AU733350B2 - Polymer film for wrapping a stent structure - Google Patents

Description

AUSTRALIA

PATENTS ACT 1990 DIVISIONAL APPLICATION NAME OF APPLICANT(S): Advanced Cardiovascular Systems, Inc.

ADDRESS FOR SERVICE: SDAVIES COLLISON CAVE Patent Attorneys 1 Little Collins Street Melbourne, 3000.

INVENTION TITLE: Polymer film for wrapping a stent structure The following statement is a full description of this invention, including the best method of performing it known to Q:\OPER\LKA\40312-95.13 13/1/0 BACKGROUND OF THE INVENTION Field of the Invention This invention relates generally to expandable intraluminal vascular grafts, generally referred to as stents, and more particularly concerns metal stents wrapped with a polymer film capable of carrying and releasing therapeutic drugs.

Description of Related Art ~Stents typically are implanted within a vessel in a contracted state and then expanded when in place in the vessel in order to maintain patency of the vessel to ••allow fluid flow through the vessel. Ideally, implantation of such stents is accomplished by mounting the stent on the balloon portion of a catheter, positioning the stent in a body lumen, and expanding the stent to an expanded state by inflation of a balloon ooooo within the stent. The stent then can be left in place by deflating the balloon and removing the catheter.

Stents commonly have a metallic structure to 20 provide the strength required to function as a stent, but :e i typically do not provide for the delivery of localized therapeutic pharmacological treatment of a vessel at the location being treated with the stent. Polymeric materials capable of absorbing and releasing therapeutic agents may not fulfill the structural and mechanical requirements of a stent, especially when the polymeric materials are loaded with a drug, because drug-loading of a polymeric material can significantly affect the structural and mechanical properties of the polymeric material. Because it often is useful to provide localized therapeutic pharmacological treatment of a vessel at the location being treated with the stent, it would be desirable to combine such polymeric materials P:OPER\ULA\I0073- spc.doc-09/05A -2with existing stent structures to provide a stent with the capability of absorbing therapeutic drugs or other agents, for placement and release of the therapeutic agents at a specific intravascular site. The present invention meets this need.

SUMMARY OF THE INVENTION Briefly, and in general terms, the present invention provides for a stent wrapped with a polymer film capable of carrying and releasing therapeutic agents. Because the polymer film is wrapped on the outside of the stent, and is not needed to provide structural strength to assist in opening the flow path of the vasculature or other body lumen where the stent is to be placed, the drug-containing section can be specially formulated for its specific function of delivering drugs locally. The stent can be used in coronary arteries or any other part of the vasculature or other body lumen where mechanical opening force is necessary or desirable to keep the vessel open or to maintain the stent flush against the lumen wall, and where an anti-restenosis, antiproliferative or other type of therapeutic drug or agent simultaneously is to be positioned and diffused.

The invention accordingly provides a drug-loaded stent, comprising: an expandable stent structural member; and 20 a planar sheet of polymeric material loaded with a therapeutic agent and wrapped in a coil around the stent structural member, said sheet of polymeric material having one end attached to the stent structural member and one free end.

The polymeric material preferably is bioabsorbable, and preferably is loaded or coated or laminated with a therapeutic agent or drug to reduce or prevent restenosis and thrombosis in the vessel being treated. The polymer material can be a thermoplastic or an elastomer, for example, so that the film can stretch or deform 0 radially when the stent structural member is expanded. The film of polymer material can be formed as a solid sheet, or can be formed as a solid sheet, or can incorporate holes of various sizes and shapes to promote rapid endothelialization.

The polymer film preferably is mounted to the stent structural member, and in a presently preferred embodiment, the polymer film can be attached to the existing stent structural member in an unexpanded state by adhesive or by heat sealing, with the stent structural member sandwiched between internal and external layers of film heat sealed around the stent structural member, or mechanically, as by such a mechanical connection as hooking one or more slots on an edge portion of the polymeric material through a corresponding slotted portion of the stent structural member, or with a metal clip. The polymer material can be attached to the stent 15 structural member at one or more points, and wrapped in a coil around the stent in an unexpanded state, so that the diameter of the outer coiled film would uncoil and expand in diameter to match the diameter of the metal ,stent. When coiled around the stent structural member, 20 the coiled polymer film can have at least one slit transverse to the longitudinal axis about which the stent is coiled to accommodate possible uneven expansion of the S.underlying stent structural member.

