Dietary Control of Arachidonic Acid Metabolism

• US 20070105957A1
• Filed: 11/14/2006
• Published: 05/10/2007
• Est. Priority Date: 02/23/1998
• Status: Active Grant

• Current Assignee: Wake Forest University
• Original Assignee: Wake Forest University
• Inventors: Chilton, Floyd
• Granted Patent: US 8,247,449 B2
• Time in Patent Office: Days
• US Class Current: 514/560
• CPC Class Codes: A23L 2/385 Concentrates of non-alcoholic beverages
• CPC Class Codes: A23L 2/52 Adding ingredients adding preservatives A23L2/44
• CPC Class Codes: A23L 33/115 Fatty acids or derivatives thereof; Fats or oils
• CPC Class Codes: A23L 33/12 Fatty acids or derivatives thereof
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2250/154 Water
• CPC Class Codes: A23V 2250/187 Eicosapentaenoic acid
• CPC Class Codes: A23V 2250/5086 Xanthan
• CPC Class Codes: A23V 2250/628 Saccharose, sucrose
• CPC Class Codes: A23V 2250/6406 Glycerol
• CPC Class Codes: A61K 31/185 Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids hydroxamic acids A61K31/16; peroxy acids A61K31/327
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/06 Antiabortive agents; Labour repressants
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 : Antidepressants
• 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 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• 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: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Compositions for the treatment of symptoms of inflammatory disorders may include gamma-linolenic acid or dihomogammalinolenic acid, an inhibitor of Δ⁵ desaturase, and optionally stearidonic acid or ω-3 arachidonic acid. Preferred formulations may be in the form of a good tasting, preferably milk or fruit based drink, or a dried powder. Compositions reduce inflammation and inhibit increase in serum arachidonic acid associated with gamma-linolenic acid.

Claims

1. A method of treating an inflammatory disorder, or a disorder having an inflammatory component, in a mammalian subject in need of such treatment by administering to said subject an effective amount of a composition in unit dosage form for delivery of a daily dose of said composition, said composition consisting essentially of:

(i) an effective amount of γ

-linolenic acid (GLA) for increasing dihomogammalinolenic acid (DGLA) levels in the inflammatory cells of said mammalian subject, thereby inhibiting the metabolism of arachidonic acid;

(ii) an effective amount of a Δ

⁵ desaturase inhibitor for inhibiting accumulation of arachidonic acid in the serum of said mammalian subject; and

, optionally,

(iii) an effective amount of a competitive inhibitor of arachidonic acid metabolism.

2. The method of claim 1, wherein the mammalian subject is a human subject.

3. The method of claim 1, wherein said disorder is at least one of asthma, allergic rhinitis, allergic rhinoconjunctivitis, psoriasis, acute myocardial infarction, glomerulonephritis, Crohn'"'"'s disease, inflammatory bowel disease, arthritis, breast cancer, colon cancer, prostate cancer, an autoimmune disease, systemic Lupus erythematosus, schizophrenia, depression, IgA nephropathy, sepsis, toxic shock, organ failure, organ transplant, coronary angioplasty, risk for Alzheimer'"'"'s disease, cystic fibrosis, atherosclerosis, menstrual discomfort, cyclic breast pain, premature labor, gout, venous leg ulcers, coronic urticaria, primary dysmenorrhea, endometriosis, or Lyme disease.

4. The method of claim 1, wherein said GLA is present in an amount from about 1 gram to about 10 grams.

5. The method of claim 4, wherein said GLA is present in an amount from about 1.5 grams to about 3 grams.

6. The method of claim 1, wherein the Δ

⁵ desaturase inhibitor is eicospentaenoic acid (EPA), sesamin, episesamin, sesaminol, sesamolin, curcumin, α

-linolinic acid, heneicosapentaenoic acid, docosahexaenoic acid, alkyl gallate, propyl gallate, or p-isopentoxyaniline.

7. The method of claim 1, wherein said Δ

⁵ desaturase inhibitor is EPA.

8. The method of claim 7, wherein said EPA is present in an amount from about 0.1 gram to about 10 grams

9. The method of claim 7, wherein said EPA is present in an amount from about 0.25 gram to about 5 grams.

10. The method of claim 7, wherein said EPA is present in an amount from about 0.5 gram to about 3 grams.

11. The method of claim 7, wherein the ratio of GLA to EPA is from 1:

1 to 2;

1.

12. The method of claim 11, wherein said EPA is present in an amount from about 0.1 gram to about 10 grams

13. The method of claim 11, wherein said EPA is present in an amount from about 0.25 gram to about 5 grams.

14. The method of claim 11, wherein said EPA is present in an amount from about 0.5 gram to about 3 grams.

15. The method of claim 11, wherein said EPA is present in an amount of about 0.1 gram.

16. The method of claim 11, wherein said EPA is present in an amount of about 0.25 gram.

17. The method of claim 11, wherein said EPA is present in an amount of about 0.5 gram.

18. The method of claim 7, wherein said composition comprises a 2:

1 ratio of GLA;

EPA.

19. The method of claim 1, wherein said composition comprises stearidonic acid.

20. The method of claim 19, wherein stearidonic acid is present in an amount from about 0.1 gram to about 15 grams.

21. The method of claim 1, wherein said Δ

⁵ desaturase inhibitor is a free fatty acid, a fatty acyl ester, a diglyceride, a triglyceride, an ethyl ester, a phospholipid, a steryl ester, a sphingolipid, or a combination of the foregoing.

22. The method of claim 1, wherein said composition comprises ω

-3 arachidonic acid.

23. The method of claim 1, wherein said composition is an emulsion wherein said Δ

⁵ desaturase inhibitor is EPA, which is present in an amount from about 0.1 gram to about 10 grams, and wherein said composition further includes an emulsifying agent, and at least one flavoring agent, sweetening agent, coloring agent or preservative.

24. The method of claim 23, wherein said EPA is present in an amount from about 0.25 gram to about 5 grams.

25. The method of claim 23, wherein said EPA is present in an amount from about 0.5 grams to about 3 grams.

26. The method of claim 1, wherein the composition is a flavored drink.

27. The method of claim 1, wherein the composition is a powder.

28. The method of claim 1, wherein the composition is a tablet or capsule.