Lubricious coatings for substrates

• US 20020182265A1
• Filed: 04/23/2002
• Published: 12/05/2002
• Est. Priority Date: 04/23/2001
• Status: Active Grant

• Current Assignee: NUCRYST Pharmaceuticals Corp. (The Westaim Corporation)
• Original Assignee: NUCRYST Pharmaceuticals Corp. (The Westaim Corporation)
• Inventors: Theodore Cholowski, Walter Carlton, Yin, Hua Qing, Burrell, Robert Edward, Moxham, Peter Howard, Naylor, Antony George, Field, David James, Bowlby, Leonard Salvin
• Granted Patent: US 6,723,350 B2
• Time in Patent Office: Days
• 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 provides methods and kits to form water swellable gel coatings, preferably lubricious coatings, on substrates, and coated substrates thus formed. The coatings contain one or more antimicrobial metals formed with atomic disorder, together with one or more antimicrobial metals formed with atomic disorder such that the coatings provide an antimicrobial and anti-inflammatory effect when wet. The invention also provides a method to produce metal powders by sputtering a coating onto a moving surface, and then scraping the coating with one or more scrapers to produce the metal powder. The method is particularly useful for producing large amounts of nanocrystalline antimicrobial metal powders formed with atomic disorder, useful in the water swellable gel coatings of this invention.

Claims

1. A method of coating a substrate comprising:

forming a liquid medium containing a water swellable polymer, a solvent and a powder of one or more antimicrobial metals formed with atomic disorder;

coating the substrate from the liquid medium to provide a gel coating that adheres to the substrate, and becomes antimicrobial and anti-inflammatory when wet.

2. The method of claim 1, wherein the one or more antimicrobial metals is formed with sufficient atomic disorder such that, in contact with an alcohol or water-based electrolyte, the coating releases ions, atoms, molecules or clusters of the antimicrobial metal on a sustainable basis.

3. The method of claim 2, wherein the water swellable polymer is a lubricious polymer to provide a lubricious coating on the substrate that becomes lubricious when wet, and which further comprises drying the coated substrate.

4. The method of claim 3, wherein the lubricious polymer is a hydrophilic polymer which is provided either in powder form, or in a form coated with the one or more antimicrobial metals.

5. The method of claim 4, wherein the lubricious polymer is one or more of cellulose and derivatives thereof, polyvinyl alcohol, starch, glycogen, gelatin, pectin, alginate, chitosan, chitin, gum arabic, locust bean gum, karaya gum, gum tragacanth, ghatti gum, agar-agar, carrageenans, carob gum, guar gum, and xanthan gum.

6. The method of claim 4, wherein the lubricious polymer is selected from one or more of carboxymethyl cellulose, polyvinyl alcohol, and alginate.

7. The method of claim 6, wherein the antimicrobial metal is one or more of Ag, Au, Pd or Pt, and wherein the antimicrobial metal powder is nanocrystalline.

8. The method of claim 1, wherein the substrate is one or more of catheters, urinary catheters, in-dwelling catheters, drainage catheters, venous catheters, arterial catheters, central line and peripheral line catheters, cannulas, endoscopes, laparoscopes, sutures, staples, myringotomy tubes, wound or nasal packings, dressings, gauze, bone screws, halo screws, total joints, vascular grafts, hernia meshes, guide wires, needles, wound drains, pacemaker leads, condoms, contact lenses, peristaltic pump chambers, arteriovenous shunts, gastroenteric feed tubes, endotracheal tubes, gloves and implants.

9. The method of claim 7, wherein the substrate is one or more of catheters, urinary catheters, in-dwelling catheters, drainage catheters, endoscopes, laparoscopes, myringotomy tubes, dressings, gauze, total joints, vascular grafts, hernia meshes, guide wires, needles, wound drains, pacemaker leads, condoms, contact lenses, peristaltic pump chambers, arteriovenous shunts, gastroenteric feed tubes, endotracheal tubes, gloves and implants.

10. The method of claim 9, wherein the grain size of the antimicrobial metal powder is less than 50 nm.

11. The method of claim 9, wherein the grain size of the antimicrobial metal powder is less than 40 nm.

12. The method of claim 9, wherein the grain size of the antimicrobial metal powder is less than 25 nm.

13. The method of claim 10, wherein the particle size of the antimicrobial metal powder is less than 100 μ

M.

14. The method of claim 11, wherein the particle size of the antimicrobial metal powder is less than 40 μ

m.

15. The method of claim 12, wherein the particle size of the antimicrobial metal powder is less than 10 μ

m.

