Dermatological compositions

• US 20050100621A1
• Filed: 11/07/2003
• Published: 05/12/2005
• Est. Priority Date: 11/07/2003
• Status: Abandoned Application

• Current Assignee: Stiefel Laboratories Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Stiefel Laboratories Incorporated (GlaxoSmithKline PLC)
• Inventors: Popp, Karl F., Santelli, Ronald J.
• Application Number:
  US10/702,782
• Publication Number:
  US 20050100621A1
• Time in Patent Office: Days
• US Class Current: 424/776
• 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 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 36/185 Magnoliopsida (dicotyledons)
• CPC Class Codes: A61K 36/28 Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
• CPC Class Codes: A61K 36/286 Carthamus (distaff thistle)
• CPC Class Codes: A61K 36/31 Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
• CPC Class Codes: A61K 36/47 Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean)
• CPC Class Codes: A61K 36/48 Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
• CPC Class Codes: A61K 36/54 Lauraceae (Laurel family), e.g. cinnamon or sassafras
• CPC Class Codes: A61K 36/55 Linaceae (Flax family), e.g. Linum
• CPC Class Codes: A61K 36/63 Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
• CPC Class Codes: A61K 36/736 Prunus, e.g. plum, cherry, peach, apricot or almond
• CPC Class Codes: A61K 36/752 Citrus, e.g. lime, orange or lemon
• CPC Class Codes: A61K 36/889 Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
• CPC Class Codes: A61K 36/899 Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
• 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 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 8/42 Amides
• CPC Class Codes: A61K 8/922 : of vegetable origin
• 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: A61Q 19/00 : Preparations for care of the skin
• CPC Class Codes: A61Q 19/007 : Preparations for dry skin

Abstract

Topical dermatological compositions comprising urea as an active ingredient, a vegetable oil or a derivative thereof, water, and conventional excipients. These compositions are used for topical medical applications, particularly to treat various skin disorders.

Claims

1. A dermatological composition suitable for topical administration comprising:

about 5 to about 50% by weight of an active ingredient consisting of urea;

about 3 to about 45% by weight of a vegetable oil or a derivative thereof;

water; and

remaining amounts of one or more dermatologically acceptable agents.

2. The dermatological composition of claim 1, comprising about 21 to about 50% by weight of said active ingredient and about 3 to about 20% by weight of said vegetable oil or derivative thereof.

3. The dermatological composition of claim 1, comprising about 5 to about 20% by weight of said active ingredient and about 15 to about 45% by weight of said vegetable oil or derivative thereof.

4. The dermatological composition of claim 1, wherein said composition has a pH of about 3 to about 11.

5. The dermatological composition of claim 4, wherein said composition has a pH of about 5 to about 10.5.

6. The dermatological composition of claim 5, wherein said composition has a pH of about 7 to about 10.

7. The dermatological composition of claim 1, wherein said composition is an emulsion having an oil phase and an aqueous phase.

8. The dermatological composition of claim 7, formulated as an oil-in-water emulsion.

9. The dermatological composition of claim 7, wherein said vegetable oil or derivative thereof is present in said oil phase and is selected from the group consisting of castor oil, sunflower oil, a liquid fraction of karite butter, cottonseed oil, canola oil, corn oil, hydrogenated vegetable oil, peanut oil, sesame oil, soybean oil, palm oil, coconut oil, rapeseed oil, safflower oil, cocoa butter, linseed oil, olive oil, almond oil, avocado oil, citrus seed oil, cohune oil, tallow, oat oil, palm kernel oil, rice bran oil, tucum oil, babassu oil, derivatives thereof, and mixtures thereof.

10. The dermatological composition of claim 9, wherein said vegetable oil or derivative thereof is castor oil or a derivative thereof.

11. The dermatological composition of claim 7, wherein said dermatologically acceptable agents are selected from the group consisting of emulsifiers, surfactants, suspending agents, antioxidants, chelates, emollients, humectants, fluid alkyl alcohols, thickening agents, polysiloxanes, modified polysiloxanes, pH modifiers, and mixtures thereof.

12. The dermatological composition of claim 11, wherein said emulsion is formed using an emulsifier selected from the group consisting of straight or branched chain fatty acids, polyoxyethylene sorbitan fatty acid esters, sorbitan fatty acid esters, propylene glycol stearate, glyceryl stearate, polyethylene glycol, fatty alcohols, polymeric ethylene oxide-propylene oxide block polymers, derivatives thereof, pharmaceutically acceptable salts thereof, and mixtures thereof.

