US20110070358A1 - Method of forming hollow tubular drug eluting medical devices - Google Patents

Abstract

A method of a forming a hollow, drug-eluting medical device includes utilizing a hollow wire having an outer member and a lumen of the outer member, and filling the lumen with a fluid to form a supported hollow wire. The supported hollow wire is shaped into a stent pattern. Openings are formed through the outer member. The supported hollow wire is processed to remove the fluid from the lumen of the outer member without adversely affecting the outer member, leaving the hollow wire shaped into a stent pattern. The lumen is filled with a biologically or pharmacologically active substance.

Description

CROSS-REFERENCE TO RELATED APPLICATION
• This application claims the benefit of U.S. Provisional Patent Application No. 61/244,049 filed Sep. 20, 2009, the contents of which is hereby incorporated by reference.
FIELD OF THE INVENTION
• The present invention relates to implantable medical devices that release a therapeutic substance and methods of forming such medical devices.
BACKGROUND OF THE INVENTION
• Drug-eluting implantable medical devices have become popular in recent times for their ability to perform their primary function (such as structural support) and their ability to medically treat the area in which they are implanted.
• For example, drug-eluting stents have been used to prevent restenosis in coronary arteries. Drug-eluting stents may administer biologically or pharmacologically active substances such as anti-inflammatory compounds that block local invasion/activation of monocytes, thus preventing the secretion of growth factors that may trigger VSMC proliferation and migration. Other potentially anti-restenotic compounds include anti-proliferative agents, such as chemotherapeutics, which include rapamycin and paclitaxel. Other classes of drugs such as anti-thrombotics, anti-oxidants, platelet aggregation inhibitors and cytostatic agents have also been suggested for anti-restenotic use.
• Drug-eluting medical devices may be coated with a polymeric material which, in turn, is impregnated with a biologically or pharmacologically active substance or a combination of biologically or pharmacologically active substances. Once the medical device is implanted at a target location, the biologically or pharmacologically active substance is released from the polymer for treatment of the local tissues. The biologically or pharmacologically active substance is released by a process of diffusion through the polymer layer for biostable polymers, and/or as the polymer material degrades for biodegradable polymers.
• Controlling the rate of elution of a biologically or pharmacologically active substance from the drug impregnated polymeric material is generally based on the properties of the polymer material. However, at the conclusion of the elution process, the remaining polymer material in some instances has been linked to an adverse reaction with the vessel, possibly causing a small but dangerous clot to form. Further, drug impregnated polymer coatings on exposed surfaces of medical devices may flake off or otherwise be damaged during delivery, thereby preventing the biologically or pharmacologically active substance from reaching the target site. Still further, drug impregnated polymer coatings are limited in the quantity of the biologically or pharmacologically active substance to be delivered by the amount of a biologically or pharmacologically active substance that the polymer coating can carry and the size of the medical devices. Controlling the rate of elution using polymer coatings is also difficult.
• Accordingly, drug-eluting medical devices that enable increased quantities of a biologically or pharmacologically active substance to be delivered by the medical device, and allow for improved control of the elution rate of the biologically or pharmacologically active substance, and improved methods of forming such medical devices are needed.
SUMMARY OF INVENTION
• In an embodiment of a method of forming a stent, the lumen of a hollow wire is filled with a fluid to form a supported hollow wire. The supported hollow wire is shaped into a stent pattern. Openings are formed through the wire to access the lumen. The supported hollow wire is processed to remove the fluid from the lumen of the outer member without adversely affecting the outer member, leaving the hollow wire shaped into a stent pattern. The lumen is filled with a biologically or pharmacologically active substance. The fluid may be pressurized prior to shaping the support hollow wire into the stent pattern.
• In another embodiment of a method of forming a stent, the lumen of a hollow wire is filled with a liquefied wax. The liquefied wax is allowed to solidify or harden within the lumen to form a supported hollow wire. The supported hollow wire is shaped into a stent pattern. Openings are formed through the wire to access the lumen. The supported hollow wire is processed to remove the wax from the lumen without adversely affecting the wire, leaving the hollow wire shaped into a stent pattern. The lumen may then be filled with a biologically or pharmacologically active substance.
