WO2002100473A1

WO2002100473A1 - Stent and delivery catheter

Info

Publication number: WO2002100473A1
Application number: PCT/AU2002/000745
Authority: WO
Inventors: Graeme Cocks; Geoffrey H. White
Original assignee: Graeme Cocks; White Geoffrey H
Priority date: 2001-06-08
Filing date: 2002-06-07
Publication date: 2002-12-19
Also published as: AUPR560201A0

Abstract

A stent (10) and an introducer catheter (30) comprising carrier means (14) for delivering a bioactive substance at the implantation site of the stent (10). The carrier means (14) comprise channels (15) and/or ridges (16) that extend longitudinally along the stent (10) and define areas spaced from the internal wall of the introducer catheter that become coated with bioactive substance passed through the introducer catheter. Alternatively, the carrier means (14) may be defined by the introducer catheter (30), which may have the channels (35) and/or ridges (37) on its internal wall (36).

Description

STENT AND DELIVERY CATHETER

Field of the Invention

The present invention relates to a stent for placement in a bodily vessel or cavity, a delivery catheter for the placement of a stent and a stent delivery system..

Background of the Invention

Occlusive diseases affecting the vasculature or other vessels are common. Such diseases include atherosclerosis which is characterised by a build up of plaque from cholesterol residues. The plaque build up subsequently thickens and hardens the arterial wall to create an arterial stenosis. The resultant narrowing of the artery has adverse effects on blood flow through the vessel.

Current medical practices employ both invasive and non-invasive procedures to address arterial stenosis. One such procedure involves the delivery of an intraluminal stent to a stenotic lesion.

Conventional stents may be inserted percutaneously through a distal and connecting vessel to that in which the stent is to be used. For example, the device may be inserted through the femoral artery in a catheter, where the device is intended to be used in the treatment of a stenotic lesion within the aorta. Upon release of the device from the catheter it may expand to a desirable size, and may extend above and below the lesion thereby bridging that lesion.

A procedure known as balloon angioplasty may also be used in the treatment of stenotic disease. This involves the delivery of a deflated balloon to the stenotic lesion. Once in place, the balloon is inflated to thereby break down the stenotic lesion.

While both the above procedures are commonly used, the rate of restenosis is unacceptably high in both procedures. An estimated 40% of patients treated by balloon angioplasty show restenosis of the vessel whereas the vessels of patients treated by the insertion of a stent are likely to restenose in 20% of cases.

The present invention aims to address the above problems of the prior art.

Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed in Australia before the priority date of each claim of this application. Throughout this specification the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps. Summary of the Invention

According to a first aspect, the present invention is a stent that is implantable within a vessel or cavity of a body, the stent including at least one carrier means to facilitate the delivery of a bioactive substance to a site of implantation of the stent. According to a second aspect, the present invention is a delivery catheter for a stent said stent being implantable within a bodily vessel or cavity, the catheter including at least one carrier means to facilitate the delivery of a bioactive substance to a site of implantation of the stent.

According to a third aspect, the present invention is a stent delivery system including a delivery catheter extending from a proximal end to a distal end, and a stent positioned within the delivery catheter at a region adjacent the distal end of the catheter, the stent and/or catheter having at least one carrier means to facilitate the delivery of a bioactive substance to a site of implantation of the stent. The stent typically comprises an elongate body made up of a series of unit cells, said elongate body extending from a proximal end to a distal end.

The carrier means of the stent may comprise one or a plurality of channels which extend in a longitudinal direction along a length of the elongate body of the stent. Alternatively, the channels may be circumferentially arranged around the elongate body of the stent.

Typically, the channels are formed on an outer surface of the elongate body, as part of the stent body. Alternatively, the channels may be formed separately of the stent body and connected to an outer surface of the stent body. The channels preferably extend in a longitudinal direction for at least a portion of the length of the stent body and preferably along the entire length of the stent body.

In another embodiment, the carrier means may be defined by one or a plurality of ridges which extend in a longitudinal direction along a length of the elongate body of the stent.