16. The method of claim 13, wherein the amount of the polymer in the solvent is in the range of 0.1 to 10 wt %.

17. The method of claim 16, wherein the amount of the antimicrobial metal is in the range of 0.001 to 30 wt %.

18. The method of claim 16, wherein the amount of the antimicrobial metal is in the range of 0.1 to 5 wt %.

19. The method of claim 16, wherein the amount of the antimicrobial metal is in the range of 1 to 3 wt %.

20. The method of claim 19, wherein the solvent is selected from water, methanol, ethanol, propanol and DMSO.

21. The method of claim 19, wherein the solvent is water.

22. The method of claim 21, wherein the antimicrobial metal is Ag, formed as a composite with oxygen.

23. The method of claim 1, wherein the coating includes one or more agents selected from preservatives, texturizing agents, thickeners, anticoagulants, β

-glucan, hormones, hyaluronic acid, cytokines, and bone morphogenetic proteins, in a therapeutically acceptable amount.

24. The method of claim 22, wherein the coating includes one or more agents selected from preservatives, texturizing agents, thickeners, anticoagulants, β

-glucan, hormones, hyaluronic acid, cytokines, and bone morphogenetic proteins, in a therapeutically acceptable amount.

25. The method of claim 22, wherein the coating includes one or more agents selected from methyl paraben, propyl paraben, polyvinyl alcohol, heparin, β

-glucan, epidermal growth factor, platelet derived growth factor, and transforming growth factor, in a therapeutically acceptable amount.

26. The method of claim 1, wherein the coating includes less than 0.01 % wt of glycerin, glycerols, chloride salts, aldehydes, ketones, long chain alcohols and triethanolamine

27. The method of claim 25, wherein the coating includes less than 0.01 % wt of glycerin, glycerols, chloride salts, aldehydes, ketones, long chain alcohols and triethanolamine.

29. The coated substrate of claim 28, wherein the one or more antimicrobial metals is formed with sufficient atomic disorder such that, in contact with an alcohol or water-based electrolyte, the coating releases ions, atoms, molecules or clusters of the antimicrobial metal on a sustainable basis.

30. The coated substrate of claim 29, wherein the water swellable polymer is a lubricious polymer to provide a lubricous coating on the substrate that becomes lubricious when wet.

31. The coated substrate of claim 30, wherein the lubricous polymer is a hydrophilic polymer which is provided either in a powder form, or in a form coated with the one or more antimicrobial metals.

32. The coated substrate of claim 31, wherein the lubricious polymer is one or more of cellulose and derivatives thereof, polyvinyl alcohol, starch, glycogen, gelatin, pectin, alginate, chitosan, chitin, gum arabic, locust bean gum, karaya gum, gum tragacanth, ghatti gum, agar-agar, carrageenans, carob gum, guar gum, and xanthan gum.

33. The coated substrate of claim 31, wherein the lubricious polymer is selected from one or more of carboxymethyl cellulose, polyvinyl alcohol, and alginate.

34. The coated substrate of claim 33, wherein the antimicrobial metal is one or more of Ag, Au, Pd or Pt, and wherein the antimicrobial metal powder is nanocrystalline.

35. The coated substrate of claim 28, wherein the substrate is one or more of catheters, urinary catheters, in-dwelling catheters, drainage catheters, venous catheters, arterial catheters, central line and peripheral line catheters, cannulas, endoscopes, laparoscopes, sutures, staples, myringotomy tubes, wound or nasal packings, dressings, gauze, bone screws, halo screws, total joints, vascular grafts, hernia meshes, guide wires, needles, wound drains, pacemaker leads, condoms, contact lenses, peristaltic pump chambers, arteriovenous shunts, gastroenteric feed tubes, endotracheal tubes, gloves and implants.

36. The coated substrate of claim 34, wherein the substrate is one or more of catheters, urinary catheters, in-dwelling catheters, drainage catheters, endoscopes, laparoscopes, myringotomy tubes, dressings, gauze, total joints, vascular grafts, hernia meshes, guide wires, needles, wound drains, pacemaker leads, condoms, contact lenses, peristaltic pump chambers, arteriovenous shunts, gastroenteric feed tubes, endotracheal tubes, gloves and implants.

37. The coated substrate of claim 36, wherein the grain size of the antimicrobial metal powder is less than 50 nm.

38. The coated substrate of claim 36, wherein the grain size of the antimicrobial metal powder is less than 40 nm.

39. The coated substrate of claim 36, wherein the grain size of the antimicrobial metal powder is less than 25 nm.

40. The coated substrate of claim 37, wherein the particle size of the antimicrobial metal powder is less than 100 μ

M.

41. The coated substrate of claim 38, wherein the particle size of the antimicrobial powder is less than 40 μ

m.

42. The coated substrate of claim 39, wherein the particle size of the antimicrobial powder is less than 10 μ

m.