In another presently preferred embodiment, the 25 polymer material can be attached to an existing stent structural member with an interference fit by tightly wrapping the polymer film at least once circumferentially around the stent structural member in an unexpanded state and attaching the polymer film to itself to form a sleeve around the stent structural member, such as by heating and melting the film to itself, adhesive bonding, solvent bonding, bonding one or more strips of elastic polymeric material on the outside edge of the polymeric film wrap to secure it, or by mechanical fastening, such as by a clip.

In one currently preferred embodiment, the polymer material can be attached to an existing stent structural member by hooking one or more slots on an edge portion of the polymeric material through a corresponding slotted portion of the stent structural member, tightly wrapping the polymer film at least once circumferentially around the stent structural member in an unexpanded state to form a coil of layers of the polymeric material, and securing the layers in a tightly wrapped coil. The coil currently is preferably secured in a tightly wrapped coil by adhesive bonding, typically by an adhesive such as a copolymer of poly-L-lactic acid (L-PLA) and polycaprolactone (PCL), although other adhesives, heat bonding, solvent bonding, or one or more mechanical fasteners, such as with a metal clip, for example, also S" may be suitable. Alternatively, the coil can be secured 15 in a tightly wrapped coil by attaching one end of at least one piece of elastic material to an exterior end portion of the coil of polymeric material, and attaching the other end of the elastic material to a portion of the exterior of the wrapped coil of polymeric material. The elastic material stretches to allow the coil of polymeric material to uncoil as the stent is expanded.

In another currently preferred embodiment, a combination of a stent structural member and a polymeric film wrapping can be provided with a coating of 25 lubricious material. The lubricious material currently preferably comprises a mixture of polyethylene oxide and polyethylene glycol, although other types of hydrophilic polymeric materials such as polyethylene acetate, polyvinyl pyrrolidone (PVP), polyvinyl alcohol, polyacrylamide, hydrophilic soft segment urethanes, soem natural gums such as gum arabic, gum tragacanth and the like, polyanhydrides or other similar hydrophilic polymers, and combinations thereof, also can be used.

The lubricious coating currently preferably is applied over a stent-and-polymer-film-wrap combination by dipping the wrapped stent in the hydrated, liquid lubricious material. The layer of lubricious material protects the stent from the guide catheter or the body lumen in which the stent is inserted by providing a low friction surface over the stent.

These and other aspects and advantages of the invention will become apparent from the following detailed description, and the accompanying drawings, which illustrate by way of example the features of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS FIGURE 1 is a cross-sectional view of a first embodiment of the stent structural member and film of polymer material of the drug-loaded stent of the invention shown in an unexpanded state; FIG. 2 is a cross-sectional view of the drugloaded stent of FIG. 1 shown in an expanded state; FIG. 3 is a perspective view of the drug-loaded stent of FIG. 1; FIG. 4 is a perspective view of an alternate embodiment of the drug-loaded stent of FIG. 1 having apertures in the exterior sheet of polymeric material; FIG. 5 is a cross-sectional view of a second embodiment of the drug-loaded stent of the invention, shown in an unexpanded state; FIG. 6 is a perspective view of an alternate embodiment of the drug-loaded stent of FIG. 5 having apertures in the polymeric material; FIG. 7 is a cross-sectional view of an alternate embodiment of the drug-loaded stent of FIG. having multiple wrappings of the polymeric material; FIG. 8 is an elevational view of a representative stent structural member, shown in a vessel; FIG. 9 is a plan view of a sheet of polymeric material in another alternative embodiment including elastic strips for securing the polymeric material wrapped around a stent structural member; FIG. 10 is a cross-sectional view of a drugloaded stent wrapped with the polymeric material of FIG. 9; *FIG. 11 is a perspective view of the drug- 15 loaded stent of FIG. FIG. 12 is a plan view of a sheet of polymeric ee material in a further alternative embodiment including an elastic strip extending the width of the polymeric material for securing the polymeric material when wrapped around a stent structural member; FIG. 13 is a perspective view of a drug-loaded stent wrapped with the polymeric material of FIG. 12; e *FIG. 14 is a plan view of a sheet of polymeric material in a further alternative embodiment including attachment tabs for securing the polymeric material to a stent structural member; FIG. 15 is an elevational view of a drug-loaded stent wrapped with the sheet of polymeric material of FIG. 14 and mounted on a balloon dilatation catheter for delivery; FIG. 16 is an enlarged partial sectional view of the drug-loaded stent of FIG. 15 showing the sheet of polymeric material wrapped around a slotted tube stent structural member; FIG. 17 is an elevational view of the drugloaded stent of FIG. 15 covered with a layer of a lubricious, hydrophilic polymeric coating; and FIG. 18 is a partial sectional view of the drug-loaded stent of FIG. 17.

