Bioabsorbable substrates and systems that controllably release antimicrobial metal ions

• US 8,999,367 B1
• Filed: 12/12/2014
• Issued: 04/07/2015
• Est. Priority Date: 06/11/2014
• 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, Mc Cormick, Robert Vincent, Lucero, Julie, Jegge, Jason A.
• Primary Examiner(s): Krass, Frederick
• Assistant Examiner(s): Liu, Tracy
• Application Number:
  US14/569,545
• Time in Patent Office: 116 Days
• Field of Search: 424/618, 424/630, 424/641, 424/423
• US Class Current: 424/423
• 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 2300/604 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 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 31/06 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

Bioabsorbable substrates having antimicrobial metal ion coatings that are well suited for implantation in to a subject'"'"'s body to treat and/or prevent infection. In particular, described herein are flexible bioabsorbable filaments that are coated with 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 the filament so that the anodic metal is galvanically released as antimicrobial ions when the apparatus is inserted into a subject'"'"'s body. The anodic metal may be at least about 30 percent by volume of the coating.

Claims

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

a substrate; and

a coating on the substrate comprising an anodic metal that is co-deposited with a cathodic metal on the substrate to form a non-uniform mixture of the anodic and cathodic metals, 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 within the matrix of cathodic metal or a continuous path of interconnected veins of cathodic metal within the matrix of anodic metal, wherein the continuous path extends from an outer surface of the coating to the substrate;

further wherein the anodic metal is galvanically released as antimicrobial ions when the apparatus is inserted into a subject'"'"'s body.

2. The apparatus of claim 1, wherein the substrate comprises an implant configured to be inserted into a human body.

3. The apparatus of claim 1, wherein the anodic metal is at least about 30 percent by volume 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 has a higher galvanic potential than the anodic metal.

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 substrate is configured to degrade within the body to form a degradation product including an anion that complexes with ions of the anodic metal and diffuses into the subject'"'"'s body to form an antimicrobial zone.

10. The apparatus of claim 1, wherein the continuous path of interconnected veins are interconnected so that less than 15% of the anodic metal is completely encapsulated within the matrix of cathodic metal, or less than 15% of the cathodic metal is completely encapsulated within the matrix of anodic metal.

11. The apparatus of claim 1, wherein the continuous path of interconnected veins are interconnected so that less than 10% of the anodic metal is completely encapsulated within the matrix of cathodic metal, or less than 10% of the cathodic metal is completely encapsulated within the matrix of anodic metal.

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

a substrate; and

a coating on the substrate comprising zinc and silver and a cathodic metal that are all co-deposited onto the substrate, wherein the zinc and silver are at least about 30 percent by volume of the coating and form a non-uniform mixture of the zinc and the cathodic metal and a non-uniform mixture of the silver and the cathodic metal, wherein the coating comprises a plurality of microregions or microdomains of zinc and silver in a matrix of cathodic metal or a plurality of microregions or microdomains of cathodic metal in a matrix of zinc and a matrix of silver, the microregions or microdomains forming a continuous path of interconnected veins of zinc and silver within the matrix of cathodic metal or a continuous path of interconnected veins of cathodic metal within the matrix of zinc and the matrix of silver, wherein the continuous paths extend from an outer surface of the substrate;

further wherein the zinc and silver are galvanically released as antimicrobial ions when the apparatus is inserted into a subject'"'"'s body.

13. The apparatus of claim 12, wherein the cathodic metal has a higher galvanic potential than the silver or zinc.

14. The apparatus of claim 12, wherein the cathodic metal comprises one or more of:

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

15. The apparatus of claim 12, wherein the coating comprises the silver and zinc and the cathodic metal that have been vapor-deposited onto the substrate so that the anodic metal is not encapsulated by the cathodic metal.

16. The apparatus of claim 12, wherein the substrate is configured to degrade within the body to form a degradation product including an anion that complexes with ions of the silver and zinc and diffuses into the subject'"'"'s body to form an antimicrobial zone.

17. The apparatus of claim 12, wherein the substrate comprises an implant configured to be inserted into a human body.

18. The apparatus of claim 12, wherein the continuous path of interconnected veins are interconnected so that less than 15% of the zinc is completely encapsulated within the matrix of cathodic metal and less than 15% of the silver is completely encapsulated within the matrix of cathodic metal, or less than 15% of the cathodic metal is completely encapsulated within the matrix of zinc and less than 15% of the cathodic metal is completely encapsulated within the matrix of silver.

19. The apparatus of claim 12, wherein the continuous path of interconnected veins are interconnected so that less than 10% of the zinc is completely encapsulated within the matrix of cathodic metal and less than 10% of the silver is completely encapsulated within the matrix of cathodic metal, or less than 10% of the cathodic metal is completely encapsulated within the matrix of zinc and less than 10% of the cathodic metal is completely encapsulated within the matrix of silver.

20. A bioabsorbable apparatus that galvanically releases antimicrobial ions, the apparatus comprising:

an implant having an outer surface comprising a substrate; and

a coating on the substrate comprising an anodic metal that is co-deposited with a cathodic metal on the substrate to form a non-uniform mixture of the anodic and cathodic metals, 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 continuous paths of interconnected veins of anodic metal within the matrix of cathodic metal or continuous paths interconnected veins of cathodic metal within the matrix of anodic metal, wherein the continuous paths extend from an outer surface of the coating to the substrate;

further wherein the anodic metal is galvanically released as antimicrobial ions when the apparatus is inserted into a subject'"'"'s body.

21. The apparatus of claim 20, wherein the continuous path of interconnected veins are interconnected so that less than 15% of the anodic metal is completely encapsulated within the matrix of cathodic metal, or less than 15% of the cathodic metal is completely encapsulated within the matrix of anodic metal.

22. The apparatus of claim 20, wherein the continuous path of interconnected veins are interconnected so that less than 10% of the anodic metal is completely encapsulated within the matrix of cathodic metal, or less than 10% of the cathodic metal is completely encapsulated within the matrix of anodic metal.