Methods of inducing apoptosis and modulating metalloproteinases

• US 20030206966A1
• Filed: 10/22/2002
• Published: 11/06/2003
• Est. Priority Date: 07/27/2000
• Status: Abandoned Application

• Current Assignee: NUCRYST Pharmaceuticals Corp. (The Westaim Corporation)
• Original Assignee: NUCRYST Pharmaceuticals Corp. (The Westaim Corporation)
• Inventors: Lam, Kan, Wright, John B., Gillis, Scott H., Schechter, Paul, Burrell, Robert E.
• Application Number:
  US10/277,320
• Publication Number:
  US 20030206966A1
• Time in Patent Office: Days
• US Class Current: 424/618
• 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 2800/413 Nanosized, i.e. having sizes below 100 nm
• CPC Class Codes: A61K 31/28 Compounds containing heavy metals
• 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 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 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 8/19 containing inorganic ingredients
• 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 9/0019 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 9/0078 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 9/1682 Processes
• CPC Class Codes: A61K 9/51 Nanocapsules; Nanoparticles; nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00
• 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: A61K 9/7023 : Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• 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 2300/104 : Silver, e.g. silver sulfadiazine
• CPC Class Codes: A61L 2300/404 : Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/606 : Coatings
• 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: A61Q 17/005 : Antimicrobial preparations
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Methods of inducing apoptosis and modulating metalloproteinases, particularly with metal-containing compounds, are disclosed. The metal-containing material can be, for example, an antimicrobial material, an antibacterial material, an anti-inflammatory material, an anti-fungal material, an anti-viral material, an anti-cancer material, a pro-apoptosis material, and/or an MMP modulating material. In certain embodiments, the metal-containing material is an atomically disordered, silver-containing material.

Claims

1. A method of inducing apoptosis in a subject, comprising:

contacting an area of the subject with a nanocrystalline metal-containing compound to induce apoptosis at the area of the subject.

2. The method of claim 1, wherein the area of the subject is selected from the group consisting of a hyperplastic tissue, a tumor tissue and a cancer lesion.

3. The method of claim 1, wherein the method modulates matrix metalloproteinases at the area of the subject.

4. The method of claim 1, wherein the metal-containing compound is selected from the group consisting of metals and alloys.

5. The method of claim 1, wherein the metal-containing compound is selected from the group consisting of metal oxides, metal nitrides, metal borides, metal halides and metal hydrides.

6. The method of claim 1, wherein the metal-containing compound comprises a metal selected from the group consisting of silver, gold, platinum and palladium.

7. The method of claim 1, wherein the metal-containing compound comprises silver.

8. The method of claim 1, wherein the metal-containing compound comprises an ionic compound.

9. The method of claim 1, wherein the metal-containing compound comprises atoms, molecules or clusters.

10. The method of claim 1, wherein the metal-containing compound comprises an atomically disordered, crystalline compound.

11. The method of claim 1, wherein the metal-containing compound comprises an antimicrobial compound.

12. The method of claim 1, wherein, when contacted with the area of the subject, the metal-containing compound is in a solution.

13. The method of claim 12, wherein the solution is injected.

14. The method of claim 13, wherein the solution is injected via a needleless injector.

15. The method of claim 12, wherein the solution is injected via a needle.

16. The method of claim 12, wherein the solution contains at least about 0.001 weight percent of the nanocrystalline metal-containing compound.

17. The method of claim 16, wherein the solution contains about 10 weight percent or less of the nanocrystalline metal-containing compound.

18. The method of claim 12, wherein the solution further comprises a solvent.

19. The method of claim 12, further comprising:

forming the solution into an aerosol; and

inhaling the aerosol.

20. The method of claim 1, wherein, when contacted with the area of the subject, the nanocrystalline metal-containing compound is disposed in a pharmaceutically acceptable carrier.

21. The method of claim 20, wherein the composition contains at least about 0.01 weight percent of the nanocrystalline metal-containing compound.

22. The method of claim 21, wherein the composition contains about 50 weight percent or less of the nanocrystalline metal-containing compound.

23. The method of claim 20, wherein the pharmaceutically acceptable carrier is selected from the group consisting of creams, ointments, gels, lotions, pastes and foams.

24. The method of claim 1, wherein, when contacted with the area of the subject, the nanocrystalline metal-containing compound is in the form of a free-standing powder.

25. The method of claim 24, wherein the free-standing powder is inhaled.

26. The method of claim 24, wherein the free-standing powder is injected.

27. A method of modulating matrix metalloproteinases in a subject, comprising:

contacting an area of the subject with a nanocrystalline metal-containing compound to modulate matrix metalloproteinases at the area of the subject.

