BRANCHED CHAIN FATTY ACIDS FOR PREVENTION OR TREATMENT OF GASTROINTESTINAL DISORDERS

• US 20100298433A1
• Filed: 09/16/2008
• Published: 11/25/2010
• Est. Priority Date: 09/17/2007
• Status: Active Grant

• Current Assignee: Cornell University
• Original Assignee: Cornell University
• Inventors: Brenna, James Thomas, Ran-Ressler, Rinat
• Granted Patent: US 9,254,275 B2
• Time in Patent Office: Days
• US Class Current: 514/560
• CPC Class Codes: A23L 33/12 Fatty acids or derivatives thereof
• CPC Class Codes: A23L 33/127 Antibiotics
• CPC Class Codes: A23L 33/135 Bacteria or derivatives thereof, e.g. probiotics
• 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 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• 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: A61K 31/201 having one or two double bonds, e.g. oleic, linoleic acids
• CPC Class Codes: A61K 35/741 Probiotics probiotic yeast, e.g. saccharomyces A61K36/06
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: C12N 1/20 Bacteria; Culture media therefor
• CPC Class Codes: C12N 1/38 Chemical stimulation of growth or activity by addition of chemical compounds which are not essential growth factors; Stimulation of growth by removal of a chemical compound C12N1/34 takes precedence
• 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

The present invention is directed to a method of preventing or treating a gastrointestinal condition in a subject, that includes administering one or more branched chain fatty acid to the subject under conditions effective to prevent 5 or treat the gastrointestinal condition in the subject. The present invention is also directed to methods of promoting gastrointestinal health in a subject and propagation of probiotic organisms. Also disclosed is a formulation which includes one or more branched chain fatty acid and an aqueous phase emulsified with the one or more branched chain fatty acids, where the formulation includes 10 over 25 wt % of the one or more branched chain fatty acid.

Claims

1. A method of preventing or treating a gastrointestinal condition in a subject, said method comprising:

administering one or more branched chain fatty acid to the subject under conditions effective to prevent or treat the gastrointestinal condition in the subject.

2. The method of claim 1 further comprising:

selecting a subject in need of treatment of the gastrointestinal condition prior to said administering.

3. The method of claim 1 further comprising:

selecting a subject in need of prevention of the gastrointestinal condition prior to said administering.

4. The method of claim 1, wherein the gastrointestinal condition is mediated by infection of the subject'"'"'s gastrointestinal tract by a pathogenic bacteria.

5. The method of claim 4, wherein the gastrointestinal condition is necrotizing enterocolitis.

6. The method of claim 1, wherein the gastrointestinal condition requires microbial colonization of the subject'"'"'s gastrointestinal tract.

7. The method of claim 6, wherein colonization of the subject'"'"'s gastrointestinal tract is carried out in conjunction with an antibiotic treatment.

8. The method of claim 1, wherein the gastrointestinal condition is a disease of the intestine involving inflammation.

9. The method of claim 8, wherein the gastrointestinal condition is inflammatory bowel disease.

10. The method of claim 1, wherein the one or more branched chain fatty acid is a C₁₁ to C₂₆ branched chain fatty acid or mixtures thereof.

11. The method of claim 1, wherein the one or more branched chain fatty acid is selected from the group consisting of 4,7-dimethyl-nonanoic acid, 4,8-dimethyl-decanoic acid, 8-methyl-undecanoic acid, iso-dodecanoic acid, 4,8-dimethyl-undecanoic acid, 4,9-dimethyl-undecanoic acid, iso-tridecanoic acid, anteiso-tridecanoic acid, 4,10-dimethyl-dodecanoic acid, iso-tetradecanoic acid, 4,11-dimethyl-tridecanoic acid, iso-pentadecanoic acid, anteiso-pentadecanoic acid, 8,10-dimethyl-tetradecanoic acid, 4,12-dimethyl-tetradecanoic acid, iso-hexadecanoic acid, 2-methyl hexadecanoic acid, 4,11-dimethyl-pentadecanoic acid, 4,13-dimethyl-pentadecanoic acid, iso-heptadecanoic acid, anteiso heptadecanoic acid, iso-octadecanoic acid, iso-eicosanoic acid, anteiso-heneicosanoic acid, iso-dodecanoic acid, iso-tetracosanoic acid, iso-pentacosanoic acid, anteiso-pentacosanoic acid, iso-hexacosanoic acid, phytanic acid, pristanic acid, and mixtures thereof.

12. The method of claim 11, wherein the one or more branched chain fatty acid is selected from the group consisting of iso-hexadecanoic acid, anteiso-hexadecanoic acid, 4,13-dimethylpentadecanoic acid, phytanic acid, pristanic acid, and mixtures thereof.

13. The method of claim 1, wherein the one or more branched chain fatty acid is selected from the group consisting of saturated and monounsaturated fatty acids and mixtures thereof.

14. The method of claim 13, wherein the one or more branched chain fatty acid is a branched form of a fatty acid selected from the group consisting of an octanoic acid, a decanoic acid, a lauric acid, a myristic acid, a palmitic acid, a stearic acid, an eicosanoic acid, a palmitoliec acid, an oleic acid, and mixtures thereof.

