Compounds, compositions and methods for treating neuropsychiatric disorders

• US 20060088614A1
• Filed: 08/05/2005
• Published: 04/27/2006
• Est. Priority Date: 02/07/2002
• Status: Active Grant

• Current Assignee: Jay W. Pettegrew, Kanagasabai Panchalingam, Samuel Gershon
• Original Assignee: Jay W. Pettegrew, Kanagasabai Panchalingam, Samuel Gershon
• Inventors: Pettegrew, Jay W., Panchalingam, Kanagasabai, Gershon, Samuel
• Granted Patent: US 7,407,778 B2
• Time in Patent Office: Days
• US Class Current: 424/764
• CPC Class Codes: A23L 33/175 Amino acids
• 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 2250/0612 Carnitine
• 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 31/205 Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 31/221 with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
• CPC Class Codes: A61K 36/28 Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea

Abstract

Acetyl-L-carnitine (ALCAR) and L-carntine (LCAR) are nutraceuticals with indications in treating a variety of mental health disorders. A metabolomics-guided bioprocess method is presented to enhance ALCAR and LCAR formation in germinating plant seeds. Metabolic fluxes are manipulated by germination in bioreactors to increase oxygen availability as well as provide an aseptic environment to alter carbohydrate consumption and feedback repress gluconeogenesis. Large shifts in sunflower seed fatty acid, phospholipid and high-energy metabolism change the germination environment and these metabolic changes lead to an approximate 1000-fold increase in natural LCAR and ALCAR production by the seeds. The resulting LCAR and ALCAR products from the seeds are used for treating mental health disorders including Alzheimer'"'"'s disease, geriatric depression, non-geriatric depression and schizophrenia.

Claims

1. A method for producing a nutraceutical for human consumption, comprising:

manipulating time-dependent metabolic fluxes in a plurality of germinating seeds with a sugar and oxygen to enhance nutraceutically selected metabolite levels in the plurality of germinating plant seeds;

producing a nutraceutical to treat mental health disorders from the manipulated the plurality of germinating plant seeds.

2. The method of claim 1 wherein the nutraceutical includes L-carnitine (LCAR) or acetyl-L-carnitine (ALCAR).

3. The method of claim 1 wherein the sugar includes sucrose.

4. The method of claim 1 wherein the oxygen includes at least 40% O₂.

5. The method of claim 1 wherein the plurality of germinating plant seeds include a plurality of germinating sunflower seeds.

6. The method of claim 1 wherein the manipulating step includes:

enhancing fatty acid β

-oxidation inside a plurality of mitochondrial matrixes with sucrose suppression of a plurality of glyoxylate cycles in the plurality of germinating plant seeds; and

stimulating mitochondrial β

-oxidation of the fatty acids in the plurality of germinating plant seeds with O₂.

7. The method of claim 1 wherein the mental health disorders include Alzheimer'"'"'s disease, geriatric depression, non-geriatric depression, and schizophrenia.

14. The method of claim 1 wherein the includes O₂ at least 40% O₂.

8. A method for producing L-carnitine (LCAR) and acetyl-L-carnitine (ALCAR), comprising:

enhancing fatty acid β

-oxidation inside a plurality of mitochondrial matrixes with sucrose suppression of a plurality of glyoxylate cycles in a plurality of germinating plant seeds over a pre-determined time period; and

stimulating mitochondrial β

-oxidation of the fatty acids in the plurality of plant seeds with O₂ for the pre-determined time period,

thereby producing enzymes to enhance LCAR and ALCAR synthesis in the plurality of germinating plant seeds.

9. The method of claim 8 further comprising:

extracting LCAR and ALCAR from the plurality of germinating plant seeds;

creating a pharmaceutically acceptable form of the extracted LCAR and ALCAR.

10. The method of claim 9 wherein the step of extracting LCAR AND ALCAR from the plurality of seeds includes extracting the LCAR AND ALCAR with an extraction protocol including hexane, methylene chloride and methyl alcohol.

11. The method of claim 9 wherein the step of creating a pharmaceutically acceptable form of the extracted LCAR and ALCAR includes a pharmaceutically acceptable solid or liquid for human consumption.

12. The method of claim 9 wherein the pharmaceutically acceptable form of ALCAR is used for treating mental health disorders including Alzheimer'"'"'s disease, geriatric depression, non-geriatric depression, and schizophrenia.

13. The method of claim 8 wherein the plurality of germinating plant seeds include a plurality of germinating sunflower seeds.

15. A method for producing L-carnitine (LCAR) and acetyl-L-carnitine (ALCAR), comprising:

enhancing fatty acid β

-oxidation inside a plurality of mitochondrial matrixes with sucrose suppression of a plurality of glyoxylate cycles in a plurality of germinating sunflower seeds over a pre-determined time period; and

stimulating mitochondrial β

-oxidation of the fatty acids in the plurality of sunflower seeds with O₂ for the pre-determined time period,

thereby producing enzymes to enhance LCAR and ALCAR synthesis in the plurality of germinating sunflower seeds.

16. The method of claim 15 wherein LCAR or ALCAR are used for treating mental health disorders including Alzheimer'"'"'s disease, geriatric depression, non-geriatric depression, and schizophrenia.

17. The method of claim 15 wherein the includes O₂ at least 40% O₂.

18. A composition for treating mental disorders in a human, comprising:

acetyl-L-carnitine (ALCAR) produced by enhancing fatty acid β

-oxidation inside a plurality of mitochondrial matrixes with sucrose suppression of a plurality of glyoxylate cycles in a plurality of germinating sunflower seeds over a pre-determined time period; and

stimulating mitochondrial β

-oxidation of the fatty acids in the plurality of sunflower seeds with O₂ for the pre-determined time period.

19. The composition of claim 18 wherein LCAR or ALCAR are used for treating mental health disorders including Alzheimer'"'"'s disease, geriatric depression, non-geriatric depression, and schizophrenia.

20. The composition of claim 19 used for treating the mental health disorders and preventing recurrent episodes thereof comprising an effective amount of ALCAR derived from the plurality of germinating sunflower seeds.