Periodate oxidative method for attachment of biomolecules to medical device surfaces

• US 5,945,319 A
• Filed: 12/31/1997
• Issued: 08/31/1999
• Est. Priority Date: 04/25/1996
• Status: Expired due to Fees

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Keogh, James R.
• Primary Examiner(s): Naff, David M.
• Application Number:
  US09/001,994
• Time in Patent Office: 608 Days
• Field of Search: 435/174, 435/176, 435/177, 435/180, 435/181, 436/518, 436/531, 436/532, 436/524, 530/810, 530/815, 530/816, 530/402, 424/422, 424/94.1
• US Class Current: 435/174
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/28 Materials for coating prostheses
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/10 Macromolecular materials
• 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: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: A61L 33/0047 Enzymes, e.g. urokinase, streptokinase
• CPC Class Codes: A61L 33/0082 by reacting with an organic compound other than heparin
• CPC Class Codes: A61L 33/12 Polypeptides, proteins or derivatives thereof , e.g. degradation products thereof
• CPC Class Codes: A61L 33/128 Other specific proteins or polypeptides not covered by A61L33/122 - A61L33/126
• CPC Class Codes: A61L 33/18 Use of ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: Y10S 530/81 Carrier - bound or immobilized peptides or proteins and the preparation thereof, e.g. biological cell or cell fragment as carrier
• CPC Class Codes: Y10S 530/811 Peptides or proteins is immobilized on, or in, an inorganic carrier
• CPC Class Codes: Y10S 530/815 Carrier is a synthetic polymer
• CPC Class Codes: Y10S 530/816 Attached to the carrier via a bridging agent

Abstract

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.

Claims

1. A method of crosslinking a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the surface being suitable for contacting tissue and bodily fluids in or temporarily removed from a living mammalian subject, the method comprising the ordered steps of:

(a) immobilizing a biomolecule on the surface, the biomolecule forming a coating comprising an amine moiety and a 2-aminoalcohol moiety;

(b) applying a periodate to the coating to oxidize the 2-aminoalcohol moiety to form an aldehyde moiety;

(c) allowing the aldehyde moiety to combine with the amine moiety to form an imine moiety; and

(d) reacting the imine moiety with a reducing agent to form a secondary amine and thereby cause at least portions of the coating to crosslink.

2. The method of claim 1, wherein the device is selected from the group consisting of a blood-contacting medical device, a tissue-contacting medical device, a bodily fluid-contacting medical device, an implantable medical device, an extracorporeal medical device, a blood oxygenator, a blood pump, tubing for carrying blood, an endoprosthesis medical device, a vascular graft, a stent, a pacemaker lead, a heart valve, temporary intravascular medical device, a catheter and a guide wire.

3. The method of claim 1, wherein the biomolecule is selected from the group consisting of an antithrombotic, a clotting agent, an anti-inflammatory, an antibody, an immunoglobulin, an enzyme, a hormone, a neurotransmitter, a cytokine, a globular protein, a regulatory agent, a cell attachment protein, a cell attachment peptide, a proteoglycan, a toxin, an antibiotic, an antibacterial agent, an antimicrobial agent, a catalyst, a drug, a vitamin, an antibody, an antigen, a protein, a peptide, a DNA segment, a RNA segment, a dye and a ligand.

4. The method of claim 1, wherein the biomolecule is a naturally occurring biomolecule.

5. The method of claim 1, wherein the biomolecule is a chemically synthesized biomolecule.

6. The method of claim 1, wherein the biomolecule comprises an amino acid residue.

7. The method of claim 6, wherein the amino acid residue is selected from the group consisting of a N-terminal serine, a N-terminal threonine and a 5-hydroxylysine.

8. The method of claim 6, wherein the amino acid residue is a lysine residue.

9. The method of claim 6, wherein the biomolecule is selected from the group consisting of a peptide and a protein.

10. The method of claim 9, wherein the peptide is selected from the group consisting of an an antithrombotic peptide, an anti-inflammatory peptide, an enzyme, a hormone, a neurotransmitter, a cytokine, a cell attachment peptide, a toxin, an antibiotic, and a ligand.

11. The method of claim 9, wherein the peptide is a naturally occurring peptide.

12. The method of claim 9, wherein the peptide is a chemically synthesized peptide.

13. The method of claim 9, wherein the protein is selected from the group consisting of an antithrombotic protein, an anti-inflammatory protein, an antibody, an immunoglobulin, an enzyme, a hormone, a globular protein, a cell attachment protein, a proteoglycan, a toxin, and a ligand.

