Identification of Free-B-Ring flavonoids as potent COX-2 inhibitors

• US 7,192,611 B2
• Filed: 02/28/2003
• Issued: 03/20/2007
• Est. Priority Date: 03/01/2002
• Status: Expired due to Term

• Current Assignee: Unigen Corporation
• Original Assignee: Unigen Pharmaceuticals (ECONET, Incorporated)
• Inventors: Nichols, Timothy C., Jia, Qi, Rhoden, Eric E., Waite, Scott
• Primary Examiner(s): MELLER, MICHAEL V
• Application Number:
  US10/469,275
• Publication Number:
  US 20040092458A1
• Time in Patent Office: 1,481 Days
• Field of Search: 424/725
• US Class Current: 424/725
• 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 treating osteoarthritis 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.

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

3. The method of claim 2 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.

4. The method of claim 2 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.

5. The method of claim 1 wherein the Free-B-Ring flavonoid composition is comprised of 0.01% to 100% of the Free-B-Ring flavonoid.

6. The method of claim 1 wherein the composition is administered in a dosage selected from 0.01 to 200 mg/kg of body weight.

7. The method of claim 1 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.

8. A method for treating osteoarthritis comprising administering to a host in need thereof an effective amount of a composition comprising a Free-B-Ring flavonoid or a composition comprising a mixture of Free-B-Ring flavonoids, wherein said Free-B-Ring flavonoid or mixture thereof are selected from the group of compounds having the following structure:

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

10. The method of claim 9 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.

11. The method of claim 9 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.

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

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

14. 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.

15. A method for improving physical function, flexibility and mobility in a host having osteoarthritis, said method comprising administering an effective amount of a composition comprising a Free-B-Ring flavonoid or a composition comprising a mixture of Free-B-Ring flavonoids.

16. The method of claim 15 wherein said Free-B-Ring flavonoid is selected from the group of compounds having the following structure:

17. The method of claim 15 wherein said Free-B-Ring flavonoid is isolated from a plant part.

18. The method of claim 17 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.

19. The method of claim 17 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.

20. The method of claim 15 wherein the Free-B-Ring flavonoid composition is comprised of 0.01% to 100% of the Free-B-Ring flavonoid.

21. The method of claim 15 wherein the composition is administered in a dosage selected from 0.01 to 200 mg/kg of body weight.

22. The method of claim 15 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.