Process for modification of implant surface with bioactive conjugates for improved integration
First Claim
1. A process for covalently coating a titanium implant with a bioactive conjugate, which comprises the steps of:
- a) chemically cleaning a titanium implant surface by electrochemical deoxidation in a solution selected from the group consisting of ethanol, perchloric acid-butanol-methanol, H2 O2 --NaCl--NaH2 PO4 ; and
b) without exposure to air, coating the cleaned titanium implant surface from step a) to form a covalently attached bioactive thiolate conjugate layer, wherein said thiolate conjugate has the following structural formula I;
space="preserve" listing-type="equation">--R--X--P IwhereinR is S covalently attached to the titanium implant surface;
X is a linker covalently attached to R and selected from a bond, linear or branched chains of 1 to 30 covalently attached atoms of at least one of C, N, O, Si or S, rings of at least one of C, N, O, Si or S, and a combination thereof, andP is a covalently attached bioactive molecule moiety which promotes tissue growth, stabilization or integration;
and wherein said bioactive moiety retains its biological activity.
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Abstract
The present invention relates to a process for the covalent coating of implants with a bioactive conjugate, which comprises the steps of: a) cleaning a metal implant surface from contaminants by deoxidation with potentiostatic electrochemical polishing in a solution selected from ethanol, perchloric acid-butanol-methanol solution, H2 O2 --NaCl--NaH2 PO4 or by chemical cleaning with a solution selected from the group consisting of HF/HNO3, H2 O2 /H2 SO4 and H2 O2 /KOH; b) coating the cleaned implant surface of step a) with a bioactive conjugate, wherein the conjugate has the following structural Formula I:
--R--X--P I
wherein, R is O or S, adapted to be covalently attached to an implant surface; X is selected from a bond, linear or branched chains of 1 to 30 covalently attached atoms of at least C, N, O, Si or S, rings of 1 to 20 covalently attached atoms of at least C, N, O, Si or S, and a combination thereof; and P is a bioactive molecule moiety which promotes tissue growth, stabilization and integration, and wherein the moiety retains its biological activity.
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Citations
19 Claims
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1. A process for covalently coating a titanium implant with a bioactive conjugate, which comprises the steps of:
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a) chemically cleaning a titanium implant surface by electrochemical deoxidation in a solution selected from the group consisting of ethanol, perchloric acid-butanol-methanol, H2 O2 --NaCl--NaH2 PO4 ; and b) without exposure to air, coating the cleaned titanium implant surface from step a) to form a covalently attached bioactive thiolate conjugate layer, wherein said thiolate conjugate has the following structural formula I;
space="preserve" listing-type="equation">--R--X--P Iwherein R is S covalently attached to the titanium implant surface; X is a linker covalently attached to R and selected from a bond, linear or branched chains of 1 to 30 covalently attached atoms of at least one of C, N, O, Si or S, rings of at least one of C, N, O, Si or S, and a combination thereof, and P is a covalently attached bioactive molecule moiety which promotes tissue growth, stabilization or integration; and wherein said bioactive moiety retains its biological activity. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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11. A process for covalently coating a titanium implant with a bioactive conjugate, which comprises the steps of:
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a) chemically cleaning a titanium implant surface by i) electrochemical deoxidation in a solution selected from the group consisting of ethanol, perchloric acid-butanol-methanol, H2 O2 --NaCl--NaH2 PO4, and subsequent controlled electrochemical reoxidation;
orii) chemical oxidation with a solution selected from the group consisting of HF/HNO3, H2 O2 /H2 SO4 and H2 O2 /KOH; and b) under an inert atmosphere, coating the cleaned titanium implant surface of step a) to form a covalently attached bioactive siloxane conjugate layer, wherein said siloxane conjugate has the following structural Formula I;
space="preserve" listing-type="equation">--R--X--P Iwherein, R is O covalently attached to the titanium implant surface; X is a linker containing Si covalently attached to R and selected from linear or branched chains of 1 to 30 covalently attached atoms of at least C, N, O, Si or S, rings of at least one of C, N, O, Si or S, and a combination thereof; and P is a bioactive molecule moiety stably attached to X via a covalent bond;
said bioactive molecule moiety promoting tissue growth, stabilization or integration;and wherein said bioactive moiety retains its biological activity. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18, 19)
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Specification