Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Arterial prosthesis – Having plural layers
Reexamination Certificate
1999-12-08
2001-06-26
O'Connor, Cary E. (Department: 3731)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Arterial prosthesis
Having plural layers
Reexamination Certificate
active
06251136
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates generally to expandable intraluminal vascular grafts, commonly referred to as stents, and more particulary pertains to the coating of stents with materials that allow for the controlled release of pharmacological agents.
Stents are implanted within vessels in an effort to maintain the patency thereof by preventing collapse and/or impeding restenosis. Implantation of a stent is typically accomplished by mounting the stent on the expandable portion of a balloon catheter, maneuvering the catheter through the vasculature so as to position the stent at the treatment site within the body lumen, and inflating the balloon to expand the stent so as to engage the lumen wall. The stent deforms in the expanded configuration allowing the balloon to be deflated and the catheter removed to complete the implantation procedure. The use of self-expanding stents obviates the need for a balloon delivery device. Instead, a constraining sheath that is initially fitted about the stent is simply retracted once the stent is in position adjacent the treatment site. Stents and stent delivery catheters are well known in the art.
The success of a stent placement can be assessed by evaluating a number of factors, such as thrombosis, neointimal hyperplasia, smooth muscle cell migration and proliferation following implantation of the stent, injury to the artery wall, overall loss of luminal patency, stent diameter in vivo, thickness of the stent, and leukocyte adhesion to the luminal lining of stented arteries. The chief areas of concern are early subacute thrombosis, and eventual restenosis of the blood vessel due to intimal hyperplasia.
Therapeutic pharmacological agents have been developed to address some of the concerns associated with the placement of a stent and it is often desirable to provide localized pharmacological treatment of a vessel at the site being supported by the stent. It has been found convenient to utilize the implanted stent for such purpose wherein the stent serves both as a support for the lumen wall as a well as delivery vehicle for the pharmacological agent. However, the metallic materials typically employed in the construction of stents in order to satisfy the mechanical strength requirements are not generally capable of carrying and releasing drugs. On the other hand, while various polymers are known that are quite capable of carrying and releasing drugs, they generally do not have the requisite strength characteristics. Moreover, the structural and mechanical capabilities of a polymer may be significantly reduced as such polymer is loaded with a drug. A previously devised solution to such dilemma has therefore been the coating of a stent's metallic structure with a drug carrying polymer material in order to provide a stent capable of both supporting adequate mechanical loads as well as delivering drugs.
Various approaches have previously been employed to join drug-carrying polymers to metallic stents including for example dipping, spraying and conforming processes. Additionally, methods have been disclosed wherein the metallic structure of the stent has been formed or treated so as to create a porous surface that enhances the ability to retain the applied materials. However, such methods have generally failed to provide a quick, easy and inexpensive way of loading drugs onto a stent, have been limited insofar as the maximum amount of drug that can be loaded onto a stent and are limited in terms of their ability to control the rate of release of the drug upon implantation of the stent. Additionally, some of the heretofore known methods are highly specific wherein they are substantially limited in terms of which underlying stent material the coating can be applied to.
SUMMARY OF THE INVENTION
The present invention overcomes the shortcomings of the prior art methods for loading a drug onto a stent. The process enables large amounts of one or more drugs to be quickly and easily loaded onto the stent and provides for the subsequent release of such drug at a very controlled rate. A stent constructed in accordance with the present invention is capable of releasing substantially greater dosages of drugs at substantially more controlled release rates than has heretofore been possible. Moreover, the present invention allows for the drug releasing materials to be applied to any stent construction material.
The method of the present invention requires the sequential application of three layers of different materials onto a stent's surfaces. A first layer is applied to all or to selected surfaces of a stent and serves as a base or primer coat which readily adheres to the material of which the stent is constructed and in turn, is able to attract and retain the subsequently applied pharmacological agent. Such pharmacological agent, in the form of dry, micronized particles is dusted directly onto all or onto only selected surfaces of the base layer coated stent to form a second layer. A membrane forming polymer is subsequently applied over the coated stent surfaces wherein such polymer is selected for its ability to permit the diffusion of the pharmacological agent therethrough.
The base layer material is selected for its ability to form a sticky coating on the particular material used in the construction of the stent. Such first layer may be applied to all or selected surfaces of the stent. The pharmacological material is used in a dry, micronized form which allows the amount of material applied to the base layer to be precisely controlled. The top layer material is selected for its ability to form a membrane over the entire surface of the stent be it the bare stent material, the base layer coat or the pharmacological agent, and for its ability to permit the diffusion of the pharmacological agent therethrough. The amount of pharmacological material deposited in the second layer determines the total dosage that can delivered while the thickness of the top layer determines the rate of delivery.
The particular surface or surfaces on which the pharmacological agent is deposited determines where the agent is delivered upon implantation. More specifically, pharmacological material deposited on the exterior surfaces of the stent causes the agent to pass directly into the lumen wall while deposition of the agent on the interior surfaces of the stent causes the agent to be released directly into the blood flow. Alternatively, coating only the upstream edge or only the downstream edge of the stent may be desirable to achieve a specific effect. By selectively coating the stent surfaces with the base layer, the distribution of the pharmacological agent may be controlled accordingly as the dry particles will only adhere to those areas that have the sticky coating. Alternatively, the entire stent may be base coated while the application of the pharmacological agent is precisely controlled by limiting its distribution to only preselected areas. Well known masking techniques may be used for such purpose. The membrane forming material may be applied by any well known technique such as for example by dipping or spraying while material is in its liquid form. Allowing the material to form a continuous membrane completes the fabrication process.
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patent:
Guruwaiya Judy A.
Millare Deborra Sanders
Wu Steven Z-H
Advanced Cardiovascular Systems Inc.
Fulwider Patton Lee & Utecht LLP
O'Connor Cary E.
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