Compositions and methods for enhancing cognitive function

• US 8,221,804 B2
• Filed: 02/03/2006
• Issued: 07/17/2012
• Est. Priority Date: 02/03/2005
• Status: Active Grant

• Current Assignee: The Trustees of Princeton University (Princeton University), Signum Biosciences, Inc.
• Original Assignee: The Trustees of Princeton University (Princeton University), Signum Biosciences, Inc.
• Inventors: Stock, Jeffry B., Stock, Maxwell, Gu, Haoming, Li, Zhu, Wolanin, Peter Michael, Stock, Gregory B
• Primary Examiner(s): Tate, Christopher R
• Assistant Examiner(s): WINSTON, RANDALL O
• Application Number:
  US11/346,706
• Publication Number:
  US 20060171938A1
• Time in Patent Office: 2,356 Days
• Field of Search: None
• US Class Current: 424/728
• CPC Class Codes: A23F 5/24 Extraction of coffee; Coffee extracts with reduced alkaloid content A23F5/20; Making instant coffee methods of roasting extracted coffee A23F5/06
• CPC Class Codes: A23F 5/267 using additives, specific extraction media or specific coffee blends
• CPC Class Codes: A23G 3/36 characterised by the composition containing organic or inorganic compounds
• CPC Class Codes: A23G 3/48 containing plants or parts thereof, e.g. fruits, seeds, extracts containing gums A23G3/42
• CPC Class Codes: A23G 4/06 characterised by the composition containing organic or inorganic compounds
• CPC Class Codes: A23G 4/068 containing plants or parts thereof, e.g. fruits, seeds, extracts containing gums A23G4/10
• CPC Class Codes: A23L 2/02 containing fruit or vegetable juices
• CPC Class Codes: A23L 2/38 Other non-alcoholic beverages drinks from legumes A23L11/60
• CPC Class Codes: A23L 33/105 Plant extracts, their artificial duplicates or their derivatives
• CPC Class Codes: A23L 33/40 Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2200/322 having an effect on the health of the nervous system or on mental function
• CPC Class Codes: A23V 2250/21 Plant extracts
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61K 36/16 Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
• CPC Class Codes: A61K 36/185 Magnoliopsida (dicotyledons)
• CPC Class Codes: A61K 36/258 Panax (ginseng)
• CPC Class Codes: A61K 36/28 Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
• CPC Class Codes: A61K 36/38 Clusiaceae, Hypericaceae or Guttiferae (Hypericum or Mangosteen family), e.g. common St. Johnswort
• CPC Class Codes: A61K 36/55 : Linaceae (Flax family), e.g. Linum
• CPC Class Codes: A61K 36/74 : Rubiaceae (Madder family)
• CPC Class Codes: A61K 36/81 : Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
• CPC Class Codes: A61K 36/82 : Theaceae (Tea family), e.g. camellia
• CPC Class Codes: A61K 36/87 : Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
• CPC Class Codes: A61K 36/8962 : Allium, e.g. garden onion, leek, garlic or chives
• CPC Class Codes: A61K 45/06 : Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The invention encompasses novel compositions containing a methylation modifying compound isolated from botanical raw materials, including a fruit of the genus Coffea, and microbial raw materials, methods of making such compositions, and methods of treating or preventing human disease using such compositions. The methylation modifying compound in botanical extracts of the present invention can dramatically increase the level of methylation of PP2A, thus increasing cognitive function, particularly in persons suffering from or prone to developing Alzheimer'"'"'s disease.