BRIEF DESCRIPTION OF DRAWINGS
• The foregoing and other features and advantages of the invention will be apparent from the following description of the invention as illustrated in the accompanying drawings. The accompanying drawings, which are incorporated herein and form a part of the specification, further serve to explain the principles of the invention and to enable a person skilled in the pertinent art to make and use the invention. The drawings are not to scale.
• FIG. 1 is a schematic illustration of an exemplary stent in accordance with an embodiment hereof.
• FIG. 2 is a cross-sectional view taken along line2-2 ofFIG. 1.
• FIG. 3 is a longitudinal cross-section of an end of the wire of the stent ofFIG. 1.
• FIGS. 4-7 are cross-sectional views of a hollow wire in accordance with an embodiment hereof.
• FIGS. 8-11 are schematic illustrations of a method of forming wave forms in a wire.
• FIG. 12-14 are cross-sectional views of hollow wire in a method of forming a hollow wire into a stent in accordance with an embodiment hereof.
• FIGS. 15-16 are schematic illustrations of a method of forming a wave form in a hollow wire in accordance with an embodiment hereof.
• FIG. 17 is a schematic illustration of an apparatus for forming a wave form in a hollow wire in accordance with an embodiment hereof.
• FIG. 18 is a cross-section view of a hollow wire taken along line18-18 ofFIG. 17.
• FIGS. 19-20 are schematic illustrations of a hollow wire including a spring element in the lumen of the hollow wire.
• FIGS. 21-22 are cross-sectional views of a portion of a hollow wire including a supporting element surrounding the hollow wire.
• FIGS. 23-25 are cross-sectional views of a hollow wire with an outer member and an inner member, wherein the outer member is deformed to form a lumen between the outer and inner members.
• FIGS. 26-30 are schematic illustrations of a method for forming a stent with hollow struts in accordance with an embodiment hereof.
• FIGS. 31-36 are schematic illustrations of method of bonding adjacent crowns of a stent.
• FIGS. 37-38 are schematic illustrations of an apparatus and methods of forming a wave form in a wire.
• FIGS. 39-40 are schematic illustrations of an apparatus and method of forming a bend in a wire.
DETAILED DESCRIPTION OF THE INVENTION
• Specific embodiments of the present invention are now described with reference to the figures, where like reference numbers indicate identical or functionally similar elements.
• An embodiment of astent100 disclosed herein is shown inFIGS. 1-3. In particular,stent100 is formed from ahollow wire102. In the embodiment shown inFIG. 1,stent100 is formed into a series of generally sinusoidal waves including generally straight segments orstruts106 joined by bent segments orcrowns108 and form a generallytubular stent100. The generally sinusoidal pattern is formed into a tube, as shown inFIG. 1. In the embodiment shown inFIG. 1, selectedcrowns108 of longitudinally adjacent sinusoids may be joined by, for example,fusion points110. The invention hereof is not limited to the pattern shown inFIG. 1.Stent100 can be formed into any pattern suitable for use as a stent. For example, and not by way of limitation,stent100 can be formed into patterns disclosed in U.S. Pat. No. 4,800,882 to Gianturco, U.S. Pat. No. 4,886,062 to Wiktor, U.S. Pat. No. 5,133,732 to Wiktor, U.S. Pat. No. 5,782,903 to Wiktor, U.S. Pat. No. 6,136,023 to Boyle, and U.S. Pat. No. 5,019,090 to Pinchuk, each of which is incorporated by reference herein in its entirety. Further, instead of a single length of wire formed into a stent pattern, a plurality of wires may be formed into a two-dimensional waveform and wrapped into individual cylindrical elements. The cylindrical elements may then be aligned along a common longitudinal axis and joined to form the stent.
