Isolation of a dual COX-2 and 5-lipoxygenase inhibitor from Acacia

• US 20030180402A1
• Filed: 03/22/2002
• Published: 09/25/2003
• Est. Priority Date: 03/22/2002
• 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 7,108,868 B2
• Time in Patent Office: Days
• US Class Current: 424/757
• CPC Class Codes: A61K 31/33 Heterocyclic compounds
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 36/00 Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines antigens from pollen A61K39/36
• CPC Class Codes: A61K 36/48 Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• 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 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• 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 simultaneously inhibiting the cyclooxygenase COX-2 and 5-lipoxygenase (5-LO) enzymes. The method for the simultaneous dual inhibition of COX-2 and 5-LO is comprised of administering a composition containing an individual and/or a mixture of multiple flavans isolated from a single plant or multiple plants in the Acacia genus of plants to a host in need thereof. The present also includes novel methods for the prevention and treatment of COX-2 and 5-LO mediated diseases and conditions. The method for preventing and treating COX-2 and 5-LO mediated diseases and conditions is comprised of administering to a host in need thereof an effective amount of a composition comprising an individual and/or a mixture of multiple flavans isolated from a single plant or multiple plants in the Acacia genus of plants and a pharmaceutically acceptable carrier. The present invention includes a method for isolating and purifying a composition of flavans having dual specificity for COX-2 and 5-LO from the Acacia genus of plants.

Claims

1. A method for the simultaneous dual inhibition of the cyclooxygenase COX-2 and 5-lipoxygenase (5-LO) enzymes comprising administering a composition comprising a flavan or a mixture of flavans isolated from a plant selected from the Acacia genus of plants.

2. The method of claim 1 wherein said flavan or mixture of flavans is selected from the group of compounds having the following structure:

3. The method of claim 1 wherein said plant is selected from the group consisting of the Acacia catechu, Acacia concinna, Acacia farnesiana, Acacia Senegal, Acacia speciosa, Acacia arabica, A. caesia, A. pennata, A. sinuata. A. mearnsii, A. picnantha, A. dealbata, A. auriculiformis, A. holoserecia and A. mangium.

4. The method of claim 1 wherein said flavan is isolated from a plant part.

5. The method of claim 4 wherein the plant part is selected from the group consisting of stems, stem barks, trunks, trunk barks, twigs, tubers, roots, root barks, young shoots, seeds, rhizomes, flowers and other reproductive organs, leaves and other aerial parts.

6. A method for simultaneously preventing and treating COX-2 and 5-LO mediated diseases and conditions comprising administering to a host in need thereof an effective amount of a composition comprising a flavan or a mixture of flavans isolated from a plant selected from the Acacia genus of plants and a pharmaceutically acceptable carrier.

7. The method of claim 6 wherein said flavan or mixture of flavans is selected from the group of compounds having the following structure:

8. The method of claim 6 wherein said plant is selected from the group consisting of the Acacia catechu, Acacia concinna, Acacia farnesiana, Acacia Senegal, Acacia speciosa, Acacia arabica, A. caesia, A. pennata, A. sinuata. A. mearnsii, A. picnantha, A. dealbata, A. auriculiformis, A. holoserecia and A. mangium.

9. The method of claim 6 wherein said flavan is isolated from a plant part.

10. The method of claim 9 wherein the plant part is selected from the group consisting of stems, stem barks, trunks, trunk barks, twigs, tubers, roots, root barks, young shoots, seeds, rhizomes, flowers and other reproductive organs, leaves and other aerial parts.

11. The method of claim 6 wherein the COX-2 and 5-LO 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 bowl disease;

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

solid cancers.

12. The method of claim 6 wherein the flavan composition is comprised of 0.01% to 100% of the flavan.

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

14. The method of claim 6 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 isolating and purifying a composition of flavans having dual specificity for COX-2 and 5-LO from the Acacia genus of plants comprising:

a) extracting the ground biomass of a plant selected from the Acacia genus of plants

b) neutralizing and concentrating said extract; and

c) purifying said neutralized and concentrated extract.

16. The method of claim 15 wherein the composition of flavans is extracted with a solvent selected from the group consisting of water, alcohol, an organic solvent and/or a combination thereof.

17. The method of claim 15 wherein the extract is purified by using a method selected from the group consisting of recrystallization, solvent partition, precipitation, sublimation, and/or chromatographic separation.

18. The method of claim 18 wherein said chromatographic separation is selected from the group consisting of methods including, but not limited to, ion exchange chromatography, absorption chromatography, reverse phase chromatography, size exclusive chromatography, ultra-filtration or a combination of two or more of those methods.