Pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders

• US 20070043119A1
• Filed: 07/28/2006
• Published: 02/22/2007
• Est. Priority Date: 03/12/2002
• Status: Active Grant

• Current Assignee: Galderma Research And Development Snc (Nestle SA)
• Original Assignee: Galderma Research And Development Snc (Nestle SA)
• Inventors: Czernielewski, Janusz, Graeber, Michael
• Granted Patent: US 7,737,181 B2
• Time in Patent Office: Days
• US Class Current: 514/569
• CPC Class Codes: A61K 31/07 Retinol compounds, e.g. vitamin A retinoic acids A61K31/203
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/203 Retinoic acids ; Salts thereof
• CPC Class Codes: A61K 47/02 Inorganic compounds
• 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 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• 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 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• 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 47/6903 the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
• CPC Class Codes: A61K 8/36 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 8/362 Polycarboxylic acids
• CPC Class Codes: A61K 8/368 with carboxyl groups directly bound to carbon atoms of aromatic rings
• 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 9/08 Solutions composition of solutions 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 17/06 : Antipsoriatics
• CPC Class Codes: A61P 17/10 : Anti-acne agents
• CPC Class Codes: A61P 17/12 : Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61P 17/18 : Antioxidants, e.g. antiradicals preparations for protection against sunlight A61Q17/00
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61Q 17/04 : Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• CPC Class Codes: A61Q 19/007 : Preparations for dry skin
• CPC Class Codes: A61Q 19/008 : Preparations for oily skin
• CPC Class Codes: C07C 2603/74 : Adamantanes

Abstract

Dermatological disorders having an inflammatory or proliferative component, notably common acne, are treated with topically applicable pharmaceutical compositions containing about 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthanoic acid (adapalene) or salt thereof, formulated into pharmaceutically acceptable media therefor, advantageously formulated into topically applicable gels, preferably aqueous gels, creams, lotions or solutions.

Claims

1. A topically applicable pharmaceutical aqueous gel composition suited for the treatment of dermatological disorders having an inflammatory or proliferative component, comprising a thus effective amount of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthanoic acid (adapalene) of about 0.3% by weight thereof, formulated into a topically applicable, pharmaceutically acceptable medium therefor.

2. The topically applicable aqueous gel composition as defined by claim 1, further comprising at least one ingredient selected from the group consisting of carbomers, polymeric emulsifying agents, polysaccharidic biopolymers, gums, alginates, modified celluloses, starch derived products, mix of polysorbate 80 and isohexadecane and acrylamide/sodium acryloyldimethyltaurate, humectant or pro-penetrant agents, and mixtures thereof.

3. The topically applicable aqueous gel composition as defined by claim 1, comprising:

Adapalene,

Carbomer 940,

Disodium edetate,

Methyl paraben,

Poloxamer 124,

Propylene glycol,

Sodium hydroxide, and

Purified water.

4. The topically applicable aqueous gel composition as defined by claim 1, comprising:

5. The topically applicable aqueous gel composition as defined by claim 1, comprising:

6. The topically applicable aqueous gel composition as defined by claim 1, comprising:

33. The topically applicable aqueous gel composition as defined by claim 1, further comprising at least one inert additive selected from the group consisting of:

wetting agents;

flavor enhancers;

preservatives;

stabilizers;

moisture regulators;

pH regulators;

osmotic pressure modifiers;

emulsifiers;

UV-A and UV-B screening agents;

Antioxidants; and

combinations thereof.

39. A regime or regimen for the treatment of a dermatological disorder having an inflammatory or proliferative component and afflicting the skin and/or mucous membranes of an individual in need of such treatment, comprising topically applying onto the affected area of the skin and/or mucous membranes of such individual, a thus effective amount of the aqueous gel composition as defined by claim 1.

45. A regime or regimen for the treatment of a dermatological disorder having an inflammatory or proliferative component selected from the group consisting of:

common acne, comedones, polymorphous acne, nodulocystic acne, acne conglobata, secondary acne, solar, drug-related or occupational acne;

widespread and/or severe forms of psoriasis;

ichtyoses and ichtyosiform states;

Darier'"'"'s disease;

actinic keratoses;

palmo plantar keratoderma and keratosis pilaris;

leucoplasias and leucoplasiform states, lichen planus; and

any benign or malignant, severe and extensive dermatological proliferations;

and afflicting the skin and/or mucous membranes of an individual in need of such treatment, comprising topically applying onto the affected area of the skin and/or mucous membranes of such individual, a thus effective amount of the aqueous gel composition as defined by claim 1.