DETAILED DESCRIPTION OF THE PREFERRED

EMBODIMENTS

Stents that have a metallic structure typically do not provide for the delivery of localized therapeutic 15 drugs in a blood vessel, while polymeric materials that •0go can be used for drug delivery may not fulfill the structural and mechanical requirements of a stent to hold ooooo open a body lumen. Polymeric materials used for the dual function of structural support and for absorbing and oo 20 releasing therapeutic agents may not fulfill either function satisfactorily, because drug-loading of a polymeric material can significantly affect the structural and mechanical properties of the polymeric material, and the ability to absorb and release therapeutic agents or drugs can affect structural characteristics.

Accordingly, as shown in FIGS. 1-4, the present invention provides for a stent 20 that can be drugloaded, comprising an expandable stent structural member 22, and a planar sheet or film 24 of polymeric material, further described below, that in a first embodiment is attached to the metal stent at one or more points of attachment 26, and is wrapped in a coil around the stent in an unexpanded state. The polymer material can be extruded as a thin film, and any processing can be done while the material is in a flat sheet form.

The attachment of the film of polymeric material 24 to the stent structural member 22 in an unexpanded state can be by adhesive; heat sealing such as with the stent structural member sandwiched between internal and external layers of film heat-sealed or otherwise laminated around the stent structural member; by mechanical connection such as by hooking one or more slots on an edge portion of the polymeric material through a corresponding slotted portion of the stent structural member, as will be described further below, or with a metal clip, for example. The film of polymeric material also has a free end 28, and can have one or more slits 30 in the polymeric film transverse to the axis 32 .*of the stent to accommodate possible uneven expansion of the underlying stent structural member. The planar sheet of polymeric material preferably is adapted to uncoil and to expand to match the expansion of the stent structural member. The planar sheet of polymeric material can be a solid sheet, or can have a surface defining a plurality of apertures 34 of various sizes and shapes to promote rapid endothelialization, as is illustrated in FIG. 4.

The stent can be mounted on a balloon dilatation catheter, for deployment of the stent in the vasculature of a patient.

As is illustrated in FIG. 5, in a second embodiment of the stent 40 that can be drug-loaded, the stent comprises a stent metal structural member 42, and a planar sheet or film of polymeric material 44, further described below. The film of polymeric material in this embodiment has a first end 46 forming a first layer 47 of the polymeric material, and a second end 48 overlapping the first end forming a second layer 49 and attached to the first layer of the polymeric film, preferably by heating and melting the film to itself to form a longitudinal heat seal bond 50 between the first and second layers. Attachment of the two outer layers of the polymeric film also can be accomplished by adhesive bonding, solvent bonding, or one or more mechanical fasteners, such as with a metal clip, for example. In this embodiment, the planar sheet of polymeric material preferably is wrapped circumferentially and cinched tightly as a sleeve around the stent structural member, and thus is attached to the stent structural member by an interference fit. In an alternative embodiment illustrated in FIG. 7, the polymeric material can be wrapped multiple times around the stent to form multiple layers that can be joined together as described with reference to FIG. 5 to form a tube around the stent.

Alternatively, the polymeric material can be formed as a seamless tube or sleeve to fit tightly around the unexpanded stent structural member.

