Anti-microbial materials

• US 5,837,275 A
• Filed: 06/02/1995
• Issued: 11/17/1998
• Est. Priority Date: 05/19/1992
• Status: Expired due to Term

• Current Assignee: NUCRYST Pharmaceuticals Corp. (The Westaim Corporation)
• Original Assignee: Westaim Technologies Inc.
• Inventors: Apte, Prasad Shrikrishna, Burrell, Robert Edward, Morris, Larry Roy, Sant, Sudhindra Bharat, Gill, Kashmir Singh
• Primary Examiner(s): Levy, Neil S.
• Application Number:
  US08/459,470
• Time in Patent Office: 1,264 Days
• Field of Search: 424/411-421, 424/617, 424/618, 424/630, 424/641, 424/649, 424/650, 424/651, 424/653, 424/405, 424/409, 427/298.6, 427/250, 106/1.05, 106/1.13-1.21, 106/723, 106/733
• US Class Current: 424/409
• CPC Class Codes: A01N 59/16 Heavy metals; Compounds thereof
• CPC Class Codes: A61B 2018/00119 with metal oxide nitride
• 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 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/63 Crystals
• CPC Class Codes: A61L 27/306 Other specific inorganic materials not covered by A61L27/303 - A61L27/32
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/106 Inorganic materials other than carbon
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C23C 14/0036 Reactive sputtering
• CPC Class Codes: C23C 14/025 Metallic sublayers
• CPC Class Codes: C23C 14/06 characterised by the coating material C23C14/0021 , C23C14/04 take precedence
• CPC Class Codes: C23C 14/0688 Cermets, e.g. mixtures of metal and one or more of carbides, nitrides, oxides or borides
• CPC Class Codes: C23C 14/086 of zinc, germanium, cadmium, indium, tin, thallium or bismuth
• CPC Class Codes: C23C 14/14 Metallic material, boron or silicon
• CPC Class Codes: C23C 14/16 : on metallic substrates or on substrates of boron or silicon
• CPC Class Codes: C23C 14/205 : by cathodic sputtering
• CPC Class Codes: C23C 14/225 : Oblique incidence of vaporised material on substrate
• CPC Class Codes: C23C 14/35 : by application of a magnetic field, e.g. magnetron sputtering C23C14/3457 takes precedence
• CPC Class Codes: C23C 14/588 : by mechanical treatment
• CPC Class Codes: H01H 2300/014 : Application surgical instrument
• CPC Class Codes: Y10S 977/899 : Electrolytic
• CPC Class Codes: Y10S 977/915 : Therapeutic or pharmaceutical composition

Abstract

Anti-microbial coatings and method of forming same on medical devices are provided. The coatings are preferably formed by depositing an anti-microbial, biocompatible metal by vapor deposition techniques to produce atomic disorder in the coating such that a sustained release of metal ions sufficient to produce an anti-microbial effect is achieved. Preferred deposition conditions to achieve atomic disorder include a lower than normal substrate temperature, and one or more of a higher than normal working gas pressure and a lower than normal angle of incidence of coating flux. Anti-microbial powders formed by vapor deposition or altered by mechanical working to produce atomic disorder are also provided. Novel anti-microbial silver materials are defined, characterized by having a positive rest potential, a T_rec /T_m less than 0.33, and a grain size less than 200 nm. Anti-microbial fine grain or nanocrystalline materials are provided, together with methods of preparation, wherein the anti-microbial metal if deposited in a matrix with atoms or molecules of a different material such as other biocompatible metals (ex. Ta), trapped or absorbed oxygen, or compounds of anti-microbial metals or biocompatible metals (ex. AgO or TaO).

Claims

1. A fine grain anti-microbial material, comprising:

one or more anti-microbial metals selected from the group consisting of Ag, Au, Pt, Pd, Ir, Sn, Cu, Sb, Bi, and Zn, or an alloy or compound thereof, said metals having a grain size less than 200 nm, and being characterized by sufficient atomic disorder such that the material, in contact with an alcohol or a water based electrolyte, provides a sustained release of atoms, ions, molecules or clusters containing at least one of the anti-microbial metals at an enhanced rate relative to its normal ordered crystalline state and at a concentration sufficient to provide a localized anti-microbial effect, wherein the atomic disorder in the material provides irregularities in surface topography and inhomogeneities in structure on a nanometer scale and is caused by high concentrations of at least one of point defects in a crystal lattice, vacancies, line defects comprising dislocations, interstitial atoms, amorphous regions and grain and sub grain boundaries, relative to a normal ordered crystalline state for the anti-microbial metal.

2. The material as set forth in claim 1, wherein the atomic disorder is created in the material under conditions which limit diffusion such that sufficient atomic disorder is retained in the material to provide release of atoms, ions, molecules, or clusters containing the anti-microbial metal into the alcohol or water based electrolyte at the enhanced rate relative to its normal ordered crystalline state.

3. The anti-microbial material as set forth in claim 1, wherein the antimicrobial effect is sufficient to generate a zone of inhibition of greater than 5 mm.

4. The anti-microbial material as set forth in claim 2, in the form of a fine grain powder, wherein the anti-microbial metal is formed in a matrix with atoms or molecules of a different material, the different material being selected from the group consisting of biocompatible metals, oxygen, nitrogen, hydrogen, boron, sulphur, halogen, an oxide, nitride, carbide, boride, sulphide and halide of an anti-microbial metal, and an oxide, nitride, carbide, boride, sulphide and halide of an biocompatible metal.

5. The anti-microbial material as set forth in claim 4, wherein the biocompatible metal is selected from the group consisting of Ta, Ti, Nb, B, Hf, Zn, Mo, Si, and Al.

6. The anti-microbial material as set forth in claim 5, wherein the anti-microbial metal is selected from Ag, Au or Pd, and wherein the biocompatible metal is selected from Ta, Ti or Nb.

7. The anti-microbial material as set forth in claim 4, comprising substantially pure silver metal, silver oxide and trapped or absorbed atoms of oxygen.

8. The anti-microbial material as set forth in claim 4, 5, 6, or 7 in the form of a nanocrystalline powder having a grain size less than about 20 nm.

9. The anti-microbial material as set forth in claim 4, 5, 6 or 7 in the form of a fine grain powder having a grain size less than about 140 nm.