Method for attachment of biomolecules to medical device surfaces

• US 20060099326A1
• Filed: 12/07/2005
• Published: 05/11/2006
• Est. Priority Date: 04/25/1996
• Status: Abandoned Application

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Keogh, James R., Trescony, Paul V.
• Application Number:
  US11/296,810
• Publication Number:
  US 20060099326A1
• Time in Patent Office: Days
• US Class Current: 427/2.26
• CPC Class Codes: A61K 38/43 Enzymes; Proenzymes; Derivatives thereof
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/22 Polypeptides or derivatives thereof , e.g. degradation products
• 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 27/3625 Vascular tissue, e.g. heart valves
• CPC Class Codes: A61L 27/3641 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3645 Connective tissue
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• 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 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• 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: C12N 11/02 : Enzymes or microbial cells immobilised on or in an organic carrier
• CPC Class Codes: C12N 11/14 : Enzymes or microbial cells immobilised on or in an inorganic carrier
• CPC Class Codes: G01N 33/543 : with an insoluble carrier for immobilising immunochemicals
• 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

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.

Claims

1-34. -34. (canceled)

35. A method of forming a coated tissue heart valve, the coating imparting improved cell binding characteristics to the surface of the heart valve, the method comprising the steps of:

(a) providing the heart valve;

(b) providing a biomolecule, the biomolecule comprising an arginine, glycine and aspartic acid amino acid sequence; and

(c) combining the biomolecule with the surface of the tissue heart valve to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.

36. The method of claim 35 wherein the biomolecule is a naturally occurring biomolecule.

37. The method of claim 35 wherein the biomolecule is a chemically synthesized biomolecule.

38. The method of claim 35 wherein the biomolecule is a peptide.

39. The method of claim 38 wherein the peptide is a cell attachment peptide.

40. The method of claim 35 wherein the biomolecule is a protein.

41. The method of claim 40 wherein the protein is a cell attachment protein.

42. The method of claim 40 wherein the protein is fibrinogen.

43. The method of claim 40 wherein the protein is fibronectin.

44. The method of claim 40 wherein the protein is vitronectin.

45. The method of claim 40 wherein the protein is collagen.

46. The method of claim 35 wherein the heart valve is implantable in a heart.

47. The method of claim 35 further comprising the step of combining at least one reducing agent selected from the group consisting of sodium borohydride, sodium cyanoborohydride and amine borane.

48. The method of claim 35 further comprising the step of combining a chemical moiety of the biomolecule with a chemical moiety of the surface to form the chemical bond.

49. The method of claim 48 wherein the chemical moiety of the biomolecule is an aldehyde moiety.

50. The method of claim 49 wherein the aldehyde moiety is formed by combining a periodate with a 2-aminoalcohol moiety.

51. The method of claim 50 wherein the periodate comprises at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate.

52. The method of claim 49 wherein the aldehyde moiety is formed by combining a periodate with a 1,2-dihydroxy moiety.

53. The method of claim 52 wherein the periodate comprises at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate.

54. The method of claim 48 wherein the chemical moiety of the biomolecule is an epoxide moiety.

55. The method of claim 48 wherein the chemical moiety of the biomolecule is an isocyanate moiety.

56. The method of claim 48 wherein the chemical moiety of the biomolecule is a 1,2-dicarbonyl moiety.

57. The method of claim 48 wherein the chemical moiety of the biomolecule is a phosphate moiety.

58. The method of claim 48 wherein the chemical moiety of the biomolecule is a sulphate moiety.

59. The method of claim 48 wherein the chemical moiety of the biomolecule is a carboxylate moiety.

60. The method of claim 48 wherein the chemical moiety of the surface is a guanidino moiety.

61. The method of claim 60 wherein the guanidino moiety is formed by combining an amine moiety with a guanidino forming agent.

62. The method of claim 61 wherein the guanidino forming agent is selected from the group consisting of S-ethylthiouronium bromide, S-ethylthiouronium chloride, O-methylisourea, O-methylisouronium sulfate, O-methylisourea hydrogen sulfate, S-methylisothiourea, 2-methyl-1-nitroisourea, aminoiminomethanesulfonic acid, cyanamide, cyanoguanide, dicyandiamide, 3,5-dimethyl-1-guanylpyrazole nitrate and 3,5-dimethylpyrazole.