43. The coated substrate of claim 40, wherein the amount of the antimicrobial metal in the coating when wet is in the range of 0.001 to 30 wt %.

44. The coated substrate of claim 42, wherein the amount of the antimicrobial metal in the coating is in the range of 0.01 to 5 wt %.

45. The coated substrate of claim 42, wherein the amount of the antimicrobial metal in the coating is in the range of 1 to 3 wt %.

46. The coated substrate of claim 45, wherein the antimicrobial metal is Ag, formed as a composite with oxygen.

47. The coated substrate of claim 28, wherein the coating includes one or more agents selected from preservatives, texturizing agents, thickeners, anticoagulants, β

-glucan, hormones, hyaluronic acid, cytokines, and bone morphogenetic proteins, in a therapeutically acceptable amount.

48. The coated substrate of claim 46, wherein the coating includes one or more agents selected from preservatives, texturizing agents, thickeners, anticoagulants, β

-glucan, hormones, hyaluronic acid, cytokines, and bone morphogenetic proteins, in a therapeutically acceptable amount.

49. The coated substrate of claim 46, wherein the coating includes one or more agents selected from methyl paraben, propyl paraben, polyvinyl alcohol, heparin, β

-glucan, epidermal growth factor, platelet derived growth factor, and transforming growth factor, in a therapeutically acceptable amount.

50. The coated substrate of claim 28, wherein the coating includes less than 0.01 % wt of glycerin, glycerols, chloride salts, aldehydes, ketones, long chain alcohols and triethanolamine

51. The coated substrate of claim 49, wherein the coating includes less than 0.01 % wt of glycerin, glycerols, chloride salts, aldehydes, ketones, long chain alcohols and triethanolamine.

28. A substrate coated with a water swellable gel coating comprising:

a substrate; and

a water swellable gel coating adhering to the substrate, wherein the gel coating includes a water swellable polymer and one or more antimicrobial metals formed with atomic disorder, and wherein the gel coating becomes antimicrobial and anti-inflammatory when wet.

52. A kit for coating a substrate comprising:

a water swellable polymer;

a powder of one or more antimicrobial metals formed with atomic disorder; and

optionally a solvent for the water swellable polymer.

53. The kit of claim 52, wherein the one or more antimicrobial metals is formed with sufficient atomic disorder such that, in contact with an alcohol or water-based electrolyte, the coating releases ions, atoms, molecules or clusters of the antimicrobial metal on a sustainable basis.

54. The kit of claim 53, wherein the water swellable polymer is a lubricious polymer to provide a lubricious coating on the substrate that becomes lubricous when wet.

55. The kit of claim 54, wherein the lubricious polymer is a hydrophilic polymer which is provided either in a powder form, or in a form coated with the one or more antimicrobial metals.

56. The kit of claim 55, wherein the lubricious polymer is one or more of cellulose and derivatives thereof, polyvinyl alcohol, starch, glycogen, gelatin, pectin, alginate, chitosan, chitin, gum arabic, locust bean gum, karaya gum, gum tragacanth, ghatti gum, agar-agar, carrageenans, carob gum, guar gum, and xanthan gum.

57. The kit of claim 55, wherein the lubricious polymer is selected from one or more of carboxymethyl cellulose, polyvinyl alcohol, and alginate.

58. The kit of claim 57, wherein the antimicrobial metal is one or more of Ag, Au, Pd or Pt, and wherein the antimicrobial metal powder is nanocrystalline.

59. The kit of claim 58, wherein the lubricious polymer and the antimicrobial metal are provided with a solvent for the polymer in a container for application to the substrate as a lubricious gel, or wherein the lubricious polymer and the one or more antimicrobial metals are provided separate from the solvent, for mixing prior to application to the substrate.

60. The kit of claim 59, wherein the antimicrobial metal is Ag, formed as a composite with oxygen.

61. A method of forming a metal powder comprising:

sputtering a metal coating in a sputtering apparatus equipped to sputter onto a moving or rotating surface; and

scraping the coating off the moving or rotating surface with one or more scrapers to form a metal powder.

62. The method as set forth in claim 61, wherein the moving or rotating surface is a continuous belt or rotating cylinder, and wherein the one or more scrapers are suspended above the belt or cylinder to contact the coating at an angle sufficient to remove the coating from the belt or cylinder.

63. The method as set forth in claim 62, wherein the belt is a metal belt in a magnetron sputtering roll coater.

64. The method as set forth in claim 63, wherein the metal is one or more antimicrobial metals.

65. The method as set forth in claim 64, wherein the antimicrobial metal is one or more of Ag, Au, Pd or Pt, and wherein the sputtering is conducted in an oxygen-containing atmosphere under conditions to form and retain atomic disorder in a nanocrystalline powder of the antimicrobial metal.