13. The dermatological composition of claim 12, wherein said emulsifier is selected from the group consisting of laureth-4, glyceryl stearate and polyethylene glycol-100/glyceryl stearate, and mixtures thereof.

14. The dermatological composition of claim 12, wherein said emulsifier is present in a phase of said emulsion selected from the group consisting of said oil phase, said aqueous phase, and a combination thereof.

15. The dermatological composition of claim 11, wherein said surfactant is selected from the group consisting of a nonionic surfactant, an anionic surfactant, an amphoteric surfactant, a cationic surfactant, and mixtures thereof.

16. The dermatological composition of claim 15, wherein said surfactant is selected from the group consisting of polyoxyl stearate, laureth-4, and mixtures thereof.

17. The dermatological composition of claim 11, comprising at least two surfactants.

18. The dermatological composition of claim 11, wherein said suspending agent is selected from the group consisting of alginic acid, bentonite, carbomer, carboxymethylcellulose and salts thereof, hydroxyethylcellulose, hydroxypropylcellulose, microcrystalline cellulose, colloidal silicon dioxide, dextrin, gelatin, guar gum, xanthan gum, kaolin, magnesium aluminum silicate, maltitol, triglycerides, methylcellulose, polyoxyethylene fatty acid esters, polyvinylpyrrolidone, propylene glycol alginate, sodium alginate, sorbitan fatty acid esters, tragacanth, and mixtures thereof.

19. The dermatological composition of claim 18, wherein said suspending agent is magnesium aluminum silicate.

20. The dermatological composition of claim 11, wherein said suspending agent and said surfactant are present in a phase of said emulsion selected from the group consisting of said oil phase, said aqueous phase, and a combination thereof.

21. The dermatological composition of claim 1, comprising about 5 to about 90% by weight of water.

22. The dermatological composition of claim 7, wherein said urea is present in said aqueous phase or said oil phase.

23. The dermatological composition of claim 1, further comprising a urea-modifying agent.

24. The dermatological composition of claim 23, wherein said urea-modifying agent is selected from the group consisting of a pyrrolidone carboxylate salt, dimethyl isosorbide, polyethylene glycol, propylene glycol, hexylene glycol, butylenes glycol, triethaline glycol, dipropylene glycol, glycerin, derivatives thereof, and mixtures thereof.

25. The dermatological composition of claim 24, wherein said pyrrolidone carboxylate salt is sodium pyrrolidone carboxylate.

26. The dermatological composition of claim 1, wherein said composition is in a lotion, cream, ointment, shampoo, gel, aerosol, solution, paste, suspension, skin cleanser, bar, or other pharmaceutically acceptable topical dosage form.

27. A method of treating a skin disorder in a mammal, comprising topically administering to skin of a mammal in need thereof a therapeutically effective amount of a dermatological composition suitable for topical administration comprising:

about 5 to about 50% by weight of an active ingredient consisting of urea;

about 3 to about 45% by weight of a vegetable oil or a derivative thereof;

water; and

remaining amounts of one or more dermatologically acceptable agents.

28. The method of claim 27, wherein said skin disorder is selected from the group consisting of cracked skin, disturbed barrier function, dry skin, eczema, icthyotic atopic eczema, acthyotic skin, subacute and chronic atopic eczema, xerosis, rough skin, dermatitis, psoriasis, ichthyosis, keratosis, keratoderma, corns, calluses, scales, nummular dermatitis, lichen simplex chronicus, pityriasis rosea, dandruff, acne, pruritus, age spots, lentigines, melasmas, wrinkles, warts, blemished skin, hyperpigmented skin, hyperkeratotic skin, inflammatory dermatoses, skin changes associated with aging, skin requiring cleansers, and combinations thereof.

29. The method of claim 27, wherein said topical administration moisturizes said skin.

30. The method of claim 27, wherein said method improves moisture content of said skin.

31. A method of treating or preventing dry skin in a mammal, comprising topically administering to skin of a mammal in need thereof a therapeutically effective amount of a dermatological composition suitable for topical administration comprising:

about 5 to about 50% by weight of an active ingredient consisting of urea;

about 3 to about 45% by weight of a vegetable oil or a derivative thereof;

water; and

remaining amounts of one or more dermatologically acceptable agents.

32. The method of claim 31, wherein said topical administration moisturizes said skin.

33. A dermatological composition suitable for topical administration comprising an oil-in-water emulsion comprising:

an oil phase comprising about 3 to about 20% by weight of the overall weight of the composition of a vegetable oil or a derivative thereof and at least one emulsifier; and

an aqueous phase comprising about 21 to about 50% by weight of the overall weight of the composition of an active ingredient consisting of urea and about 35 to about 55% by weight of the overall weight of the composition of water,

wherein said emulsion further comprises at least two surfactants and at least one suspending agent present in a phase of said emulsion selected from the group consisting of said oil phase, said aqueous phase, and a combination thereof, and wherein said dermatological composition has a pH of from about 3 to about 11.

