Hemocompatible polymers on hydrophobic porous polymers

• US 7,807,210 B1
• Filed: 04/05/2004
• Issued: 10/05/2010
• Est. Priority Date: 10/31/2000
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Shah, Niraj, Lundkvist, Andre-Jean, Roorda, Wouter E.
• Primary Examiner(s): Meeks; Timothy H
• Assistant Examiner(s): Sellman; Cachet I
• Application Number:
  US10/818,927
• Time in Patent Office: 2,374 Days
• Field of Search: 427/2.1, 427/2.24, 427/2.25, 604/266
• US Class Current: 427/2.1
• CPC Class Codes: A61L 2300/208 Quaternary ammonium compounds
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: C08L 27/18 Homopolymers or copolymers or tetrafluoroethene

Abstract

The present invention relates to providing a porous, hydrophobic polymer with a hemocompatible substance and to the materials produced thereby. One embodiment of the present invention relates to the providing of expanded poly(tetrafluoroethylene) with one or more complexes of heparin, typically containing heparin in combination with a hydrophobic counter ion. The hemocompatible substance is dissolved in a mixture of solvents in which a first solvent wets the polymer to be coated and the second solvent enhances the solubility of the hemocompatible substance material in the solvent mixture. Typical first solvents wetting hydrophobic polymers include non-polar such as hydrochlorofluorocarbons. Typical second solvents include polar solvents such as organic alcohols and ketones. Azeotropic mixtures of the second solvent in the first solvent are used in some embodiments of the present invention although second solvents may be employed in a range of concentration ranges from less than 0.1% up to saturation. A typical example providing a heparin complex to an endoluminal stent, consisting of coating DURAFLO onto an ePTFE stent-covering material.

Claims

1. A method comprising:

providing a medical device comprising a porous hydrophobic polymer substrate,

providing a hemocompatible substance,

preparing an azeotropic solution comprising the hemocompatible substance and an azeotropic mixture of;

a first solvent that wets the porous hydrophobic polymer substrate;

a second solvent that enhances the solubility of the hemocompatible substance in the azeotropic solution; and

depositing the hemocompatible substance onto the porous hydrophobic polymer substrate by contacting the porous hydrophobic polymer substrate with the azeotropic solution,

wherein the first solvent of the azeotropic mixture is trichloro trifluoro ethanes, and the amount of the trichloro trifluoro ethanes in the azeotropic mixture is 10 wt % or less.

2. The method of claim 1 wherein the porous hydrophobic polymer substrate composes a blood-contacting component of a medical device.

3. The method of claim 2 wherein the medical device is a stent.

4. The method of claim 1 wherein the porous hydrophobic polymer substrate includes at least one polymer material selected from the group consisting of porous polyethylene materials, porous polypropylene materials, porous polyurethane materials, porous polyacrylate materials, porous polymethacrylate materials and porous fluoropolymer materials.

5. The method of claim 4 wherein the porous fluoropolymer material comprises an expanded poly(tetrafluoroethylene) material.

6. The method of claim 1 wherein the hemocompatible substance comprises ionic heparin and a hydrophobic counter ion.

7. The method of claim 6 wherein the hydrophobic counter ion is a hydrophobic quaternary ammonium ion.

8. The method of claim 6 wherein the hydrophobic counter ion is one or more of benzylalkonium ion and tridodecylmethylammonium ion.

9. The method of claim 1 wherein the second solvent is one or more of organic alcohols, and ketones.

10. The method of claim 1 wherein the amount of the second solvent dissolved in the first solvent is from about 0.00001% by weight up to the saturation point of the second solvent in the first solvent.

11. The method of claim 10 wherein the amount of the second solvent mixed in the first solvent is from about 0.1 to about 10% by weight.

12. The method of claim 11 wherein the amount of the second solvent mixed in the first solvent is from about 0.1 to about 2% by weight.

13. The method of claim 12 wherein the amount of the second solvent mixed in the first solvent is from about 0.5 to about 1% by weight.

14. The method of claim 1 wherein the hemocompatible substance is deposited on the hydrophobic polymer substrate by dipping.

15. A method comprising:

providing a medical device comprising a porous hydrophobic polymer substrate,

providing a hemocompatible substance,

preparing an azeotropic solution comprising a mixture of;

a first solvent that wets the porous hydrophobic polymer substrate;

a second solvent that enhances the solubility of the hemocompatible substance in the solution, wherein the second solvent and the first solvent form an azeotropic mixture; and

the hemocompatible substance; and

depositing the hemocompatible substance onto the porous hydrophobic polymer substrate by contacting the porous hydrophobic polymer substrate with the azeotropic solution,

provided that the hemocompatible substance is not subjected to a dialdehyde cross-linking or dialdehyde stabilization step before in vivo use, wherein the first solvent is a mixture of isomers of dichloropentafluoropropanes, the second solvent is methanol, and the first solvent and second solvent are mixed to form a 6% solution by weight.

16. A method comprising:

providing a medical device comprising a porous hydrophobic polymer substrate,

providing a hemocompatible substance,

preparing an azeotropic solution comprising a mixture of;

a first solvent that wets the porous hydrophobic polymer substrate;

a second solvent that enhances the solubility of the hemocompatible substance in the solution, wherein the second solvent and the first solvent form an azeotropic mixture; and

the hemocompatible substance; and

depositing the hemocompatible substance onto the porous hydrophobic polymer substrate by contacting the porous hydrophobic polymer substrate with the azeotropic solution,

provided that the hemocompatible substance is not subjected to a dialdehyde cross-linking or dialdehyde stabilization step before in vivo use, wherein the first solvent is cyclohexane, the second solvent is n-propanal, and the first solvent and second solvent are mixed to form a 5% solution by weight.