TOPICAL FORMULATION FOR A JAK INHIBITOR

• US 20110288107A1
• Filed: 05/20/2011
• Published: 11/24/2011
• Est. Priority Date: 05/21/2010
• Status: Abandoned Application

• Current Assignee: Incyte Holdings Corporation And Incyte Corporation
• Original Assignee: Incyte Holdings Corporation And Incyte Corporation
• Inventors: SHAH, BHAVESH, YELESWARAM, KRISHNASWAMY, PARIKH, BHAVNISH
• Application Number:
  US13/112,370
• Publication Number:
  US 20110288107A1
• Time in Patent Office: Days
• US Class Current: 514/265.1
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• 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 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 37/02 Immunomodulators
• 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

Abstract

This invention relates to pharmaceutical formulations for topical skin application comprising (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, and use in the treatment of skin disorders.

Claims

1. A pharmaceutical formulation for topical skin application, comprising:

an oil-in-water emulsion; and

a therapeutically effective amount of a therapeutic agent which is (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof

2. A pharmaceutical formulation according to claim 1, wherein the emulsion comprises water, an oil component, and an emulsifier component.

5. A pharmaceutical formulation according to claim 2, wherein the oil component is present in an amount of about 20% to about 27% by weight of the formulation.

7. A pharmaceutical formulation according to claim 2, wherein the oil component comprises one or more substances independently selected from white petrolatum, cetyl alcohol, stearyl alcohol, light mineral oil, medium chain triglycerides, and dimethicone.

8. A pharmaceutical formulation according to claim 2, wherein the oil component comprises an occlusive agent component.

10. A pharmaceutical formulation according to claim 8, wherein the occlusive agent component is present in an amount of about 5% to about 10% by weight of the formulation.

12. A pharmaceutical formulation according to claim 8, wherein the occlusive agent component comprises white petrolatum.

13. A pharmaceutical formulation according to claim 2, wherein the oil component comprises a stiffening agent component.

16. A pharmaceutical formulation according to claim 13, wherein the stiffening agent component is present in an amount of about 4% to about 7% by weight of said formulation.

19. A pharmaceutical formulation according to claim 13, wherein the stiffening agent component comprises one or more substances independently selected from C_16-18 fatty alcohols.

21. A pharmaceutical formulation according to claim 2, wherein the oil component comprises an emollient component.

23. A pharmaceutical formulation according to claim 21, wherein the emollient component is present in an amount of about 7% to about 13% by weight of the formulation.

26. A pharmaceutical formulation according to claim 21, wherein the emollient component comprises one or more substances independently selected from light mineral oil, medium chain triglycerides, and dimethicone.

29. A pharmaceutical formulation according to claim 2, wherein the water is present in an amount of about 45% to about 55% by weight of the formulation.

33. A pharmaceutical formulation according to claim 2, wherein the emulsifier component is present in an amount of about 4% to about 7% by weight of the formulation.

35. A pharmaceutical formulation according to claim 2, wherein the emulsifier component comprises one or more substances independently selected from glyceryl fatty esters and sorbitan fatty esters.

37. A pharmaceutical formulation according to claim 1, wherein said pharmaceutical formulation further comprises a stabilizing agent component.

40. A pharmaceutical formulation according to claim 37, wherein the stabilizing agent component is present in an amount of about 0.3 to about 0.5% by weight of the formulation.

42. A pharmaceutical formulation according to claim 37, wherein the stabilizing agent component comprises xanthan gum.

43. A pharmaceutical formulation according to claim 1, wherein said pharmaceutical formulation further comprises a solvent component.

46. A pharmaceutical formulation according to claim 43, wherein the solvent component is present in an amount of about 20% to about 25% by weight of the formulation.

47. A pharmaceutical formulation according to claim 43, wherein the solvent component comprises one or more substances independently selected from alkylene glycols and polyalkylene glycols.

49. A pharmaceutical formulation according to claim 1, wherein the therapeutic agent is present in an amount of about 0.5% to about 1.5% by weight of the formulation on a free base basis.