• As shown inFIG. 2,hollow wire102 ofstent100 allows for a biologically or pharmacologicallyactive substance112 to be deposited within thelumen103 ofhollow wire102. Althoughhollow wire102 is shown as generally having a circular cross-section,hollow wire102 may be generally elliptical or rectangular in cross-section.Hollow wire102 further includes cuts oropenings104 dispersed along its length to permit biologically or pharmacologicallyactive substance112 to be released fromlumen103.Openings104 may be disposed only on generallystraight segments106 ofstent100, only oncrowns108 ofstent100, or both generallystraight segments106 and crowns108.Openings104 may be sized and shaped as desired to control the elution rate of biologically or pharmacologicallyactive substance112 fromstent100. Largersized openings104 generally permit a faster elution rate and smallersized openings104 generally provide a slower elution rate. Further, the size and/or quantity ofopenings104 may be varied alongstent100 in order to vary the quantity and/or rate of biologically or pharmacologicallyactive substance112 being eluted fromstent100 at different portions ofstent100.Openings104 may be, for example and not by way of limitation, 5-30 μm in diameter.Openings104 may be provided only on an outwardly facing orabluminal surface116 ofstent100, as shown inFIG. 2, only on the inwardly facing orluminal surface118 ofstent100, both surfaces, or may be provided anywhere along the circumference ofwire102.Openings104 may have a constant diameter through the depth or have a tapered or conical shape.
• Ends114 ofwire102 may be closed, as shown inFIG. 3.Ends114 may be closed by crimping excess material ofwire102 to closelumen103. Closing ends114 preventsdrug114 from prematurely releasing from ends114. However, closing ends114 is not required asdrug112 may be dried, provided within a polymer matrix, enclosed within a liner (not shown), or otherwise protected from premature release from ends114. Further, ends114 may be welded, crimped or otherwise connected to other portions ofwire102 such that the ends114 are not free ends.Ends114 may alternatively be provided as free ends.
Embodiments for Bending a Hollow Wire
• Forming a hollow wire stent by bending a hollow wire into a stent form may cause kinking, cracking, or other undesirable properties in the finished stent. Accordingly, co-pending U.S. application Ser. No. 12/500,359, filed Jul. 9, 2009, incorporated by reference herein in its entirety, describes methods for forming a hollow wire stent by forming a core wire, bending the core wire into the selected stent shape, and then removing the sacrificial or inner member of the core wire. However, it may be beneficial to form the stent using a hollow wire if concerns regarding kinking or cracking can be overcome.
• A method for forming a stent pattern from a wire utilizes fingers to bend the wire into the desired pattern. An example of such a system is described in co-pending U.S. patent application Ser. No. 12/428,581, filed Apr. 23, 2009, which is incorporated by reference herein in its entirety. Other systems may also be used to bend the wire into the desired pattern. The pattern, such as a sinusoidal pattern, is then wrapped around a mandrel and selected crowns may be bonded together to form a stent. The crowns may be bonded together by welding, or other methods of bonding such as mechanical means, spring clips, interconnecting crowns, adhesives, brazing, solder, rivets, sutures, or other suitable means known to those skilled in the art.FIGS. 31-36 show examples of such alternative bonding methods.FIGS. 31 and 32 show interconnecting crowns. The crowns can be electropolished, swaged, or otherwise processed after interconnection in order to reduce the profile of the interconnection.FIG. 33 also shows interconnecting crowns in ball and socket type of interconnection. The crowns can be swaged to lock the “ball” into the “socket”.FIG. 34 shows the crowns coupled to each other with a suture. The suture can be made of any material suitable to couple the crowns together.FIGS. 35-36 show a rivet connection, wherein the holes are drilled through the crowns as shown inFIG. 35 and a rivet is inserted through the holes to connect the crowns, as shown inFIG. 36. It is understood that these are merely examples of connections between the crowns, and that those skilled in the art would recognize other alternative connections.
• FIGS. 4-7 show cross-sectional views ofhollow wire102 in a method of forming a stent from a hollow wire. Wires forming stents are generally as thin as possible while still providing radial strength in the stent form. In a hollow wire coronary stent, an example of an inner diameter for the wire is about 0.0015 inch and an outer diameter is of about 0.0035 inch. The dimension range for the wire in a coronary hollow wire stent is an outside diameter range of 0.002 inches to 0.005 inches with an inside diameter of 50% or less of the outside diameter. The dimension range for the wire in a peripheral or other anatomy location hollow wire stent/implant is an outside diameter range of 0.002 inches to 0.012 inches with an inside diameter of 75% or less of the outside diameter. In the embodiment shown inFIGS. 4-7, ahollow wire102 is shaped into a stent pattern. In this embodiment, a relatively large outer diameter D₁compared to the inner diameter D₂is utilized, resulted in a relatively thick wall ofhollow wire102. Due to the relatively large outer diameter D₁relative to the inner diameter D₂, (i.e., thick wall) kinking, cracking, or closing of thelumen103 is reduced or prevented. The stent pattern can be the pattern shown inFIG. 1 or any other suitable pattern formed from a wire. Shapingwire102 into the stent pattern shown inFIG. 1 generally includes the steps of formingwire102 into a two dimensional sinusoid pattern followed by wrapping the pattern around a mandrel, as known to those skilled in the art. The end result is a helical stent pattern formed onto a mandrel.