63. The method of claim 61 further comprising the step of combining a stabilizing agent.

64. The method of claim 63 wherein the stabilizing agent is a borate ion.

65. The method of claim 61 wherein the amine moiety is formed by combining an unsubstituted amide moiety with an amine forming agent.

66. The method of claim 65 wherein the amine forming agent is selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene.

67. The method of claim 48 wherein the chemical moiety of the surface is a primary amine moiety.

68. The method of claim 67 wherein the primary amine moiety is formed by combining an unsubstituted amide moiety with an amine forming agent.

69. The method of claim 68 wherein the amine forming agent is selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene.

70. The method of claim 48 wherein the chemical moiety of the surface is an aldehyde moiety.

71. The method of claim 70 wherein the aldehyde moiety is formed by combining a periodate with a 2-aminoalcohol moiety.

72. The method of claim 71 wherein the periodate comprises at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate.

73. The method of claim 70 wherein the aldehyde moiety is formed by combining a periodate with a 1,2-dihydroxy moiety.

74. The method of claim 73 wherein the periodate comprises at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate.

75. The method of claim 48 wherein the chemical moiety of the surface is an epoxide moiety.

76. The method of claim 48 wherein the chemical moiety of the surface is an isocyanate moiety.

77. The method of claim 48 wherein the chemical moiety of the surface is a 1,2-dicarbonyl moiety.

78. The method of claim 48 wherein the chemical moiety of the surface is a phosphate moiety.

79. The method of claim 48 wherein the chemical moiety of the surface is a sulphate moiety.

80. The method of claim 48 wherein the chemical moiety of the surface is a carboxylate moiety.

81. The method of claim 48 wherein the chemical moiety of the biomolecule is a guanidino moiety.

82. The method of claim 81 wherein the guanidino moiety is formed by combining an amine moiety with a guanidino forming agent.

83. The method of claim 82 wherein the guanidino forming agent is selected from the group consisting of S-ethylthiouronium bromide, S-ethylthiouronium chloride, O-methylisourea, O-methylisouronium sulfate, O-methylisourea hydrogen sulfate, S-methylisothiourea, 2-methyl-1-nitroisourea, aminoiminomethanesulfonic acid, cyanamide, cyanoguanide, dicyandiamide, 3,5-dimethyl-1-guanylpyrazole nitrate and 3,5-dimethylpyrazole.

84. The method of claim 82 further comprising the step of combining a stabilizing agent.

85. The method of claim 84 wherein the stabilizing agent is a borate ion.

86. The method of claim 82 wherein the amine moiety is formed by combining an unsubstituted amide moiety with an amine forming agent.

87. The method of claim 86 wherein the amine forming agent is selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene.

88. The method of claim 48 wherein the chemical moiety of the biomolecule is a primary amine moiety.

89. The method of claim 88 wherein the primary amine moiety is formed by combining an unsubstituted amide moiety with an amine forming agent.

90. The method of claim 89 wherein the amine forming agent is selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene.

91. A method of making a tissue heart valve comprising:

(a) providing the heart valve;

(b) providing a biomolecule, the biomolecule comprising an arginine, glycine and aspartic acid amino acid sequence; and

(c) reacting a chemical moiety of the biomolecule with a chemical moiety of the tissue heart valve to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface of the tissue heart valve.

92. The method of claim 91 wherein the biomolecule is a naturally occurring biomolecule.

93. The method of claim 91 wherein the biomolecule is a chemically synthesized biomolecule.

94. The method of claim 91 wherein the biomolecule is a peptide.

95. The method of claim 94 wherein the peptide is a cell attachment peptide.

96. The method of claim 91 wherein the biomolecule is a protein.

97. The method of claim 96 wherein the protein is a cell attachment protein.

98. The method of claim 96 wherein the protein is fibrinogen.

99. The method of claim 96 wherein the protein is vitronectin.

100. The method of claim 96 wherein the protein is collagen.

101. The method of claim 91 wherein the heart valve is implantable in a heart.

98-1. The method of claim 96 wherein the protein is fibronectin.