Drug-eluting stent and methods of making the same Number:7,144,422 from the United States Patent and Trademark Office (PTO) owispatent An intravascular stent having a prefabricated, patterned polymeric sleeve for controlled release of therapeutic drugs and for delivery of the therapeutic drugs in localized drug therapy in a blood vessel is disclosed. The polymeric sleeve is attached to at least a portion of an outside surface area of the stent structure. Alternatively, a plurality of individual microfilament strands are longitudinally attached to an outer surface of a stent structure in a spaced apart orientation and loaded with at least one therapeutic drug for the release thereof at a treatment site. The stent has a high degree of flexibility in the longitudinal direction, yet has adequate vessel wall coverage and radial strength sufficient to hold open an artery or other body lumen. Methods for making the same are also disclosed.<H methods, eluting, Drug, eluting, st, 7144422.html, Patent, pto, 7144422

Title: Drug-eluting stent and methods of making the same

Abstract: An intravascular stent having a prefabricated, patterned polymeric sleeve for controlled release of therapeutic drugs and for delivery of the therapeutic drugs in localized drug therapy in a blood vessel is disclosed. The polymeric sleeve is attached to at least a portion of an outside surface area of the stent structure. Alternatively, a plurality of individual microfilament strands are longitudinally attached to an outer surface of a stent structure in a spaced apart orientation and loaded with at least one therapeutic drug for the release thereof at a treatment site. The stent has a high degree of flexibility in the longitudinal direction, yet has adequate vessel wall coverage and radial strength sufficient to hold open an artery or other body lumen. Methods for making the same are also disclosed.

Patent Number: 7,144,422 Issued on 12/05/2006 to Rao

Inventors: Rao; K. T. Venkateswara (San Jose, CA)
Assignee: Advanced Cardiovascular Systems, Inc. (Santa Clara, CA)

Appl. No.: 10/293,108

Filed: November 13, 2002

Current U.S. Class: 623/1.42 ; 623/1.13; 623/1.15

Current International Class: A61F 2/06 (20060101)

Field of Search: 623/1.15,1.13,1.12,1.23,1.39,1.42,1.44

References Cited [Referenced By]