• Afterwire102 has been shaped into the stent pattern,wire102 is electropolished or otherwise processed to remove material fromwire102. Additional removal processes include but are not limited to plasma etching, sand blasting, bead blasting, acid etching, tumbling, grinding and laser etching. The acid etching processes may include any wet chemical etching mixture that attacks the metals directly. Examples are heated mixtures of, HF:HNO₃(hydrofluoric & nitric acids) or HCl:H₂O₂(hydrochloric & hydrogen peroxide), both mixtures can etch the metals directly. Many other wet metal etch mixtures exist. Such processing reduces the outer diameter ofwire102. Accordingly, as shown inFIG. 6, outer diameter D₃ofwire102 may be about 0.0035 inch while inner diameter D₂remains about 0.0015 inch, with a wall thickness T₂of about .001 inches. The material removal process will alter the dimension, but the proportion of outside diameter to inside diameter dimension would stay within the limits of inside diameter being 50% or less of the outside diameter for coronary applications and the inside diameter being 75% or less of the outside diameter for applications outside of the coronary vasculature. After removing the appropriate amount of material, selectedcrowns108 of the helical pattern may be bonded together or alternatively the material can be removed after the bonding process.
• Openings104 may then be provided throughwire102.Openings104 may be laser cut, drilled, etched, or otherwise provided inwire102, as shown inFIG. 6. A biologically or pharmacologicallyactive substance112 may be injected intolumen103 ofouter member102 as shownFIG. 7. This produces ahollow wire102 with biologically or pharmacologicallyactive substance112 disposed inlumen103 thereof, andopenings104 through which biologically or pharmacologicallyactive substance112 may be eluted, as shown inFIG. 7.
• In another embodiment of a method for forming a hollow wire stent, a hollow metal wire is provided. The wire is heated to a temperature to soften the material. The wire is then shaped into a stent pattern, as described above. By heating the hollow wire prior to shaping the hollow wire into the stent pattern, kinking, cracking, and other deformations may be reduced or eliminated. In a particular, non-limiting example, a hollow wire made from MP35N is heated to 1140 Kelvin to 1450 Kelvin and formed into a stent shape at this elevated temperature. Openings are then formed through the hollow wire to the lumen and the stent is filled with a drug, as described above. Other materials such as but not limited to 316 stainless steel, tantalum, niobium, molybdenum-rhenium alloys, nickel-titanium alloys, L605, magnesium and magnesium alloys may be used to form the hollow wire, and may be heated to 65% to 85% of the absolute melting temperature to soften the material prior to forming
• Another method for forming a stent from a hollow wire is shown inFIGS. 8-11. As discussed above, a method process for forming a wire into a stent form utilizes fingers to bend a straight wire. Schematically represented inFIGS. 8-11, and described in more detail in U.S. application Ser. No. 12/428,581, filed Apr. 23, 2009, which is incorporated herein in its entirety, is a portion of anapparatus200 for forming a wave form for a stent from ahollow wire102. Briefly describingapparatus200, thehollow wire102 is provided to theapparatus200 by asupply210, which may include a spool upon which thehollow wire102 is wound. Alternatively the hollow wire can be provided to the apparatus in discrete sections. Thehollow wire102 may be fed in thefirst direction1D along an axis into a wire forming area. Asuitable clamp220 may be located just outside the wire forming area, as illustrated, or may be located within the wire forming area. Theclamp220 is configured to clamp thehollow wire102 so that tension may be applied to thehollow wire102 as thehollow wire102 is formed into a predetermined shape. Theapparatus200 also includes a plurality of first forming members orfingers202 located on one side of thehollow wire102 and a plurality of second forming members orfingers204 located on the opposite side of thehollow wire102. The first and second formingmembers202,204 have substantially elongated shapes and includewire engaging surfaces206,208, respectively.
