Treatment of inflammatory skin conditions

• US 6,939,568 B2
• Filed: 04/23/2002
• Issued: 09/06/2005
• Est. Priority Date: 04/23/2001
• Status: Expired due to Term

• Current Assignee: NUCRYST Pharmaceuticals Corp. (The Westaim Corporation)
• Original Assignee: NUCRYST Pharmaceuticals Corp. (The Westaim Corporation)
• Inventors: Yin, Hua Qing, Burrell, Robert Edward
• Primary Examiner(s): PAK, JOHN D
• Application Number:
  US10/131,511
• Publication Number:
  US 20030054046A1
• Time in Patent Office: 1,232 Days
• Field of Search: 424/59, 424/400, 424/402, 424/404, 424/405, 424/484, 424/485, 424488-490, 424/600, 424/604, 424617-619, 424630-635, 424637-638, 424641-643, 424/646, 424649-651, 424/653, 514492-495, 514499-500, 514/503, 514829-831, 514858-865, 514/880, 514/881, 514/886, 514/887, 514/944, 514/951, 514/964, 514/859, 514/825, 514/870, 514/871, 514/918, 514/919
• US Class Current: 424/618
• CPC Class Codes: A01N 25/04 Dispersions, emulsions, suspoemulsions, suspension concentrates or gels foams A01N25/16
• CPC Class Codes: A01N 25/10 Macromolecular compounds
• CPC Class Codes: A01N 25/12 Powders or granules A01N25/26 takes precedence
• CPC Class Codes: A01N 59/16 Heavy metals; Compounds thereof
• 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 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/242 Gold; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 33/38 Silver; Compounds thereof
• CPC Class Codes: A61K 33/40 Peroxides
• 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 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61L 15/46 Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
• CPC Class Codes: A61L 17/145 Coating
• CPC Class Codes: A61L 2300/102 : Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
• CPC Class Codes: A61L 2300/104 : Silver, e.g. silver sulfadiazine
• CPC Class Codes: A61L 2300/404 : Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/452 : Lubricants
• CPC Class Codes: A61L 2300/606 : Coatings
• CPC Class Codes: A61L 2300/624 : Nanocapsules
• CPC Class Codes: A61L 2300/63 : Crystals
• CPC Class Codes: A61L 27/30 : Inorganic materials
• CPC Class Codes: A61L 29/10 : Inorganic materials
• CPC Class Codes: A61L 31/082 : Inorganic materials
• CPC Class Codes: A61P 1/00 : Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 : Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 : Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/04 : for throat disorders
• CPC Class Codes: A61P 13/00 : Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/08 : of the prostate
• CPC Class Codes: A61P 15/00 : Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• 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 17/04 : Antipruritics
• CPC Class Codes: A61P 17/06 : Antipsoriatics
• CPC Class Codes: A61P 17/08 : Antiseborrheics
• CPC Class Codes: A61P 17/10 : Anti-acne agents
• CPC Class Codes: A61P 19/00 : Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/16 : Otologicals
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• 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
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: Y10S 424/15 : Suppositories
• CPC Class Codes: Y10T 428/31855 : Of addition polymer from unsaturated monomers

Abstract

The invention relates to the use of one or more antimicrobial metals, most preferably silver, preferably formed with atomic disorder, and preferably in a nanocrystalline form, for the treatment of inflammatory skin conditions. The nanocrystalline antimicrobial metal of choice may be used in the form of a nanocrystalline coating of one or more antimicrobial metals, a nanocrystalline powder of one or more antimicrobial metals, or a solution containing dissolved species from a nanocrystalline powder or coating of one or more antimicrobial metals.