14. The method of claim 9, wherein the protein is a naturally occurring protein.

15. The method of claim 9, wherein the protein is a chemically synthesized protein.

16. The method of claim 1, wherein the periodate comprises at least one of periodic acid, sodium periodate, alkali metal periodates, and potassium periodate.

17. The method of claim 1, wherein the periodate is combined with 2-aminoalcohol moiety and the amine moiety in an aqueous solution having a pH between about 4 and about 9.

18. The method of claim 1, wherein the periodate is combined with the 2-aminoalcohol moiety and the amine moiety in an aqueous solution having a temperature between about 0 and about 50 degrees Celsius.

19. The method of claim 1, wherein the oxidizing step is performed in the absence of light.

20. The method of claim 1, wherein the reducing agent comprises at least one of sodium borohydride, sodium cyanoborohydride, and amine borane.

21. The method of claim 1, wherein the reducing agent is combined with the material comprising an imine moiety in an aqueous solution having a pH between about 6 and about 10.

22. The method of claim 1, wherein the reducing agent is combined with the imine moiety in an aqueous solution having a temperature between about 0 and about 50 degrees Celsius.

23. The method of claim 1, wherein at least a portion of the surface forms at least one of a tube, a rod, a membrane, a balloon, a bag and a sheet.

24. The method of claim 1, wherein the medical device comprises at least one of a biocompatible material selected from the group consisting of metal, titanium, titanium alloys, tin-nickel alloys, shape memory alloys, aluminum oxide, platinum, platinum alloys, stainless steel, MP35N stainless steel, elgiloy, stellite, pyrolytic carbon, silver carbon, glassy carbon, polymer, polyamide, polycarbonate, polyether, polyester, polyolefin, polyethylene, polypropylene, polystyrene, polyurethane, polyvinyl chloride, polyvinylpyrrolidone, silicone elastomer, fluoropolymer, polyacrylate, polyisoprene, polytetrafluoroethylene, rubber, ceramic, hydroxapatite, human protein, human tissue, animal protein, animal tissue, bone, skin, teeth, collagen, laminin, elastin, fibrin, wood, cellulose, compressed carbon and glass.

25. A method of forming a crosslinked biomaterial for use in a medical device, the biomaterial being suitable for contacting tissue and bodily fluids in or temporarily removed from a living mammalian subject, the method comprising the ordered steps of:

(a) combining a periodate with two or more biomolecules, the biomolecules comprising an amine moiety and a 2-aminoalcohol moiety, the periodate to oxidize the 2-aminoalcohol moiety to form an aldehyde moiety;

(b) allowing the aldehyde moiety of one biomolecule to combine with the amine moiety of another biomolecule to form an imine moiety; and

(c) reacting the imine moiety with a reducing agent to form a secondary amine and thereby forming a crosslinked biomaterial.

26. The method of claim 25, wherein the medical device is selected from the group consisting of a blood-contacting medical device, a tissue-contacting medical device, a bodily fluid-contacting medical device, an implantable medical device, an extracorporeal medical device, a blood oxygenator, a blood pump, tubing for carrying blood, an endoprosthesis medical device, a cell seeding medical device, a cell binding medical device, a cell separating medical device, a vascular graft, a stent, a heart valve, a collagen glue, a tissue adhesive, and a temporary intravascular medical device.

27. The method of claim 25, wherein at least a portion of the crosslinked biomaterial forms at least one of a tube, a rod, a membrane, a balloon, a bag and a sheet.

28. The method of claim 25, wherein at least one of the at least two biomolecules is selected from the group consisting of an antithrombotic, a clotting agent, an antiinflammatory, an antibody, an immunoglobulin, an enzyme, a hormone, a neurotransmitter, a cytokine, a globular protein, a cell attachment protein, a cell attachment peptide, a proteoglycan, a toxin, an antibiotic, an antibacterial agent, an antimicrobial agent, a catalyst, a drug, a vitamin, an antibody, an antigen, a protein, a peptide, a DNA segment, a RNA segment, a dye and a ligand.

29. The method of claim 25, wherein at least one of the at least two biomolecules is a naturally occurring biomolecule.

30. The method of claim 25, wherein at least one of the at least two biomolecules is a chemically synthesized biomolecule.

31. The method of claim 25, wherein at least one of the at least two biomolecules comprises an amino acid residue.

32. The method of claim 31, wherein the amino acid residue comprises a 2-aminoalcohol moiety.

33. The method of claim 32, wherein the amino acid residue is selected from the group consisting of a N-terminal serine, a N-terminal threonine and a 5-hydroxylysine.

