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1. (WO2019032910) THERAPEUTIC FORMULATIONS AND USES THEREOF
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What is claimed is:

1. An injectable pharmaceutical composition, comprising:

a) a cyclooxygenase-2 (COX-2) inhibitor, wherein the COX-2 inhibitor is mavacoxib, a compound of Formula (I):


(I)

or an isomer or pharmaceutically acceptable salt thereof, a compound of Formula (II):


(II)

or an isomer or pharmaceutically acceptable salt thereof, or any combination thereof; and b) a solvent, wherein the composition is formulated for subcutaneous administration.

2. The composition of claim 1, wherein the COX-2 inhibitor is selected from the group consisting of: Tris(hydroxymethyl)aminomethane (±)-6-(trifluoromethoxy)-2- (trifluoromethyl)-2H-chromene-3-carboxylate, (±)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid, Tris(hydroxymethyl)aminomethane (R)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate, (R)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid, Tris(hydroxymethyl)aminomethane (S)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3 -carboxylate, (S)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3 -carboxylic acid, and any combination thereof.

3. The composition of claim 1, wherein the COX -2 inhibitor is a compound of Formula (III):


(III)

or an isomer or pharmaceutically acceptable salt thereof.

4. The composition of claim 1, wherein the COX-2 inhibitor is mavacoxib.

5. The composition of claim 1, wherein the composition is non-aqueous.

6. The composition of claim 1, further comprising propylene glycol present at over 1% w/w of the composition.

7. The composition of claim 6, wherein the propylene glycol is present at about 60% w/w or less of the composition.

8. The composition of claim 6, wherein the propylene glycol is present at about 50% w/w.

9. The composition of claim 1, further comprising polyethylene glycol present at about 85% w/w or less of the composition.

10. The composition of claim 9, wherein the polyethylene glycol is present at about 30 to 35% w/w or less of the composition.

11. The composition of claim 1, further comprising ethanol present at about 25% w/w or less of the composition.

12. The composition of claim 1, wherein the COX-2 inhibitor is present at about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% w/w of the composition.

13. The composition of claim 1, further comprising an anti -oxidant.

14. The composition of claim 13, wherein the anti-oxidant is present at no more than about 10% w/w of the composition.

15. The composition of claim 1, wherein the composition comprises:

i) COX-2 inhibitor;

ii) propylene glycol;

iii) polyethylene glycol;

iv) ethanol; and optionally

v) an anti-oxidant.

16. The composition of claim 1, wherein the composition comprises:

i) COX-2 inhibitor at a concentration of about 0.5 to 50% w/w;

ii) propylene glycol at a concentration of about 1 to 60% w/w;

iii) polyethylene glycol at a concentration of about 0.5 to 85% w/w; and iv) ethanol at a concentration of about 0.001 to 25% w/w.

17. The composition of claim 1, wherein the composition comprises:

i) COX-2 inhibitor at a concentration of about 5 to 15% w/w;

ii) propylene glycol at a concentration of about 45 to 55% w/w;

iii) polyethylene glycol at a concentration of about 30 to 35% w/w; and iv) ethanol at a concentration of about 1 to 10% w/w.

18. The composition of claim 1, wherein at least about 5,000, 10,000, 15,000 or 20,000 ng/ml of the COX-2 inhibitor is present in the blood stream of the subject for at least about 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 hours or greater upon administration to a mammal.

19. The composition of claim 1, further comprising buprenorphine.

20. The composition of claim 19, wherein buprenorphine is present in a dose of about 0.1, 0.2, 0.3, 0.4, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5 or 7.0 mg/kg.

21. The composition of claim 1, wherein the composition is stable at room temperature for at least 6 months.

22. The composition of claim 21, wherein the composition is stable at room temperature for at least 12 months.

23. A pharmaceutical composition for topical administration, comprising:

a) a cyclooxygenase-2 (COX-2) inhibitor, wherein the COX-2 inhibitor is mavacoxib, a compound of Formula (I):


(I)

or an isomer or pharmaceutically acceptable salt thereof, a compound of Formula (II):


(II)

or an isomer or pharmaceutically acceptable salt thereof, or any combination thereof; and b) a solvent; wherein the composition is formulated as a topical dosage form.

