COMPOSITIONS AND METHODS FOR REDUCING CHRONIC LOW-LEVEL INFLAMMATION

• US 20170014432A1
• Filed: 03/06/2015
• Published: 01/19/2017
• Est. Priority Date: 03/13/2014
• Status: Abandoned Application

• Current Assignee: Barry D. Sears
• Original Assignee: Barry D. Sears
• Inventors: SEARS, Barry D.
• Application Number:
  US15/124,057
• Publication Number:
  US 20170014432A1
• Time in Patent Office: Days
• US Class Current: 1/1
• 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 31/065 Diphenyl-substituted acyclic alcohols
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/36 Compounds containing methylenedioxyphenyl groups, e.g. sesamin
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61K 31/77 of oxiranes
• CPC Class Codes: A61K 35/60 Fish, e.g. seahorses; Fish eggs
• CPC Class Codes: A61K 36/889 Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/4825 Proteins, e.g. gelatin gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 : for osteoporosis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• 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 27/02 : Ophthalmic agents
• 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 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• 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 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

The invention relates to compositions and methods for reducing chronic low-level inflammation associated with chronic conditions. Specifically, the invention relates to compositions of hydrophobic derivatives of aspirin and/or hydrophobic derivatives of sesamol in combination with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and their methods for reducing chronic low-level inflammation associated with chronic conditions including obesity, metabolic syndrome, diabetes, cardiovascular disease, cancer, auto-immune disorders, ocular and neurological disorders in a mammal.

Claims

1. A composition comprising hydrophobic derivatives of aspirin and/or hydrophobic derivatives of sesamol in combination with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for reducing chronic low-level inflammation associated with chronic conditions including obesity, metabolic syndrome, diabetes, cardiovascular disease, cancer, auto-immune disorders, ocular and neurological disorders in a mammal.

2. The composition of claim 1, wherein the EPA and DHA can be in the form of ethyl esters, triglycerides, free fatty acids, phospholipids, or other formats that are hydrophobic.

3. The composition of claim 1, wherein the level of hydrophobic aspirin is 0.1-10% of the combined level of EPA and DHA.

4. The composition of claim 1, wherein combined the level of hydrophobic aspirin and hydrophobic sesamol is 0.1-10% of the combined level of EPA and DHA.

5. The composition of claim 1, wherein reduction of inflammation is through concomitantly reducing the initiation phase and enhancing the resolution phase of the inflammation.

6. The composition of claim 1, wherein the amount of EPA and DHA is adjusted so that the arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio in the blood is reduced to range between 1 and 10, and preferably between 1 and 5.

7. The composition of claim 5, wherein enhancing the resolution phase is indicated by enhancing the level of resolvins in the blood.

8. The composition of claim 1, wherein the amount of EPA and DHA ranges from 1 to 25 grams per day.

9. The composition of claim 1, wherein the derivative of sesamol is an acylated sesamol.

10. The composition of claim 9, wherein the acylated sesamol is obtained by reacting a sesamol compound with an activated carboxylic acid.

11. The composition of claim 10, wherein the activated carboxylic acid is an acid chloride, an acid anhydride, or obtained by reacting a carboxylic acid with 1,1 carbonyl diimidazole.

12. The composition of claim 10, wherein the activated carboxylic acid is an activated fatty acid.

13. The composition of claim 12, wherein the activated fatty acid comprises 2 to 22 carbon atoms.

14. The composition of claim 10, wherein the degree of unsaturation of the activated fatty acid ranges from 0 to 6 double bonds.

15. The composition of claim 10, wherein the activated fatty acid is an activated derivative of palmitic acid, oleic acid, linoleic acid, alpha-linolenic acid, arachidic acid, gadoleic acid, 5,8,11,14,17-eicosapentaenoic acid, or 4,7,10,13,16,19-docosahexaenoic acid.

16. The composition of claim 1, wherein the derivative of sesamol is sesamol oleate.

17. The composition of claim 10, wherein the activated carboxylic acid is an acid chloride or an acid anhydride of CH₃O(CH₂CH₂O)_nCH₂C(O)OH, or obtained by reacting CH₃O(CH₂CH₂O)_nCH₂C(O)OH with 1,1 carbonyl diimidazole, wherein n ranges from 2 to 400.

18. The composition of claim 1, wherein the derivative of aspirin is obtained through esterification with an acyl chloride.

19. The composition of claim 18, wherein the esterification is carried out by reacting an aspirin compound with an acyl chloride.

20. The composition of claim 19, wherein the acyl chloride is derived from a fatty acid.

21. The composition of claim 20, wherein the fatty acid comprises 2 to 22 carbon atoms.

22. The composition of claim 21, wherein the degree of unsaturation of the fatty acid ranges from 0 to 6 double bonds.

23. The composition of claim 19, wherein the acyl moiety is a carboxylic derivative of methoxy polyethylene glycol.

24. The composition of claim 23, wherein the carboxyl methoxy polyethylene glycol compound is characterized by CH₃O(CH₂CH₂O)_nCH₂C(O)OH, wherein n ranges from 2 to 400.

25. The composition of claim 1, wherein the composition is prepared as a pharmaceutical, a liquid, a soft gelatin capsule, or an emulsion.