Again, the ridges are preferably formed on an outer surface of the stent as part of the stent body. Alternatively, the ridges may be formed separately of the stent body and connected to an outer surface of the stent body. Preferably, the ridges extend in a longitudinal direction along the entire length of the stent body.

The ridges of this embodiment, when formed on or connected to, the outer surface of the stent body define a series of trough-like areas relative to said ridges on the surface of said stent. As discussed further below, the formation of such trough-like areas provides a carrier means for a bioactive substance.

In a still further embodiment, the carrier means may be defined by a combination of both channels and ridges which extend in a longitudinal direction along at least part of the length of the elongate body of the stent. Preferably, the channels and ridges extend along the entire length of the elongate body of the stent.

In another embodiment, the carrier means may comprise a series of depot members located along the length of the elongate body of the stent. In this regard, each depot member may comprise an indented area which may be filled with a bioactive agent. The depot member may further include a cover member to retain the contents therein. The cover member may break down upon positioning of the stent in a target vessel thereby releasing the contents of the depot member to the surrounding environment.

During implantation of the stent into a vessel of a subject, the stent typically undergoes a change in state from a compressed state during introduction via an introducer catheter, to an expanded state upon deployment from said introducer catheter. The introducer catheter typically comprises an elongate, substantially tubular body which extends from a proximal end to a distal end. The stent of the present invention may be packaged within the introducer catheter at a region adjacent the distal end of the introducer catheter. When in use, the distal end of the introducer catheter is typically advanced through a vessel of the body to the target site of implantation of the stent.

In one embodiment, the stent may be self-expandable upon deployment. In this embodiment, the stent may be maintained in its compressed state by the compressive force of the introducer catheter during insertion into a vessel of a subject. Once at the site of implantation, the introducer catheter may be withdrawn thereby releasing the compressive force and allowing the stent to self-expand to its expanded state and into contact with the wall of the target vessel or a cavity. In another embodiment, the stent may be balloon expandable. In this case, a balloon catheter may be positioned within the introducer catheter, said balloon catheter comprising an inflatable balloon which is positioned internal the stent body. Upon reaching the target site of implantation, the introducer catheter may be relatively withdrawn and the balloon of the balloon catheter inflated such that it applies an outward force on the stent body thereby causing the stent body to move from its compressed state to its expanded state. When in its expanded state, the outer surface of the stent body typically abuts with the wall of a target vessel or cavity thereby forming a good fit within said vessel or cavity. The stent may be formed of a thin biocompatible material such as

Nitinol™ or stainless steel. Other alloys such as tantalum or Elgiloy may be used.

In the embodiment wherein the stent is made from Nitinol™, the stent may self expand upon exposure to the surrounding body temperature at the site of implantation.

The stent body may include channels or ridges along at least part of its length both when the stent body is in its compressed state during introduction of the stent to a target site via an introducer catheter and when the stent body is in an expanded state upon deployment of the stent body from the introducer catheter and into a vessel of a subject.

Alternatively, the stent may include said channels or ridges on an outer surface of the stent body when in its compressed state only. In this embodiment, it is desirable that when the stent takes on its expanded configuration, the outer circumference of the stent body is substantially cylindrical, that is, the channels and/or ridges either disappear or form only relatively small channels or ridges respectively in the surface of the expanded stent body. This embodiment has the advantage that the outer surface of the expanded stent provides a good fit within a target vessel or cavity.

The bio-active substance is preferably added to the carrier means of the stent immediately prior to insertion of the stent into the body of the patient. This has the advantage that a surgeon may select a bioactive substance of choice for a patient prior to surgery.

With the stent packaged at or adjacent a distal end of an introducer catheter, it is envisaged that a surgeon may introduce the bioactive substance from the distal end of the introducer catheter and in manner such that the bioactive substance passes over the elongate body of the stent. The bioactive substance may, however, also be introduced from the proximal end of the introducer catheter. Because the stent is compressed by the introducer catheter, the flow of bioactive substance over the stent body is limited to the carrier means of the stent. In the embodiment of the invention wherein the carrier means comprises one or a plurality of channels formed in the surface of the stent body, the bioactive substance passes along said channels, effectively coating the surface of the channels with bioactive substance.