• As shown inFIG. 9, first formingmembers202 move in asecond direction2D that is substantially orthogonal to thefirst direction1D to engagehollow wire102. After thewire engaging surfaces206 have engaged thehollow wire102, the first formingmembers202 continue to move in thesecond direction2D to deform thehollow wire102, as shown inFIG. 9. Each of the first formingmembers202 may be moved in thesecond direction2D by a respectivefirst actuator212, all of which may be configured to move in thefirst direction1D along a suitable structure, such as arail214. Similarly, second formingmembers204 move in athird direction3D such thatwire engaging surfaces208 engagehollow wire102. After thewire engaging surfaces206 have engaged thehollow wire102, the second formingmembers204 continue to move in thethird direction3D to deform thehollow wire102, as shown inFIG. 9.
• As illustrated inFIG. 10, after a wave form has been formed, the first formingmembers202 may be moved in thethird direction3D to disengage from the wire hollow102, and the second formingmembers204 may be moved in thesecond direction2D to disengage from thehollow wire102. Theclamp220 may then be opened andwire102 may be advances bysupply210 so that a new section ofhollow wire102 may be advanced into the wire forming area, as shown inFIG. 11. At about the same time, the first and second formingmembers202,204 may be moved along theirrespective rails212,214 in thefourth direction4D so that another cycle may begin. It would be understood by those skilled in the art that this description is merely an example of method to bend a wire into a wave form for a stent.
• In order to reduce or eliminate the kinking, cracking, closing oflumen103, or other deformations,hollow wire102 may be swaged or otherwise processed to alter its cross-sectional shape to be generally elliptical. Thus, ahollow wire102 of generally circular cross-section, as shown inFIG. 12, is swaged or otherwise processed to form awire102 with a generally elliptical cross-section, as shown inFIG. 13. Swaging or other processes to alter the cross-sectional shape could be done only at select locations such as crowns. The generally elliptically shaped wire includes along axis250 in cross-section, as shown inFIG. 13. The formingmembers204,206 (only one is shown inFIG. 14) are aligned with thelong axis250 of thehollow wire102, as shown inFIG. 14. The process as described with respect toFIGS. 8-11 is then performed to bendhollow wire102 into the wave form for a stent and wrapped around a mandrel to form the stent pattern. Selected crowns of the stent pattern may then be bonded together,openings104 may be cut through the wall ofhollow wire102 to accesslumen103, and the lumen filled with a biologically or pharmacologically active substance, as described above. Alternatively, the swaging or other processes to alter the cross-sectional shape could be done after forming to return the cross section to a circular or more circular shape if the wires become elliptical during forming. The forming could be done only at select locations such as crowns.
• Using the method described generally atFIGS. 8-11,hollow wire102 is bent into shape at a speed of 20-100 mm/s for the forming members with a preferable speed of approximately 60 mm/s. In another method of reducing kinking, cracking, closing of the lumen, and other deformations, the rate of bending is reduced to the speed to 0.5-19 mm/s for the forming members. The radii of the forming members contacting the hollow wire should be 1-2.5 times the radius of the wire. An alternative forming movement to reduce tension and thereby reduce elongation of the hollow wire during bending is described inFIGS. 37 and 38.FIG. 37 shows steps A-D for forming a waveform in a wire in a similar fashion as described, for example, in U.S. application Ser. No. 12/428,581, filed Apr. 23, 2009, which is incorporated herein in its entirety.FIG. 38 shows steps A-E of an embodiment of a method for forming a waveform in a hollow wire, wherein a less severe angle θ is created in the wire, thereby reducing tension and elongation of the hollow wire.
• In another method, thehollow wire102 is bent incrementally in order to reduce the risk of kinking, cracking, or other deformations. In particular, ahollow wire102 is partially bent.Hollow wire102 is then annealed to allow stress relief using a temperature of 50% of the absolute melt temperature of the material or greater. Thehollow wire102 is then further bent. The bending and annealing process may be repeated as necessary to bendhollow wire102 while limiting kinking, cracking, or other deformation of thelumen103. An embodiment of anapparatus3900 for incrementally bending thehollow wire102 is shown inFIGS. 39-40, although other apparatuses or methods for incrementally bendingwire102 may be used.Bending apparatus3900 includes aroller element3902 and asupport element3904. Rotatingbending apparatus3900 as indicated by the arrow bendswire102.
