published: 05/13/2004
• Est. Priority Date: 03/01/2002
• Status: Active Grant

• Current Assignee: Unigen Corporation
• Original Assignee: Unigen Pharmaceuticals (ECONET, Incorporated)
• Inventors: Nichols, Timothy C., Jia, Qi, Rhoden, Eric E., Waite, Scott
• Granted Patent: US 7,192,611 B2
• Time in Patent Office: Days
• US Class Current: 514/27
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• 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 36/18 Magnoliophyta (angiosperms)
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides a novel method for inhibiting the cyclooxygenase enzyme COX-2. The method is comprised of administering a composition containing a Free-B-Ring flavonoid or a composition containing a mixture of Free-B-Ring flavonoids to a host in need thereof. The present also includes novel methods for the prevention and treatment of COX-2 mediated diseases and conditions. The method for preventing and treating COX-2 mediated diseases and conditions is comprised of administering to a host in need thereof an effective amount of a composition containing a Free-B-Ring flavonoid or a composition containing a mixture of Free-B-Ring flavonoids and a pharmaceutically acceptable carrier.

Claims

1. A method for inhibiting the cyclooxygenase enzyme COX-2 comprising administering a composition comprising a Free-B-Ring flavonoid or a composition containing a mixture of Free-B-Ring flavonoids.

2. The method of claim 1 wherein said Free-B-Ring flavonoid is selected from the group of compounds having the following structure:

3. The method of claim 1 wherein said Free-B-Ring flavonoid is obtained by organic synthesis.

4. The method of claim 1 wherein said Free-B-Ring flavonoid is isolated from a plant part.

5. The method of claim 4 wherein said plant is selected from a family consisting of Annonaceae, Asteraceae, Bignoniaceae, Combretaceae, Compositae, Euphorbiaceae, Labiatae, Lauranceae, Leguminosae, Moraceae, Pinaceae, Pteridaceae, Sinopteridaceae, Ulmaceae and Zingiberacea.

6. The method of claim 4 wherein said plant is selected from a genus consisting of Desmos, Achyrocline, Oroxylum, Buchenavia, Anaphalis, Cotula, Gnaphalium, Helichrysum, Centaurea, Eupatorium, Baccharis, Sapium, Scutellaria, Molsa, Colebrookea, Stachys, Origanum, Ziziphora, Lindera, Actinodaphne, Acacia, Derris, Glycyrrhiza, Millettia, Pongamia, Tephrosia, Artocarpus, Ficus, Pityrogramma, Notholaena, Pinus, Ulmus and Alpinia.

7. The method of claim 4 wherein the Free-B-Ring flavonoid is isolated from a plant part selected from the group consisting of stems, stem barks, twigs, tubers, roots, root barks, young shoots, seeds, rhizomes, flowers and other reproductive organs, leaves and other aerial parts.

8. A method for preventing and treating COX-2 mediated diseases and conditions comprising administering to a host in need thereof an effective amount of a composition comprising a Free-B-Ring flavonoid or a composition containing a mixture of Free-B-Ring flavonoids and a pharmaceutically acceptable carrier.

9. The method of claim 8 wherein said Free-B-Ring flavonoid is selected from the group of compounds having the following structure:

10. The method of claim 8 wherein said Free-B-Ring flavonoid is obtained by organic synthesis.

11. The method of claim 8 wherein said Free-B-Ring flavonoid is isolated from a plant part.

12. The method of claim 11 wherein said plant is selected from a family consisting of Annonaceae, Asteraceae, Bignoniaceae, Combretaceae, Compositae, Euphorbiaceae, Labiatae, Lauranceae, Leguminosae, Moraceae, Pinaceae, Pteridaceae, Sinopteridaceae, Ulmaceae and Zingiberacea.

13. The method of claim 11 wherein said plant is selected from a genus consisting Desmos, Achyrocline, Oroxylum, Buchenavia, Anaphalis, Cotula, Gnaphalium, Helichrysum, Centaurea, Eupatorium, Baccharis, Sapium, Scutellaria, Molsa, Colebrookea, Stachys, Origanum, Ziziphora, Lindera, Actinodaphne, Acacia, Derris, Glycyrrhiza, Millettia, Pongamia, Tephrosia, Artocarpus, Ficus, Pityrogramma, Notholaena, Pinus, Ulmus and Alpinia.

14. The method of claim 11 wherein the Free-B-Ring flavonoid is isolated from the plant part selected from the group consisting of stems, stem barks, twigs, tubers, roots, root barks, young shoots, seeds, rhizomes, flowers and other reproductive organs, leaves and other aerial parts.

15. The method of claim 8 wherein the COX-2 mediated disease or condition is selected from the group consisting of inflammation associated with osteoarthritis, rheumatoid arthritis, menstrual cramps, Systemic Lupus Erythromatosis, psoriasis, chronic tension headache, migraine headaches, inflammatory bowel disease;

topical wound and minor inflammation conditions selected from the group consisting of minor abrasions, sunburn and contact dermatitis; and

solid cancers.

16. The method of claim 8 wherein the Free-B-Ring flavonoid composition is comprised of 0.01% to 100% of the Free-B-Ring flavanoid.

17. The method of claim 8 wherein the composition is administered in a dosage selected from 0.01 to 200 mg/kg of body weight.

18. The method of claim 8 wherein the routes of the administration are selected from the group consisting of oral, topical, suppository, intravenous, and intradermic, intragaster, intramusclar, intraperitoneal and intravenous administration in an appropriate pharmaceutical formula.