Where the carrier means includes one or a plurality of ridges, said ridges typically abut with an internal wall of the introducer catheter when compressed by said introducer catheter thereby causing the remainder of the stent body to form trough-like areas, that is, slightly spaced from the internal wall of the introducer catheter. The bioactive substance therefore passes through said spaced areas effectively coating a percentage of the surface of the stent body with bioactive substance.

The bioactive substance may, however, be added to the carrier means of the stent during or subsequent to manufacture of the stent. For example, the bioactive substance may be stored in the carrier means of the prepackaged stent of the stent delivery means of the third aspect of the present invention. Different packages may have different bioactive substances or dosages of a particular bioactive substance. This provides the physician with a range of pre-packaged stent options without the need to separately order or draw up a bioactive substance for use in a surgical procedure.

It is envisaged that the carrier means may not retain all of the bioactive substance added to the carrier means. If some of the bioactive substance is not retained, this is not presently envisaged to constitute a problem as potentially only a relatively small quantity of bioactive substance need reach the implantation site (depending upon the substance and its concentration). It is, however, preferred that the bioactive substance coat at least a portion and preferably a substantial area of the outer surface of the stent either prior to or during its implantation.

The channels or the trough-like areas defined by the ridges of the carrier means may either be open to the surrounding environment or covered by a protection member. In this regard, it is envisaged, particularly where the carrier means comprises a channel or a plurality of channels, that the channel has a cover which retains the bioactive substance within the channel(s) during delivery of the stent but which breaks down or degrades upon deployment of the stent to a target site of implantation,

The carrier means of the stent may be formed during the manufacture of the stent of the invention. In this embodiment, where the stent body is made from a shape memory material such as Nitinol™, a cylinder of Nitinol™ is taken to a desired temperature to allow the material to achieve a "memory" of a certain configuration. If the carrier means is a channel which longitudinally extends along the stent body as described above, when the cylinder of Nitinol™ is taken to this temperature, a template is used to push the area of the cylinder which is to become the channel inwardly relative to the remainder of the cylindrical tubular body. Where the stent only includes the channel(s) when in its compressed state, it is desirable that the temperature at which the Nitinol™ takes on its "memorised" shape is room temperature. When the Nitinol™ is taken to body temperature, the stent may resume the configuration of a cylindrical tube thereby providing a good fit in vessel or cavity.

In an embodiment wherein the material of the stent is not a shape memory material, it is envisaged that a pre-formed tubular body is laser cut to a desired shape including either or both channels or ridges. The delivery catheter of the second aspect may comprise a substantially tubular, elongate body which extends from a first end to a second end and which is adapted to receive a stent.

The carrier means of the delivery catheter may comprise one or a plurality of channels on an inner wall of the delivery catheter. Alternatively, the carrier means may be defined by one or a plurality of ridges on the inner wall of the delivery catheter. In one embodiment, the delivery catheter comprises both channels and ridges on said inner wall.

Typically, the channels and/or ridges extend in a longitudinal direction along the elongate body of the delivery catheter and extend a distance which is substantially equal to the length of a stent to be placed or pre-packaged within the elongate body of the delivery catheter.

In use, when a stent is packaged within the delivery catheter, the channels and/or ridges typically define areas wherein the stent is substantially spaced from the inner wall of the delivery catheter. The bioactive substance may then be introduced into the delivery catheter such that said spaced areas of the stent are coated with bioactive substance.

The delivery catheter may be formed from any suitable plastics material, particularly, a biocompatible plastic.

The bioactive substance may include a pharmaceutical substance. The bioactive substance may also include a radioactive substance.

By use of the word "substance", it is to be understood that more than one substance may be carried in the carrier means of the devices of the present invention. The bioactive substance can be a substance which stimulates fibrin or cellular ingrowth into the stent from the surrounding tissue. Such ingrowth further secures the stent within the vessel wall. An example of a material which increases tissue ingrowth into the tubular graft bodies is polyurethane. Alternatively, a polyurethane/polycarbonate composite may be used to enhance cellular ingrowth.