50. A pharmaceutical formulation according to claim 1, wherein said therapeutic agent is present in an amount of about 0.5% by weight of the formulation on a free base basis.

51. A pharmaceutical formulation according to claim 1, wherein said therapeutic agent is present in an amount of about 1% by weight of the formulation on a free base basis.

52. A pharmaceutical formulation according to claim 1, wherein said therapeutic agent is present in an amount of about 1.5% by weight of the formulation on a free base basis.

53. A pharmaceutical formulation according to claim 1, wherein said therapeutic agent is (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile phosphoric acid salt.

54. A pharmaceutical formulation according to claim 1, comprising:

from about 35% to about 65% of water by weight of the formulation;

from about 10% to about 40% of an oil component by weight of the formulation;

from about 1% to about 9% of an emulsifier component by weight of the formulation;

from about 10% to about 35% of a solvent component by weight of the formulation;

from about 0.05% to about 5% of a stabilizing agent component by weight of the formulation; and

from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.

55. A pharmaceutical formulation according to claim 1, comprising:

from about 40% to about 60% of water by weight of the formulation;

from about 15% to about 30% of an oil component by weight of the formulation;

from about 2% to about 6% of an emulsifier component by weight of the formulation;

from about 15% to about 30% of a solvent component by weight of the formulation;

from about 0.1% to about 2% of a stabilizing agent component by weight of the formulation; and

from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.

56. A pharmaceutical formulation according to claim 1, comprising:

from about 45% to about 55% of water by weight of the formulation;

from about 17% to about 27% of an oil component by weight of the formulation;

from about 3% to about 5% of an emulsifier component by weight of the formulation;

from about 20% to about 25% of a solvent component by weight of the formulation;

from about 0.3% to about 0.5% of a stabilizing agent component by weight of the formulation; and

from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.

57. A pharmaceutical formulation according to claim 1, comprising:

from about 45% to about 55% of water by weight of the formulation;

from about 17% to about 27% of an oil component by weight of the formulation;

from about 4% to about 7% of an emulsifier component by weight of the formulation;

from about 20% to about 25% of a solvent component by weight of the formulation;

from about 0.3% to about 0.5% of a stabilizing agent component by weight of the formulation; and

from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.

58. A pharmaceutical formulation according to claim 54, wherein:

the oil component comprises one or more substances independently selected from petrolatums, fatty alcohols, mineral oils, triglycerides, and dimethicones;

the emulsifier component comprises one or more substances independently selected from glyceryl fatty esters and sorbitan fatty esters;

the solvent component comprises one or more substances independently selected from alkylene glycols and polyalkylene glycols; and

the stabilizing agent component comprises one or more substances independently selected from polysaccharides.

59. A pharmaceutical formulation according to claim 54, wherein:

the oil component comprises one or more substances independently selected from white petrolatum, cetyl alcohol, stearyl alcohol, light mineral oil, medium chain triglycerides, and dimethicone;

the emulsifier component comprises one or more substances independently selected from glyceryl stearate and polysorbate 20;

the solvent component comprises one or more substances independently selected from propylene glycol and polyethylene glycol; and

the stabilizing agent component comprises xanthan gum.

60. A pharmaceutical formulation according to claim 1, comprising:

from about 35% to about 65% of water by weight of the formulation;

from about 2% to about 15% of an occlusive agent component by weight of the formulation;

from about 2% to about 8% of a stiffening agent component by weight of said formulation;

from about 5% to about 15% of an emollient component by weight of the formulation;

from about 1% to about 9% of an emulsifier component by weight of the formulation;

from about 0.05% to about 5% of a stabilizing agent component by weight of the formulation;

from about 10% to about 35% of a solvent component by weight of the formulation; and

from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.