34. The dermatological composition of claim 33, comprising about 30 to about 45% by weight of said active ingredient and about 5 to about 15% by weight of said vegetable oil or derivative thereof.

35. The dermatological composition of claim 33, wherein said composition has a pH of about 7 to about 10.

36. The dermatological composition of claim 33, wherein said vegetable oil or derivative thereof is present in said oil phase and is selected from the group consisting of castor oil, sunflower oil, a liquid fraction of karite butter, cottonseed oil, canola oil, corn oil, hydrogenated vegetable oil, peanut oil, sesame oil, soybean oil, palm oil, coconut oil, rapeseed oil, safflower oil, cocoa butter, linseed oil, olive oil, almond oil, avocado oil, citrus seed oil, cohune oil, tallow, oat oil, palm kernel oil, rice bran oil, tucum oil, babassu oil, derivatives thereof, and mixtures thereof.

37. The dermatological composition of claim 36, wherein said vegetable oil or derivative thereof is castor oil or a derivative thereof.

38. The dermatological composition of claim 33, wherein said at least one emulsifier is selected from the group consisting of straight or branched chain fatty acids, polyoxyethylene sorbitan fatty acid esters, sorbitan fatty acid esters, propylene glycol stearate, glyceryl stearate, polyethylene glycol, fatty alcohols, polymeric ethylene oxide-propylene oxide block polymers, derivatives thereof, pharmaceutically acceptable salts thereof, and mixtures thereof.

39. The dermatological composition of claim 38, wherein said at least one emulsifier is selected from the group consisting of laureth-4, glyceryl stearate and polyethylene glycol-100/glyceryl stearate, and mixtures thereof.

40. The dermatological composition of claim 33, wherein said at least two surfactants are selected from the group consisting of nonionic surfactants, anionic surfactants, amphoteric surfactants, cationic surfactants, and mixtures thereof.

41. The dermatological composition of claim 40, wherein said at least two surfactants are selected from the group consisting of polyoxyl stearate, laureth-4, and mixtures thereof.

42. The dermatological composition of claim 33, wherein said at least one suspending agent is magnesium aluminum silicate.

43. The dermatological composition of claim 33, further comprising a urea-modifying agent.

44. The dermatological composition of claim 43, wherein said urea-modifying agent is selected from the group consisting of a pyrrolidone carboxylate salt, dimethyl isosorbide, polyethylene glycol, propylene glycol, hexylene glycol, butylenes glycol, triethaline glycol, dipropylene glycol, glycerin, derivatives thereof, and mixtures thereof.

45. The dermatological composition of claim 44, wherein said pyrrolidone carboxylate salt is sodium pyrrolidone carboxylate.

46. The dermatological composition of claim 33, further comprising an additional excipient selected from the group consisting of antioxidants, chelates, preservatives, emollients, humectants, fluid alkyl alcohols, thickening agents, polysiloxanes, modified polysiloxanes, pH modifiers, and mixtures thereof.

47. The dermatological composition of claim 33, wherein said composition is in a lotion, cream, ointment, shampoo, gel, aerosol, solution, paste, suspension, skin cleanser, bar, or other pharmaceutically acceptable topical dosage form.

48. A method of treating a skin disorder in a mammal, comprising topically administering to skin of a mammal in need thereof a therapeutically effective amount of a dermatological composition suitable for topical administration comprising an oil-in-water emulsion comprising:

an oil phase comprising about 3 to about 20% by weight of the overall weight of the composition of a vegetable oil or a derivative thereof and at least one emulsifier; and

an aqueous phase comprising about 21 to about 50% by weight of the overall weight of the composition of an active ingredient consisting of urea and about 35 to about 55% by weight of the overall weight of the composition of water,

wherein said emulsion further comprises at least two surfactants and at least one suspending agent present in a phase of said emulsion selected from the group consisting of said oil phase, said aqueous phase, and a combination thereof, and wherein said dermatological composition has a pH of from about 3 to about 11.