*e.o The primary function of the sheet of polymeric material is to deliver therapeutic agents or drugs to help prevent thrombosis and/or restenosis. The planar ooeoo sheet of polymeric material preferably is selected from the group of polymers consisting of thermoplastic and elastomeric polymers, so that the polymeric film can stretch or deform radially when the stent structural member is expanded.

e As is shown in FIG. 6, the planar sheet of polymeric material also can have a surface defining a plurality of apertures 52 of various sizes and shapes to *promote rapid endothelialization, similar to the embodiment illustrated in FIG. 4. The stent can be mounted on a balloon dilatation catheter, for deployment of the stent in the vasculature of a patient.

In each of these embodiments, the stent structural member is of the type that can be implanted within a vessel in a contracted state and expanded to maintain patency of the vessel and to allow fluid flow through the vessel, such as the expanding stents available from Advanced Cardiovascular Systems, Inc., Santa Clara, CA (ACS), the Johnson Johnson Corporation Palmaz-Shatz stents) Cook Incorporated (ec Gianturco stents), and the like. The metal structural member, for example, can be formed from a metal selected from the group of metals consisting of stainless steel, MP20N, elastinite (nitinol), tantalum, nickeltitanium alloy, platinum-iridium alloy, gold, and magnesium, although the stent structural member also can be formed of suitable non-metallic materials. and "MP20N" are trade names for alloys of cobalt, nickel, chromium and molybdenum that are available from Standard Pressed Steel Co. of Jenkintown, Pennsylvania. consists of 35% cobalt, 35% nickel, 20% nickel, chromium, and 10% molybdenum.

A representative stent structural member with which a sheet of polymeric material can be combined 15 according to the principles of the invention is illustrated in FIG. 8. In one preferred embodiment, the stent structural member 60 can be formed of metal, and comprises a plurality of radially expandable cylindrical elements 62 disposed coaxially and interconnected by 20 members 63 disposed between adjacent cylindrical elements. The stent structural member is shown without a covering sheet of polymeric material, in a typical OO**o setting within a vessel 65, for repairing a detached vessel lining 66, for example, and for maintaining the patency of the vessel.

SThe polymeric material preferably is selected from thermoplastic and elastomeric polymers. In one currently preferred embodiment, the polymeric material can be a material available under the trade name "C-Flex" from Concept Polymer Technologies of Largo, Florida. In another currently preferred embodiment, the polymeric material can be ethylene vinyl acetate (EVA); and in yet another currently preferred embodiment, the polymeric material can be a material available under the trade name "BIOSPAN." Other suitable polymeric materials include latexes, urethanes, polysiloxanes, and modified styreneethylene/butylene-styrene block copolymers (SEBS) and their associated families, as well as elastomeric, bioabsorbable, linear aliphatic polyesters. The polymeric material typically can have a thickness in the range of about 0.051 to 0.508 millimeters (about 0.002 to about 0.020 inches), for example. The polymeric material preferably is bioabsorbable, and is preferably loaded or coated with a therapeutic agent or drug, including, but not limited to, antiplatelets, antithrombins, cytostatic and antiproliferative agents, for example, to reduce or prevent restenosis in the vessel being treated. The therapeutic agent or drug preferably is selected from the group of therapeutic agents or drugs consisting of sodium heparin, low molecular weight heparin, hirudin, argatroban, forskolin, vapiprost, prostacyclin and 15 prostacyclin analogues, dextran, D-phe-pro-argchloromethylketone, dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antibody, recombinant hirudin, thrombin inhibitor, angiopeptin, angiotensin converting enzyme inhibitors, (such as Captopril, available from the 20 Squibb Corporation; Cilazapril, available from the Hoffman-La Roche Company; or Lisinopril, available from the Merck Company) calcium channel blockers, colchicine, S" fibroblast growth factor antagonists, fish oil, omega 3fatty acid, histamine antagonists, HMG-CoA reductase 25 inhibitor, methotrexate, monoclonal antibodies, nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitor, seramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine and other PDGF antagonists, alpha-interferon and genetically engineered epithelial cells, and combinations thereof.

While the foregoing therapeutic agents have been used to prevent or treat restenosis and thrombosis, they are provided by way of example and are not meant to be limiting, as other therapeutic drugs may be developed which equally are applicable for use with the present invention.