51. A regime or regimen for the treatment of acne, comprising topically applying onto the affected area of the skin of an individual in need of such treatment, a thus effective amount of the aqueous gel composition as defined by claim 1.

7. A topically applicable pharmaceutical cream gel composition suited for the treatment of dermatological disorders having an inflammatory or proliferative component, comprising a thus effective amount of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthanoic acid (adapalene) of about 0.3% by weight thereof, formulated into a topically applicable, pharmaceutically acceptable medium therefor.

8. The topically applicable cream gel composition as defined by claim 7, comprising:

9. The topically applicable cream gel composition as defined by claim 7, comprising:

10. The topically applicable cream gel composition as defined by claim 7, comprising:

11. The topically applicable cream gel composition as defined by claim 7, comprising:

34. The topically applicable cream gel composition as defined by claim 7, further comprising at least one inert additive selected from the group consisting of:

wetting agents;

flavor enhancers;

preservatives;

stabilizers;

moisture regulators;

pH regulators;

osmotic pressure modifiers;

emulsifiers;

UV-A and UV-B screening agents;

Antioxidants; and

combinations thereof.

40. A regime or regimen for the treatment of a dermatological disorder having an inflammatory or proliferative component and afflicting the skin and/or mucous membranes of an individual in need of such treatment, comprising topically applying onto the affected area of the skin and/or mucous membranes of such individual, a thus effective amount of the cream gel composition as defined by claim 7.

46. A regime or regimen for the treatment of a dermatological disorder having an inflammatory or proliferative component selected from the group consisting of:

common acne, comedones, polymorphous acne, nodulocystic acne, acne conglobata, secondary acne, solar, drug-related or occupational acne;

widespread and/or severe forms of psoriasis;

ichtyoses and ichtyosiform states;

Darier'"'"'s disease;

actinic keratoses;

palmo plantar keratoderma and keratosis pilaris;

leucoplasias and leucoplasiform states, lichen planus; and

any benign or malignant, severe and extensive dermatological proliferations;

and afflicting the skin and/or mucous membranes of an individual in need of such treatment, comprising topically applying onto the affected area of the skin and/or mucous membranes of such individual, a thus effective amount of the cream gel composition as defined by claim 7.

52. A regime or regimen for the treatment of acne, comprising topically applying onto the affected area of the skin of an individual in need of such treatment, a thus effective amount of the cream gel composition as defined by claim 7.

12. A topically applicable pharmaceutical cream composition suited for the treatment of dermatological disorders having an inflammatory or proliferative component, comprising a thus effective amount of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthanoic acid (adapalene) of about 0.3% by weight thereof, formulated into a topically applicable, pharmaceutically acceptable medium therefor.

13. The topically applicable cream composition as defined by claim 12, comprising at least one ingredient selected from the group consisting of mineral oils, silicone oils, siliconed oily substances, siliconed fatty substances, non-siliconed fatty substances, vegetable, mineral, animal or synthetic oils, tensioactive agents or emulsifying agents, and mixtures thereof.

14. The topically applicable cream composition as defined by claim 13, comprising at least one ingredient selected from the group consisting of perhydrosqualene, cyclomethicone, PEG-20 methyl glucose sequistearate, methyl glucose sequistearate, and mixtures thereof.

15. The topically applicable cream composition as defined by claim 12, comprising

16. The topically applicable cream composition as defined by claim 12, comprising:

35. The topically applicable cream composition as defined by claim 12, further comprising at least one inert additive selected from the group consisting of:

wetting agents;

flavor enhancers;

preservatives;

stabilizers;

moisture regulators;

pH regulators;

osmotic pressure modifiers;

emulsifiers;

UV-A and UV-B screening agents;

Antioxidants; and

combinations thereof.

41. A regime or regimen for the treatment of a dermatological disorder having an inflammatory or proliferative component and afflicting the skin and/or mucous membranes of an individual in need of such treatment, comprising topically applying onto the affected area of the skin and/or mucous membranes of such individual, a thus effective amount of the cream composition as defined by claim 12.

