MIXTURE OF FATTY ACIDS AND PALMITOYLETHANOLAMIDE FOR USE IN THE TREATMENT OF INFLAMMATORY AND ALLERGIC PATHOLOGIES

Abstract

The present invention relates to a mixture containing up to two fatty acids selected from palmitic acid, oleic acid, stearic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, azelaic acid and myristic acid and palmitoylethanolamide. In one embodiment of the present invention said mixture is characterized in that at least one of said up to two fatty acids is saturated. The present invention also relates to the use of the aforesaid mixture in the treatment of inflammatory and allergic pathologies.

Claims

1-21. (canceled)

22. A mixture comprising up to two fatty acids selected from palmitic acid, oleic acid, stearic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (PHA), azelaic acid and myristic acid and palmitoylethanolamide.

23. The mixture according to claim 22, wherein at least one of the up to two fatty acids is saturated.

24. The mixture according to claim 22, which comprises a fatty acid and palmitoylethanolamide.

25. The mixture according to claim 22, which comprises two fatty acids and palmitoylethanolamide.

26. The mixture according to claim 24, wherein the fatty acid is present in the mixture in a quantity in weight comprised between 15% and 55%, preferably between 20% and 53%, of the total weight of the mixture.

27. The mixture according to claim 24, wherein the palmitoylethanolamide is present in the mixture in a quantity in weight comprised between 45% and 85%, preferably between 47% and 80%, of the total weight of the mixture.

28. The mixture according to claim 25, wherein the two fatty acids are present in the mixture in a weight ratio from one to another comprised between 0.25 and 2.33, preferably between 0.33 and 1.5, more preferably about 1.

29. The mixture according to claim 25, wherein the two fatty acids are present in a weight ratio with respect to the palmitoylethanolamide comprised between 0.25 and 1.5, preferably between 0.43 and 1, more preferably about 0.67.

30. The mixture according to claim 25, wherein the palmitoylethanolamide is present in the mixture in a weight quantity comprised between 25% and 70%, preferably between 35% and 60%, more preferably about 40%, of the total weight of the mixture.

31. The mixture according to claim 25, wherein the two fatty acids are present in the mixture in a weight quantity comprised between 30% and 75%, preferably between 40% and 65%, more preferably about 60%, of the total weight of the mixture.

32. A composition comprising the mixture according to claim 22 and at least one pharmaceutically acceptable excipient.

33. The composition according to claim 32, formulated in an oral, topical, rectal, vaginal, ophthalmic or parenteral form.

34. The composition according to claim 33, which is an oral form selected from a tablet, capsule, granule, oily pearl, solution, suspension and aerosol, preferably the oral form is a tablet, capsule or solution.

35. The composition according to claim 33, which is a topical form selected from cream, ointment, gel, salve, solution, suspension, eyewash, spray, drops and powder, preferably the topical form is a cream, gel, spray, otological drops or ointment.

36. The composition according to claim 33, which is a parenteral form selected from a water buffer solution and oily suspension, preferably the parental form is an oily suspension.

37. The composition according to claim 33, which is a rectal form selected from a suppository, a cream and an enema.

38. The composition according to claim 33, which is a vaginal form selected from a pessary, a cream and a vaginal douche or it is administered with a cannula.

39. The composition according to claim 33, which is an ophthalmic form selected from an eyewash, a cream and a bath.

40. The composition according to claim 32, wherein the mixture is present in the composition in a weight quantity comprised between 15% and 70%, preferably comprised between 20% and 65% of the total weight of the composition.

41. A method of treating a condition selected froth inflammatory and allergic pathologies, including neuroinflammatory pathologies of the peripheral nervous system, in a subject in need thereof, comprising administering an effective amount of the mixture according to claim 22, alone or in combination with one or more pharmaceutically acceptable excipients.

42. The method according to claim 41, wherein the mixture is administered daily, from one to four doses a day, wherein the dose contains from 0.1 to 50 mg of composition/kg of patient body weight, preferably from 0.5 to 20 mg/kg of patient body weight, for at least 4 weeks.

43. The composition of claim 22, wherein the composition is appropriately packaged for once-a-day administration of the mixture, from one to four doses a day, wherein the dose contains from 0.1 to 50 mg of composition/kg of patient body weight, preferably from 0.5 to 20 mg/kg of patient body weight, for at least 4 weeks.

Description

EXAMPLES

[0109] The following mixtures according to the present invention were prepared.

Example 1

Formulation in Topical Cream

[0110]

TABLE-US-00001 Eicosapentaenoic acid 40% Palmitoylethanolamide 60%

Example 2

Formulation in Vaginal Pessary

[0111]

TABLE-US-00002 Docosahexaenoic acid 45% Palmitoylethanolamide 55%

Example 3

Formulation in Otological Drops

[0112]

TABLE-US-00003 Eicosapentaenoic acid 30% Docosahexaenoic acid 30% Palmitoylethanolamide 40%

Example 4

Formulation in Cream for Periophthalmic Use

[0113]

TABLE-US-00004 Eicosapentaenoic acid 35% Docosahexaenoic acid 30% Palmitoylethanolamide 35%

Example 5

Evaluation of the Anti-Inflammatory Activity In Vitro

[0114] A mixture of fatty acids containing: palmitoylethanolamide (33%), linoleic acid (33%) and palmitic acid (33%) (defined in the tables as Fatty Acids) was tested in vitro on a human cell line THP1 (monocyte-macrophage) previously sensitized with LPS (1 μg/ml), a known inflammatory agent, to evaluate the activity of the mixture to reduce the release of pro-inflammatory mediators (IL-6 and IL-8).

Results

[0115] All doses of the mixture analyzed have proved to be able to inhibit the release of both cytokines checked IL-6 and IL-8 (FIGS. 1 and 2, Table 1 and 2). The tests performed have identified two effective doses 0.06 mg/ml and 0.03 mg/ml: at these concentrations in fact the anti-inflammatory effectiveness of fatty acids mixture determines a strong reduction of IL-6 release equal to 100% and 58% respectively, and at 0.06 mg/ml it causes a IL-8 release inhibition equal to 42.7%.

TABLE-US-00005 TABLE 1 Acidi Grassi + LPS pg/ml IL8 % Inhib. IL8 0.06 mg/ml 323.70 41.06 0.03 mg/ml 488.02 11.13 0.01 mg/ml 526.12 4.19 Quality Control 369.76 32.67 Pos. Control 549 0

TABLE-US-00006 TABLE 2 Acidi Grassi + LPS g/ml IL6 % Inhib. IL6 0.06 mg/ml 0 100 0.03 mg/ml 15.74 58 0.01 mg/ml 39.62 0 Quality Control 0 100 Pos. Control 38 0