U.S. Patent Documents


3839743	October 1974	Schwarcz
4346028	August 1982	Griffith
4377030	March 1983	Beck et al.
4417576	November 1983	Baran
4423725	January 1984	Baran et al.
4633873	January 1987	Dumican et al.
4656083	April 1987	Hoffman et al.
4718907	January 1988	Karwoski et al.
4722335	February 1988	Vilasi
4723549	February 1988	Wholey et al.
4732152	March 1988	Wallsten et al.
4733665	March 1988	Palmaz
4739762	April 1988	Palmaz
4768507	September 1988	Fischell et al.
4776337	October 1988	Palmaz
4816339	March 1989	Tu et al.
4877030	October 1989	Beck et al.
4878906	November 1989	Lindemann et al.
4879135	November 1989	Greco et al.
4902289	February 1990	Yannas
4994298	February 1991	Yasuda
5019090	May 1991	Pinchuk
5059211	October 1991	Stack et al.
5062829	November 1991	Pryor et al.
5064435	November 1991	Porter
5084065	January 1992	Weldon et al.
5085629	February 1992	Goldberg et al.
5100429	March 1992	Sinofsky et al.
5108370	April 1992	Walinsky
5108755	April 1992	Daniels et al.
5123917	June 1992	Lee
5151105	September 1992	Kwan-Gett
5156623	October 1992	Hakamatsuka et al.
5158548	October 1992	Lau et al.
5163951	November 1992	Pinchuk et al.
5163952	November 1992	Froix
5163958	November 1992	Pinchuk
5192311	March 1993	King et al.
5197977	March 1993	Hoffman, Jr. et al.
5199951	April 1993	Spears
5234456	August 1993	Silvestrini
5234457	August 1993	Andersen
5236447	August 1993	Kubo et al.
5279594	January 1994	Jackson
5282860	February 1994	Matsuno et al.
5289831	March 1994	Bosley
5290271	March 1994	Jernberg
5306286	April 1994	Stack et al.
5330500	July 1994	Song
5342348	August 1994	Kaplan
5342621	August 1994	Eury
5356433	October 1994	Rowland et al.
5383928	January 1995	Scott et al.
5389106	February 1995	Tower
5411551	May 1995	Winston et al.
5413597	May 1995	Krajicek
5419760	May 1995	Narciso, Jr.
5421955	June 1995	Lau et al.
5439446	August 1995	Barry
5441515	August 1995	Khosravi et al.
5458605	October 1995	Klemm
5514154	May 1996	Lau et al.
5527337	June 1996	Stack et al.
5578075	November 1996	Dayton
5605696	February 1997	Eury et al.
5700286	December 1997	Tartaglia et al.
5707385	January 1998	Williams
5780807	July 1998	Saunders
5830217	November 1998	Ryan
5843172	December 1998	Yan
6131266	October 2000	Saunders
6146322	November 2000	Papirov et al.
6152869	November 2000	Park et al.
6168602	January 2001	Ryan
6254632	July 2001	Wu et al.
6261316	July 2001	Shaolian et al.
6261320	July 2001	Tam et al.
6273908	August 2001	Ndondo-Lay
6379381	April 2002	Hossainy et al.
6391033	May 2002	Ryan
6419692	July 2002	Yang et al.
6432133	August 2002	Lau et al.
6436132	August 2002	Patel et al.
6530950	March 2003	Alvarado et al.
6540776	April 2003	Sanders Millare et al.
6613084	September 2003	Yang
6629992	October 2003	Bigus et al.
6629994	October 2003	Gomez et al.
6663665	December 2003	Shaolian et al.
6899727	May 2005	Armstrong et al.
6939368	September 2005	Simso
2002/0138129	September 2002	Armstrong et al.
2003/0078647	April 2003	Vallane et al.
2003/0114919	June 2003	McQuiston et al.
2003/0166779	September 2003	Kishan et al.
2003/0181973	September 2003	Sahota
2003/0212447	November 2003	Euteneuer et al.

Foreign Patent Documents


36 40 745	Jun., 1987	DE
44 07 079	Sep., 1994	DE
0 567 788	Nov., 1993	EP
0 604 022	Jan., 1994	EP
0 578 998	Jun., 1994	EP
0 621 017	Oct., 1994	EP
0 623 354	Nov., 1994	EP
WO 91/17789	Nov., 1991	WO
WO 93/06792	Apr., 1993	WO
WO 95/29647	Nov., 1995	WO

Other References

Bull, "Parylene Coating for Medical Applicaitons", Medical Product Manufacturing News, 2 pgs, Mar. 1993. cited by other .
Casper et al., "Fiber-Reinforced Absorbable Composite for Orthopedic Surgery", Science and Engineering, vol. 53, pp. 497-501, Fall Meeting 1985. cited by other .
Hahn et al., "Glow Discharge Polymers as Coatings for Implanted Devices", Univ. of Missouri, pp. 109-113, 1981. cited by other .
Hahn et al., "Biocompability of Glow-Discharge-Polymerized Films and Vacuum-Deposited Parylene", Applied Polymer Symposium 38, pp. 55-64, 1984. cited by other .
Kelley et al., "Totally Resortable High-Strength Composite Material", Advances in Biomedical Polymers, Ed. By Charles G. Gebelein, pp. 75-85, 1987. cited by other .
Muller et al., "Advances in Coronary Angioplasty: Endovascular Stents", Coronary Artery Disease, vol. 1, No. 4, 10 pgs, 1990. cited by other .
Nichols et al., "Electrical Insulation of Implantable Devices by Composite Polymer Coatings", Univ. of Missouri, Paper No. 87-0110, pp. 57-62, 1987. cited by other .
Olson "Parylene, a Biostable Coating for Medical Applications", Nova Tran Parylene Coating Services Jul. 25, 1988 and Nov. 14, 1988 10 pgs. cited by other .
"Parylene Conformal coating" by Nova Tran Custom Coating Services, 8 pgs, (undated). cited by other .
Schatz "A View of vascular Stents", Arizona Heart Institute Foundation, Phoenix Arizona, 15 pgs, 1988. cited by other .
Schmidt et al., "Long-Term Implants of Parylene-C Coated Microelectrodes" Medical & Biological Engineering & Computing, pp. 96-191, 1988. cited by other .
Shing-Chiu Wong et al., "An Update on Coronary Stents", Cardio, Feb. 1992, 8 pgs. cited by other.

