Compositions and methods for treating hyperproliferative epidermal diseases

• US 9,173,835 B2
• Filed: 05/10/2006
• Issued: 11/03/2015
• Est. Priority Date: 05/10/2005
• Status: Expired due to Fees

• Current Assignee: Dermipsor Ltd.
• Original Assignee: Dermipsor Ltd.
• Inventors: Harel, Avikam, Even-Chen, Zeev, Bloch, Olga
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US11/914,102
• Publication Number:
  US 20090131488A1
• Time in Patent Office: 3,464 Days
• Field of Search: 514/167, 514/356, 514/729, 552/653
• 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 31/355 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. A stable pharmaceutical composition for topical application, comprising calcipotriol at a concentration of about 50 μ

g/g;

nicotinamide at a concentration of about 2 to about 20 mg/g;

about 0.1 to about 1% (w/w) vitamin E; and

a polyethylene glycol-based dermatologically acceptable carrier comprising a mixture of PEG-4000, PEG-400 and polyoxyethylated stearyl alcohol (Steareth-20), wherein the PEG-400 comprises about 70% to about 80% (w/w) of the composition and the PEG-4000 comprises about 15% to about 25% (w/w) of the composition.

2. The pharmaceutical composition according to claim 1, wherein less than 5% of the calcipotriol penetrates the skin.

3. A stable pharmaceutical composition for topical application, comprising calcipotriol at a concentration of about 50 μ

g/g;

nicotinamide at a concentration of about 6.3 to about 18.9 mg/g;

Vitamin E at a concentration of about 0.1 to about 1% (w/w) of the composition; and

a polyethylene glycol-based dermatologically acceptable carrier comprising a mixture of PEG-4000, PEG-400 and polyoxyethylated stearyl alcohol, wherein the PEG-400 is present in an amount of about 70% to about 80% (w/w) of the composition, the PEG-4000 is present in an amount of about 15% to about 25% (w/w) of the composition and the polyoxyethylated stearyl alcohol is present in an amount of about 1% to about 5% (w/w) of the composition.

4. The stable pharmaceutical composition according to claim 3, in the form of a dermatological ointment wherein the carrier comprises:

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

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

about 2% (w/w) Steareth-20.

5. The stable pharmaceutical composition according to claim 3, wherein less than 5% of the calcipotriol penetrates the skin.

6. A stable pharmaceutical composition for topical application, consisting of calcipotriol at a concentration of about 50 μ

g/g;

nicotinamide at a concentration of about 2 to about 20 mg/g;

about 0.1 to about 1% (w/w) vitamin E; and

a polyethylene glycol-based dermatologically acceptable carrier comprising a mixture of PEG-4000, PEG-400 and polyoxyethylated stearyl alcohol (Steareth-20), wherein the PEG-400 comprises about 70% to about 80% (w/w) of the composition and the PEG-4000 comprises about 15% to about 25% (w/w) of the composition.

7. The stable pharmaceutical composition according to claim 6, wherein nicotinamide is present at a concentration of about 6.3 to about 18.9 mg/g.

8. The stable pharmaceutical composition according to claim 6, in the form of a dermatological ointment wherein the carrier comprises:

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

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

about 2% (w/w) Steareth-20.

9. The stable pharmaceutical composition according to claim 6, wherein less than 5% of the calcipotriol penetrates the skin.