15. The method of claim 1, wherein the subject is human.

16. The method of claim 15, wherein the subject is a fetus.

17. The method of claim 15, wherein the subject is an infant.

18. The method of claim 17, wherein the subject is a newborn infant.

19. The method of claim 15, wherein the subject is a child.

20. The method of claim 15, wherein the subject is an adult.

21. A method of promoting gastrointestinal health in a subject, said method comprising:

administering one or more branched chain fatty acid to the subject under conditions effective to promote gastrointestinal health in the subject.

22. The method of claim 21 further comprising:

selecting a subject in need of promoting gastrointestinal health prior to said administering.

23. The method of claim 21, wherein the one or more branched chain fatty acid is a C₁₁ to C₂₆ branched chain fatty acid or mixtures thereof.

24. The method of claim 21, wherein the one or more branched chain fatty acid is selected from the group consisting of 4,7-dimethyl-nonanoic acid, 4,8-dimethyl-decanoic acid, 8-methyl-undecanoic acid, iso-dodecanoic acid, 4,8-dimethyl-undecanoic acid, 4,9-dimethyl-undecanoic acid, iso-tridecanoic acid, anteiso-tridecanoic acid, 4,10-dimethyl-dodecanoic acid, iso-tetradecanoic acid, 4,11-dimethyl-tridecanoic acid, iso-pentadecanoic acid, anteiso-pentadecanoic acid, 8,10-dimethyl-tetradecanoic acid, 4,12-dimethyl-tetradecanoic acid, iso-hexadecanoic acid, 2-methyl hexadecanoic acid, 4,11-dimethyl-pentadecanoic acid, 4,13-dimethyl-pentadecanoic acid, iso-heptadecanoic acid, anteiso heptadecanoic acid, iso-octadecanoic acid, iso-eicosanoic acid, anteiso-heneicosanoic acid, iso-dodecanoic acid, iso-tetracosanoic acid, iso-pentacosanoic acid, anteiso-pentacosanoic acid, iso-hexacosanoic acid, phytanic acid, pristanic acid, and mixtures thereof.

25. The method of claim 24, wherein the one or more branched chain fatty acid is selected from the group consisting of iso-hexadecanoic acid, anteiso-hexadecanoic acid, 4,13-dimethylpentadecanoic acid, phytanic acid, pristanic acid, and mixtures thereof.

26. The method of claim 21, wherein the one or more branched chain fatty acid is selected from the group consisting of saturated and monounsaturated fatty acids and mixtures thereof.

27. The method of claim 26, wherein the one or more branched chain fatty acid is a branched form of a fatty acid selected from the group consisting of an octanoic acid, a decanoic acid, a lauric acid, a myristic acid, a palmitic acid, a stearic acid, an eicosanoic acid, a palmitoliec acid, an oleic acid, and mixtures thereof.

28. The method of claim 21, wherein the subject is human.

29. A method of promoting propagation of probiotic organisms, said method comprising:

providing a population of cells comprising probiotic organisms and

administering one or more branched chain fatty acid to the population of cells under conditions effective to promote propagation of probiotic organisms in the population of cells.

30. The method of claim 29, wherein the one or more branched chain fatty acid is a C₁₁ to C₂₆ branched chain fatty acid or mixtures thereof.

31. The method of claim 29, wherein the one or more branched chain fatty acid is selected from the group consisting of 4,7-dimethyl-nonanoic acid, 4,8-dimethyl-decanoic acid, 8-methyl-undecanoic acid, iso-dodecanoic acid, 4,8-dimethyl-undecanoic acid, 4,9-dimethyl-undecanoic acid, iso-tridecanoic acid, anteiso-tridecanoic acid, 4,10-dimethyl-dodecanoic acid, iso-tetradecanoic acid, 4,11-dimethyl-tridecanoic acid, iso-pentadecanoic acid, anteiso-pentadecanoic acid, 8,10-dimethyl-tetradecanoic acid, 4,12-dimethyl-tetradecanoic acid, iso-hexadecanoic acid, 2-methyl hexadecanoic acid, 4,11-dimethyl-pentadecanoic acid, 4,13-dimethyl-pentadecanoic acid, iso-heptadecanoic acid, anteiso heptadecanoic acid, iso-octadecanoic acid, iso-eicosanoic acid, anteiso-heneicosanoic acid, iso-dodecanoic acid, iso-tetracosanoic acid, iso-pentacosanoic acid, anteiso-pentacosanoic acid, iso-hexacosanoic acid, phytanic acid, pristanic acid, and mixtures thereof.

32. The method of claim 31, wherein the one or more branched chain fatty acid is selected from the group consisting of iso-hexadecanoic acid, anteiso-hexadecanoic acid, 4,13-dimethylpentadecanoic acid, phytanic acid, pristanic acid, and mixtures thereof.

33. The method of claim 29, wherein the one or more branched chain fatty acid is selected from the group consisting of saturated and monounsaturated fatty acids and mixtures thereof.