Primary Examiner: Snow; Bruce
Attorney, Agent or Firm: Squire, Sanders & Dempsey L.L.P.

Claims

What is claimed is:

1. A drug-eluting stent delivery system for controlled release of therapeutic drugs and for delivery of the therapeutic drugs in localized drug therapy in a blood vessel, comprising: a pattern of struts interconnected to form a structure capable of contacting the walls of a body lumen to maintain the patency of the vessel, wherein a polymeric sleeve, fabricated as a prepatterned tube comprising polymer elements, is loaded with at least one therapeutic drug for the release thereof at a treatment site, the polymeric sleeve being attached to at least a portion of an outside surface area of the stent structure and wherein the prepatterning enables the detachment of the polymer elements upon stent expansion, wherein the polymeric sleeve includes a plurality of four-sided, filament strands attached to the surface of the stent, and wherein a barrier coating layer is disposed on three sides of the plurality of four-sided filament strands to enable drug elution along the fourth side.

2. The drug-eluting stent delivery system of claim 1, wherein the pattern of struts comprises a plurality of flexible cylindrical rings being expandable in a radial direction, each of the rings having a first delivery diameter and a second implanted diameter and being aligned on a common longitudinal axis.

3. The drug-eluting stent delivery system of claim 1, wherein the stent is formed at least in part of a metallic material.

4. The drug-eluting stent delivery system of claim 3, wherein the metallic material forming the stent is from the group consisting of stainless steel, platinum, titanium, tantalum, nickel-titanium, cobalt-chromium, and alloys thereof.

5. The drug-eluting stent delivery system of claim 1, wherein the therapeutic drug is selected from the group consisting of antiplatelets, anticoagulants, antifibrins, antithrombins, and antiproliferatives.

6. The drug-eluting stent delivery system of claim 1, wherein the polymeric sleeve comprises a material selected from the group consisting of PMMA, EVAL, PBMA, PGA, and PLLA, and copolymers and blends thereof.

7. The drug-eluting stent delivery system of claim 1, wherein the polymeric sleeve is fabricated from a predesigned pattern having individual drug-loaded elements to form a desired local drug-elution profile.

8. The drug-eluting stent delivery system of claim 7, wherein upon expansion of the stent structure, the drug-loaded polymeric sleeve breaks away in the predesigned pattern and individual drug-loaded filament strands are held against the vessel wall by the stent structure.

9. The drug-eluting stent delivery system of claim 7, wherein the predesigned pattern is fabricated to expand along a length of the stent to overcome strain.

10. The drug-eluting stent delivery system of claim 1, wherein the drug-loaded polymeric sleeve is prefabricated in a desired dimension using at least one of the polymer processing techniques comprising extrusion, injection molding, laser cutting, slip casting, and plasma polymerization.

11. The drug-eluting stent delivery system of claim 1, wherein the polymeric sleeve includes at least one additional layer of polymer material as a barrier layer to further control elution of the therapeutic drug at the treatment site.

12. The drug-eluting stent delivery system of claim 1, wherein the drug-loaded polymeric sleeve has a thickness in the range of about 0.001 to about 100 microns.

13. A method of making a drug-eluting stent delivery system for controlled release of therapeutic drug(s) and for delivery of the therapeutic drug(s) in localized drug therapy in a blood vessel, comprising: forming a pattern of struts that form a stent capable of contacting the walls of a body lumen to maintain the patency of the vessel, wherein at least a portion of the outside surface of the stent surface attaches to a polymeric sleeve that is fabricated as a prepatterned tube comprising a plurality of four-sided, filament strands attached to the surface of the stent, and is loaded with at least one therapeutic drug for the release thereof at a treatment site, wherein the prepatterning enables the detachment of the filament strands upon stent expansion, and wherein a barrier coating layer is disposed on three sides of the plurality of four-sided filament strands to enable drug elution along the fourth side.