34. The method of claim 31, wherein the amino acid residue comprises an amine moiety.

35. The method of claim 34, wherein the amino acid residue is a lysine residue.

36. The method of claim 31, wherein at least one of the at least two biomolecules is selected from the group consisting of a peptide and a protein.

37. The method of claim 36, wherein the peptide is selected from the group consisting of an antithrombotic peptide, an anti-inflammatory peptide, an enzyme, a hormone, a neurotransmitter, a cytokine, a cell attachment peptide, a toxin, an antibiotic, and a ligand.

38. The method of claim 36, wherein the peptide is a naturally occurring peptide.

39. The method of claim 36, wherein the peptide is a chemically synthesized peptide.

40. The method of claim 36, wherein the protein is selected from the group consisting of an antithrombotic protein, an anti-inflammatory protein, an antibody, an immunoglobulin, an enzyme, a hormone, a globular protein, a cell attachment protein, a proteoglycan, a toxin, and a ligand.

41. The method of claim 36, wherein the protein is a naturally occurring protein.

42. The method of claim 36, wherein the protein is a chemically synthesized protein.

43. The method of claim 25, wherein the periodate comprises at least one of periodic acid, sodium periodate, alkali metal periodates, and potassium periodate.

44. The method of claim 25, wherein the periodate is combined with 2-aminoalcohol moiety and the amine moiety in an aqueous solution having a pH between about 4 and about 9.

45. The method of claim 25, wherein the periodate is combined with the 2-aminoalcohol moiety and the amine moiety in an aqueous solution having a temperature between about 0 and about 50 degrees Celsius.

46. The method of claim 25, wherein the oxidizing step is performed in the absence of light.

47. The method of claim 25, wherein the reducing agent comprises at least one of sodium borohydride, sodium cyanoborohydride, and amine borane.

48. The method of claim 25, wherein the reducing agent is combined with the material comprising an imine moiety in an aqueous solution having a pH between about 6 and about 10.

49. The method of claim 25, wherein the reducing agent is combined with the imine moiety in an aqueous solution having a temperature between about 0 and about 50 degrees Celsius.

50. The method of claim 25, further comprising the step of combining the crosslinked biomaterial with a biomolecule, the biomolecule imparting improved biocompatibility characteristics to the crosslinked biomaterial.

51. The method of claim 50, wherein the biomolecule is selected from the group consisting of an antithrombotic, a clotting agent, an anti-inflammatory, an antibody, an immunoglobulin, an enzyme, a hormone, a neurotransmitter, a cytokine, a globular protein, a cell attachment protein, a cell attachment peptide, a proteoglycan, a toxin, an antibiotic, and a ligand.

52. The method of claim 25, wherein the crosslinked biomaterial is employed as a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the surface being suitable for contacting tissue and bodily fluids in or temporarily removed from a living mammalian subject.

53. The method of claim 52, wherein the device is selected from the group consisting of a blood-contacting medical device, a tissue-contacting medical device, a bodily fluid-contacting medical device, an implantable medical device, an extracorporeal medical device, a blood oxygenator, a blood pump, tubing for carrying blood, an endoprosthesis medical device, a vascular graft, a stent, a pacemaker lead, a heart valve, temporary intravascular medical device, a catheter and a guide wire.

54. The method of claim 52, wherein at least a portion of the surface forms at least one of a tube, a rod, a membrane, a balloon, a bag and a sheet.

55. The method of claim 52, wherein the medical device comprises at least one of a biocompatible material selected from the group consisting of metal, titanium, titanium alloys, tin-nickel alloys, shape memory alloys, aluminum oxide, platinum, platinum alloys, stainless steel, MP35N stainless steel, elgiloy, stellite, pyrolytic carbon, silver carbon, glassy carbon, polymer, polyamide, polycarbonate, polyether, polyester, polyolefin, polyethylene, polypropylene, polystyrene, polyurethane, polyvinyl chloride, polyvinylpyrrolidone, silicone elastomer, fluoropolymer, polyacrylate, polyisoprene, polytetrafluoroethylene, rubber, ceramic, hydroxapatite, human protein, human tissue, animal protein, animal tissue, bone, skin, teeth, collagen, laminin, elastin, fibrin, wood, cellulose, compressed carbon and glass.

56. The method of claim 52, comprising the further step of combining the coating with a biomolecule, the biomolecule imparting improved biocompatibility characteristics to the crosslinked biomaterial.