Other bioactive substances which may be carried by the stent or delivery catheter of the present invention include, but are not limited to, anti- sense antibodies, immune suppressants such as serolimus and chemotherapeutic agents such as taxol and rabamycin Brief Description of the drawings

By way of example only, a preferred embodiment of the invention is now described with reference to the accompanying drawings, in which:

Figure 1 is a perspective view of a stent according to the present invention;

Figure 2 is a further perspective view of a stent according to the present invention; Figure 3 is a perspective view of one embodiment of the stent of the present invention; Figure 4 is a perspective view of an embodiment of a delivery catheter according to the present invention; and

Figure 5 is a perspective view of another embodiment of a delivery catheter according to the present invention. Preferred Mode of Carrying Out the Invention

The stent of the present invention is generally depicted as 10 in accompanying Figures 1 to 3. The stent 10 comprises an elongate body 11 which extends from a proximal end 12 to a distal end 13. The stent 10 further includes a carrier means 14 to facilitate the delivery of one or more bioactive substances to a site of implantation of the stent 10.

As depicted in Figures 1 and 2, the carrier means 14 comprises longitudinal channels 15 formed in the outer surface 17 of the stent 10 and longitudinal ridges 16 formed in said outer surface 17 of the stent 10. While not depicted, the carrier means of the stent of the present invention may comprise either channels 15 or ridges 16 rather than a combination of the two. The channels 15 and ridges 16 are shown as extending longitudinally along the entire length of the elongate body 11, from proximal end 12 to distal end 13.

As can be seen in Figures 2 and 3, the elongate body 11 is made up of a series of unit cells 18. The channels 15 and ridges 16 of the embodiments depicted in Figures 1 and 2 are formed from the unit cells 18 of the elongate body 11, that is, the channels 15 and ridges 16 are integral the elongate body

11.

Alternatively, and as depicted in Figure 3, the channels 15 and ridges 16 are not formed from the unit cells 18 and, instead are solid in structure. The channels 15 and ridges 16 of this embodiment while typically made from the material of the elongate body 11 are formed as a solid structure during the manufacture of the stent 10.

The ridges 16, when formed on or connected to, the outer surface 17 of the stent 10 define a series of trough-like areas 19 relative to said ridges 16. As discussed further below, the formation of such trough-like areas 19 provides a carrier means for a bioactive substance.

During implantation of stent 10 into a vessel of a subject, the stent 10 typically undergoes a change in state from a compressed state (not shown) during introduction via an introducer catheter (not shown), to an expanded state (Figures 1 to 3) upon deployment from said introducer catheter. The introducer catheter is typically an elongate, substantially tubular structure which extends from a proximal end to a distal end. The stent of the present invention may be packaged within the introducer catheter at a region adjacent the distal end of the delivery catheter. When in use, the distal end of the introducer catheter is typically advanced through a vessel of the body to the target site of implantation of the stent.

In one embodiment, the stent 10 is self-expandable upon deployment. In this embodiment, the stent is maintained in its compressed state by the compressive force of the introducer catheter during insertion into a vessel of a subject. Once at the site of implantation, the introducer catheter may be withdrawn thereby releasing the compressive force and allowing the stent 10 to self-expand to its expanded state and into contact with the wall of a target vessel or a cavity.

In another embodiment, the stent is balloon expandable. In this case, a balloon catheter (not shown) is positioned within the introducer catheter, said balloon catheter comprising an inflatable balloon which is positioned internal the elongate body 11. Upon reaching the target site of implantation, the introducer catheter is relatively withdrawn and the balloon of the balloon catheter inflated such that it applies an outward force on the elongate body 11 of the stent 10 thereby causing the stent 10 to move from its compressed state to its expanded state. When in its expanded state, the outer surface 17 of the stent body abuts with the wall of a target vessel or cavity thereby forming a good fit within said vessel or cavity.