14. The method of claim 13 wherein the therapeutic drug is selected from the group consisting of antiplatelets, anticoagulants, antifibrins, antithrombins, and antiproliferatives.

15. The method of claim 13 wherein the polymeric sleeve comprises a material selected from PMMA, EVAL, PBMA, PGA, PLLA, copolymers thereof or blends thereof.

16. The method of claim 13 wherein the polymeric sleeve includes at least one additional layer of polymer material as a barrier layer to further control elution of the therapeutic drug at the treatment site.

Description

BACKGROUND OF THE INVENTION

This invention relates to vascular repair devices, and in particular intravascular stents, which are adapted to be implanted into a patient's body lumen, such as a blood vessel or coronary artery, to maintain the patency thereof. Stents are particularly useful in the treatment of atherosclerotic stenosis in arteries and blood vessels. More particularly, the invention concerns a drug-eluting stent delivery system consisting of an intravascular device having a local drug-eluting component that is capable of eluting therapeutic drugs with uniform and controlled drug distribution at the treatment site while providing the intravascular device with a biocompatible and/or hemocompatible surface.

Intravascular interventional devices such as stents are typically implanted within a vessel in a contracted state, and expanded when in place in the vessel in order to maintain the patency of the vessel to allow fluid flow through the vessel. Stents have a support structure such as a metallic structure to provide the strength required to maintain the patency of the vessel in which it is to be implanted, and are typically provided with an exterior surface coating to provide a biocompatible and/or hemocompatible surface. Since it is often useful to provide localized therapeutic pharmacological treatment of a blood vessel at the location being treated with the stent, it is also desirable to provide intravascular interventional devices such as stents with a biocompatible and/or hemocompatible surface coating of a polymeric material with the capability of being loaded with therapeutic agents, to function together with the intravascular devices for placement and release of the therapeutic drugs at a specific intravascular site.

Drug-eluting stent devices have shown great promise in treating coronary artery disease, specifically in terms of reopening and restoring blood flow in arteries stenosed by atherosclerosis. Restenosis rates after using drug-eluting stents during percutaneous intervention are significantly lower compared to bare metal stenting and balloon angioplasty. However, current design and fabrication methods for drug-eluting stent devices are not optimal. Accordingly, various limitations exist with respect to such current design and fabrication methods for drug-eluting stents.

One significant limitation, for example, is that current designs for drug-eluting stents fail to provide for uniform drug distribution in the artery. Since unformity is dictated by metal stent skeletal structure, increasing uniformity by increasing the metal stent surface area makes the stent stiff and compromises flexibility and deliverability. Additionally, current device designs incorporate expandable ring elements and connectors, which are then coated using a polymer plus drug coating or loaded with microreservoirs of drug. The expandable nature of the rings limits the extent of uniformity in coverage and drug distribution that can be achieved. Further limitations include the mixture of the drug in a polymer and/or solvent solution which is then spray coated on the entire stent surface with a primer, drug, and topcoat layers being used to control release kinetics. This approach, tends to cause cracking in the drug-coating layer, since the layer also undergoes stretching during stent expansion, and considerable washout of the drug into the blood stream, and only a fraction gets into the tissue/artery. Further, the amount of the drug that can be loaded on the stent is limited by mechanical properties of the coating, since the higher the drug content in the polymer makes the coating more brittle and causes cracking thereto. Therefore, loading a higher drug dose requires coating with more polymer on the device. Other limitations in current fabrication methods of drug-eluting stents include the necessity of several coating steps along the length of the stent which is time consuming. Special equipment for crimping the drug-eluting stent on the balloon and to securely attach the stent on the balloon is also needed in accordance with current fabrication methods. As conventional spray coating is capable of programming only one drug release rate kinetics, variation of drug dosing and release kinetics along the length of the stent is not possible using the current coating process.