57. The method of claim 56, wherein the biomolecule is selected from the group consisting of an antithrombotic, a clotting agent, an anti-inflammatory, an antibody, an immunoglobulin, an enzyme, a hormone, a neurotransmitter, a cytokine, a globular protein, a cell attachment protein, a cell attachment peptide, a proteoglycan, a toxin, an antibiotic, and a ligand.

58. A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the surface being suitable for contacting tissue and bodily fluids in or temporarily removed from a living mammalian subject, the method comprising the ordered steps of:

(a) combining a periodate with a medical device, the device having a suitable biomaterial forming the surface, a 2-aminoalcohol moiety being disposed on the surface, the periodate oxidizing the 2-aminoalcohol moiety to form an aldehyde-functional material;

(b) providing a biomolecule, the biomolecule comprising an amine moiety;

(c) combining the aldehyde-functional material with the amine moiety to bond the aldehyde-functional material to the amine moiety and thereby form an imine moiety; and

(d) reacting the imine moiety with a reducing agent to form an amine linkage, the amine linkage immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.

59. The method of claim 58, wherein the device is selected from the group consisting of a blood-contacting medical device, a tissue-contacting medical device, a bodily fluid-contacting medical device, an implantable medical device, an extracorporeal medical device, a blood oxygenator, a blood pump, tubing for carrying blood, an endoprosthesis medical device, a vascular graft, a stent, a pacemaker lead, a heart valve, temporary intravascular medical device, a catheter and a guide wire.

60. The method of claim 58, wherein the biomolecule is selected from the group consisting of an antithrombotic, a clotting agent, an anti-inflammatory, an antibody, an immunoglobulin, an enzyme, a hormone, a neurotransmitter, a cytokine, a globular protein, a cell attachment protein, a cell attachment peptide, a proteoglycan, a toxin, an antibiotic, an antibacterial agent, an antimicrobial agent, a catalyst, a drug, a vitamin, an antibody, an antigen, a protein, a peptide, a DNA segment, a RNA segment, a dye and a ligand.

61. The method of claim 58, wherein the biomolecule is a naturally occurring biomolecule.

62. The method of claim 58, wherein the biomolecule is a chemically synthesized biomolecule.

63. The method of claim 58, wherein the biomolecule comprises an amino acid residue.

64. The method of claim 63, wherein the amino acid residue comprises an amine moiety.

65. The method of claim 64, wherein the amino acid residue is lysine residue.

66. The method of claim 58, wherein the periodate comprises at least one of periodic acid, sodium periodate, alkali metal periodates, and potassium periodate.

67. The met of claim 58, wherein the periodate is combined with the 2-aminoalcohol moiety in an aqueous solution having a pH between about 4 and about 9.

68. The method of claim 58, wherein the periodate is combined with the 2-aminoalcohol moiety in an aqueous solution having a temperature between about 0 and about 50 degrees Celsius.

69. The method of claim 58, wherein the oxidizing step is performed in the absence of light.

70. The method of claim 58, wherein the aldehyde-functional material and the amine-functional biomolecule are combined in an aqueous solution having a pH between about 6 and about 10.

71. The method of claim 58, wherein the aldehyde-functional material and the amine-functional biomolecule are combined in an aqueous solution having a temperature between about 0 and about 50 degrees Celsius.

72. The method of claim 58, wherein the reducing agent comprises at least one of sodium borohydride, sodium cyanoborohydride, and amine borane.

73. The method of claim 58, wherein the reducing agent is combined with the imine moiety in an aqueous solution having a pH between about 6 and about 10.

74. The method of claim 58, wherein the reducing agent is combined with the imine moiety in an aqueous solution having a temperature between about 0 and about 50 degrees Celsius.

75. The method of claim 58, wherein at least a portion of the surface forms at least one of a tube, a rod, a membrane, a balloon, a bag and a sheet.

76. The method of claim 58, wherein the medical device comprises at least one of a biocompatible material selected from the group consisting of metal, titanium, titanium alloys, tin-nickel alloys, shape memory alloys, aluminum oxide, platinum, platinum alloys, stainless steel, MP35N stainless steel, elgiloy, stellite, pyrolytic carbon, silver carbon, glassy carbon, polymer, polyamide, polycarbonate, polyether, polyester, polyolefin, polyethylene, polypropylene, polystyrene, polyurethane, polyvinyl chloride, polyvinylpyrrolidone, silicone elastomer, fluoropolymer, polyacrylate, polyisoprene, polytetrafluoroethylene, rubber, ceramic, hydroxapatite, human protein, human tissue, animal protein, animal tissue, bone, skin, teeth, collagen, laminin, elastin, fibrin, wood, cellulose, compressed carbon and glass.