Claims

1. A method of reducing inflammation of an inflammatory skin condition which comprises:

contacting an inflammatory problem area of a patient with said condition, with a therapeutically effective amount of one or more antimicrobial metals in crystalline form to provide a localized anti-inflammatory effect, wherein the one or more antimicrobial metals are characterized by sufficient atomic disorder so that the one or more antimicrobial metals, when in contact with an alcohol or water-based electrolyte, releases atoms, ions, molecules, or clusters of the one or more antimicrobial metals on a sustainable basis,

wherein said condition is selected from the group consisting of a form of eczema, contact irritant dermatitis, seborrheic dermatitis, an insect bite, an insect sting, sunburn, mycosis fungoides, pyoderma gangrenosum and rosacea.

2. The method as set forth in claim 1, wherein the one or more antimicrobial metals further provide a localized antimicrobial effect.

3. The method as set forth in claim 1, wherein the antimicrobial metal is selected from the group consisting of silver, gold, platinum and palladium.

4. The method as set forth in claim 3, wherein the condition is a form of eczema.

5. The method as set forth in claim 3, wherein the antimicrobial metal is nanocrystalline silver.

6. The method as set forth in claim 4, wherein the antimicrobial metal is silver, formed as a composite with oxygen.

7. The method as set forth in claim 3, wherein the condition is a form of eczema selected from the group consisting of atopic eczema, acrodermatitis eczema, contact allergic dermatitis, dyshydrotic eczema, lichen simplex chronicus, nummular eczema, and statis eczema.

8. The method as set forth in claim 3, wherein the one or more antimicrobial metals are provided as a coating on, or filler in, a dressing, or in a pharmaceutical composition with one or more pharmaceutically and dermatogically acceptable carriers, diluents, or excipients suitable for topical application.

9. The method as set forth in claim 8, wherein the pharmaceutical composition includes a nanocrystalline powder of the one or more antimicrobial metals, or a solution containing dissolved species from a nanocrystalline powder or coating of one or more antimicrobial metals.

10. The method as set forth in claim 9, wherein the pharmaceutical composition is a gel, cream, lotion, paste or ointment containing the antimicrobial metal powder in an amount of 0.01-10% by weight, or a liquid formulated as a topical solution, spray, mist, or drops containing 0.001-10% by weight of the antimicrobial metal.

11. The method as set forth in claim 10, wherein the antimicrobial metal is nanocrystalline silver.

12. The method as set forth in claim 10, wherein the antimicrobial metal is silver, formed as a composite with oxygen.

13. The method of claim 8, wherein the dressing or pharmaceutical composition is fixed in place or occluded with an occlusive or semi-occlusive layer which maintains the dressing or composition in a moist condition.

14. The method as set forth claim 8, wherein the coating is provided on a dressing.

15. The method as set forth in claim 8, wherein the coating is 150-3000 nm thick.

16. The method as set forth in claim 9, wherein the one or more antimicrobial metals are provided in a hydrated dressing.

17. The method as set forth in claim 10, wherein the gel, cream, lotion, paste, or ointment is occluded by a hydrated dressing.

18. The method as set forth in claim 16 or 17, wherein the hydrated dressing is selected from the group consisting of a hydrocolloid, hydrogel, polyethylene, polyurethane, polyvinylidine, siloxane and silicone dressing.

19. The method as set forth in claim 18, wherein the hydrated dressing is a hydrocolloid dressing.

20. The method as set froth in claim 19, wherein the hydrocolloid dressing contains a hydrocolloid selected from the group consisting of alginates, starch, glycogen, gelatin, pectin, chitosan, chitin, cellulose and derivatives thereof, gum Arabic, locust bean gum, karaya gum, gum tragacanth, ghatti gum, agar-agar, carrageenans, carob gum, guar gum, xanthan gum, and glyceryl polymethacrylate.

21. The method as set forth in claim 20, wherein the hydrocolloid is one or more of carboxymethyl cellulose, alginates, pectin and glyceryl polymethacrylate.

22. The method of claim 4, wherein the antimicrobial metal is in a powder form and is delivered directly to the skin.

23. The method of claim 22, wherein the powder is sized with particulates no larger than 2 μ

m.