What has been needed and heretofore unavailable is a novel design that decouples the two major functional characteristics of the drug-eluting stent device, namely the purely mechanical stent structure and the local drug-eluting component. Current devices are constrained by their design construct which necessitates optimizing both factors-mechanical stent expansion and drug-elution kinetics simultaneously. Thus, it would be desirable to have a stent structure that is optimally designed for expansion (i.e., allowable stress/strain, scaffolding, radial strength, etc.) independent of the drug-eluting component, and the drug-eluting component designed for local drug release independent of mechanical factors associated with stent expansion. The present invention meets these and other needs.

SUMMARY OF THE INVENTION

The present invention is directed to intraluminal devices, and more particularly, to a drug-eluting stent delivery system for controlled release of therapeutic drugs and for delivery of the therapeutic drugs in localized drug therapy in a blood vessel. Alternatively, the drug-eluting stent delivery system includes a plurality of individual filament strands attached in a spaced apart orientation around an outside surface area of the stent and loaded with at least one therapeutic drug for the controlled release thereof at a treatment site. Methods for making different types of a drug-eluting stent delivery system are also disclosed herein.

In one embodiment, the present invention accordingly provides for a drug-eluting stent delivery system for controlled release of therapeutic drugs and for delivery of the therapeutic drugs in localized drug therapy in a blood vessel. A pattern of struts are interconnected to form a structure that contacts the walls of a body lumen to maintain the patency of the vessel. The pattern of struts include a plurality of flexible cylindrical rings being expandable in a radial direction with each of the rings having a first delivery diameter and a second implanted diameter while aligned on a common longitudinal axis. At least one link of the stent is attached between adjacent rings to form the stent. The stent is formed at least in part of a metallic material such as stainless steel, platinum, titanium, tantalum, nickel-titanium, cobalt-chromium or alloys thereof.

A polymeric sleeve, fabricated as a prepatterned tube, is loaded with at least one therapeutic drug for the release thereof at a treatment site. The polymeric sleeve is attached to at least a portion of an outside surface area of the stent structure. Various therapeutic drugs that can be used in combination with the polymeric sleeve include antiplatelets, anticoagulants, antifibrins, antiinflammatories, antithrombins, and antiproliferatives. Several drug-loadable polymers, such as PMMA, EVAL, PBMA, PGA, PLLA, copolymers and blends thereof, and nanotubes of carbon can be used to fabricate the drug-loaded sleeve of the invention. The thickness of the drug-loaded polymeric sleeve ranges from about 0.001 to about 100 microns.

The polymeric sleeve is fabricated from a predesigned pattern having individual drug-loaded elements to form a desired local drug-elution profile. The predesigned pattern of the polymeric sleeve as a solid tube can be formed by various techniques such as etching or cutting. The drug-loaded polymeric sleeve is prefabricated in a desired dimension by using one of the known polymer processing techniques in the art including extrusion, injection molding, laser cutting, slip casting, and plasma polymerization. As a further mechanism of controlling elution of the therapeutic drug at the treatment site, the polymeric sleeve can be coated with at least one additional layer of polymer material as a barrier layer.

In use, the drug-loaded polymeric sleeve breaks away in the predesigned pattern upon expansion of the underlying stent structure and individual drug-loaded elements are held against the vessel wall by the stent structure. The predesigned pattern is fabricated to expand along a length of the stent to overcome strain.

In another embodiment, the present invention provides for a drug-eluting stent delivery system for controlled release of therapeutic drugs and for delivery of the therapeutic drugs in localized drug therapy in a blood vessel. A pattern of struts are interconnected to form a first stent structure that contacts the walls of a body lumen to maintain the patency of the vessel, wherein a second stent structure, fabricated as a prepatterned thin metallic sheet having a polymer layer disposed thereon, is loaded with at least one therapeutic drug for the release thereof at a treatment site. The second stent structure is attached to at least a portion of an outside surface area of the stent structure. The second stent structure is not limited to a tubular form and can be wrapped around the first stent structure in a jelly roll configuration.