In another currently preferred embodiment illustrated in FIGS. 9-13, the stent 70 that can be drugloaded comprises a stent metal structural member 72, such as the stent structural member 60 illustrated for example in FIG. 8, and a planar sheet or film of polymeric material 74, preferably including a plurality of apertures 88, as will be explained further below. The polymeric material can be attached to an existing stent structural member by tightly wrapping the polymer film at least once, and preferably multiple times, circumferentially around the stent structural member 72 in an unexpanded state to form a coil of layers of the polymeric material. The film of polymeric material in *L *e this embodiment has an interior end 76, multiple S 15 wrappings forming a plurality of layers 77 of the polymeric material, and an exterior end 78 overlapping the multiple layers. The coil of polymeric material preferably is secured snugly over the stent structure by at least one piece or strip of elastic material 80. One 0*0 20 end 82 of at least one such piece or strip of elastic material is attached to the exterior end portion 78 of the coil of polymeric material, and an opposing end 83 of 5 the piece of elastic material is attached to another portion 84 of the exterior of the wrapped coil of 25 polymeric material, across the edge of the exterior end portion 78 of the coil of polymeric material, to secure the coil on the stent. In one currently preferred embodiment illustrated in FIGS. 9-11, the coil of polymeric material advantageously can be secured on the stent structural member by two strips of such elastic material. Additional strips of elastic material also can be used to secure the coil of polymeric material, as needed. The elastic material stretches to allow the coil of polymeric material to uncoil as the stent is expanded.

In a currently preferred embodiment, the strips of elastic material are heat-bonded to the coil of polymeric material. Attachment of the elastic material also can be accomplished by adhesive bonding, solvent bonding, or by one or more mechanical fasteners, such as with a metal clip, for example. In this embodiment, the planar sheet of polymeric material preferably is wrapped circumferentially and cinched tightly as a sleeve around the stent structural member, and thus is attached to the stent structural member by an interference fit.

In a currently preferred alternative embodiment shown in FIGS. 12 and 13, similar to that illustrated in FIGS. 9-11, the elastic strip of material 80 can extend and be bonded along the entire width of the exterior end 78 of the coil of polymeric material as is shown in FIG. 12, and can be bonded to the other portion 84 of the exterior of the wrapped coil of polymeric material, across the edge of the exterior end portion 78 of the coil of polymeric material, to secure the coil on the stent, as is illustrated in FIG. 13. The strip of elastic material also can be perforated, such as with apertures 86 formed in the strip of elastic material for example, to decrease the cross-sectional area of the elastic material and thus to permit the elastic material to stretch more easily. The polymeric film material also currently preferably includes a plurality of apertures 88 so that the polymeric material is porous, to allow blood to flow through the stent structural member 72 to the vessel wall, such as for oxygenation of and nutrient exchange with the vessel wall, and in order to present a decreased surface area for purposes of reducing thrombogenicity. The apertures also improve the flexibility of the polymeric material, allowing the stent segment to be more easily rolled and uncoiled during expansion of the stent structural member, and also facilitate the process of cell growth over the surface of the stent.

The primary function of the sheet of polymeric material 24,44,74 is to deliver therapeutic agents or drugs to help prevent thrombosis and/or restenosis. The planar sheet of polymeric material preferably is selected from the group of polymers consisting of thermoplastic and elastomeric polymers, that however can be substantially inelastic, so as not to lose a significant part of their thickness during expansion of the stent structural member, such as polycaprolactone, for example, allowing a high upper threshold for the amount of one or more drugs that can be loaded in the polymeric material and delivered. The inelastic polymeric material currently preferred is of a thickness that will guarantee drug delivery over at least approximately a seven-day period, which currently is not possible with radiallyexpanding elastic films. In the embodiment illustrated in FIGS. 9-13, an inelastic drug-loaded polymeric material is currently preferred which is no greater than about 0.0508 millimeter (0.002 inch) thick, and typically approximately is 0.0381 to 0.0508 millimeter (0.0015 inch to 0.002 inch) thick, to prevent the profile of the stent i and wrap of polymeric material from becoming too large.

The elastic portion of the sleeve of polymeric material keeps the coiled polymeric film secured snugly over the expandable stent structural member, so that the polymeric material can be applied over the stent structural member without the need for additional internal points of attachment to the stent structural member. The elastic portion of the sleeve of polymeric material also keeps tension on the coiled, inelastic drug-containing material while the stent structural member is expanding, without providing so much resistance so as to impede expansion of the stent structural member, or the unrolling of the inelastic polymeric material.