The stent 10 depicted in Figures 1 to 3 is made from a shape memory material such as Nitinol™. In these embodiments, the material of the stent 10 has a "memory" such that said stent 10 self expands upon exposure to its surrounding temperature at the site of implantation.

In addition to self expansion, the stent 10 of this embodiment may also include a "memory" of other configurations. In this regard, the carrier means 14 of the stent 10 can be formed during the manufacture of the stent 10. For example, a cylinder of Nitinol™ is taken to a desired temperature to allow the material to achieve a "memory" of a certain configuration. If the carrier means 14 is a channel 15 which longitudinally extends along the elongate body 11 as described above, when the cylinder of Nitinol™ is held at the "memory" temperature, a template is used to push the area of the cylinder which is to become the channel inwardly relative to the remainder of the cylindrical tubular body. When the stent 10 is exposed to this "memory" temperature, channels will form in the elongate body 11.

It may be desirable that the stent 10 only includes said channels 15 when in its compressed state, in which case, the temperature upon which the Nitinol™¹ takes on its "memorised" shape is room temperature. The bioactive substance may therefore by introduced into the channels by a surgeon prior to surgery. When the Nitinol™- is taken to body temperature, the stent may resume the configuration of a cylindrical tube (said channels substantially disappearing) thereby providing a good fit in vessel or cavity. As mentioned above, in use, the bio-active substance is added to the carrier means of the stent immediately prior to insertion of the stent 10 into the body of the patient. This has the advantage that a surgeon may select a bioactive substance of choice for a patient prior to surgery.

With the stent 10 packaged at or adjacent a distal end of an introducer catheter, the surgeon may syringe the bioactive substance into the distal end of the introducer catheter and in manner such that the bioactive substance passes over the elongate body 11 of the stent 10. The bioactive substance may, however, also be introduced from the proximal end of the introducer catheter. Because the outer surface 17 of the stent 10 abuts with an inner surface of the introducer catheter, when the bioactive substance is syringed into the introducer catheter, the flow of bioactive substance over the elongate body 11 is limited to the carrier means 14 of the stent 10, that is, the channels 15 or the trough-like areas 19 which are defined by ridges 16. Where the carrier means 14 comprises channels 15, the bioactive substance passes along said channels 15, effectively coating the surface of the channels 15 with bioactive substance.

Where the carrier means comprises ridges 16, the ridges 16 abut with an internal wall of the introducer catheter thereby causing the remainder of the stent body to form trough-like areas 19, that is, slightly spaced from the internal wall of the introducer catheter. The bioactive substance therefore passes over said trough-like areas 19, effectively coating a percentage of the outer surface 17 of the elongate body 11 with bioactive substance.

The delivery catheter of the second aspect of the present invention is generally depicted as 30 in Figures 4 and 5. The delivery catheter 30 comprises a substantially tubular, elongate body 31 which extends from a first end 32 to a second end 33 and which is adapted to receive a stent (shown in phantom). The delivery catheter further includes a carrier means 34 to facilitate the delivery of a bioactive substance to a site of implantation of said stent.

As shown in Figure 4, the carrier means 34 comprises longitudinal channels 35 formed in an inner wall 36 of the delivery catheter 30. In the embodiment depicted in Figure 5, the carrier means 34 is defined by longitudinal ridges 37 formed along the inner wall 36 of the delivery catheter 30. While not depicted, the carrier means 34 may be defined by both channels 35 and ridges 37 formed in the inner wall 36 of the delivery catheter 30.

The channels 35 and/or ridges 37 extend a distance which is substantially equal to the length of the stent to be placed or pre-packaged in the delivery catheter.

In use, when a stent is packaged within the delivery catheter 30, the channels and/or ridges define areas 38 wherein the stent is substantially spaced from the inner wall 36 of the delivery catheter 30. The bioactive substance is introduced into the delivery catheter (shown by arrows A) such that it substantially coats the stent at said spaced areas 38.