In a further embodiment, the present invention provides for a drug-eluting stent delivery system for controlled release of therapeutic drugs and for delivery of the therapeutic drugs in localized drug therapy in a blood vessel. A pattern of struts are interconnected to form a structure that contacts the walls of the body lumen to maintain the patency of the vessel. A plurality of individual filament strands are attached to an outside surface of the stent structure in a spaced apart orientation and loaded with at least one therapeutic drug for the release thereof at a treatment site. The plurality of individual filament strands are positioned longitudinally across the outside surface of the stent structure.

The pattern of struts include a plurality of flexible cylindrical rings being expandable in a radial direction, each of the rings having a first delivery diameter and a second implanted diameter while aligned on a common longitudinal axis. At least one link of the stent is attached between adjacent rings to form the stent. The stent is formed at least in part of a metallic material such as stainless steel, platinum, titanium, tantalum, nickel-titanium, cobalt-chromium, and alloys thereof.

Various therapeutic drugs can be used in combination with the drug-eluting stent delivery system of the present invention including antiplatelets, anticoagulants, antifibrins, antiinflammatories, antithrombins, and antiproliferatives. The plurality of individual filament strands can be fabricated using different therapeutic drug combinations for the release thereof at the treatment site. The drug-loaded filament strands each have a thickness in the range of about 0.001 to about 100 microns and a width in the range of about 0.001 to about 50 microns. Several drug-loadable polymers, such as PMMA, EVAL, PBMA, PGA, PLLA, copolymers and blends thereof, and nanotubes of carbon can be used to fabricate the individual filament strands. Alternatively, the plurality of individual filament strands are fabricated from a porous metal having a polymeric drug release layer disposed thereon.

Each of the individual filament strands have a rectangular cross-section with a first side, a second side, a third side, and a fourth side. A barrier coating layer is disposed on the first, second, and third sides of each of the drug-loaded filament strands to enable drug elution along the fourth side at the treatment site. Alternatively, the plurality of individual filament strands can be configured to assume a different cross-sectional design such as circular, oval, triangular, trapezoidal, and tubular designs. The individual filament strands can be fabricated from either a micron-scale level or a nano-scale level to form microfilament strands or nanofilament strands, respectively.

In another embodiment, the present invention provides for a drug-eluting stent delivery system for controlled release of therapeutic drugs and for delivery of the therapeutic drugs in localized drug therapy in a blood vessel. A pattern of struts are interconnected to form a structure that contacts the walls of a body lumen to maintain the patency of the vessel. A polymeric sleeve, fabricated as a prepatterned tube, is loaded with at least one therapeutic drug for the release thereof at a treatment site, the polymeric sleeve being attached to at least a portion of an inside surface area of the stent structure for the treatment of the inner arterial region of the vessel.

In yet another embodiment, the present invention provides for a method of making a drug-eluting stent delivery system for controlled release of therapeutic drugs and for delivery of the therapeutic drugs in localized drug therapy in a blood vessel. The method includes providing a pattern of struts interconnected to form a structure that contacts the walls of a body lumen to maintain the patency of the vessel. A polymeric sleeve, fabricated as a prepatterned tube, is attached to at least a portion of an outside surface area of the stent structure. The polymeric sleeve is loaded with at least one therapeutic drug for the release thereof at a treatment site.

In a further embodiment, the present invention provides for a method of making a drug-eluting stent delivery system for controlled release of therapeutic drugs and for delivery of the therapeutic drugs in localized drug therapy in a blood vessel. The method includes providing a pattern of struts interconnected to form a structure that contacts the walls of the body lumen to maintain the patency of the vessel. A plurality of individual filament strands are positioned longitudinally across an outside surface of the stent structure in a spaced apart orientation and attached thereto. The plurality of individual filament strands are loaded with at least one therapeutic drug for the release thereof at a treatment site.

Other features and advantages of the invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the features of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an elevational view, partially in section, of a stent embodying features of the invention which is mounted on a delivery catheter and disposed within a damaged artery.

FIG. 2 is an elevational view, partially in section, similar to that shown in FIG. 1 wherein the stent is expanded within a damaged artery.

FIG. 3 is an elevational view, partially in section, depicting the expanded stent within the artery after withdrawal of the delivery catheter.

FIG. 4A is a plan view of a flattened stent of the invention which illustrates the pattern of the stent shown in FIGS. 1 3 in an unexpanded condition.

