Coatings for the controllable release of antimicrobial metal ions

• US 9,114,197 B1
• Filed: 04/06/2015
• Issued: 08/25/2015
• Est. Priority Date: 06/11/2014
• Status: Active Grant

• Current Assignee: Silver Bullet Therapeutics, Inc.
• Original Assignee: Silver Bullet Therapeutics, Inc.
• Inventors: Dehnad, Houdin, Chirico, Paul E., Chopko, Bohdan Wolodymyr, Barr, John, McCormick, Robert Vincent, Lucero, Julie, Jegge, Jason A.
• Primary Examiner(s): Krass, Frederick
• Assistant Examiner(s): Liu, Tracy
• Application Number:
  US14/679,893
• Time in Patent Office: 141 Days
• Field of Search: 424/618, 424/423, 424/682, 424/641
• US Class Current: 1/1
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 55/02 containing metal atoms
• CPC Class Codes: A01N 59/16 Heavy metals; Compounds thereof
• CPC Class Codes: A01N 59/20 Copper
• CPC Class Codes: A61K 33/30 Zinc; Compounds thereof
• CPC Class Codes: A61K 33/34 Copper; Compounds thereof
• CPC Class Codes: A61K 33/38 Silver; Compounds thereof
• 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 2300/80 characterised by a special chemical form
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• 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 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/022 Metals or alloys
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/088 : Other specific inorganic materials not covered by A61L31/084 or A61L31/086
• CPC Class Codes: A61L 31/148 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Antimicrobial metal ion coatings. In particular, described herein are coatings including an anodic metal (e.g., silver and/or zinc and/or copper) that is co-deposited with a cathodic metal (e.g., palladium, platinum, gold, molybdenum, titanium, iridium, osmium, niobium or rhenium) on a substrate so that the anodic metal is galvanically released as antimicrobial ions when the apparatus is exposed to a bodily fluid. The anodic metal may be at least about 25 percent by volume of the coating, resulting in a network of anodic metal with less than 20% of the anodic metal in the coating fully encapsulated by cathodic metal.

Claims

1. An apparatus that galvanically releases antimicrobial ions, the apparatus comprising:

a substrate surface; and

a coating on the outer substrate surface, the coating comprising a mixture of between about 25% and 75% by volume of an anodic metal, and between about 25% to 75% by volume of a cathodic metal co-deposited on the substrate surface, wherein the coating comprises a plurality of microregions or microdomains of anodic metal in a matrix of cathodic metal or a plurality of microregions or microdomains of cathodic metal in a matrix of anodic metal, the microregions or microdomains forming a continuous path of interconnected veins of anodic metal through the coating thickness, or a continuous path of interconnected veins of cathodic metal through the coating thickness, wherein the continuous path extends from an outer surface of the coating through the coating to an opposite side of the coating;

wherein the anodic metal is galvanically released as antimicrobial ions when the apparatus is exposed to a bodily fluid.

2. The apparatus of claim 1, wherein less than 30% of the anodic metal is fully encapsulated within the matrix of cathodic metal and connects through a microregion or microdomain of anodic metal to the outer surface of the coating.

3. The apparatus of claim 1, wherein less than 20% of the anodic metal is fully encapsulated within the matrix of cathodic metal and connects through a microregion or microdomain of anodic metal to the outer surface of the coating.

4. The apparatus of claim 1, wherein the anodic metal comprises both zinc and silver.

5. The apparatus of claim 1, wherein the anodic metal comprises silver, zinc or copper.

6. The apparatus of claim 1, wherein the cathodic metal comprises one or more of:

palladium, platinum, or gold.

7. The apparatus of claim 1, wherein the cathodic metal comprises one or more of:

palladium, platinum, gold, molybdenum, titanium, iridium, osmium, niobium and rhenium.

8. The apparatus of claim 1, wherein the coating comprises the anodic metal and the cathodic metal that have been vapor-deposited onto the substrate so that the anodic metal is not encapsulated by the cathodic metal.

9. The apparatus of claim 1, wherein the surface is an outer surface of one of:

a pacemaker, defibrillator, neurostimulator, or ophthalmic implant.

10. The apparatus of claim 1, wherein the surface is an outer surface of one of:

an implantable shunt, an artificial joint, a hip implant, a knee implant, a catheter, a stent, an implantable coil, a pump, an intrauterine device (IUD), a heart valve, a surgical fastener, a surgical staple, a surgical pin, a surgical screw, an implantable electrical lead, or an implantable plate.

11. The apparatus of claim 1, wherein the surface is an outer surface of one of:

a retractor, a bariatric balloon, an orthodontic brace, a breast implant, a surgical sponge, a gauze, or a wound packing material.

12. The apparatus of claim 1, wherein the coating is fractured.

13. The apparatus of claim 1, wherein the coating is fractured so that a surface area of the coating is increased by at least 25% compared to the surface area of the coating in an unfractured state.

14. A method of galvanically releasing antimicrobial ions to form an antimicrobial zone around an implant that is inserted into a subject'"'"'s tissue, the method comprising:

inserting into the subject'"'"'s tissue an apparatus comprising a coating on an outer surface, the coating comprising a mixture of between about 25% and 75% by volume of an anodic metal, and between about 25% to 75% by volume of a cathodic metal co-deposited on the substrate surface, wherein the coating comprises a plurality of microregions or microdomains of anodic metal in a matrix of cathodic metal or a plurality of microregions or microdomains of cathodic metal in a matrix of anodic metal, the microregions or microdomains forming a continuous path of interconnected veins of anodic metal through the coating thickness, or a continuous path of interconnected veins of cathodic metal through the coating thickness, wherein the continuous path extends from an outer surface of the coating through the coating to an opposite side of the coating;

galvanically releasing antimicrobial ions of the anodic metal from the coating.

15. The method of claim 14, wherein inserting comprises inserting a pacemaker.

16. The method of claim 14, wherein inserting comprises inserting a defibrillator.

17. The method of claim 14, wherein inserting comprises inserting a neurostimulator.

18. The method of claim 14, wherein inserting comprises inserting one of:

an implantable shunt, an artificial joint, a hip implant, a knee implant, a catheter, a stent, an implantable coil, a pump, an intrauterine device (IUD), a heart valve, a surgical fastener, a surgical staple, a surgical pin, a surgical screw, an implantable electrical lead, or an implantable plate.

19. The method of claim 14, wherein galvanically releasing antimicrobial ions from the coating comprises galvanically releasing ions of silver, zinc or silver and zinc.

20. The method of claim 14, wherein the antimicrobial zone around the implant is sustained for greater than two weeks.

21. The method of claim 14, wherein the antimicrobial zone around the implant is sustained for greater than thirty days.