47. A regime or regimen for the treatment of a dermatological disorder having an inflammatory or proliferative component selected from the group consisting of:

common acne, comedones, polymorphous acne, nodulocystic acne, acne conglobata, secondary acne, solar, drug-related or occupational acne;

widespread and/or severe forms of psoriasis;

ichtyoses and ichtyosiform states;

Darier'"'"'s disease;

actinic keratoses;

palmo plantar keratoderma and keratosis pilaris;

leucoplasias and leucoplasiform states, lichen planus; and

any benign or malignant, severe and extensive dermatological proliferations;

and afflicting the skin and/or mucous membranes of an individual in need of such treatment, comprising topically applying onto the affected area of the skin and/or mucous membranes of such individual, a thus effective amount of the cream composition as defined by claim 12.

53. A regime or regimen for the treatment of acne, comprising topically applying onto the affected area of the skin of an individual in need of such treatment, a thus effective amount of the cream composition as defined by claim 12.

17. A topically applicable pharmaceutical lotion composition suited for the treatment of dermatological disorders having an inflammatory or proliferative component, comprising a thus effective amount of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthanoic acid (adapalene) of about 0.3% by weight thereof, formulated into a topically applicable, pharmaceutically acceptable medium therefor.

18. The topically applicable lotion composition as defined by claim 17, further comprising at least one ingredient selected from the group consisting of humectant agent or pro-penetrant agent, propylene glycol, PEG400, mineral oils, lipophilic substances, caprilic/capric triglycerides, emulsifying agent, and mixtures thereof.

19. The topically applicable lotion composition as defined by claim 18, further comprising at least one ingredient selected from the group consisting of propylene glycol, glycerine, sorbitol, polyethylene glycol, mineral oils, perhydrosqualene, caprilic/capric triglycerides, PEG-20 methyl glucose sequistearate, methyl glucose sequistearate, and mixtures thereof.

20. The topically applicable lotion composition as defined by claim 17, comprising:

21. The topically applicable lotion composition as defined by claim 17, comprising:

22. The topically applicable lotion composition as defined by claim 17, comprising:

23. The topically applicable lotion composition as defined by claim 17, comprising:

24. The topically applicable lotion composition as defined by claim 17, comprising:

25. The topically applicable lotion composition as defined by claim 17, comprising:

36. The topically applicable lotion composition as defined by claim 17, further comprising at least one inert additive selected from the group consisting of:

wetting agents;

flavor enhancers;

preservatives;

stabilizers;

moisture regulators;

pH regulators;

osmotic pressure modifiers;

emulsifiers;

UV-A and UV-B screening agents;

Antioxidants; and

combinations thereof.

42. A regime or regimen for the treatment of a dermatological disorder having an inflammatory or proliferative component and afflicting the skin and/or mucous membranes of an individual in need of such treatment, comprising topically applying onto the affected area of the skin and/or mucous membranes of such individual, a thus effective amount of the lotion composition as defined by claim 17.

48. A regime or regimen for the treatment of a dermatological disorder having an inflammatory or proliferative component selected from the group consisting of:

common acne, comedones, polymorphous acne, nodulocystic acne, acne conglobata, secondary acne, solar, drug-related or occupational acne;

widespread and/or severe forms of psoriasis;

ichtyoses and ichtyosiform states;

Darier'"'"'s disease;

actinic keratoses;

palmo plantar keratoderma and keratosis pilaris;

leucoplasias and leucoplasiform states, lichen planus; and

any benign or malignant, severe and extensive dermatological proliferations;

and afflicting the skin and/or mucous membranes of an individual in need of such treatment, comprising topically applying onto the affected area of the skin and/or mucous membranes of such individual, a thus effective amount of the lotion composition as defined by claim 17.

54. A regime or regimen for the treatment of acne, comprising topically applying onto the affected area of the skin of an individual in need of such treatment, a thus effective amount of the lotion composition as defined by claim 17.

26. A topically applicable pharmaceutical spray solution composition suited for the treatment of dermatological disorders having an inflammatory or proliferative component, comprising a thus effective amount of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthanoic acid (adapalene) of about 0.3% by weight thereof, formulated into a topically applicable, pharmaceutically acceptable medium therefor.

