Methods and Compositions for Enhancing Vascular Access

• US 20110229549A1
• Filed: 03/04/2011
• Published: 09/22/2011
• Est. Priority Date: 12/08/2004
• Status: Abandoned Application

• Current Assignee: Shire Regenerative Medicine Incorporated (Shire plc)
• Original Assignee: Shire Regenerative Medicine Incorporated (Shire plc)
• Inventors: Epperly, Scott, Edelman, Elazer, Nugent, Helen Marie, Bollinger, Steve, Dalal, Anupam
• Application Number:
  US13/040,650
• Publication Number:
  US 20110229549A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 27/3808 Endothelial cells
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Disclosed is an implantable material comprising a biocompatible matrix and cells which, when provided to a vascular access structure, can promote functionality generally. For example, implantable material of the present invention can enhance maturation of an arteriovenous native fistula as well as prolong the fistula in a mature, functional state suitable for dialysis. Additionally, the present invention can promote formation of a functional arteriovenous graft suitable for dialysis as well as promote formation of a functional peripheral bypass graft. Implantable material can be configured as a flexible planar form or a flowable composition with shape retaining properties suitable for implantation at, adjacent or in the vicinity of an anastomoses or arteriovenous graft. According to the methods disclosed herein, the implantable material is provided to an exterior surface of a blood vessel. Certain embodiments of the flexible planar form define a slot. The materials and methods of the present invention comprises cells, preferably endothelial cells or cells having an endothelial-like phenotype.

Claims

1-70. -70. (canceled)

71. A method of promoting repetitive cannulation of an arteriovenous graft or arteriovenous native fistula sufficient to permit dialysis, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed on an exterior surface of, adjacent to or in the vicinity of said graft or fistula in an amount effective to promote repetitive cannulation of said graft or fistula sufficient to permit dialysis.

72. The method of claim 71, wherein the arteriovenous graft or fistula is radiocephalic, brachiocephalic, or brachiobasilic.

73. The method of claim 71, wherein application of the implantable material is preceded by or coincident with administration of a therapeutic agent.

74. A method of maintaining blood flow sufficient to permit dialysis, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed at, adjacent or in the vicinity of an arteriovenous graft or arteriovenous native fistula in an amount effective to maintain blood flow sufficient to permit dialysis.

75. The method of claim 74, wherein the arteriovenous graft or fistula is radiocephalic, brachiocephalic, or brachiobasilic.

76. The method of claim 74, wherein application of the implantable material is preceded by or coincident with administration of a therapeutic agent.

77. The method of claim 74, wherein blood flow is at a rate sufficient to prevent re-circulation during dialysis.

78. The method of claim 77, wherein the blood flow rate at the venous outflow region of said arteriovenous graft or said native fistula is substantially similar to the blood flow rate upstream of the outflow region.

79. The method of claim 77, wherein sufficient blood flow is a rate of about 350 ml/min.

80. A method for enhancing maturation of an arteriovenous native fistula in a human, the method comprising the step of disposing at, adjacent or in the vicinity of the fistula an implantable material comprising a biocompatible matrix and cells wherein the implantable material is effective to enhance maturation of the fistula suitable for dialysis.

81. The method of claim 80, wherein the arteriovenous graft or fistula is radiocephalic, brachiocephalic, or brachiobasilic.

82. The method of claim 80, wherein application of the implantable material is preceded by or coincident with administration of a therapeutic agent.

83. The method of claim 80, wherein the arteriovenous fistula is a pre-existing fistula which is clinically failing and the implantable material is effective to prevent failure of the pre-existing fistula by enhancing maturation and prolonging its suitability for dialysis.

84. The method of claim 80, wherein the arteriovenous fistula is a failed pre-existing fistula and the implantable material is effective to treat the failed pre-existing fistula by returning the fistula to a clinically stable state suitable for dialysis.

85. The method of claim 80, wherein enhancing maturation of the arteriovenous native fistula is characterized by an ability to repetitively cannulate the fistula for dialysis.

86. The method of claim 80, wherein enhancing maturation of the arteriovenous native fistula is characterized by an ability to obtain sufficient blood flow during dialysis.

87. The method of claim 86, wherein sufficient blood flow is a rate of about 350 ml/min.

88. A method of preventing or reducing the incidence of dehiscence of an arteriovenous graft or arteriovenous native fistula, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed on an exterior surface of said fistula or disposed at, adjacent or in the vicinity of a prosthetic bridge of said arteriovenous graft in an amount effective to prevent or reduce the incidence of dehiscence of said graft or fistula.

89. The method of claim 88, wherein the arteriovenous graft or fistula is radiocephalic, brachiocephalic, or brachiobasilic.

90. The method of claim 88, wherein application of the implantable material is preceded by or coincident with administration of a therapeutic agent.

91. The method of claim 88, wherein the providing step is performed as an interventional therapy following failure of a native arteriovenous fistula.

92. The method of claim 88, wherein the providing step is performed as an interventional therapy following failure of a native or saphenous vein peripheral bypass.