28. The method of claim 27, wherein the area is selected from the group consisting of a hyperplastic tissue, a tumor tissue and a cancer lesion.

29. The method of claim 27, wherein the metal-containing compound is selected from the group consisting of metals and alloys.

30. The method of claim 27, wherein the metal-containing compound is selected from the group consisting of metal oxides, metal nitrides, metal borides, metal halides and metal hydrides.

31. The method of claim 27, wherein the metal-containing compound comprises a metal selected from the group consisting of silver, gold, platinum and palladium.

32. The method of claim 27, wherein the metal-containing compound comprises silver.

33. The method of claim 27, wherein the metal-containing compound comprises an ionic compound.

34. The method of claim 27, wherein the metal-containing compound comprises atoms, molecules or clusters.

35. The method of claim 27, wherein the metal-containing compound comprises a disordered, crystalline compound.

36. The method of claim 27, wherein the metal-containing compound comprises an antimicrobial compound.

37. The method of claim 27, wherein, when contacted with the area of the subject, the metal-containing compound is in a solution.

38. The method of claim 37, wherein the solution is injected.

39. The method of claim 38, wherein the solution is injected via a needleless injector.

40. The method of claim 38, wherein the solution is injected via a needle.

41. The method of claim 37, wherein the solution contains at least about 0.001 weight percent of the nanocrystalline metal-containing compound.

42. The method of claim 41, wherein the solution contains about 10 weight percent or less of the nanocrystalline metal-containing compound.

43. The method of claim 37, wherein the solution further comprises a solvent.

44. The method of claim 37, further comprising:

forming the solution into an aerosol; and

inhaling the aerosol.

45. The method of claim 27, wherein, when contacted with the area of the subject, the metal-containing compound is disposed in a pharmaceutically acceptable carrier.

46. The method of claim 45, wherein the composition contains at least about 0.01 weight percent of the metal-containing compound.

47. The method of claim 46, wherein the composition contains about 50 weight percent or less of the metal-containing compound.

48. The method of claim 45, wherein the pharmaceutically acceptable carrier is selected from the group consisting of creams, ointments, gels, lotions, pastes and foams.

49. The method of claim 27, wherein, when contacted with the area of the subject, the nanocrystalline metal-containing compound is in the form of a free-standing powder.

50. The method of claim 49, wherein the free-standing powder is inhaled.

51. The method of claim 49, wherein the free-standing powder is injected.

52. A method of inducing apoptosis in a subject, comprising:

contacting an area of the subject with an atomically disordered, crystalline metal-containing compound to induce apoptosis at the area of the subject.

53. The method of claim 52, wherein the area is selected from the group consisting of a hyperplastic tissue, a tumor tissue and a cancer lesion.

54. The method of claim 52, wherein the method modulates matrix metalloproteinases at the area of the subject.

55. The method of claim 52, wherein the metal-containing compound is selected from the group consisting of metals and alloys.

56. The method of claim 52, wherein the metal-containing compound is selected from the group consisting of metal oxides, metal nitrides, metal borides, metal halides and metal hydrides.

57. The method of claim 52, wherein the metal-containing compound comprises a metal selected from the group consisting of silver, gold, platinum and palladium.

58. The method of claim 52, wherein the metal-containing compound comprises silver.

59. The method of claim 52, wherein the metal-containing compound comprises an ionic compound.

60. The method of claim 52, wherein the metal-containing compound comprises atoms, molecules or clusters.

61. The method of claim 52, wherein the metal-containing compound comprises an antimicrobial compound.

62. A method of modulating matrix metalloproteinases in a subject, comprising:

contacting an area of the subject with an atomically disordered, crystalline metal-containing compound to modulate matrix metalloproteinases at the area of the subject.

63. The method of claim 62, wherein the area is selected from the group consisting of a hyperplastic tissue, a tumor tissue and a cancer lesion.

64. The method of claim 62, wherein the metal-containing compound is selected from the group consisting of metals and alloys.

65. The method of claim 62, wherein the metal-containing compound is selected from the group consisting of metal oxides, metal nitrides, metal borides, metal halides and metal hydrides.

66. The method of claim 62, wherein the metal-containing compound comprises a metal selected from the group consisting of silver, gold, platinum and palladium.

67. The method of claim 62, wherein the metal-containing compound comprises silver.

68. The method of claim 62, wherein the metal-containing compound comprises an ionic compound.

69. The method of claim 62, wherein the metal-containing compound comprises atoms, molecules or clusters.

70. The method of claim 62, wherein the metal-containing compound comprises an antimicrobial compound.