34. The method of claim 33, wherein the one or more branched chain fatty acid is a branched form of a fatty acid selected from the group consisting of an octanoic acid, a decanoic acid, a lauric acid, a myristic acid, a palmitic acid, a stearic acid, an eicosanoic acid, a palmitoliec acid, an oleic acid, and mixtures thereof.

35. The method of claim 29, wherein the method is carried out in vitro.

36. The method of claim 29, wherein the method is carried out in vivo.

37. The method of claim 36 further comprising:

selecting a subject in need of probiotic organism propagation prior to said administering.

38. The method of claim 29, wherein the probiotic organism comprises an organism selected from the group consisting of Lactobacillus species, Bifidobacterium species, other lactic acid bacteria, nonlactic acid bacteria, and mixtures thereof.

39. The method of claim 38, wherein the probiotic organism comprises a Lactobacillus species selected from the group consisting of L. acidophilus, L. amylovorus, L. brevis, L. casei, L. casei subsp. rhamnosus (Lactobacillus GG), L. caucasicus, L. crispatus, L. delbrueckii subsp. bulgaricus (L. bulgaricus), L. fermentum (L. fermenti), L. gasseri, L. helveticus, L. johnsonii, L. lactis, L. leichmannii, L. paracasei, L. plantarum, L. reuteri, L. rhamnosus, and mixtures thereof.

40. The method of claim 38, wherein the probiotic organism comprises a Bifidobacterium species selected from the group consisting of B. adolescentis, B. bifidum, B. breve, B. infantis, B. lactis (B. animalis), B. licheniformis, B. longum, and mixtures thereof.

41. The method of claim 38, wherein the probiotic organism comprises a lactic acid bacteria selected from the group consisting of Enterococcus faecium, Lactococcus lactis, Leuconstoc mesenteroides, Pediococcus acidilactici, Streptococcus thermophilus, and mixtures thereof.

42. The method of claim 38, wherein the probiotic organism comprises a nonlactic acid bacteria selected from the group consisting of Bacillus subtilis, Escherichia coli strain nissle, Saccharomyces boulardii, Saccharomyces cerevisiae, and mixtures thereof.

43. A formulation comprising:

one or more branched chain fatty acids and

an aqueous phase emulsified with said one or more branched chain fatty acids, wherein said formulation comprises over 25 wt % of said one or more branched chain fatty acids.

44. The formulation of claim 43, wherein the one or more branched chain fatty acid is a C₁₁ to C₂₆ branched chain fatty acid or a mixture thereof.

45. The formulation of claim 43, wherein the one or more branched chain fatty acid is selected from the group consisting of 4,7-dimethyl-nonanoic acid, 4,8-dimethyl-decanoic acid, 8-methyl-undecanoic acid, iso-dodecanoic acid, 4,8-dimethyl-undecanoic acid, 4,9-dimethyl-undecanoic acid, iso-tridecanoic acid, anteiso-tridecanoic acid, 4,10-dimethyl-dodecanoie acid, iso-tetradecanoic acid, 4,11-dimethyl-tridecanoic acid, iso-pentadecanoic acid, anteiso-pentadecanoic acid, 8,10-dimethyl-tetradecanoic acid, 4,12-dimethyl-tetradecanoic acid, iso-hexadecanoic acid, 2-methyl hexadecanoic acid, 4,11-dimethyl-pentadecanoic acid, 4,13-dimethyl-pentadecanoic acid, iso-heptadecanoic acid, anteiso heptadecanoic acid, iso-octadecanoic acid, iso-eicosanoic acid, anteiso-heneicosanoic acid, iso-dodecanoic acid, iso-tetracosanoic acid, iso-pentacosanoic acid, anteiso-pentacosanoic acid, iso-hexacosanoic acid, phytanic acid, pristanic acid, and mixtures thereof.

46. The formulation of claim 45, wherein the one or more branched chain fatty acid is selected from the group consisting of iso-hexadecanoic acid, anteiso-hexadecanoic acid, 4,13-dimethylpentadecanoic acid, phytanic acid, pristanic acid, and mixtures thereof.

47. The formulation of claim 43, wherein the one or more branched chain fatty acid is selected from the group consisting of saturated and monounsaturated fatty acids and mixtures thereof.

48. The formulation of claim 47, wherein the one or more branched chain fatty acid is a branched form of a fatty acid selected from the group consisting of an octanoic acid, a decanoic acid, a lauric acid, a myristic acid, a palmitic acid, a stearic acid, an eicosanoic acid, a palmitoliec acid, an oleic acid, and mixtures thereof.

49. The formulation of claim 45, wherein the formulation comprises up to 70 wt % of said one or more branched chain fatty acid.

50. The formulation of claim 45, further comprising:

an emulsifier.

51. The formulation of claim 45, wherein said one or more branched chain fatty acid comprises up to 20 wt % of isomyristic acid, isopentadecoanoic acid, anteisopentadecanoic acid, isopalmitic acid, isoeicosanoic acid, anteisoeicosanoic acid, isodocosanoic acid, isotetracosanoic acid, isohexacosanoic acid, or combinations thereof.