FIG. 4B is a plan view of a flattened drug-eluting component of the drug-eluting stent delivery system in accordance with the invention shown in the unexpanded condition.

FIG. 4C is a plan view of the drug-eluting stent delivery system in accordance with the invention shown in the unexpanded condition.

FIG. 5A is a transverse, cross-sectional view of the drug-eluting stent delivery system shown in FIG. 4A in the unexpanded condition.

FIG. 5B is a transverse, cross-sectional view of the drug-eluting component of the drug-eluting stent delivery system shown in FIG. 4B in the unexpanded condition.

FIG. 5C is a transverse, cross-sectional view of the drug-eluting stent delivery system shown in FIG. 4C in the unexpanded condition.

FIG. 6A is a plan view of the drug-eluting stent delivery system in accordance with the invention shown in the expanded condition.

FIG. 6B is a transverse, cross-sectional view of the drug-eluting stent delivery system of FIG. 6A shown in the expanded condition.

FIG. 7A is a plan view of an alternative embodiment of the invention in an expanded condition depicting a plurality of individual filament strands for holding the therapeutic drug prior to being released.

FIG. 7B is a transverse, cross-sectional view of the alternative embodiment depicting a stent with the plurality of individual filament strands attached thereto in the expanded condition.

FIG. 7C is an enlarged, transverse, cross-sectional view of a section shown in FIG. 7B in the expanded condition.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As shown in the drawings for purposes of illustration, the present invention is directed to a drug-eluting stent delivery system which includes a mechanical component and a local drug-eluting component, namely an intravascular stent and a prepatterned polymeric sleeve for controlled release of therapeutic drugs and for delivery of the therapeutic drugs in localized drug therapy in a blood vessel. The present invention is also directed to an intravascular stent having a drug-eluting component in the form of a plurality of microfilament strands attached to an outside surface of the stent structure in a spaced apart orientation. Methods of making a drug-eluting stent delivery system having a drug-eluting component disposed in the form of a prepatterned polymeric sleeve or a plurality of microfilament strands for controlled release and delivery of therapeutic drugs in localized drug therapy in a blood vessel are also disclosed herein.

Turning to the drawings, FIG. 1 depicts a metallic stent 10, incorporating features of the invention, mounted on a catheter assembly 12 which is used to deliver the stent and implant it in a body lumen, such as a coronary artery, carotid artery, peripheral artery, or other vessel or lumen within the body. The stent generally comprises a plurality of radially expandable cylindrical rings 11 disposed generally coaxially and interconnected by undulating links 15 disposed between adjacent cylindrical elements. The catheter assembly includes a catheter shaft 13 which has a proximal end 14 and a distal end 16. The catheter assembly is configured to advance through the patient's vascular system by advancing over a guide wire by any of the well known methods of an over the wire system (not shown) or a well known rapid exchange catheter system, such as the one shown in FIG. 1.

Catheter assembly 12 as depicted in FIG. 1 is of the well known rapid exchange type which includes an RX port 20 where the guide wire 18 will exit the catheter. The distal end of the guide wire 18 exits the catheter distal end 16 so that the catheter advances along the guide wire on a section of the catheter between the RX port 20 and the catheter distal end 16. As is known in the art, the guide wire lumen which receives the guide wire is sized for receiving various diameter guide wires to suit a particular application. The stent is mounted on the expandable member 22 (balloon) and is crimped tightly thereon so that the stent and expandable member present a low profile diameter for delivery through the arteries.

As shown in FIG. 1, a partial cross-section of an artery 24 is shown with a small amount of plaque that has been previously treated by an angioplasty or other repair procedure. Stent 10 of the present invention is used to repair a diseased or damaged arterial wall which may include the plaque 25 as shown in FIG. 1, or a dissection, or a flap which are commonly found in the coronary arteries, carotid arteries, peripheral arteries and other vessels.