27. The topically applicable spray solution composition as defined by claim 26, further comprising at least one ingredient selected from the group consisting of humectant agent or pro-penetrant agent, propylene glycol, polyethylene glycol, PEG400, a lipophilic substance, siliconed or non-siliconed fatty substances, caprilic/capric triglycerides, and mixtures thereof.

28. The topically applicable spray solution composition as defined by claim 26, comprising:

Adapalene

Caprilic/capric triglycerides

N-methylpyrrolidone

Ethanol.

29. The topically applicable spray solution composition as defined by claim 26, comprising:

37. The topically applicable spray solution composition as defined by claim 26, further comprising at least one inert additive selected from the group consisting of:

wetting agents;

flavor enhancers;

preservatives;

stabilizers;

moisture regulators;

pH regulators;

osmotic pressure modifiers;

emulsifiers;

UV-A and UV-B screening agents;

Antioxidants; and

combinations thereof.

43. A regime or regimen for the treatment of a dermatological disorder having an inflammatory or proliferative component and afflicting the skin and/or mucous membranes of an individual in need of such treatment, comprising topically applying onto the affected area of the skin and/or mucous membranes of such individual, a thus effective amount of the spray solution composition as defined by claim 26.

49. A regime or regimen for the treatment of a dermatological disorder having an inflammatory or proliferative component selected from the group consisting of:

common acne, comedones, polymorphous acne, nodulocystic acne, acne conglobata, secondary acne, solar, drug-related or occupational acne;

widespread and/or severe forms of psoriasis;

ichtyoses and ichtyosiform states;

Darier'"'"'s disease;

actinic keratoses;

palmo plantar keratoderma and keratosis pilaris;

leucoplasias and leucoplasiform states, lichen planus; and

any benign or malignant, severe and extensive dermatological proliferations;

and afflicting the skin and/or mucous membranes of an individual in need of such treatment, comprising topically applying onto the affected area of the skin and/or mucous membranes of such individual, a thus effective amount of the spray solution composition as defined by claim 26.

55. A regime or regimen for the treatment of acne, comprising topically applying onto the affected area of the skin of an individual in need of such treatment, a thus effective amount of the spray solution composition as defined by claim 26.

30. A topically applicable pharmaceutical alcoholic solution composition suited for the treatment of dermatological disorders having an inflammatory or proliferative component, comprising a thus effective amount of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthanoic acid (adapalene) of about 0.3% by weight thereof, formulated into a topically applicable, pharmaceutically acceptable medium therefor.

31. The topically applicable pharmaceutical alcoholic solution composition as defined by claim 30, comprising:

32. The topically applicable pharmaceutical alcoholic solution composition as defined by claim 30, comprising:

38. The topically applicable alcoholic solution composition as defined by claim 30, further comprising at least one inert additive selected from the group consisting of:

wetting agents;

flavor enhancers;

preservatives;

stabilizers;

moisture regulators;

pH regulators;

osmotic pressure modifiers;

emulsifiers;

UV-A and UV-B screening agents;

Antioxidants; and

combinations thereof.

44. A regime or regimen for the treatment of a dermatological disorder having an inflammatory or proliferative component and afflicting the skin and/or mucous membranes of an individual in need of such treatment, comprising topically applying onto the affected area of the skin and/or mucous membranes of such individual, a thus effective amount of the alcoholic solution composition as defined by claim 30.

50. A regime or regimen for the treatment of a dermatological disorder having an inflammatory or proliferative component selected from the group consisting of:

common acne, comedones, polymorphous acne, nodulocystic acne, acne conglobata, secondary acne, solar, drug-related or occupational acne;

widespread and/or severe forms of psoriasis;

ichtyoses and ichtyosiform states;

Darier'"'"'s disease;

actinic keratoses;

palmo plantar keratoderma and keratosis pilaris;

leucoplasias and leucoplasiform states, lichen planus; and

any benign or malignant, severe and extensive dermatological proliferations;

and afflicting the skin and/or mucous membranes of an individual in need of such treatment, comprising topically applying onto the affected area of the skin and/or mucous membranes of such individual, a thus effective amount of the alcoholic solution composition as defined by claim 30.

56. A regime or regimen for the treatment of acne, comprising topically applying onto the affected area of the skin of an individual in need of such treatment, a thus effective amount of the alcoholic solution composition as defined by claim 30.