The elastic strip of material can be joined on the interior or exterior of the end portion of the coiled polymeric material. The elastic material attached over the coil of polymeric material helps keep the coil of drug-loaded material snug on the stent structural member before it is expanded, and guides its linear expansion during inflation of a balloon dilatation catheter used for deployment of the stent and polymeric drug-loaded material in the vasculature or other body lumen of a patient.

The elastic material currently typically is formed of ethylene vinyl acetate, but also can also be formed of silicone polymers. The drug-loaded layer of polymeric material and the stent structural member can be formed of the materials as described above in the previous embodiments.

In another alternative embodiment illustrated in FIGS. 14-16, another preferred type of stent 90 that can be drug-loaded comprises a stent metal structural member 92, that, for example, can be a slotted tube type of stent having a plurality of slotted openings 91 and structural ribs 93 as is illustrated in FIG. 16, such as is available from Advanced Cardiovascular Systems, in combination with a planar sheet or film of polymeric material 94. The stent structural member also can be other types of stents that preferably have a relatively significant proportion of space provided by openings, slots, or the like in the otherwise solid material of the stent structure. The polymeric material can be attached to such a stent structural member by tightly wrapping the S 25 polymer film at least once, and preferably multiple times, circumferentially around the stent structural member 92 in an unexpanded state to form a coil of layers S. of the polymeric material. The film of polymeric material in this embodiment has an interior end 96 with at least one attachment member or tab 100 adapted to be received in openings 91 of the stent structural member and thereby attached to the stent structural member, and provides multiple wrappings forming a plurality of layers 97 of the polymeric material, with an exterior end 98 overlapping the interior multiple layers. As is shown in FIG. 14, the polymeric film of material currently preferred has a plurality of attachment tabs 100, and typically has two of such attachment tabs. Each attachment tab currently preferably includes an aperture 101 therethrough, which is adapted to receive and to hook onto a structural rib portion 93 of the stent structural member. The attachment tab also includes a slit 102 extending from the aperture I01 to the outer edge 103 of the attachment tab, to allow the attachment tab to be hooked onto the stent structural member. After the attachment tab is hooked onto a portion of the stent structural member, the slit 102 preferably is sealed closed, such as by application of an adhesive material, typically a copolymer of poly-L-lactic acid (L-PLA) and polycaprolactone (PCL), other suitable adhesives, or by heat bonding. The coil of polymeric material preferably 15 is formed of a thermoplastic material such as polycaprolactone that can be drug-loaded, and can be wrapped and secured snugly over the stent structure by heat bonding the exterior end 98 to another portion of the exterior of the wrapped coil of polymeric material as described above. The polymeric film of material tensions the attachment tabs as the stent structural member is expanded and as the wrapping of polymeric material uncoils, to bias the attachment tab extending into the lumen of the stent structural member against the inner a25 surface of the lumen of the stent structural member to insure that the attachment tabs do not obstruct the lumen .within the stent structural member. Attachment of the exterior edge of the polymeric material to the wrapping of polymeric material currently preferably is accomplished by adhesive bonding, typically by an adhesive such as a copolymer of poly-L-lactic acid (L- PLA) and polycaprolactone (PCL), although other adhesives, heat bonding, solvent bonding, or one or more mechanical fasteners, such as with a metal clip, for example, may also be suitable.

In a currently preferred embodiment, the polymeric film material typically is about 0.0508 millimeter (about 0.002 inch) thick, and also currently preferably includes a plurality of apertures 108 so that the polymeric material is porous, to allow blood to flow through the stent structural member to the vessel wall, such as for oxygenation and nutrient exchange to the vessel wall, and in order to present a decreased surface area for purposes of reducing thrombogenicity. The apertures also improve the flexibility of the polymeric material, allowing the stent segment to be more easily rolled and uncoiled during expansion of the stent structural member, and also to facilitate the process of cell growth over the surface of the stent.

The primary function of the sheet of polymeric material is to deliver therapeutic agents or drugs to 15 help prevent thrombosis and/or restenosis. The planar sheet of polymeric material preferably is selected from the group of polymers consisting of thermoplastic and eeoc elastomeric polymers that may be inelastic, and that do not lose a significant part of their thickness during expansion of the stent structural member, allowing a high upper threshold for the amount of one or more drugs that can be loaded in the polymeric material and delivered.