In a typical procedure to implant stent 10, the guide wire 18 is advanced through the patient's vascular system by well known methods so that the distal end of the guide wire is advanced past the plaque or diseased area 25. Prior to implanting the stent, the cardiologist may wish to perform an angioplasty procedure or other procedure (i.e., atherectomy) in order to open the vessel and remodel the diseased area. Thereafter, the stent delivery catheter assembly 12 is advanced over the guide wire so that the stent is positioned in the target area. The expandable member or balloon 22 is inflated by well known means so that it expands radially outwardly and in turn expands the stent radially outwardly until the stent is apposed to the vessel wall. The expandable member is then deflated and the catheter withdrawn from the patient's vascular system. The guide wire typically is left in the lumen for post-dilatation procedures, if any, and subsequently is withdrawn from the patient's vascular system. As depicted in FIGS. 2 and 3, the balloon is fully inflated with the stent expanded and pressed against the vessel wall, and in FIG. 3, the implanted stent remains in the vessel after the balloon has been deflated and the catheter assembly and guide wire have been withdrawn from the patient.

The stent 10 serves to hold open the artery 24 after the catheter is withdrawn, as illustrated by FIG. 3. Due to the formation of the stent from an elongated tubular member, the undulating components of the stent are relatively flat in transverse cross-section, so that when the stent is expanded, it is pressed into the wall of the artery and as a result does not interfere with the blood flow through the artery. The stent is pressed into the wall of the artery and will eventually be covered with endothelial cell growth which further minimizes blood flow interference. The undulating portion of the stent provides good tacking characteristics to prevent stent movement within the artery. Furthermore, the closely spaced cylindrical elements at regular intervals provide uniform support for the wall of the artery, and consequently are well adapted to tack up and hold in place small flaps or dissections in the wall of the artery, as illustrated in FIGS. 2 and 3.

The stent patterns shown in FIGS. 1 3 are for illustration purposes only and can vary in size and shape to accommodate different vessels or body lumens. Further, the metallic stent 10 is of a type that can be used in accordance with the present invention.

The drug-eluting stent delivery system of the present invention is applicable to all vascular stent applications in the body including coronary and peripheral arterial system. Further, the present invention can be used in the treatment of vulnerable plaque such as thin fibrous-capped atheromatic vulnerable lesions using desired drug and release kinetics with site specificity. In addition, the drug-eluting component of the stent system can be incorporated on all stent platforms for all sizes and lengths including a bifurcated stent structure to achieve uniform drug distribution along the entire vessel including the carina. It is also contemplated that the drug-eluting component of the present invention can be used for designing drug-eluting stent devices with thinner stent struts (i.e., thickness ranging between 5-100 microns) without compromising the structural integrity of the stent, deliverability and optimal drug elution.

The present invention overcomes all of the earlier mentioned limitations through a novel design that decouples the two major functional characteristics of the drug-eluting stent delivery system, namely the purely mechanical stent structure and the local drug-eluting component. Each component is independently designed and optimized for its functional characteristics and the optimal drug-eluting stent delivery system is conceived and assembled. The stent structure is optimally designed for expansion (i.e., allowable stress/strain, scaffolding, and radial strength), and the local drug-eluting component is optimally designed for controlled release of therapeutic drugs.

As shown in one embodiment, FIG. 4A is a plan view of a flattened stent of the drug-eluting stent delivery system which illustrates the pattern of the stent shown in FIGS. 1 3 in an unexpanded condition. The stent 10 is shown in a flattened condition so that the pattern can be clearly viewed, even though the stent is never in this form. The stent is typically formed from a tubular member, however, it can be formed from a flat sheet such as shown in FIG. 4A and rolled into a cylindrical configuration.

FIG. 4B is a flattened, plan view of a prepatterned polymeric sleeve 26 of the stent 10 in accordance with the invention shown in the unexpanded condition. In this embodiment, the stent having a polymeric sleeve for controlled release of therapeutic drugs and for delivery of the therapeutic drugs in localized drug therapy in a blood vessel includes a pattern of struts interconnected to form a structure that contacts the walls of a body lumen to maintain the patency of the vessel. The pattern of struts include a plurality of flexible cylindrical rings 11 (FIG. 4A) being expandable in a radial direction, each of the rings having a first delivery diameter and a second implan