61. A pharmaceutical formulation according to claim 1, comprising:

from about 40% to about 60% of water by weight of the formulation;

from about 5% to about 10% of an occlusive agent component by weight of the formulation;

from about 2% to about 8% of a stiffening agent component by weight of said formulation;

from about 7% to about 12% of an emollient component by weight of the formulation;

from about 2% to about 6% of an emulsifier component by weight of the formulation;

from about 0.1% to about 2% of a stabilizing agent by weight of the formulation;

from about 15% to about 30% of a solvent component by weight of the formulation; and

from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.

62. A pharmaceutical formulation according to claim 1, comprising:

from about 45% to about 55% of water by weight of the formulation;

from about 5% to about 10% of an occlusive agent component by weight of the formulation;

from about 3% to about 6% of a stiffening agent component by weight of said formulation;

from about 7% to about 13% of an emollient component by weight of the formulation;

from about 3% to about 5% of an emulsifier component by weight of the formulation;

from about 0.3% to about 0.5% of a stabilizing agent component by weight of the formulation;

from about 20% to about 25% of a solvent component by weight of the formulation; and

from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.

63. A pharmaceutical formulation according to claim 1, comprising:

from about 45% to about 55% of water by weight of the formulation;

from about 5% to about 10% of an occlusive agent component by weight of the formulation;

from about 4% to about 7% of a stiffening agent component by weight of said formulation;

from about 7% to about 13% of an emollient component by weight of the formulation;

from about 4% to about 7% of an emulsifier component by weight of the formulation;

from about 0.3% to about 0.5% of a stabilizing agent component by weight of the formulation;

from about 20% to about 25% of a solvent component by weight of the formulation; and

from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.

64. A pharmaceutical formulation according to claim 1, comprising:

from about 45% to about 55% of water by weight of the formulation;

about 7% of an occlusive agent component by weight of the formulation;

from about 4.5% to about 5% of a stiffening agent component by weight of said formulation;

about 10% of an emollient component by weight of the formulation;

from about 4% to about 4.5% of an emulsifier component by weight of the formulation;

about 0.4% of a stabilizing agent component by weight of the formulation;

about 22% of a solvent component by weight of the formulation; and

from about 0.5% to about 1.5% of (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, by weight of the formulation on a free base basis.

65. A pharmaceutical formulation according to claim 60, wherein the combined amount of the stiffening agent component and the emulsifier component is at least about 8% by weight of the formulation.

66. A pharmaceutical formulation according to claim 60, wherein:

the occlusive agent component comprises a petrolatum;

the stiffening agent component comprises one or more substances independently selected from one or more fatty alcohols;

the emollient component comprises one or more substances independently selected from mineral oils and triglycerides;

the emulsifier component comprises one or more substances independently selected from glyceryl fatty esters and sorbitan fatty esters;

the stabilizing agent component comprises one or more substances independently selected from polysaccharides; and

the solvent component comprises one or more substances independently selected from alkylene glycols and polyalkylene glycols.

67. A pharmaceutical formulation according to claim 60, wherein:

the occlusive agent component comprises white petrolatum;

the stiffening agent component comprises one or more substances independently selected from cetyl alcohol and stearyl alcohol;

the emollient component comprises one or more substances independently selected from light mineral oil, medium chain triglycerides, and dimethicone;

the emulsifier component comprises one or more substances independently selected from glyceryl stearate and polysorbate 20;

the stabilizing agent component comprises xanthan gum; and

the solvent component comprises one or more substances independently selected from propylene glycol and polyethylene glycol.

75. A method of treating a skin disorder in a patient in need thereof, comprising applying a pharmaceutical formulation according to claim 1 to an area of skin of said patient.

76. The method of claim 75, wherein the skin disorder is a topic dermatitis or psoriasis.

77. The method of claim 75, wherein the skin disorder is psoriasis.

78. The method of claim 75, wherein said skin disorder is skin sensitization, skin irritation, skin rash, contact dermatitis or allergic contact sensitization.

79. The method of claim 75, wherein said skin disorder is a bullous skin disorder.

80. The method of claim 79, wherein said bullous skin disorder is pemphigus vulgaris (PV) or bullous pemphigoid (BP).

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