7-hydroxy chromones as potent antioxidants

• US 8,110,555 B2
• Filed: 03/10/2010
• Issued: 02/07/2012
• Est. Priority Date: 05/03/2002
• Status: Active Grant

• Current Assignee: Unigen Corporation
• Original Assignee: Unigen Corporation
• Inventors: Jia, Qi, Farrow, Thomas M.
• Primary Examiner(s): McIntosh, III, Traviss C
• Application Number:
  US12/721,371
• Publication Number:
  US 20100168223A1
• Time in Patent Office: 699 Days
• Field of Search: None
• US Class Current: 514/23
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/7034 attached to a carbocyclic compound, e.g. phloridzin
• 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 36/185 Magnoliopsida (dicotyledons)
• CPC Class Codes: A61K 36/282 Artemisia, e.g. wormwood or sagebrush
• CPC Class Codes: A61K 36/296 Epimedium
• CPC Class Codes: A61K 36/38 Clusiaceae, Hypericaceae or Guttiferae (Hypericum or Mangosteen family), e.g. common St. Johnswort
• CPC Class Codes: A61K 36/48 Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
• CPC Class Codes: A61K 36/489 Sophora, e.g. necklacepod or mamani
• CPC Class Codes: A61K 36/704 Polygonum, e.g. knotweed
• CPC Class Codes: A61K 36/886 Aloeaceae (Aloe family), e.g. aloe vera
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/12 for cataracts
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

The present invention describes the identification and purification of 7-hydroxychromes that exhibit potent antioxidant activity. In one embodiment the present invention includes a method for providing an antioxidant to a host in need thereof, comprising administering an effective amount of a 7-hydroxychrome or a mixture of 7-hydroxychromones. The present invention includes methods that are effective in inhibiting free radical and oxidation caused damage through the simultaneous suppression of free radical generation and the suppression of the production of reactive oxygen species (ROS). The present invention also includes methods for preventing and treating ROS mediated diseases and conditions and diseases and conditions associated with other oxidative processes. The method for preventing and treating ROS mediated diseases and conditions and diseases and conditions associated with other oxidative processes is comprised of administering to a host in need thereof an effective amount of a composition comprised of a 7-hydroxychrome or a mixture of 7-hydroxychromones and a pharmaceutically acceptable carrier. Included in this invention is an improved method to isolate and purify 7-hydroxychromones from plant sources.

Claims

1. A method for treating ROS mediated diseases and conditions comprising administering to a host in need thereof an effective amount of a composition comprising a 7-hydroxychromone or a mixture of 7-hydroxychromones wherein said 7-hydroxychromone or a mixture thereof is selected from the group of compounds having the following structure:

2. The method of claim 1 wherein said composition comprises a 7-hydroxychromone selected from aloesin or aloeresin A.

3. The method of claim 1 wherein said 7-hydroxychromone is obtained by organic synthesis.

4. The method of claim 1 wherein said 7-hydroxychromone is extracted from a plant or a plant part.

5. The method of claim 4 wherein said plant is selected from the group consisting of the genus of Acacia, Adina, Aloe, Alternaria, Amoora, Antidesma, Artemisia, Baeckia, Cassia, Clusea, Cnidium, Convolvulus, Epimedium, Eriosema, Eriostemon, Eugenia, Garcinia, Hypericum, Lindenbergia, Pancratium, Penicillium, Polygonum, Ptaeroxylon, Rheum, Sophora, Stephanitis, Syzygium, Talaromyces and Zonaria.

6. The method of claim 4 wherein said plant is selected from the group consisting of Acacia catechu, Acacia concinna, Aloe arborescens, Aloe barbadensis, Aloe cremnophila, Aloe ferox, Aloe saponaria, Aloe vera, Aloe vera var. chinensis, Antidesma membranaceum, Artemisia capillaries, Baeckia frutescens, Epimedium sagittatum, Garcinia dulcis, Hypericum japonicum, Polygonum cuspidatum, Sophora tomentosa, and Stephanitis rhododendri.

7. The method of claim 4 wherein said 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.

8. The method of claim 1 wherein the ROS mediated diseases and conditions are selected from the group consisting of atherosclerosis, coronary heart diseases, cataracts, dementia, Alzheimer'"'"'s disease, cognitive dysfunction, diabetes mellitus, cancer, skin photo aging, skin wrinkles, sun burns, melanoma, and other degenerative processes associated with aging.

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

10. The method of claim 1 wherein 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.

11. The method of claim 1 wherein said composition comprises a 7-hydroxychromone wherein R₂ is alkyl;

and R₃ is an ester selected from the group consisting of gallate, acetate, cinnamoyl and hydroxyl-cinnamoyl esters, trihydroxybenzoyl esters and caffeoyl esters;

a carbon, oxygen, nitrogen or sulfur glycoside of a single or a combination of multiple sugars selected from the group consisting of aldopentoses, methyl aldopentose, aldohexoses, ketohexoses.

12. A method for providing an antioxidant to a host in need thereof, comprising administering to a host in need thereof an effective amount of a composition comprising a 7-hydroxychromone or a mixture of 7-hydroxychromones wherein said 7-hydroxychromone or a mixture thereof is selected from the group of compounds having the following structure:

13. The method of claim 12 wherein said composition comprises a 7-hydroxychromone wherein R₂ is alkyl;

and R₃ is an ester selected from the group consisting of gallate, acetate, cinnamoyl and hydroxyl-cinnamoyl esters, trihydroxybenzoyl esters and caffeoyl esters;

a carbon, oxygen, nitrogen or sulfur glycoside of a single or a combination of multiple sugars selected from the group consisting of aldopentoses, methyl aldopentose, aldohexoses, ketohexoses.

14. The method of claim 13 wherein said composition comprises a 7-hydroxychromone selected from aloesin or and aloeresin A.

15. The method of claim 12 wherein said 7-hydroxychromone is obtained by organic synthesis.

16. The method of claim 12 wherein said 7-hydroxychromone is extracted from a plant or a plant part.

17. The method of claim 16 wherein said plant is selected from the group consisting of the genus of Acacia, Adina, Aloe, Alternaria, Amoora, Antidesma, Artemisia, Baeckia, Cassia, Clusea, Cnidium, Convolvulus, Epimedium, Eriosema, Eriostemon, Eugenia, Garcinia, Hypericum, Lindenbergia, Pancratium, Penicillium, Polygonum, Ptaeroxylon, Rheum, Sophora, Stephanitis, Syzygium, Talaromyces and Zonaria.

18. The method of claim 16 wherein said plant is selected from the group consisting of Acacia catechu, Acacia concinna, Aloe arborescens, Aloe barbadensis, Aloe cremnophila, Aloe ferox, Aloe saponaria, Aloe vera, Aloe vera var. chinensis, Antidesma membranaceum, Artemisia capillaries, Baeckia frutescens, Epimedium sagittatum, Garcinia dulcis, Hypericum japonicum, Polygonum cuspidatum, Sophora tomentosa, and Stephanitis rhododendri.

19. The method of claim 16 wherein 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.

20. The method of claim 12 wherein the composition is administered in a dosage selected from 0.01 to 200 mg/kg of body weight.

21. The method of claim 12 wherein 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.