Claims

1. A method of treating a disease, condition, or disorder selected from the group consisting of a cardiac disorder;

atherosclerosis;

a neurodegenerative disorder;

a cerebrovascular disorder;

a neuropsychiatric disorder;

diabetes; and

a combination thereof, the method comprising steps of;

administering to a subject in need thereof an effective amount of a composition comprising a botanical extract prepared from a botanical raw material selected from the group consisting of coffea, ginkgo, garlic, bacopa, butcher'"'"'s broom, flaxseed oil, ginseng, grape seed, St. John'"'"'s wort, artichoke powder, tea leaf, tobacco, cocoa, and a combination thereof,

wherein the composition comprising the botanical extract is prepared by a process comprising steps of;

(a) solubilizing the botanical raw material in a polar solvent below a pH of about 5 to yield a solubilized botanical material;

(b) partitioning the solubilized botanical material between an aqueous phase and an organic phase corresponding to the polar solvent above a pH of about 10 to yield a partitioned botanical material in the organic phase;

(c) separating the partitioned botanical material into a plurality of fractions;

(d) assessing each fraction of the plurality of fractions to identify an activity inhibiting demethylation of a protein phosphatase 2A (PP2A) enzyme in at least one fraction; and

(e) collecting the at least one fraction containing the activity inhibiting demethylation of the protein phosphatase 2A (PP2A) enzyme or the combination of fractions containing the activity inhibiting demethylation of the protein phosphatase 2A (PP2A) enzymes to constitute the composition,

wherein the composition is further characterized as having the following properties;

(1) the botanical extract is essentially free of chlorogenic acid; and

(2) the botanical extract contains at least 5 units per microliter of the activity inhibiting demethylation of the protein phosphatase 2A (PP2A) enzyme and thereby stimulates methylation of the protein phosphatase 2A (PP2A) enzyme.

2. The method according to claim 1, wherein demethylation of the protein phosphatase 2A (PP2A) enzyme results from activity of a demethylating enzyme, wherein the demethylating enzyme is a protein phosphatase 2A (PP2A) specific protein methylesterase.

3. The method according to claim 1, wherein the effective amount of the composition is from 1 mg to about 10 g.

4. The method according to claim 1, wherein the botanical raw material comprises a fruit of a species of plant genus Coffea.

5. The method according to claim 4, wherein the fruit of the plant genus Coffea is a coffee bean.

6. The method according to claim 1, wherein the botanical raw material comprises a ground coffee.

7. The method according to claim 1, wherein the botanical raw material comprises an instant coffee.

8. The method according to claim 1, wherein the polar solvent is a lower alcohol.

9. The method according to claim 8, wherein the lower alcohol is ethanol.

10. The method according to claim 1, wherein the polar solvent is ethyl acetate.

12. The method according to claim 1, wherein the composition is in the form of a powder.

13. The method according to claim 1, wherein the composition is in the form of a tablet.

14. The method according to claim 1, wherein the composition is in the form of a capsule.

15. The method according to claim 1, wherein the composition is in the form of a lozenge.

16. The method according to claim 1, wherein the composition is in the form of a suppository.

17. The method according to claim 1, wherein the composition comprising the botanical extract contains, at least 10 units of inhibitory activity per microliter.

18. The method according to claim 1, wherein the composition comprising the botanical extract is essentially free of at least one substance selected from the group consisting of caffeine and caffeic acid.

19. The method according to claim 1, wherein the disease, condition, or disorder is a cardiac disorder.

20. The method according, to claim 1, wherein the disease, condition, or disorder is a neurodegenerative disorder.

21. The method according to claim 20, wherein the neurodegenerative disorder is Alzheimer'"'"'s disease.

22. The method according to claim 1, wherein the disease, condition, or disorder is a neuropsychiatric disorder.

23. The method according to claim 22, wherein the neuropsychiatric disorder is Parkinson'"'"'s disease.

24. The method according to claim 22, wherein the neuropsychiatric disorder is bipolar disorder.

25. The method according to claim 1, wherein the disease, condition, or disorder is diabetes.

26. The method according to claim 1, wherein the disease, condition, or disorder is a cerebrovascular disorder.

27. The method according to claim 1, wherein the disease, condition, or disorder is atherosclerosis.

11. The method according to claiin 1, wherein the composition is administered orally.