Progenitor endothelial cell capturing with a drug eluting implantable medical device
First Claim
1. An implantable medical device having a lumen, a luminal surface, a tissue-contacting surface, and a coating;
- said coating comprising;
one or more covalently bound luminal surface layers of a matrix comprising a natural fiber selected from elastin, tropoelastin;
cross-linked tropoelastin or combinations thereof;
a tissue-contacting biodegradable and biocompatible synthetic polymer layer comprising a therapeutically effective amount of one or more intimal hyperplasia inhibitory pharmaceutical substances, and one or more pharmaceutically acceptable carriers on said tissue-contacting surface; and
a therapeutically effective amount of a ligand selected from an antibody, an antibody fragment and combinations thereof,said ligand being covalently attached to said matrix and configured specifically to bind in situ to a cell surface antigen or cell membrane molecule comprising CD133, CD45, CD34, CD31, CD14, CDw90, CD117, VEGFR-1, VEGFR-2, Muc-I8 (CD146), CD130, stem cell antigen (Sca-1), stem cell factor 1 (SCF/c-Kit ligand), Tie-2, or MHC-H-2Kk of circulating autologous endothelial progenitor cells in peripheral blood for in vivo capture and proliferation of said endothelial progenitor cells to form a functional endothelial layer on said luminal surface of the implantable medical device, in situ.
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Accused Products
Abstract
A medical device for implantation into vessels or luminal structures within the body is provided, which stimulates positive blood vessel remodeling. The medical device, such as a stent and a synthetic graft, is provided with a coating with a pharmaceutical composition containing a controlled-release matrix and one or more pharmaceutical substances for direct delivery of drugs to surrounding tissues. The coating on the medical device further comprises one or more barrier layers, and a ligand such as a peptide, an antibody or a small molecule for capturing progenitor endothelial cells in the blood contacting surface of the device for restoring an endothelium at the site of injury. In particular, the drug-coated stents are for use, for example, in balloon angioplasty procedures for preventing or inhibiting restenosis.
1059 Citations
17 Claims
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1. An implantable medical device having a lumen, a luminal surface, a tissue-contacting surface, and a coating;
- said coating comprising;
one or more covalently bound luminal surface layers of a matrix comprising a natural fiber selected from elastin, tropoelastin;
cross-linked tropoelastin or combinations thereof;a tissue-contacting biodegradable and biocompatible synthetic polymer layer comprising a therapeutically effective amount of one or more intimal hyperplasia inhibitory pharmaceutical substances, and one or more pharmaceutically acceptable carriers on said tissue-contacting surface; and a therapeutically effective amount of a ligand selected from an antibody, an antibody fragment and combinations thereof, said ligand being covalently attached to said matrix and configured specifically to bind in situ to a cell surface antigen or cell membrane molecule comprising CD133, CD45, CD34, CD31, CD14, CDw90, CD117, VEGFR-1, VEGFR-2, Muc-I8 (CD146), CD130, stem cell antigen (Sca-1), stem cell factor 1 (SCF/c-Kit ligand), Tie-2, or MHC-H-2Kk of circulating autologous endothelial progenitor cells in peripheral blood for in vivo capture and proliferation of said endothelial progenitor cells to form a functional endothelial layer on said luminal surface of the implantable medical device, in situ. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 14, 15)
- said coating comprising;
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9. A stent having tissue contacting surface, a lumen, a luminal surface, and a coating;
- said coating comprising;
a layered matrix comprising a natural fiber selected from tropoelastin;
cross-linked tropoelastin and combinations thereof,a therapeutically effective amount of one or more antibody, antibody fragment or combinations thereof, covalently attached to said layered matrix and specifically configured to bind selectively in situ to a cell surface antigen or cell surface membrane molecule, CD34, of circulating autologous endothelial progenitor cells in peripheral blood for capture and proliferation in vivo to form a confluent endothelial cell layer on said luminal surface of the device in less than 72 hours; and one or more biodegradable barrier layers situated within said layered matrix, said biodegradable barrier layers comprising a therapeutically effective amount of one or more pharmaceutical substances and one or more pharmaceutically acceptable carriers for release to adjacent vascular tissue. - View Dependent Claims (10, 11, 12, 13, 16)
- said coating comprising;
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17. A vascular stent for in situ capture of circulating progenitor cells and therapeutically effective drug release, comprising:
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a tissue-adjacent surface, a luminal surface, and a multilayer coating; the multilayer coating comprising a luminal surface matrix consisting of covalently bound elastin, tropoelastin, cross-linked tropoelastin, or combinations thereof to which matrix one or more antibodies or antibody fragments are covalently bound, specifically directed against a surface antigen selected from CD34, CD31, and CD133 of circulating native or genetically engineered progenitor cells; and the multilayer coating comprising one or more tissue-adjacent biodegradable synthetic polymer layers comprising one or more intimal hyperplasia inhibitory pharmaceutical substances.
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Specification