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Method for attachment of biomolecules to medical device surfaces

a biomolecule and surface technology, applied in medical science, special packaging, dentistry, etc., can solve the problems of affecting the useful life of many devices, and not all biomolecules, including some proteins and peptides, comprise terminal amine moieties

Inactive Publication Date: 2006-08-31
MEDTRONIC INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides methods for attaching biomolecules to medical device surfaces using amine-functional materials. These methods involve converting the biomolecule into an amine-functional material and combining it with a chemical moiety on the surface of the device. This creates a strong bond between the biomolecule and the device surface, allowing for the immobilization of the biomolecule on the device. The invention also provides methods for crosslinking biomolecules with other biomolecules or chemical moieties to create a crosslinked material with additional biomolecules attached. The crosslinked material can be used as a biomaterial or coating on the device. Overall, the invention provides methods for securely attaching biomolecules to medical device surfaces and creating materials with improved biological performance.

Problems solved by technology

A major problem with such articles is that their surfaces tend to adsorb a layer of proteins from tissues and fluids such as tears, urine, lymph fluid, blood, blood products, and other fluids and solids derived from blood.
Adverse biological reactions such as thrombosis and inflammation can diminish the useful lifetime of many devices.
However, not all biomolecules, including some proteins and peptides, comprise terminal amine moieties.
In some cases, covalently coupling of a biomolecule to a biomaterial surface is not desirable.
The main limit to utilization of ionically bonding methods is the creation of opposing charges on either a biomolecule or a biomaterial surface or both.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Periodate Oxidation of a Peptide Containing an N-terminal Serine Amino Acid Residue

[0079] Two biomolecules, a tripeptide made of three serine amino acid residues and a dipeptide made of two lysine amino acid residues, both obtained from Sigma Chemical Co. (St. Louis, Mo.), were incubated in sodium metaperiodate (NaIO4) also obtained from Sigma Chemical Co. (St. Louis, Mo.). The tripeptide, 0.90 mmoles, was incubated in the dark while shaking at room temperature for 3 hours in 10 ml deionized water containing 1.2 mmoles NaIO4. The resultant solution, 2.5 ml, was added to 2 ml of a solution containing 0.8 g NaOH, 0.2 g 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole, which is available under the trade designation PURPALD from Sigma Chemical Co. (St. Louis, Mo.), in 20 ml deionized water, and shaken vigorously for 15 minutes at room temperature. The dipeptide, 0.72 mmoles, was incubated in the dark while shaking at room temperature for 3 hours in 10 ml deionized water containing 1.2 mmo...

example 2

Periodate Oxidation of a Peptide Containing an N-terminal Threonine Amino Acid Residue

[0080] A biomolecule, a dipeptide made of N-terminal threonine and leucine amino acid residues obtained from Sigma Chemical Co. (St. Louis, Mo.), was incubated in sodium metaperiodate (NaIO4) also obtained from Sigma Chemical Co. (St. Louis, Mo.). The dipeptide, 4.3 mmoles, was incubated in the dark while shaking at room temperature for 3 hours in 10 ml deionized water containing 1.2 mmoles NaIO4. The resultant solution, 10 ml, was added to 2 ml of the PURPALD solution described in Example 1 and shaken vigorously for 15 minutes at room temperature. After the 15 minutes of shaking at room temperature, the resultant solution was analyzed spectrophotometrically at 550 nm. Sample absorbance obtained at 550 nm was 0.62 indicating the periodate had successfully oxidized the N-terminal threonine amino acid present in the dipeptide, thereby forming an aldehyde moiety.

example 3

Periodate Oxidation of a Peptide Containing an N-terminal Serine Amino Acid Residue

[0081] A biomolecule, a pentapeptide made of N-terminal serine, aspartic acid, glycine, arginine, and glycine amino acid residues obtained from Sigma Chemical Co. (St. Louis, Mo.), was incubated in sodium metaperiodate (NaIO4) also obtained from Sigma Chemical Co. (St. Louis, Mo.). The pentapeptide, 0.01 mmoles, was incubated in the dark while shaking at room temperature for 3 hours in 2 ml deionized water containing 0.23 mmoles NaIO4. The resultant solution, 10 ml, was added to 2 ml of the PURPALD solution described in Example 1 and shaken vigorously for 15 minutes at room temperature. After the 15 minutes of shaking at room temperature, the resultant solution was analyzed spectrophotometrically at 550 nm. Sample absorbance obtained at 550 nm was 0.74, indicating the periodate had successfully oxidized the N-terminal serine amino acid residue present in the pentapeptide, thereby forming an aldehyde ...

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PUM

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Abstract

A method for making a medical device having at least one biomolecule immobilized on a substrate surface is provided. One method of the present invention includes immobilizing a biomolecule comprising an unsubstituted amide moiety on a biomaterial surface. Another method of the present invention includes immobilizing a biomolecule on a biomaterial surface comprising an unsubstituted amide moiety. Still another method of the present invention may be employed to crosslink biomolecules comprising unsubstituted amide moieties immobilized on medical device surfaces. Additionally, one method of the present invention may be employed to crosslink biomolecules comprising unsubstituted amide moieties in solution, thereby forming a crosslinked biomaterial or a crosslinked medical device coating.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of U.S. patent application Ser. No. 09 / 001,994 for “Oxidative Method for Attachment of Biomolecules to Medical Device Surfaces” to Keogh filed Dec. 31, 1997, which is a continuation-in-part of U.S. patent application Ser. No. 08 / 635,187 for “Oxidative Method of Attachment of Biomolecules to Surfaces of Medical Devices” to Keogh filed Apr. 25, 1996. [0002] This application is further a continuation-in-part of U.S. patent application Ser. No. 08 / 984,922 for “Oxidative Method for Attachment of Glycoproteins or Glycopeptides to Surfaces of Medical Devices” to Keogh filed Dec. 4, 1997, which is a continuation-in-part of U.S. patent application Ser. No. 08 / 694,535 for “Oxidative Method of Attachment of Glycoproteins to Surfaces of Medical Devices” to Keogh filed Aug. 9, 1996, now U.S. Pat. No. 5,728,420 issued Mar. 17, 1998. [0003] This application is also a continuation-in-part of U.S. patent applic...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): B05D3/02A61L27/28A61L27/34A61L29/08A61L31/08A61L31/10A61L33/00
CPCA61L27/22A61L27/24A61L27/28A61L27/34A61L27/3625A61L27/3641A61L27/3645A61L27/54A61L29/085A61L31/08A61L31/10A61L31/16A61L33/0011A61L33/0029A61L33/0047A61L33/0082A61L33/12A61L33/128A61L33/18A61L2300/606C08L89/00Y10S530/81Y10S530/815Y10S530/811Y10S530/816C12N11/02C12N11/14A61K38/43G01N33/543
Inventor KEOGH, JAMES R.TRESCONY, PAUL V.
Owner MEDTRONIC INC
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