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Biologically absorbable coatings for implantable devices and methods for fabricating the same

This application is a continuation application of U.S. application Ser. No. 11/641,250, filed on Dec. 18, 2006, the teaching of which is incorporated herein in its entirety by reference.

1. Field of the Invention

This invention is directed to coatings for drug delivery devices, such as drug eluting vascular stents, and methods for producing the same.

2. Description of the State of the Art

Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating heart disease. A catheter assembly having a balloon portion is introduced percutaneously into the cardiovascular system of a patient via the brachial or femoral artery. The catheter assembly is advanced through the coronary vasculature until the balloon portion is positioned across the occlusive lesion. Once in position across the lesion, the balloon is inflated to a predetermined size to radially compress against the atherosclerotic plaque of the lesion to remodel the lumen wall. The balloon is then deflated to a smaller profile to allow the catheter to be withdrawn from the patient's vasculature.

A problem associated with the above procedure includes formation of intimal flaps or torn arterial linings which can collapse and occlude the conduit after the balloon is deflated. Moreover, thrombosis and restenosis of the artery may develop over several months after the procedure, which may require another angioplasty procedure or a surgical bypass operation. To reduce the partial or total occlusion of the artery by the collapse of arterial lining and to reduce the chance of the development of thrombosis and restenosis, a stent is implanted in the lumen to maintain the vascular patency.

Stents are used not only as a mechanical intervention but also as a vehicle for providing biological therapy. As a mechanical intervention, stents act as scaffoldings, functioning to physically hold open and, if desired, to expand the wall of the passageway. Typically, stents are capable of being compressed, so that they can be inserted through small vessels via catheters, and then expanded to a larger diameter once they are at the desired location. Examples in patent literature disclosing stents which have been applied in PTCA procedures include stents illustrated in U.S. Pat. No. 4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued to Gianturco, and U.S. Pat. No. 4,886,062 issued to Wiktor.

Biological therapy can be achieved by medicating the stents. Medicated stents provide for the local administration of a therapeutic substance at the diseased site. In order to provide an efficacious concentration to the treated site, systemic administration of such medication often produces adverse or toxic side effects for the patient. Local delivery is a preferred method of treatment in that smaller total levels of medication are administered in comparison to systemic dosages, but are concentrated at a specific site. Local delivery thus produces fewer side effects and achieves more favorable results. One proposed method for medicating stents involves the use of a polymeric carrier coated onto the surface of a stent. A solution which includes a solvent, a polymer dissolved in the solvent, and a therapeutic substance dispersed in the blend is applied to the stent. The solvent is allowed to evaporate, leaving on the stent surface a coating of the polymer and the therapeutic substance impregnated in the polymer.

Local administration of therapeutic agents via stents has shown favorable results in reducing restenosis. However, there is a great need for better and more effective coatings for local drug delivery.

A medical article comprising an implantable substrate having a coating is provided the coating includes an ABA or an AB block copolymer, the block copolymer having moieties A and B, wherein one of the moieties produces a biological response and the other moiety provides the block copolymer with structural functionality. Examples of the biological moiety include poly(alkylene glycols), poly(ethylene oxide), poly(ethylene oxide-co-propylene oxide), poly(N-vinyl pyrrolidone), poly(acrylamide methyl propane sulfonic acid) and salts thereof, sulfonated dextran, hyaluronic acid, heparin, or copolymers thereof. Examples of the structural moiety include poly(caprolactone), poly(butylene terephthalate), poly(ester amide), or copolymers thereof. The coating can include a biologically active agent incorporated into the coating, and can include a biologically active agent conjugated to the block copolymer. Examples of the biologically active agents that can be conjugated to the ABA block copolymer include paclitaxel, antisense agents, polyarginine, rapamycin and structural derivatives or functional analogs thereof, such as EVEROLIMUS, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, and sources of nitrogen oxide, such as diazenium diolates.

A medical article comprising an implantable substrate having a coating is provided, the coating includes phosphoryl choline or polyaspirin.

A method for fabricating a medical article is provided. The method includes applying a coating to at least a portion of an implantable substrate, the coating including an ABA or an AB block copolymer, wherein one of the moieties in the block copolymer produces a biological response and the other moiety provides the block copolymer with structural functionality.

The following definitions apply:

The terms “biologically degradable,” “biologically erodable,” “bioabsorbable,” and “bioresorbable” coatings and/or polymers are defined as coatings and/or polymers that are capable of being completely degraded and/or eroded when exposed to bodily fluids such as blood and are gradually resorbed, absorbed and/or eliminated by the body. The processes of breaking down and eventual absorption and elimination of the coating and/or polymer can be caused, for example, by hydrolysis, metabolic processes, bulk or surface erosion, and the like.