As is illustrated in FIGS. 15 and 16, the drug-loaded stent can be mounted on an expandable balloon member 110 of a dilatation catheter 112, near radiopaque markers 114 of the catheter, for delivery of the stent in an artery, other blood vessel, or other body lumen, such as through a protective sheath 116, shown cutaway for convenience of illustration.

In another currently preferred embodiment illustrated in FIGS. 17-18, a combination of a stent structural member and a polymeric film wrapping can be provided with a coating of lubricious material 120. The lubricious material currently preferred is a mixture of polyethylene oxide and polyethylene glycol, providing both high and low molecular weight components in the lubricious material, although other types of hydrophilic r polymeric materials such as polyethylene acetate, polyvinyl pyrrolidone (PVP), polyvinyl alcohol, polyacrylamide, hydrophilic soft segment urethanes, some natural gums such as gum arabic or gum tragacanth and the like, polyanhydrides or other similar hydrophilic polymers, and combinations thereof, also can be used.

The lubricious material also can carry an antithrombogenic drug that can be the same as, or complementary to, the anti-thrombogenic or antiproliferative drug or drugs carried in the polymeric material of the stent.

The lubricious coating currently preferably is applied over a stent-and-polymer-film-wrap combination by dipping the wrapped stent in the hydrated, liquid 15 lubricious material. The lubricious material typically is prepared to be sufficiently viscous to allow the stent to be coated sufficiently by a single dipping. The lubricious coating initially is quite sticky when .applied, but it is dried to provide a non-sticky tight cocoon around the wrapped stent, and helps to keep the polymer wrapping tight. While the lubricious coating is shown applied to a wrapped stent such as that of FIGS.

14-16, the lubricious coating advantageously can be applied to any of the foregoing wrapped stent 25 combinations, and other suitable stents as well. The lubricious coating becomes hydrated again upon exposure to the blood during delivery of the stent. When a sheath is used in the delivery system to protect the stent during delivery, the lubricious coating initially can be hydrated before contacting the blood by flushing the sheath with saline solution. Due to the gel-like nature of the lubricious coating, the lubricious coating eventually dissolves in a short period of time, and typically will be completely degraded and dissolved by the time the stent is deployed and expanded.

The layer of lubricious material protects the stent from the guide catheter or the anatomy by providing a low friction surface over the stent. If a sheath or sleeve is used for delivering the stent, the lubricious coating aids in retraction of the sheath by decreasing friction between internal and external layers of the delivery system. The deployment of the stent also can be improved by decreasing friction between the stent and the balloon used to deliver the stent, decreasing friction between the layers of the stent itself, or decreasing friction between the vessel or lumen wall and the stent.

The need for a sheath for protecting the stent during delivery also can be mitigated if the coating is of a thickness suited to providing a smooth transition through the delivery system, and still provides a low profile of the uninflated, undeployed stent. Alternatively, the 15 lubricious coating also can be formed as a dried sheet of lubricious material, cut into a strip, wrapped in spiral fashion over the length of the polymeric drug carrying wrapping, and bonded in place by an adhesive such as a copolymer of poly-L-lactic acid (L-PLA) and polycaprolactone (PCL), although other adhesives, or heat bonding may also be suitable.

It thus has been demonstrated that the invention provides for a stent combining polymeric materials with stent structures with the capability of absorbing therapeutic drugs or other agents, for placement and release of the therapeutic agents at a specific intravascular site. A complex locking design is not needed, and the stent can be re-dilated if necessary.

The polymeric, drug-containing section can be bioabsorbable, and can be specially formulated for its specific function of delivering drugs locally, since it is not necessary for the polymeric component to provide assistance in keeping the blood vessel open. The polymeric material can be extruded as a film, using simple technology, and can be processed while the material is a flat sheet. The stent can be used in coronary arteries or any other part of the vasculature P \OPERU I 01734K I Spe dr41905AR I 20 where mechanical opening force is necessary or desirable to keep the vessel open, and where anti-restenosis, anti-proliferative or other types of therapeutic drugs or agents can be useful in combatting thrombosis and restenosis.