49. A method of treating or preventing dry skin in a mammal, comprising topically administering to skin of a mammal in need thereof a therapeutically effective amount of a dermatological composition suitable for topical administration comprising an oil-in-water emulsion comprising:

an oil phase comprising about 3 to about 20% by weight of the overall weight of the composition of a vegetable oil or a derivative thereof and at least one emulsifier; and

an aqueous phase comprising about 21 to about 50% by weight of the overall weight of the composition of an active ingredient consisting of urea and about 35 to about 55% by weight of the overall weight of the composition of water,

wherein said emulsion further comprises at least two surfactants and at least one suspending agent present in a phase of said emulsion selected from the group consisting of said oil phase, said aqueous phase, and a combination thereof, and wherein said dermatological composition has a pH of from about 3 to about 11.

50. A dermatological composition suitable for topical administration comprising an oil-in-water emulsion comprising:

an oil phase comprising about 15 to about 45% by weight of the overall weight of the composition of a vegetable oil or a derivative thereof and at least one emulsifier; and

an aqueous phase comprising about 5 to about 20% by weight of the overall weight of the composition of an active ingredient consisting of urea and about 45 to about 90% by weight of the overall weight of the composition of water,

wherein said emulsion further comprises at least two surfactants and at least one suspending agent present in a phase of said emulsion selected from the group consisting of said oil phase, said aqueous phase, and a combination thereof, and wherein said dermatological composition has a pH of from about 3 to about 11.

51. The dermatological composition of claim 50, comprising about 10 to about 18% by weight of said active ingredient and about 20 to about 35% by weight of said vegetable oil or derivative thereof.

52. A method of treating a skin disorder in a mammal, comprising topically administering to skin of a mammal in need thereof a therapeutically effective amount of a dermatological composition suitable for topical administration comprising an oil-in-water emulsion comprising:

an oil phase comprising about 15 to about 45% by weight of the overall weight of the composition of a vegetable oil or a derivative thereof and at least one emulsifier; and

an aqueous phase comprising about 5 to about 20% by weight of the overall weight of the composition of an active ingredient consisting of urea and about 45 to about 90% by weight of the overall weight of the composition of water,

wherein said emulsion further comprises at least two surfactants and at least one suspending agent present in a phase of said emulsion selected from the group consisting of said oil phase, said aqueous phase, and a combination thereof, and wherein said dermatological composition has a pH of from about 3 to about 11.

53. A method of treating or preventing dry skin in a mammal, comprising topically administering to skin of a mammal in need thereof a therapeutically effective amount of a dermatological composition suitable for topical administration comprising an oil-in-water emulsion comprising:

an oil phase comprising about 15 to about 45% by weight of the overall weight of the composition of a vegetable oil or a derivative thereof and at least one emulsifier; and

an aqueous phase comprising about 5 to about 20% by weight of the overall weight of the composition of an active ingredient consisting of urea and about 45 to about 90% by weight of the overall weight of the composition of water,

wherein said emulsion further comprises at least two surfactants and at least one suspending agent present in a phase of said emulsion selected from the group consisting of said oil phase, said aqueous phase, and a combination thereof, and wherein said dermatological composition has a pH of from about 3 to about 11.

54. A process for preparing a dermatological composition suitable for topical administration comprising an emulsion, said process comprising:

1) preparing an aqueous phase comprising about 5 to about 50% by weight of the overall weight of the composition of an active ingredient consisting of urea, and about 5 to about 90% by weight of the overall weight of the composition of water,

2) heating said aqueous phase to a temperature of about 60 to about 80°

C. while mixing;

3) preparing an oil phase comprising about 3 to about 45% by weight of the overall weight of the composition of a vegetable oil or a derivative thereof and at least one emulsifier;

4) combining said oil phase with said aqueous phase while mixing at a temperature of about 60 to about 80°

C. to obtain a homogenous emulsion;

5) cooling said emulsion to a temperature of about 15 to about 30°

C.; and

6) recovering a topical emulsion dermatological composition.

55. The process of claim 54, wherein said aqueous phase is prepared by first mixing said active ingredient in purified water before adding at least one suspending agent.

56. The process of claim 55, wherein said aqueous phase is mixed after adding said at least one suspending agent until said aqueous phase is uniform in appearance.

57. The process of claim 54, wherein said oil phase is prepared by heating said vegetable oil or derivative thereof, said at least one emulsifier, and at least two surfactants at a temperature of about 60 to about 80°

C. until melted.

58. The process of claim 57, wherein after each of said vegetable oil or derivative thereof, said at least one emulsifier, and said at least two surfactants are melted, said oil phase is mixed until uniform.

59. The process of claim 54, wherein said process comprises adding at least two surfactants and at least one suspending agent to a phase selected from the group consisting of said oil phase, said aqueous phase, and a combination thereof in either or both of said step 1) and said step 3).

60. The process of claim 54, wherein said oil phase is added to said aqueous phase while mixing until uniform in appearance.