Immobilization of an active agent on a substrate using compounds including trihydroxyphenyl groups

• US 10,428,200 B2
• Filed: 04/18/2017
• Issued: 10/01/2019
• Est. Priority Date: 06/07/2013
• Status: Active Grant

• Current Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc., Northwestern University
• Original Assignee: Baxter International Inc.
• Inventors: Hai, Ton That, Green, John-Bruce Devault, Fulghum, Timothy Michael, Messersmith, Phillip Byron, Sileika, Tadas Stanislovas
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Al-Awadi, Danah
• Application Number:
  US15/490,412
• Publication Number:
  US 20170218174A1
• Time in Patent Office: 896 Days
• Field of Search: None
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/08 acyclic, e.g. paraformaldehyde
• CPC Class Codes: A61K 31/11 Aldehydes
• CPC Class Codes: A61K 31/132 having two or more amino groups, e.g. spermidine, putrescine
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/042 Polysaccharides
• 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 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08K 5/13 Phenols; Phenolates
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393
• CPC Class Codes: G01N 33/551 : the carrier being inorganic

Abstract

The invention provides methods of immobilizing an active agent to a substrate surface, including the steps of, providing a substrate, contacting the substrate with a solution of a compound including a trihydroxyphenyl group, thereby forming a trihydroxyphenyl-treated substrate, and contacting the trihydroxyphenyl-treated substrate with an active agent, thereby immobilizing the active agent on the substrate. Further provided are methods of immobilizing an active agent on a substrate, including the steps of providing a substrate, combining a solution of a compound including a trihydroxyphenyl group with a solution of an active agent, thereby forming a solution of an active agent-trihydroxyphenyl conjugate, and contacting the substrate with the solution of the active agent-trihydroxyphenyl conjugate, thereby immobilizing the active agent on the substrate. The invention further provides substrates and medical device or device components with active agents immobilized on the surface thereof.

Claims

1. A substrate having an active agent immobilized on a surface thereof, the substrate having a compound including a trihydroxyphenyl group coupled to the substrate surface, wherein the compound includes an active agent coupled thereto, such that the active agent is immobilized on the surface, and the compound including a trihydroxyphenyl group is selected from the group consisting of gallic acid, phloroglucinol carboxylic acid, gallamide, benzenetriol, 5-methyl-benzene-1,2,3-triol, 3,4,5-trihydroxybenzaldehyde, 2,3,4-trihydroxybenzaldehyde, gallacetophenone, 3,4,5-trihydroxybenzamide, 2,3,4-trihydroxybenzoic acid, 5-hydroxydopamine hydrochloride, methyl gallate, pyrogallol, salts of the foregoing, and combinations thereof.

2. The substrate of claim 1, wherein the substrate is metal, inorganic oxide, ceramic, semiconductor or polymeric.

3. The substrate of claim 2, wherein the substrate comprises a non-metal substrate having a coating comprising metal.

4. The substrate of claim 2, wherein the substrate comprises a polymer selected from the group consisting of acrylonitrile butadiene styrenes, polyacrylonitriles, polyamides, polycarbonates, polyesters, polyetheretherketones, polyetherimides, polyethylenes, polyethylene terephthalates, polylactic acids, polymethyl methacrylates, polypropylenes, polystyrenes, polyurethanes, polyvinyl chloride, polyvinylidene chlorides, polyethers, polysulfones, silicones, polydimethylsiloxanes, polytetrafluoroethylene, and blends and copolymers thereof.

5. The substrate of claim 2, wherein the metal is selected from the group consisting of stainless steel, cobalt, titanium, nickel, zirconium, tantalum, chromium, tungsten, molybdenum, manganese, iron, vanadium, niobium, hafnium, aluminum, tin, palladium, ruthenium, iridium, rhodium, gold, silver, platinum, oxides of the foregoing, alloys of the foregoing, and combinations of the foregoing.

6. The substrate of claim 1, further comprising a linker compound coupled to the trihydroxyphenyl group, wherein the linker compound includes an active agent coupled thereto, thereby forming a substrate with an active agent immobilized on the surface thereof.

7. The substrate of claim 1, wherein the active agent is selected from the group consisting of antimicrobial agents, antifouling agents, anticoagulants, anti-inflammatory agents, and antithrombogenic agents.

8. The substrate of claim 1, wherein the active agent comprises an antimicrobial agent and the antimicrobial agent is an antibacterial agent.

9. The substrate of claim 1, wherein the active agent comprises an anti-inflammatory agent and the anti-inflammatory agent is a complement inhibitor.

10. The substrate of claim 1, wherein the active agent is selected from the group consisting of chitosan, linear polyethylene glycol, looped polyethylene glycol, polyethylene glycol derivatives, polyvinylpyrrolidone, polyvinylpyrrolidone derivatives, fractionated heparin, unfractionated heparin, heparin derivatives, quaternary ammonium polymers, albumin, polyethylenimine, 4-hydroxycoumarin derivatives, and combinations of the foregoing.

11. The substrate of claim 1, wherein the trihydroxyphenyl group is covalently bound to the active agent.

12. A medical device comprising the substrate of claim 1.

13. The medical device of claim 12, wherein the medical device comprises an extracorporeal blood circuit or component of an extracorporeal blood circuit.

14. The medical device of claim 12, wherein the medical device is selected from the group consisting of tubing, fluid bags, septa, stopcocks, clamps, filters, catheters, needles, and cannulae.

15. The medical device of claim 12, wherein the medical device comprises tubing, the tubing comprises polydimethylsiloxane, the compound including a trihydroxyphenyl group comprises gallic acid, and the active agent comprises chitosan or heparin.

16. The medical device of claim 12, wherein the medical device substrate comprises polydimethylsiloxane and the polydimethylsiloxane is modified to include terminal hydroxyl groups.

17. The medical device of claim 12, wherein the substrate comprises stainless steel, the compound including a trihydroxyphenyl group comprises gallic acid, and the active agent comprises chitosan.