24. The composition of claim 23, wherein the COX-2 inhibitor is selected from the group consisting of: Tris(hydroxymethyl)aminomethane (±)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate, (±)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid, Tris(hydroxymethyl)aminomethane (R)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate, (R)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid, Tris(hydroxymethyl)aminomethane (S)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3 -carboxylate, (S)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3 -carboxylic acid, and any combination thereof.

25. The composition of claim 23, wherein the COX-2 inhibitor is a compound of Formula (III):


(HI)

or an isomer or pharmaceutically acceptable salt thereof.

26. The composition of claim 23, wherein the COX-2 inhibitor is mavacoxib.

27. The composition of claim 23, wherein the composition is non-aqueous.

28. The composition of claim 23, further comprising propylene glycol present at w/w of the composition.

29. The composition of claim 28, wherein the propylene glycol is present at about 99% w/w or less of the composition.

30. The composition of claim 28, wherein the propylene glycol is present at about 40% w/w or less of the composition.

31. The composition of claim 23, further comprising propylene carbonate present at about 75% w/w or less of the composition.

32. The composition of claim 31, wherein the propylene carbonate is present at about 40% w/w.

33. The composition of claim 23, further comprising ethanol present at about 25% w/w or less of the composition.

34. The composition of claim 23, wherein the COX-2 inhibitor is present at about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% w/w of the composition.

35. The composition of claim 23, further comprising an anti -oxidant.

36. The composition of claim 35, wherein the anti-oxidant is present at no more than about 10% w/w of the composition.

37. The composition of claim 23, wherein the composition comprises:

i) COX-2 inhibitor;

ii) propylene glycol;

iii) propylene carbonate;

iv) ethanol; and optionally

v) an anti-oxidant.

38. The composition of claim 23, wherein the composition comprises:

i) COX-2 inhibitor at a concentration of about 0.5 to 50% w/w;

ii) propylene glycol at a concentration of about 1 to 99% w/w;

iii) propylene carbonate at a concentration of about 0.001 to 75% w/w; and iv) ethanol at a concentration of about 0.001 to 25% w/w.

39. The composition of claim 23, wherein the composition comprises:

i) COX-2 inhibitor at a concentration of about 5 to 15% w/w;

ii) propylene glycol at a concentration of about 35 to 45% w/w;

iii) propylene carbonate at a concentration of about 35 to 45% w/w; and iv) ethanol at a concentration of about 5 to 20% w/w.

40. The composition of claim 23, wherein at least about 5,000, 10,000, 15,000 or 20,000 ng/ml of the COX-2 inhibitor is present in the blood stream of the subject for at least about 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 hours or greater upon administration to a mammal.

41. The composition of claim 23, further comprising buprenorphine.

42. The composition of claim 41 , wherein buprenorphine is present in a dose of about 0.1 , 0.2, 0.3, 0.4, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5 or 7.0 mg/kg.

43. The composition of claim 23, wherein the composition is stable at room temperature for at least 6 months.

44. The composition of claim 43, wherein the composition is stable at room temperature for at least 12 months.

45. A pharmaceutical composition for oral administration, comprising:

a) a cyclooxygenase-2 (COX-2) inhibitor, wherein the COX-2 inhibitor is mavacoxib, a compound of Formula (I):


(I)

or an isomer or pharmaceutically acceptable salt thereof, a compound of Formula (II):


(II)

or an isomer or pharmaceutically acceptable salt thereof, or any combination thereof; and b) a pharmaceutically acceptable carrier, wherein the composition is formulated as a solid or semi-solid oral dosage form.

