Compositions and methods for treating hyperproliferative epidermal diseases

• US 20090131488A1
• Filed: 05/10/2006
• Published: 05/21/2009
• Est. Priority Date: 05/10/2005
• Status: Active Grant

• Current Assignee: Dermipsor Ltd.
• Original Assignee: Dermipsor Ltd.
• Inventors: Olga, Bloch, Harel, Avikam, Even-Chen, Zeev
• Granted Patent: US 9,173,835 B2
• Time in Patent Office: Days
• US Class Current: 514/356
• 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 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61K 31/455 Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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: 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 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/08 Antiseborrheics
• CPC Class Codes: A61P 17/12 Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides compositions and methods for use in the treatment of hyperproliferative dermal diseases. Specifically, the present invention teaches pharmaceutical compositions for topical administration where the compositions contain nicotinamide and a vitamin D metabolite, calcipotriol, which are particularly effective in treating and in the maintenance treatment of psoriasis and other related dermal disorders and diseases.

Claims

1-59. -59. (canceled)

60. A pharmaceutical composition for topical application, consisting essentially of calcipotriol;

nicotinamide; and

a polyethylene glycol-based dermatologically acceptable excipient.

61. The pharmaceutical composition according to claim 60, wherein the excipient comprises a mixture of PEG-4000 and PEG-400.

62. The pharmaceutical composition according to claim 60, which consists essentially of calcipotriol, nicotinamide and a mixture of PEG-4000 and PEG-400.

63. The pharmaceutical composition according to claim 62, having the following formulation:

about 10 to about 100 μ

g/g calcipotriol;

about 0.5 to about 25 mg/g nicotinamide;

about 70% to about 80% (w/w) PEG-400;

about 15% to about 25% (w/w) PEG-4000;

about 1% to about 5% (w/w) Steareth-20; and

about 0.1 to about 1% (w/w) vitamin E.

64. The pharmaceutical composition according to claim 63, wherein calcipotriol is provided at a concentration of about 20 μ

g/g to about 70 μ

g/g and wherein nicotinamide is provided at a concentration of about 1 to about 20 mg/g.

71. A method of preventing or treating a hyperproliferative skin disease or disorder in a subject in need thereof, the method comprising the step of:

topically administering to the subject a therapeutically effective amount of a pharmaceutical composition according to claim 63,

thereby preventing or treating a hyperproliferative skin disease or disorder in the subject.

72. The method according to claim 71, wherein the hyperproliferative skin disease or disorder is selected from the group consisting of a benign hyperproliferative disease or disorder and a malignant hyperproliferative disease or disorder.

73. The method according to claim 72, wherein the benign hyperproliferative disease or disorder is selected from the group consisting of psoriasis, solar keratosis, ichthyosis, Grover'"'"'s disease, common warts, keratoacanthoma, seborrhoeic keratosis, scleroderma, and seborrhea.

74. The method according to claim 72, wherein the malignant hyperproliferative skin disease or disorder is selected from squamous-cell carcinoma (SCC) and basal-cell carcinoma (BCC).

75. The method according to claim 71, wherein calcipotriol is provided at a concentration of about 50 μ

g/g and nicotinamide is provided at a concentration of about 2.1 mg/g in a pharmaceutical composition that optionally includes a PEG-based carrier.

76. The method according to claim 75, wherein the pharmaceutical composition is a dermatological ointment having the formulation:

about 50 μ

g/g calcipotriol;

about 2.1 mg/g nicotinamide;

about 77.7% (w/w) PEG-400;

about 20% (w/w) PEG-4000;

about 2% (w/w) Steareth-20; and

about 0.3% (w/w) vitamin E.

77. The method according to claim 71, wherein the subject is a mammal.

78. The method according to claim 77, wherein the subject is a human subject.

79. The method according to claim 71, wherein the hyperproliferative disease is psoriasis and the topically administering comprises administering a therapeutically effective amount of the composition once or twice daily.

65. A pharmaceutical composition comprising calcipotriol;

and a dermatologically acceptable excipient or carrier;

wherein the calcipotriol does not significantly penetrate the skin.

66. The pharmaceutical composition according to claim 65, wherein less than 5% of the calcipotriol penetrates the skin.

67. The pharmaceutical composition according to claim 65, wherein the excipient is a PEG-based excipient comprising a mixture of PEG-400 and PEG-4000.

68. The pharmaceutical composition according to claim 65, consisting essentially of calcipotriol and a PEG-based excipient.

69. The pharmaceutical composition according to claim 68, having the following formulation:

about 10 μ

g/g to about 100 μ

g/g calcipotriol;

about 70% to about 80% (w/w) PEG-400;

about 15% to about 25% (w/w) PEG-4000;

about 1% to about 5% (w/w) Steareth-20;

about 0.1 to about 1% (w/w) vitamin E.

70. The pharmaceutical composition according to claim 68, which further comprises nicotinamide at a concentration of about 0.5 to about 25 mg/g.

80. A method of preventing or treating a hyperproliferative skin disease or disorder in a subject in need thereof, the method comprising the steps of:

topically administering to the subject a therapeutically effective amount of a composition consisting essentially of calcipotriol at a concentration of about 10 μ

g/g to about 100 μ

g/g;

nicotinamide at a concentration of about 0.5 to about 25 mg/g; and

a dermatologically acceptable excipient or carrier for an initial period of time effective to reduce the symptoms of the hyperproliferative disease,

and thereafter,

topically administering to the subject a therapeutically effective amount of a composition consisting essentially of calcipotriol at a concentration of about 10 μ

g/g to about 50 μ

g/g;

nicotinamide at a concentration of about 0.5 to about 25 mg/g; and

a dermatologically acceptable excipient or carrier for a second period of time, effective to prevent the relapse or progression of the hyperproliferative disease.

81. The method according to claim 80, wherein the composition administered during the initial period of time consists essentially of calcipotriol at a concentration of about 50 μ

g/g;

nicotinamide at a concentration of about 2.1 mg/g; and

a dermatologically acceptable excipient or carrier; and

wherein the composition administered during the second period of time consists essentially of calcipotriol at a concentration of about 15 μ

g/g to about 35 μ

g/g;

nicotinamide at a concentration of about 2.1 mg/g; and

a dermatologically acceptable excipient.

82. The method according to claim 80, wherein the initial period of time is about 4 weeks to about 24 weeks.

83. The method according to claim 80 wherein the second period of time is about 8 weeks to about 52 weeks.