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Periodate oxidative method for attachment of biomolecules to medical device surfaces
| Details |
Inventors: Keogh, James R.;
Assignee: Medtronic, Inc. (Minneapolis, MN)
Primary Examiner: Naff; David M.
Assistant Examiner:
Attorney, Agent or Firm: Woods; Thomas F., Patton; Harold R.
Methods are provided for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A 2-aminoalcohol moiety of a biomolecule is oxidized with a periodate to an aldehyde moiety which is reacted with an amine moiety on the surface of a medical device to form an imine moiety, and the imine moiety is reduced to form an amine linkage immobilizing a coating of the biomolecule on the surface. In another method, a biomolecule coating containing an amine moiety and a 2-aminoalcohol moiety is immobilized on the surface of a medical device, the 2-aminoalcohol moiety is oxidized with a periodate to an aldehyde moiety which is reacted with the amine moiety to form an imine moiety, and the imine moiety is reduced to form a secondary amine and crosslink the coating. Each biomolecule may contain an amine moiety and a 2-aminoalcohol moiety, and the aldehyde moiety of one biomolecule resulting from periodate oxidation may react with the amine moiety of another biomolecule. In a further embodiment, a 2-aminoalcohol moiety on the surface of a medical device is oxidized with a periodate to an aldehyde moiety, and an amine moiety of a biomolecule is reacted with the aldehyde moiety to form an imine moiety which is reduced to form an amine linkage immobilizing the biomolecule on the surface. |
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DETAILED DESCRIPTION OF THE INVENTION As used in the specification and claims hereof, the following terms have the particular meanings and definitions set forth below.
I define the term "biomolecule" appearing herein as meaning any one or more of a biomolecule alone or a combination of different biomolecules.
I define the term "biomaterial" appearing herein as a material that is substantially insoluble in body fluids and that is designed and constructed to be placed in or onto the body or to contact fluid of the body.
Ideally, a biomaterial will not induce undesirable reactions in the body such as blood clotting, tissue death, tumor formation, allergic reaction, foreign body reaction (rejection) or inflammatory reaction; will have the physical properties such as strength, elasticity, permeability and flexibility required to function for the intended purpose; may be purified, fabricated and sterilized easily; will substantially maintain its physical properties and function during the time that it remains implanted in or in contact with the body.
Biomaterials suitable for use in the present invention either include a 2-aminoalcohol moiety, an amine moiety, or both.
Additionally, biomaterials may be fabricated by crosslinking biomolecules, comprising both a 2-aminoalcohol and a primary amine moiety, according to one method of the present invention.
I define the term "medical device" appearing herein as a device having surfaces that contact tissue, blood, or other bodily fluids in the course of their operation, which fluids are subsequently used in patients.
This definition includes within its scope, for example, extracorporeal devices for use in surgery such as blood oxygenators, blood pumps, blood sensors, tubing used to carry blood and the like which contact blood which is then returned to the patient.
The definition includes within its scope endoprostheses implanted in blood contact in a human or animal body such as vascular grafts, stents, pacemaker leads, heart valves, and the like that are implanted in blood vessels or in the heart
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