It therefore will be apparent from the foregoing that while particular forms of the invention have been illustrated and described, various modifications can be made without departing from the spirit and scope of the invention. Accordingly, it is not intended that the invention be limited, except as by the appended claims.

Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and 1 0 "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

The reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that the prior art forms part of the common general knowledge in Australia.

°•ooo6 ooo o• go S. S ••Soo

Claims (13)

1. A drug-loaded stent, comprising: an expandable stent structural member; and a planar sheet of polymeric material loaded with a therapeutic agent and wrapped in a coil around the stent structural member, said sheet of polymeric material having one end attached to the stent structural member and one free end.

2. The drug-loaded stent of claim 1, wherein said planar sheet of polymeric material is wrapped circumferentially around the stent structural member at least one time, and said planar sheet of polymeric material is attached to itself.

3. The drug-loaded stent of claim 1, wherein said planar sheet of polymeric material is wrapped circumferentially around the stent structural member at least one time, and said planar sheet of polymeric material is attached to the stent structural member by adhesive.

4. The drug loaded stent of claim 1, wherein said stent structural member has a surface defining a plurality of slotted openings therethrough and a plurality of structural ribs, said planar sheet of polymeric material has at least one attachment tab having an aperture therethrough and a slit extending from said aperture to an outside edge of said attachment tab, said planar sheet of 20 polymeric material being attached to the stent structural member by inserting said attachment tab into one said stent slotted opening and booking said slit and said aperture of said attachment tab to a structural rib of said stent structural member, and said sheet of polymeric material is wrapped circumferentially around the stent structural member at least one time. 25

5. The drug-loaded stent of claim 2, wherein said planar sheet of polymeric material is selected from the group of polymers consisting of thermoplastic and elastomeric polymers, whereby said film stretches radially when said stent structural member is expanded.

6. The drug-loaded stent of claim 1, wherein said planar sheet of polymeric Smaterial is adapted to uncoil and expand to substantially match the expansion of said stent structural member. P:\OPERlKA\10073-4X) sp.doc )9AIM) -22-

7. The drug-loaded stent of claim 1, wherein said stent structural member has a longitudinal axis, and said planar sheet of polymeric material has at least one slit transverse to the axis of said stent structural member to accommodate uneven expansion of the stent structural member.

8. The drug-loaded stent of claim 1, wherein said therapeutic agent is selected from the group consisting of therapeutic agents consisting of antiplatelets, antithrombins, cytostatic and antiproliferative agents.

9. The drug-loaded stent of claim 1, wherein said therapeutic agent is selected from the group of therapeutic agents consisting of sodium heparin, low molecular weight heparin, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone, dipyridamole, glycoprotein Ilb/Illa platelet membrane receptor antibody, recombinant hirudin, thrombin inhibitor, angiopeptin, angiotensin converting enzyme inhibitors, calcium channel blockers, cochicine, fibroblast growth factor antagonists, fish oil, omega 3-fatty acid, histamine antagonists, HMG- **CoA reductase inhibitor, methotrexate, monoclonal antibodies, nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitor, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine, PDGF antagonists, alpha- interferon, genetically engineered epithelial cells, and combinations thereof. 20

10. The drug-loaded stent of claim 1, wherein said stent structural member is formed from a metal selected from the group of metals consisting of stainless steel, tantalum, nickel-titanium alloy, platinum-iridium alloy, gold, magnesium, and

11. The drug-loaded stent of claim 1, wherein said planar sheet of polymeric 25 material has a surface defining a plurality of openings to promote rapid endothelialization.

12. The drug-loaded stent of claim 1, wherein said planar sheet of polymeric material is coated with a layer of hydrophilic lubricious polymeric material.

13. The drug-loaded stent of claim 12, wherein said lubricious material is selected from the group consisting of polyethylene oxide, polyethylene glycol, P:\OPER\UXA\10073-00 spc.do-09I5/00 23 polyethylene acetate, polyvinyl propylene, polyvinyl alcohol, polyanhydrides, and combinations thereof. DATED this 9th day of May, 2000 Advanced Cardiovascular Systems, Inc. DAVIES COLLISON CAVE Patent Attorneys for the Applicant *oo eoe oo