Compositions and methods for treating hyperproliferative epidermal diseases

• US 9,603,861 B2
• Filed: 09/30/2015
• Issued: 03/28/2017
• 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:
  US14/871,072
• Publication Number:
  US 20160015723A1
• Time in Patent Office: 545 Days
• Field of Search: 514/167, 514/356, 514/729
• 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 consisting essentially of a vitamin D metabolite, calcipotriol, and nicotinamide, which are particularly effective in treating and in the maintenance therapy of psoriasis and other related dermal disorders and diseases.

Claims

1. A method of treating a hyperproliferative skin disease or disorder in a subject in need thereof, the method comprising topically administering to the subject a therapeutically effective amount of a pharmaceutical composition, the composition comprising:

calcipotriol at a concentration of about 20 μ

g/g to about 70 μ

g/g;

nicotinamide at a concentration of about 1 to about 20 mg/g; 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;

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

2. The method according to claim 1, wherein the hyperproliferative disease or disorder is psoriasis.

3. The method according to claim 1, wherein calcipotriol is present at a concentration of about 50 μ

g/g.

4. The method according to claim 1, wherein said composition further comprises vitamin E.

5. The method according to claim 4, wherein the vitamin E is present at a concentration of about 0.1% to about 1% (w/w).

6. The method according to claim 1, wherein said polyoxyethylated stearyl alcohol (Steareth-20) is present at a concentration of about 1% to 5% (w/w).

7. The method according to claim 6, wherein said polyoxyethylated stearyl alcohol (Steareth-20) is present at a concentration of about 2% (w/w).

8. The method according to claim 1, wherein less than 5% of the calcipotriol penetrates the skin.

9. The method according to claim 1, wherein the composition is a topical composition.

10. The method according to claim 9, wherein the topical composition is in the form of a dermatological ointment.

14. The method according to claim 1, wherein the composition comprises:

calcipotriol at a concentration of about 50 μ

g/g;

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

PEG-400 at a concentration of about 70% to about 80% (w/w);

PEG-4000 at a concentration of about 20% (w/w);

Steareth-20 at a concentration of about 2%; and

Vitamin E at a concentration of about 0.3% (w/w).

15. The method according to claim 1, wherein topically administering comprises administering a therapeutically effective amount of the composition once or twice daily.

16. The method according to claim 1, wherein the subject is a mammal.

17. The method according to claim 16, wherein the subject is a human subject.

11. A method of treating a hyperproliferative skin disease or disorder in a subject in need thereof, the method comprising topically administering to the subject a therapeutically effective amount of a pharmaceutical composition, wherein the composition comprises:

calcipotriol at a concentration of about 50 μ

g/g;

nicotinamide at a concentration of about 2 to about 20 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, wherein the 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.

12. The method according to claim 11, wherein nicotinamide is present at a concentration of about 6.3 to about 18.9 mg/g.

13. The method according to claim 11, wherein said polyoxyethylated stearyl alcohol (Steareth-20) is at a concentration of about 2% (w/w).