24. The method of claim 23, wherein the powder is sized with particulates no larger than 1 μ

m.

25. The method of claim 24, wherein the antimicrobial metal is nanocrystalline silver.

26. The method of claim 24, wherein the antimicrobial metal is nanocrystalline silver, formed as a composite with oxygen.

27. The method as set forth in claim 1, wherein the condition is a form of eczema.

28. The method as set forth in claim 27, wherein the condition is a form of eczema selected from the group consisting of atopic eczema, acrodermatitis eczema, contact allergic dermatitis, dyshydrotic eczema, lichen simplex chronicus, nummular eczema, and statis eczema.

29. The method as set forth in claim 1, wherein the antimicrobial metal is nanocrystalline silver, formed as a composite with oxygen.

30. The method as set forth in claim 1, wherein the pharmaceutical composition includes a nanocrystalline powder of the one or more antimicrobial metals, or a solution containing dissolved species from a nanocrystalline powder or coating of one or more antimicrobial metals.

31. The method as set forth in claim 1, wherein the pharmaceutical composition is a gel, cream, lotion, paste or ointment containing the antimicrobial metal powder in an amount of 0.01-10% by weight, or a liquid formulated as a topical solution, spray, mist, or drops containing 0.001-10% by weight of the antimicrobial metal.

32. The method as set forth in claim 1, wherein the antimicrobial metal is silver, formed as a composite with oxygen.

33. The method as set forth in claim 1, wherein the one or more antimicrobial metals are provided as a coating on, or filler in, a dressing, or in a pharmaceutical composition with one or more pharmaceutically and dermatogically acceptable carriers, diluents, or excipients suitable for topical application.

34. The method of claim 33, wherein the dressing or pharmaceutical composition is fixed in place or occluded with an occlusive or semi-occlusive layer which maintains the dressing or composition in a moist condition.

35. The method of claim 33, wherein the coating is provided on a dressing.

36. The method o claim 34, wherein the coating is 150-3000 nm thick.

37. The method of claim 33, wherein the one or more antimicrobial metals are provided in a hydrated dressing.

38. The method of claim 31, wherein the gel, cream, lotion, paste, or ointment is occluded by a hydrated dressing.

39. The method as set forth in claim 37 or 38, wherein the hydrated dressing is selected from the group consisting of a hydrocolloid, hydrogel, polyethylene, polyurethane, polyvinylidine, siloxane and silicone dressing.

40. The method as set forth in claim 39, wherein the hydrated dressing is a hydrocolloid dressing.

41. The method as set froth in claim 40, wherein the hydrocolloid dressing contains a hydrocolloid selected from the group consisting of alginates, starch, glycogen, gelatin, pectin, chitosan, chitin, cellulose and derivatives thereof, gum Arabic, locust bean gum, karaya gum, gum tragacanth, ghatti gum, agar-agar, carrageenans, carob gum, guar gum, xanthan gum, and glyceryl polymethacrylate.

42. The method as set forth in claim 41, wherein the hydrocolloid is one or more of carboxymethyl cellulose, alginates, pectin, and glyceryl polymethacrylate.

43. The method of claim 1, wherein the antimicrobial metal is in a powder form and is delivered directly to the skin.

44. The method of claim 42, wherein the powder is sized with particulates no larger than 2 μ

m.

45. The method of claim 42, wherein the powder is sized with particulates no larger than 1 μ

m.

46. The method of claim 42, wherein the antimicrobial metal is nanocrystalline silver.

47. The method of claim 42, wherein the antimicrobial metal is nanocrystalline silver, formed as a composite with oxygen.

48. The method of claim 1, wherein the condition is an insect bite.

49. The method of claim 1, wherein the condition is an insect sting.

50. The method of claim 1, wherein the condition is sunburn.

51. The method of claim 1, wherein the condition is mycosis fungoides.

52. The method of claim 1, wherein the condition is pyoderma gangrenosum.

53. The method of claim 1, wherein the condition is rosacea.