Anti-microbial materials

• US 6,017,553 A
• Filed: 06/02/1995
• Issued: 01/25/2000
• 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, Morris, Larry Roy, Sant, Sudhindra Bharat, Gill, Kashmir Singh, Burrell, Robert Edward
• Primary Examiner(s): Levy, Neil S.
• Application Number:
  US08/459,469
• Time in Patent Office: 1,698 Days
• Field of Search: 424/411, 424/405, 424/421, 424/489, 424/617-618, 424/630, 424/649, 424/653, 427/248.1, 427/250, 106/1.05, 106/1.13, 106/1.14, 106/1.15, 106/1.16, 106/1.17, 106/1.18, 106/1.19, 106/1.21, 106/723, 106/733
• US Class Current: 424/405
• 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. Ag0 or TaO).

Claims

1. A method of producing a fine grain anti-microbial material, comprising:

depositing, in powder form onto a substrate, one or more anti-microbial metals in a matrix with atoms or molecules of a different material by vapour deposition under conditions which limit diffusion, including working gas or ambient gas pressures, for sputtering greater than 75 mTorr, for magnetron sputtering greater than 10 mTorr, for ion plating greater than 200 mtorr, for e-beam or arc evaporation greater than 0.01 mTorr, for gas scattering evaporation or reactive arc evaporation greater than 200 mTorr and for inert gas condensation between 5 and 7 Torr, to provide a crystalline material having a grain size less than 200 nm and atomic disorder such that the powder, in contact with an alcohol or a water based electrolyte, provides a sustained release of ions, atoms, molecules or clusters of at least one of the anti-microbial metals into the alcohol or water based electrolyte at a concentration sufficient to provide a localized anti-microbial effect, wherein the atomic disorder in the powder provides irregularities in surface topography and inhomogeneities in structure on a nanometre scale and is caused by high concentrations of one or more of point defects in a crystal lattice, vacancies, line defects comprising dislocations, interstitial atoms, amorphous regions, grain and sub grain boundaries, relative to the normal ordered crystalline state for the anti-microbial metal, wherein the different material is selected from the group consisting of;

biocompatible metals, oxygen, nitrogen, hydrogen, boron, sulphur, halogens, and oxides, nitrides, carbides, borides, sulphides and halides of either or both of an anti-microbial metal or a biocompatible metal.

2. The method as set forth in claim 1, wherein the antimicrobial effect is sufficient to generate a zone of inhibition greater than 5 mm.

3. The method as set forth in claims 1, wherein the anti-microbial metal is Ag, and the substrate is cooled to less than about 90°

C.

4. The method as set forth in claim 1, wherein the material is deposited by an inert gas condensation method at pressures in the range of about 5 to 7 Torr, onto a substrate cooled with liquid nitrogen.

5. The method as set forth in claim 1, wherein the anti-microbial metal is selected from the group consisting of Ag, Au, Pt, Pd, Ir, Sn, Cu, Sb, Bi and Zn or alloys or compounds of one or more of these metals, wherein the biocompatible metal is selected from the group consisting of Ta, Ti, Nb, B, Hf, Zn, Mo, Si and Al or alloys or compounds of one or more of these metals, and wherein the substrate is cooled to less than about 100°

C.

6. The method as set forth in claim 1, wherein the anti-microbial metal is selected from Ag, Au, and Pd, and wherein the biocompatible metal is selected from Ta, Ti, and Nb.

7. The method as set forth in claim 6, wherein oxygen is included in the working gas atomosphere during vapour deposition such that atoms or molecules of oxygen are trapped or absorbed in the matrix.

8. The method as set forth in claim 7, wherein the anti-microbial metal which is deposited is substantially pure silver metal or silver oxide and wherein oxygen may be included in the working gas atmosphere such that the deposited material includes substantially pure silver metal, and one or both of silver oxide and atoms or molecules of trapped or absorbed oxygen.

9. The method as set forth in claim 5, 6, or 1, wherein the material is deposited as a fine grain powder having a grain size less than about 140 nm.

10. The method as set forth in claim 5, 6, or 1, wherein the material is deposited as a nanocrystalline powder.

11. The method as set forth in claim 5, 6, or 1, wherein the material is deposited as a nanocrystalline powder having a grain size less than about 20 nm.