Bone implant and systems and coatings for the controllable release of antimicrobial metal ions

• US 10,265,435 B2
• Filed: 11/21/2017
• Issued: 04/23/2019
• Est. Priority Date: 08/27/2009
• Status: Expired due to Fees

• 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): Liu, Tracy
• Application Number:
  US15/820,393
• Publication Number:
  US 20180093013A1
• Time in Patent Office: 518 Days
• CPC Class Codes: A01N 25/34 Shaped forms, e.g. sheets, not provided for in any other sub-group of this main group
• CPC Class Codes: A01N 59/16 Heavy metals; Compounds thereof
• CPC Class Codes: A01N 59/20 Copper
• CPC Class Codes: A61B 17/864 hollow, e.g. with socket or cannulated
• CPC Class Codes: A61B 17/866 Material or manufacture
• CPC Class Codes: A61B 2017/00889 antimicrobial, disinfectant
• CPC Class Codes: A61B 2017/561 Implants with special means for releasing a drug
• 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 33/30 Zinc; Compounds thereof
• CPC Class Codes: A61K 33/38 Silver; Compounds thereof
• 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 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/606 Coatings
• 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 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 31/06 : 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 and implants including them. 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, rhodium, manganese, 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. The implant may be configured as an implant such as a bone-screw or intramedullary rod-like body configured to receive a treatment cartridge having a coating as described.

Claims

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

a cartridge; and

a coating on the cartridge, the coating comprising a mixture of an anodic metal and a cathodic metal co-deposited on the cartridge, 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 interconnected veins of anodic metal through the coating thickness, or interconnected veins of cathodic metal through the coating thickness, wherein the interconnected veins extend 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 the coating form a pattern on the cartridge.

3. The apparatus of claim 1, wherein the coating forms one or more of:

a sinusoidal pattern, cross-hatched pattern, a mesh pattern, a web pattern, and a zig-zag pattern.

4. 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.

5. 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.

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

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

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

palladium, platinum, and gold.

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

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

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

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

12. A method of delivering silver, zinc, or silver and zinc ions from an implant to prevent or treat infection, the method comprising:

engaging the implant with a removable cartridge having a coating comprising a mixture of an anodic metal and a cathodic metal co-deposited on the cartridge, 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 interconnected veins of anodic metal through the coating thickness, or interconnected veins of cathodic metal through the coating thickness, wherein the interconnected veins extend from an outer surface of the coating through the coating to an opposite side of the coating; and

activating a control to initiate the galvanic release of silver, zinc or silver and zinc from the cartridge.

13. The method of claim 12, wherein engaging the implant comprises coupling the removable cartridge with the implant when the implant is already inserted into a patient.

14. The method of claim 12, further comprising placing at least a portion of the cartridge in communication with a source of oxygen comprising greater than 7×

10<sup>−

5</sup> mol/L of oxygen.

15. The method of claim 12, further comprising inserting the implant into a patient'"'"'s body.

16. The method of claim 12, further comprising inserting the implant into a bone.

17. The method of claim 12, wherein activating comprises extending the cartridge from a chamber within the implant into a patient tissue.

18. The method of claim 12, wherein engaging the implant comprises extending a plurality of ion release members from the cartridge out of openings in the implant body.