46. The composition of claim 45, wherein the COX-2 inhibitor is selected from the group consisting of: Tris(hydroxymethyl)aminomethane (±)-6-(trifluoromethoxy)-2- (trifluoromethyl)-2H-chromene-3-carboxylate, (±)-6-(trifluoromethoxy)-2-(trifluoromethyl)- 2H-chromene-3-carboxylic acid, Tris(hydroxymethyl)aminomethane (R)-6-(lTifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate, (R)-6-(lTifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid, Tris(hydroxymethyl)aminomethane (S)-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3 -carboxylate, (S)-6-(lTifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3 -carboxylic acid, and any combination thereof.

47. The composition of claim 45, wherein the COX-2 inhibitor is a compound of Formula (III):


(III)

or an isomer or pharmaceutically acceptable salt thereof.

48. The composition of claim 45, wherein the COX-2 inhibitor is mavacoxib.

49. The composition of claim 45, further comprising lactose monohydrate present at over 1% w/w of the composition.

50. The composition of claim 49, wherein the lactose monohydrate is present at about 99% w/w or less of the composition.

51. The composition of claim 49, wherein the lactose monohydrate is present at about 50% w/w or less of the composition.

52. The composition of claim 45, further comprising microcrystalline cellulose present at about 99% w/w or less of the composition.

53. The composition of claim 31, wherein the microcrystalline cellulose is present at about 15 to 20% w/w.

54. The composition of claim 45, further comprising flavoring, croscaremellose sodium, stearic acid, colloidal silicon dioxide, magnesium stearate, or any combination thereof.

55. The composition of claim 45, wherein the COX-2 inhibitor is present at about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% w/w of the composition.

56. The composition of claim 45, wherein the composition comprises:

i) COX-2 inhibitor;

ii) lactose monohydrate;

iii) microcrystalline cellulose;

iv) flavoring; and optionally

v) one or more of croscarmellose sodium, stearic acid, colloidal silicon dioxide and magnesium stearate.

57. The composition of claim 45, wherein the composition comprises:

i) COX-2 inhibitor at a concentration of about 0.5 to 90% w/w;

ii) lactose monohydrate at a concentration of about 1 to 99% w/w;

iii) microcrystalline cellulose at a concentration of about 1 to 99% w/w; and iv) flavoring at a concentration of about 0.001 to 40% w/w.

58. The composition of claim 45, wherein the composition comprises:

i) COX-2 inhibitor at a concentration of about 5 to 15% w/w;

ii) lactose monohydrate at a concentration of about 50 to 60% w/w;

iii) microcrystalline cellulose at a concentration of about 10 to 20% w/w; and iv) flavoring at a concentration of about 5 to 20% w/w.

59. The composition of claim 45, wherein at least about 5,000, 10,000, 15,000 or 20,000 ng/ml of the COX-2 inhibitor is present in the blood stream of the subject for at least about 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 hours or greater upon administration to a mammal.

60. The composition of claim 45, further comprising buprenorphine.

61. The composition of claim 60, wherein buprenorphine is present in a dose of about 0.1, 0.2, 0.3, 0.4, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5 or 7.0 mg/kg.

62. A method of treating a disease or disorder in a subject, comprising administering to the subject an effective amount of a composition of any of claims 1-61.

63. The method of claim 62, wherein the subject is a mammal.

64. The method of claim 63, wherein the subject is a canine.

65. The method of claim 63, wherein the subject is a feline.

66. The method of claim 63, wherein the disease or disorder is pain or inflammation.

67. The method of claim 62, wherein the disease or disorder is an inflammatory disease.

68. The composition of claim 62, wherein at least about 5,000, 10,000, 15,000 or 20,000 ng/ml of the COX-2 inhibitor is present in the blood stream of the subject for at least about 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 hours or greater upon administration to a mammal.

69. The method of claim 62, comprising administering the injectable pharmaceutical composition followed by administration of the oral pharmaceutical composition or the topical pharmaceutical composition.

70. The method of claim 69, wherein the injectable pharmaceutical composition is administered weekly and the oral pharmaceutical composition or the topical pharmaceutical composition is administered weekly.