It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims

CLAIMS:

I. A stent that is implantable within a vessel or cavity of a body, the stent including at least one carrier means to facilitate the delivery of a bioactive substance to a site of implantation of the stent.

2. The stent of claim 1 wherein the stent comprises an elongate body which extends from a proximal end to a distal end and wherein the carrier means of the stent comprises one or a plurality of channels which extend in a longitudinal direction along a length of the elongate body of the stent.

3. The stent of claim 2 wherein the channels are formed on an outer surface of the elongate body.

4. The stent of claim 2 or claim 3 wherein the channels extend along the entire length of the elongate body of the stent.

5. The stent of claim 1 wherein the carrier means is defined by one or a plurality of ridges which extend in a longitudinal direction along a length of the elongate body of the stent.

6. The stent of claim 5 wherein the ridges are formed on an outer surface of the elongate body.

7. The stent of claim 5 or claim 6 wherein the one or a plurality of ridges extend along the entire length of the elongate body of the stent.

8. The stent of claim 6 or claim 7 wherein the one or a plurality of ridges define one or more trough-like areas relative to said ridges on the outer surface of said elongate body of the stent.

9. The stent of claim 1 wherein the carrier means comprises both channels and ridges which extend in a longitudinal direction along a length of the elongate body of the stent.

10. The stent of any one of the preceding claims, the elongate body of said stent being capable of moving from a first substantially compressed state to a second substantially expanded state.

II. The stent of claim 10 wherein the elongate body is made from a biocompatible material selected from the group consisting of Nitinol™-, stainless steel, tantalum or Elgiloy.

12. The stent of claim 11 wherein the elongate body is made from Nitinol™ and wherein the elongate body moves from the first substantially compressed state to the second substantially expanded state upon exposure to the surrounding temperature at the site of implantation.

13. The stent of claim 10 wherein the elongate body of the stent comprises the carrier means when the elongate body is in its substantially compressed state and wherein the carrier means is not present when the elongate body is in its substantially expanded state.

14. The stent of claim 2 wherein the channels are covered by a protection member which degrades upon deployment of the stent to a target site of implantation to expose the bioactive substance to said target site.

15. A delivery catheter for a stent, said stent being implantable within a bodily vessel or cavity, the catheter including at least one carrier means to facilitate the delivery of a bioactive substance to a site of implantation of the stent.

16. The delivery catheter of claim 15, said delivery catheter comprising a substantially tubular, elongate body which extends from a first end to a second end and which is adapted to receive said stent within a lumen of the elongate body.

17. The delivery catheter of claim 16 wherein the carrier means of the delivery catheter comprises one or a plurality of channels on an inner wall of the delivery catheter.

18. The delivery catheter of claim 17 wherein the channels extend in a longitudinal direction along the elongate body of the delivery catheter and wherein said channels extend a distance which is substantially equal to the length of a stent to be received within the lumen of the elongate body of the delivery catheter.

19. The delivery catheter of claim 16 wherein the carrier means is defined by one or a plurality of ridges on an inner wall of the delivery catheter.

20. The delivery catheter of claim 19 wherein the ridges extend in a longitudinal direction along the elongate body of the delivery catheter and extend a distance which is substantially equal to the length of a stent to be received within the lumen of the elongate body of the delivery catheter.

21. The delivery catheter of claim 16 wherein the carrier means comprises channels and is defined by ridges on an inner wall defining the lumen of the delivery catheter.

22. A stent delivery system including a delivery catheter which extends from a proximal end to a distal end, and a stent positioned within the delivery catheter at a region adjacent the distal end of the catheter, the stent and/or catheter having at least one carrier means to facilitate the delivery of a bioactive substance to a site of implantation of the stent.

23. The stent of any one of claims 1 to 14, the delivery catheter of any one of claims 15 to 21 and the stent delivery system of claim 22 when used to deliver a bioactive substance selected from the group consisting of fibrin or cellular stimulators including polyurethane or a polyurethane/polycarbonate, anti-sense antibodies, immune suppressants including serolimus, and chemotherapeutic agents including taxol and rabamycin.