Surgery – Blood vessel or graft preparation
Reexamination Certificate
1997-06-26
2001-01-09
Prebilic, Paul B. (Department: 3738)
Surgery
Blood vessel or graft preparation
C623S001420, C623S001460, C623S901000, C427S002250, C424S423000
Reexamination Certificate
active
06171232
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention generally relates to coated medical devices and to procedures for coating and administering same. More particularly, a thiol group containing agent is loaded onto a medical device for in vivo interaction with a nitric oxide donor. In the illustrated preferred embodiment, protected sulfur containing compounds are covalently attached onto medical device surfaces of polymer-coated metals, polymers and the like. These thus immobilized compounds, when deprotected, present sulfhydryl groups which are useful for enhancing local release of nitric oxide in vivo, or at the site of an implanted medical device and the like, when a nitric oxide donor such as a vasodilator is administered. Such nitric oxide release is of value, for example, in preventing platelet aggregation and smooth muscle cell proliferation. Possible thrombosis and/or restenosis which might be associated with the device implant is thereby minimized or even eliminated.
The liberation of nitric oxide from vasodilators, particularly nitric oxide donors, is generally believed to be potentiated by thiol donors. To the extent that thiol group containing agents are efficacious with respect to nitric oxide release, such can enhance the effectiveness of a nitric oxide containing agent or compound. It is accordingly believed that the effectiveness of vasodilators can be enhanced by their interaction with compounds which contain thiol groups. Observations made in this regard are discussed in Anderson, et al., “Nitric Oxide and Nitrovasodilators: Similarities, Differences and Potential Interactions”,
Journal American College of Cardiology
, Vol. 24, pages 555-566, August, 1994, and in Welch, et al., “Nitric Oxide as a Vascular Modulator”,
Circulation
, Vol. 87, pages 1461-1467, 1993, both incorporated hereinto by reference.
Concerns with respect to clinical and interventional procedures, including those involving vascular implants for example, include stenosis development or restenosis over time. In this regard, endoprostheses such as stents, catheters or any other device which is contacted by blood during a clinical or interventional procedure in the vascular system, run the risk of stenosis development. For example, a stent which had been implanted in order to address a stenosis situation would be much more desirable and efficacious if the stent itself discouraged stenosis at the implantation site.
Accordingly, approaches are needed which will directly address stenosis and restenosis concerns with respect to vascular implants. For example, it can be important to prevent smooth muscle cell proliferation, which has been associated with restenosis. Also to be prevented is platelet aggregation and its attendant thrombosis development.
Biocompatibility enhancement of vascular implants such as stents and the like can include coating treatment approaches. An example in this regard is Narayanan et al U.S. Pat. No. 5,336,518, incorporated by reference hereinto. With this technology, bioactive agents are secured to a metal surface of a medical device by an approach which includes treating a metal surface having a polymeric coating with water vapor plasma in order to facilitate attachment of the biologically active agent to the polymer coating. Various biologically active agents are discussed, including numerous agents such as the heparins and vasodilators.
SUMMARY OF THE INVENTION
In accordance with the present invention, important advances in the efficacy of vascular devices and implants can be facilitated. More particularly, it has been determined that compounds having thiol groups can be loaded onto an implant, intervention tool or other medical device for use in the vascular system. One such loading procedure couples a protected sulfur compound to the surface of the endoprosthesis, interventional tool or other medical device by bonding same to reactive groups formed on a polymeric surface of the device. The sulfurs are protected in an thio form of the compound and are deprotected thiol groups prior to implantation or use. Such surface thiol group moieties, when implanted, will be positioned at a location at which it is desired to retard or eliminate stenosis development or achieve other benefits as generally discussed herein and in the publications incorporated by reference. When a nitrovasodilator is administered to the patient and/or loaded onto the treated device, the nitrovasodilator has the opportunity to directly contact the compound having the thiol group properties as discussed. This contact is particularly advantageous because it is at the location at which stenosis and restenosis can be advantageously addressed. This interaction between a nitrovasodilator and the thiol groups has the opportunity to release nitric oxide and experience the benefits associated with it, including retarding or preventing platelet aggregation and smooth muscle cell proliferation. By having the desired coating on the device itself, the nitric oxide release is locally targeted. Stenosis or restenosis is thus addressed locally.
It is accordingly a general object of the present invention to provide improved procedures, coatings and medical devices for enhancing local nitric oxide release.
Another object of this invention is to provide improved procedures, coatings and medical devices for at least minimizing and substantially retarding restenosis of a medical device after its implantation within the vascular system.
Another object of the present invention is to provide improved medical devices having chemical compounds loaded thereon for enhancing the effectiveness of nitrovasodilators when they are administered to patients having endoprostheses or other devices implanted within the vascular system of the patient.
Another object of this invention is the improvement of medical devices, coatings and procedures relating to minimizing or eliminating restenosis through the use of carbodiimide chemistry in attaching compounds with operative groups to work with nitrovasodilators in accelerating release of nitric oxide at a specific location within the body.
A further object of the present invention is to provide medical devices having sulfhydryl groups on their working or engagement surfaces to provide the favorable property of accelerating release of nitric oxide locally when patients within which the medical devices are implanted are administered nitrovasodilators such as nitroglycerin.
Another object of the present invention is to provide an improved stent which has been treated so as to address possible restenosis when the patient within which the stent is implanted is administered a nitrovasodilator.
These and other objects, features and advantages of the present invention will be apparent from and clearly understood through a consideration of the following detailed description.
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Epstein, “The New Miracle Drug May Be—Smog?”,Science&Technology, pp. 108-109, Dec. 5, 1994.
Welch, et al., “Nitric Oxide as a Vascular Modulator”,Circulation,vol. 87, pp. 1461-1467.
Anderson, et al., “Nitric Oxide and Nitrovasodilators: Similarities, Differences and Potential Interactions”,Journal of American College of Cardiology,vol. 24, pp. 555-556, Aug., 1994.
Hawley's Condensed Chemical Dictionary, Eleventh Edition, Van Nostrand Reinhold (1987), pp. 31 and 341.
Stamler et al., “S-Nitrosylation of proteins with nitric oxide: Synthesis and characterization of biologically active compounds”, Proc. Natl. Acad. Sci. USA, vol 89, pp. 444-448, Jan. 1992.
David S. Marks et al., “Inhibition of Neointimal Proliferation in Robbits after Vascular Injury by a Single Treat
Narayanan Pallassana V.
Papandreou George
Cook Alex McFarron Manzo Cummings & Mehler, Ltd.
Cordis Corporation
Prebilic Paul B.
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