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

• US 9,655,917 B2
• Filed: 06/06/2014
• Issued: 05/23/2017
• 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 Healthcare SA (Baxter International Inc.), Baxter International Inc., Northwestern University
• Inventors: Messersmith, Phillip Byron, Sileika, Tadas Stanislovas, Hai, Ton That, Green, John-Bruce Devault, Fulghum, Timothy Michael
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Al-Awadi, Danah
• Application Number:
  US14/298,693
• Publication Number:
  US 20140364391A1
• Time in Patent Office: 1,082 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 method of immobilizing an active agent on a substrate, comprising the steps of:

providing a substrate with a surface, the substrate surface comprising a surface of a medical device or medical device component;

contacting the substrate with a solution of a compound including a trihydroxyphenyl group thereby coupling the trihydroxyphenyl group to the substrate surface to provide a trihydroxyphenyl-treated substrate; and

contacting the trihydroxyphenyl-treated substrate with an active agent, thereby coupling the active agent to the compound including a trihydroxyphenyl group and immobilizing the active agent on the substrate, 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, derivatives thereof, salts of the foregoing, and combinations thereof.

3. The method of claim 1, further comprising, prior to contacting the trihydroxyphenyl-treated substrate with the active agent, the steps of rinsing the trihydroxyphenyl-treated substrate with water thereby forming a washed trihydroxyphenyl-treated substrate and optionally flowing an inert gas over the washed trihydroxyphenyl-treated substrate.

4. The method of claim 1, wherein the compound including a trihydroxyphenyl group comprises gallic acid.

5. The method of claim 1, further comprising activating the substrate so as to introduce a reactive moiety on the substrate surface.

6. The method of claim 1, wherein the substrate is selected from the group consisting of metal substrates, inorganic oxide substrates, ceramic substrates, polymer substrates, semiconductor substrates and combinations thereof.

7. The method of claim 1, wherein the medical device comprises an extracorporeal blood circuit or component of an extracorporeal blood circuit.

8. The method of claim 1, wherein the active agent is selected from the group consisting of antimicrobial agents, antifouling agents, anti-inflammatory agents, antithrombogenic agents, and combinations thereof.

9. The method 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.

2. A method of immobilizing an active agent on a substrate, comprising the steps of:

providing a substrate with a surface, the substrate surface comprising a surface of a medical device or medical device component;

combining in solution a compound including a trihydroxyphenyl group and an active agent, thereby coupling the active agent to the compound including a trihydroxyphenyl group and forming a solution of an active agent-trihydroxyphenyl conjugate; and

contacting the substrate with the solution of the active agent-trihydroxyphenyl conjugate, thereby coupling the trihydroxyphenyl group of the active agent-trihydroxyphenyl conjugate to the substrate surface and immobilizing the active agent on the substrate 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, derivatives thereof, salts of the foregoing, and combinations thereof.