26. The composition of claim 1, wherein the hydrophobic derivatives of sesamol and aspirin are formulated in capsule, liquid or emulsion compatible with EPA and DHA formulations.

27. The composition of claim 1, wherein the composition further comprises carotenoids such as lutein and zeaxanthin.

28. The composition of claim 1, wherein the composition further comprises gamma-linolenic acid ester.

29. The composition of claim 1, wherein the composition is co-administered with a food product containing proteins and carbohydrates, wherein the proteins and the carbohydrates are present at a ratio of between about 0.5 and about 1.0.

30. The composition of claim 1, wherein the composition is prepared for topical administration.

31. A method for reducing chronic low-level inflammation associated with chronic conditions including obesity, metabolic syndrome, diabetes, cardiovascular disease, cancer, auto-immune disorders, ocular and neurological disorders in a mammal, comprising administering to a mammal a composition comprising hydrophobic derivatives of aspirin and/or hydrophobic derivatives of aspirin and sesamol in combination with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

32. The method of claim 31, wherein the level of hydrophobic aspirin is 0.1-10% of the combined level of EPA and DHA.

33. The method of claim 31, wherein the combined level of hydrophobic aspirin and sesamol is 0.1-10% of the combined level of EPA and DHA.

34. The method of claim 31, wherein reduction of inflammation is through concomitantly reducing the initiation phase and enhancing the resolution phase of the inflammation.

35. The method of claim 31, wherein the amount of EPA and DHA is adjusted so that the arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio in the blood is reduced to range between 1 and 10, and preferably between 1 and 5.

36. The method of claim 34, wherein enhancing the resolution phase is indicated by enhancing the level of resolvins in the blood.

37. The method of claim 31, wherein the amount of EPA and DHA ranges from 1 to 25 grams per day.

38. The method of claim 31, wherein the derivative of sesamol is an acylated sesamol.

39. The method of claim 38, wherein the acylated sesamol is obtained by reacting a sesamol compound with an activated carboxylic acid.

40. The method of claim 39, wherein the activated carboxylic acid is an acid chloride, an acid anhydride, or obtained by reacting a carboxylic acid with 1,1 carbonyl diimidazole.

41. The method of claim 39, wherein the activated carboxylic acid is an activated fatty acid.

42. The method of claim 41, wherein the activated fatty acid comprises 2 to 22 carbon atoms.

43. The method of claim 41, wherein the degree of unsaturation of the activated fatty acid ranges from 0 to 6 double bonds.

44. The method of claim 39, wherein the activated fatty acid is an activated derivative of palmitic acid, oleic acid, linoleic acid, alpha-linolenic acid, arachidic acid, gadoleic acid, 5,8,11,14,17-eicosapentaenoic acid, or 4,7,10,13,16,19-docosahexaenoic acid.

45. The method of claim 31, wherein the derivative of sesamol is sesamol oleate.

46. The method of claim 39, wherein the activated carboxylic acid is an acid chloride or an acid anhydride of CH₃O(CH₂CH₂O)_nCH₂C(O)OH, or obtained by reacting CH₃O(CH₂CH₂O)_nCH₂C(O)OH with 1,1 carbonyl diimidazole, wherein n ranges from 2 to 400.

47. The method of claim 31, wherein the derivative of aspirin is obtained through esterification with an acyl chloride

48. The method of claim 47, wherein esterification is carried out by reacting an aspirin compound with an acyl chloride.

49. The method of claim 48, wherein the acyl chloride is derived from a fatty acid.

50. The method of claim 49, wherein the fatty acid comprises 2 to 22 carbon atoms.

51. The method of claim 50, wherein the degree of unsaturation of the fatty alcohol ranges from 0 to 6 double bonds.

52. The method of claim 48, wherein the acyl group is a carboxyl derivative of methoxy polyethylene glycol.

53. The method of claim 52, wherein the carboxyl derivative of methoxy polyethylene glycol is characterized by CH₃O(CH₂CH₂O)_nCH₂C(O)OH, wherein n ranges from 2 to 400.

54. The method of claim 31, wherein the composition is prepared as a pharmaceutical in a form selected from the group consisting of a liquid, a capsule, or an emulsion.

55. The method of claim 31, wherein the hydrophobic derivatives of sesamol and aspirin are formulated in capsule, liquid or emulsion compatible with EPA and DHA formulations.

56. The method of claim 31, wherein the composition further comprises carotenoids such as lutein and zeaxanthin.

57. The method of claim 31, wherein the composition further comprises gamma-linolenic acid ester.

58. The method of claim 31, wherein the composition is co-administered with a food product, wherein the proteins and the carbohydrates are present at a ratio of between about 0.5 and about 1.0.

59. The method of claim 31, wherein the administering step is carried out enterally or parenterally.

60. The method of claim 31, wherein the composition is administered to the mammal in an amount that is effective to reduce inflammation in the mammal.

61. The method of claim 31, wherein the composition can be administered in soft gelatin capsule, liquid administration or emulsion (both micro and macro), as well as in other delivery systems.

62. The method of claim 31, wherein the composition can be administered in a single daily dose.

63. The method of claim 62 wherein the single daily dose comprises 20 mg of hydrophobic aspirin.

64. The method of claim 31, wherein the composition is prepared for topical administration.