METHOD OF TREATING ACTINIC KERATOSIS

• US 20100120820A1
• Filed: 01/29/2010
• Published: 05/13/2010
• Est. Priority Date: 12/17/2004
• Status: Active Grant

• Current Assignee: Medicis Pharmaceutical Corporation (Bausch Health Cos., Inc.)
• Original Assignee: 3M Innovative Properties Company (3M Company)
• Inventors: Statham, Alexis S., Nelson, Robert J.
• Granted Patent: US 7,928,116 B2
• Time in Patent Office: Days
• US Class Current: 514/293
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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: 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 17/12 Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators

Abstract

Pharmaceutical formulations and methods including an immune response modifier (IRM) compound and an oleic acid component are provided where stability is improved by using oleic acid have low polar impurities such as peroxides.

Claims

1. A method of treating actinic keratosis with a pharmaceutical cream formulated with 1-(2-methylpropyl)-1H imidazo[4,5-c]quinolin-4-amine (imiquimod) and having enhanced imiquimod stability, said method comprising:

applying the pharmaceutical cream following storage of the pharmaceutical cream to skin of a subject diseased with actinic keratosis for a period of time sufficient to deliver a therapeutically effective amount of imiquimod to the skin to induce a therapeutic effect selected from a group of therapeutic effects consisting of reducing actinic keratosis lesions, reducing pre-actinic keratosis lesions and reducing recurrence of actinic keratosis;

wherein the pharmaceutical cream comprises the imiquimod and a pharmaceutically acceptable vehicle containing a refined oleic acid component;

wherein said refined oleic acid component contains at least about 80% oleic acid by weight as a fatty acid and has a peroxide value of no more than about 5 milliequivalents of oxygen per kilogram and contains less than about 1% by weight polar impurities at or prior to formulation of said pharmaceutical cream; and

wherein the pharmaceutical cream, at the time of said applying, contains a greater amount of imiquimod by weight to treat the actinic keratosis, as compared to an amount of imiquimod by weight present in an identical pharmaceutical imiquimod cream but formulated with a compendial grade oleic acid component rather than a refined oleic acid component when the pharmaceutical cream and the identical pharmaceutical imiquimod cream are each stored under identical storage conditions.

2. The method of claim 1, wherein said pharmaceutical cream has been stored for at least six months prior to the use of the pharmaceutical cream.

3. The method of claim 1, wherein said pharmaceutical cream has been stored for at least four months prior to the use of the pharmaceutical cream.

4. The method of claim 1, wherein said pharmaceutical cream has been stored for at least two months prior to the use of the pharmaceutical cream.

5. The method of claim 1, wherein said pharmaceutical cream further comprises an antioxidant selected from the group consisting of butylated hydroxyl toluene (BHT) and butylated hydroxyanisole (BHA).

6. The method of claim 1, wherein the imiquimod is present in an amount of not more than 10% by weight based on the total weight of said pharmaceutical cream and wherein the oleic acid component is present in an amount of no more than about 40% by weight based on the total weight of said pharmaceutical cream.

7. A method of treating actinic keratosis with a pharmaceutical cream formulated with 1-(2-methylpropyl)-1H imidazo[4,5-c]quinolin-4-amine (imiquimod) and having reduced imiquimod impurities following storage of the pharmaceutical cream, said method comprising:

applying the pharmaceutical cream following storage of the pharmaceutical cream to skin of a subject diseased with actinic keratosis for a period of time sufficient to deliver a therapeutically effective amount of imiquimod to the skin to induce a therapeutic effect selected from a group of therapeutic effects consisting of reducing actinic keratosis lesions, reducing pre-actinic keratosis lesions and reducing recurrence of actinic keratosis;

wherein the pharmaceutical cream comprises the imiquimod and a pharmaceutically acceptable vehicle containing a refined oleic acid component;

wherein said refined oleic acid component contains at least about 80% oleic acid by weight as a fatty acid and has a peroxide value of no more than about 5 milliequivalents of oxygen per kilogram and contains less than about 1% by weight polar impurities at or prior to formulation of said pharmaceutical cream; and

wherein the pharmaceutical cream, at the time of said applying, contains a reduced amount of imiquimod impurities by weight to treat the actinic keratosis, as compared to an amount of imiquimod impurities by weight present in an identical pharmaceutical imiquimod cream but formulated with a compendial grade oleic acid component rather than a refined oleic acid component when the pharmaceutical cream and the identical pharmaceutical imiquimod cream are each stored under identical storage conditions.

8. The method of claim 7, wherein said pharmaceutical cream has been stored for at least six months prior to the use of the pharmaceutical cream.

9. The method of claim 7, wherein said pharmaceutical cream has been stored for at least four months prior to the use of the pharmaceutical cream.

10. The method of claim 7, wherein said pharmaceutical cream has been stored for at least two months prior to the use of the pharmaceutical cream.

11. The method of claim 7, wherein said pharmaceutical cream further comprises an antioxidant selected from the group consisting of butylated hydroxyl toluene (BHT) and butylated hydroxyanisole (BHA).

12. The method of claim 7, wherein the imiquimod is present in an amount of not more than 10% by weight based on the total weight of said pharmaceutical cream and wherein the oleic acid component is present in an amount of no more than about 40% by weight based on the total weight of said pharmaceutical cream.

13. A method of treating actinic keratosis with a pharmaceutical cream that is formulated with 1-(2-methylpropyl)-1H imidazo[4,5-c]quinolin-4-amine (imiquimod) and substantially free of imiquimod impurities following storage of the pharmaceutical cream, said method comprising:

applying the pharmaceutical cream following storage of the pharmaceutical cream to skin of a subject diseased with actinic keratosis for a period of time sufficient to deliver a therapeutically effective amount of imiquimod to the skin to induce a therapeutic effect selected from a group of therapeutic effects consisting of reducing actinic keratosis lesions, reducing pre-actinic keratosis lesions and reducing recurrence of actinic keratosis;

wherein the pharmaceutical cream comprises the imiquimod and a pharmaceutically acceptable vehicle containing a refined oleic acid component;

wherein said refined oleic acid component contains at least about 80% oleic acid by weight as a fatty acid and has a peroxide value of no more than about 5 milliequivalents of oxygen per kilogram and contains less than about 1% by weight polar impurities at or prior to formulation of said pharmaceutical cream; and

wherein the pharmaceutical cream, at the time of said applying, is substantially free of imiquimod-related impurities by weight to treat the actinic keratosis.

14. The method of claim 13, wherein said pharmaceutical cream has been stored for at least six months prior to the use of the pharmaceutical cream.

15. The method of claim 13, wherein said pharmaceutical cream has been stored for at least four months prior to the use of the pharmaceutical cream.

16. The method of claim 13, wherein said pharmaceutical cream has been stored for at least two months prior to the use of the pharmaceutical cream.

17. The method of claim 13, wherein said pharmaceutical cream further comprises an antioxidant selected from the group consisting of butylated hydroxyl toluene (BHT) and butylated hydroxyanisole (BHA).

18. The method of claim 13, wherein the imiquimod is present in an amount of not more than 10% by weight based on the total weight of said pharmaceutical cream and wherein the oleic acid component is present in an amount of no more than about 40% by weight based on the total weight of said pharmaceutical cream.

19. The method of claim 13, wherein the imiquimod is present in an amount of about 5% by weight based on the total weight of said pharmaceutical cream and wherein the oleic acid component is present in an amount of about 28% by weight based on the total weight of said pharmaceutical cream.