Immobilizing mediator molecules via anchor molecules on metallic implant materials containing oxide layer

• US 6,635,269 B1
• Filed: 05/23/2000
• Issued: 10/21/2003
• Est. Priority Date: 11/24/1997
• Status: Expired due to Term

• Current Assignee: Morphoplant GmbH
• Original Assignee: Morphoplant GmbH
• Inventors: Jennissen, Herbert Peter
• Primary Examiner(s): Naff, David M.
• Application Number:
  US09/554,972
• Time in Patent Office: 1,246 Days
• Field of Search: 435/176, 435/180, 435/181, 435/325, 435/395, 424/423, 514/2, 530/402, 530/811
• US Class Current: 424/423
• CPC Class Codes: A61L 2300/414 Growth factors
• 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 27/06 Titanium or titanium alloys
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/28 Materials for coating prostheses
• CPC Class Codes: A61L 27/30 Inorganic materials
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/047 Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/082 Inorganic materials
• 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: Y10S 530/811 Peptides or proteins is immobilized on, or in, an inorganic carrier

Abstract

A mediator molecule is immobilized on the surface of a metallic or ceramic implant material. An anchor molecule such as a dialdehyde having a functional group that covalently binds the mediator molecule is covalently bound to the surface, and the mediator molecule is coupled to the functional group of the anchor molecule. The implant material may be composed of titanium, titanium alloy, aluminum, stainless steel or hydroxylapatite. Oxide units on the surface of the implant material can be increased preferably by treating with hot chromic-sulphuric acid for 0.5 to 3 hours at a temperature between 100 to 250° C. prior to binding the anchor molecule. Also, prior to binding the anchor molecule, the surface of the implant material can be activated by reacting with a silane derivative. Mediator molecules include BMP protein, ubiquitin and antibiotics, and the implant material may be an artificial joint or coronary vessel support such as a stent.

Claims

1. A method of application of an oxide layer on a metallic substrate, comprising treating a surface of the metallic substrate with hot chromic-sulphuric acid for 0.5% 3 hours at a temperature of between 100% 250°

C.

2. The method according to claim 1 wherein the chromic-sulphuric acid has a density of more than 1.40 g/cm³.

3. The method according to claim 1, wherein the metallic substrate comprises an implant.

4. A method of immobilization of a mediator molecule on an implant material, comprising:

covalently binding an anchor molecule to a chemically activated surface of an implant material, wherein the anchor molecule has a functional group that covalently binds the mediator molecule, and wherein the activated surface of the implant material is provided with an oxide layer prior to covalent binding of the anchor molecule;

immobilizing the mediator molecule on the implant material using the functional group of the anchor molecule;

wherein the mediator molecule is selected from the group consisting of a BMP protein as a bone growth factor, an ubiquitin, and an antibiotic; and

wherein the implant material is selected from the group consisting of titanium, a titanium alloy, aluminum, and stainless steel, and wherein the surface of the implant material is provided with an oxide layer by treating the surface with hot chromic-sulphuric acid for 0.5% 3 hours at a temperature of between 100% 250°

C. prior to covalent binding of the anchor molecules.

5. An implant that is formed using a process comprising a method according to claim 4, and wherein the mediator molecule is BMP-2 or BMP-7.

6. A method of immobilization of a mediator molecule on an implant material, comprising:

covalently binding an anchor molecule to a chemically activated surface of an implant material, wherein the anchor molecule has a functional group that covalently binds the mediator molecule, and wherein the activated surface of the implant material is provided with an oxide layer by treating the surface with hot chromic-sulphuric acid for 0.5% 3 hours at a temperature of between 100% 250°

C. prior to covalent binding of the anchor molecule;

immobilizing the mediator molecule on the implant material using the functional group of the anchor molecule by covalent binding;

wherein the mediator molecule comprises a BMP protein as a bone growth factor; and

wherein the implant material comprises a material selected from the group consisting of titanium, a titanium alloy, aluminum, and stainless steel.