• In another embodiment,hollow wire102 is bent into the desired waveform using aclamshell type apparatus300. As shown inFIGS. 15 and 16,hollow wire102 is provided to theapparatus300 by asupply310, which may include a spool upon which thehollow wire102 is wound. Alternatively the hollow wire can be provided to the apparatus in discrete sections. Thehollow wire102 may be fed in thefirst direction1D along an axis. A suitable clamp (not shown) may be provided to clamp thewire102 so that tension may be applied to thewire102 ashollow wire102 is formed into a predetermined shape, as described above with respect toapparatus300. Theapparatus300 also includes afirst clamshell half302 located on one side ofhollow wire102 and asecond clamshell half304 located on the opposite side ofhollow wire102. An end offirst clamshell half302 facinghollow wire102 is shaped as awaveform306 with a plurality ofpeaks330 andvalleys332. An end ofsecond clamshell half304 facinghollow wire102 is shaped as a waveform including a plurality of peaks334 andvalleys336.Peaks330 offirst clamshell half302 align withvalleys336 ofsecond clamshell half304 and peaks334 ofsecond clamshell half304 align withvalleys332 offirst clamshell half302. The ends ofclamshell halves302,304 opposite thewaveforms306,308 are coupled toactuators312,314, respectively.Actuators312,314 may be coupled torails316,318, respectively, or other suitable support structures.
• Actuators312 movefirst clamshell half302 indirection2D andactuators314 movesecond clamshell half304 indirection3D, as shown inFIG. 16.Hollow wire102 is deformed betweenpeaks330,334 andvalleys336,332, respectively such thathollow wire102 becomes a waveform.Actuators312,314 then move first and second clamshell halves302,304 back to the position ofFIG. 15,supply310 feedshollow wire102 indirection1D, and the process is repeated for another section ofwire102. By usingclamshell halves302,304,hollow wire102 is supported while being bent into the waveform to reduce kinking, cracking, and other deformations. Other forming options include using pair(s) of matching gears wherein the hollow wire sample is formed by the interlocking of the gear teeth.
Embodiments Bending a Supported Wire
• As disclosed in co-pending U.S. application Ser. No. 12/500,359, filed Jul. 9, 2009, which is incorporated herein in its entirety, a method for reducing or preventing kinking, cracking, and other deformations in a hollow wire when shaping the hollow wire into a stent pattern is to internally support the wire during the shaping step, and then removing the supporting element after the wire has been shaped into the stent pattern. In some applications where the lumen is small, it may be difficult to remove the supporting element.
• FIGS. 17 and 18 show an embodiment wherein thelumen103 of ahollow wire102 is coupled to apump260.Tubing262 may be used to couple thepump260 to thehollow wire102. An end oflumen103 may be plugged or otherwise closed to assist in building pressure in the lumen.Pump260 pressurizeslumen103 with a fluid, such as air, water, alcohol, oils (hydrocarbon or silicone based), waxes, meltable polymers, slurries of water and/or organic solvents and particles where the particles can be metal, silica or polymeric or other suitable fluids. As shown by thearrows264 inFIG. 18, this fluid pressure supports the walls ofhollow wire102 whilehollow wire102 is shaped into a stent pattern using theapparatus200 as described with respect toFIGS. 8-11, the method and apparatus described in co-pending U.S. application Ser. No. 12/428,581, filed Apr. 23, 2009, or suitable shaping apparatuses and methods. In certain embodiments, pump260 may not be required. For example, when using relatively non-compressible fluids such as oils, water, and other non-compressible fluids known to those of ordinary skill in the art, the non-compressible fluid itself may sufficiently supporthollow wire102 during the process of shapinghollow wire102 into a stent pattern.
• Oncehollow wire102 has been shaped into the stent pattern, pump260 is turned off (if used) and the fluid is drained fromhollow wire102. The fluid may be drained/removed by vacuum or pressure applied to the lumen, flushing the fluid out with another fluid, or other methods known to those skilled in the art. Further, any residual fluid remaining fluid may be vaporized during an annealing process step typically performed on stents.
• In a non-limiting embodiment, a wax, such as an industrial grade wax such as paraffin, is liquefied/melted and inserted into thelumen103 ofhollow wire102. Pressure or vacuum may be used to assist the liquefiedwax fill lumen103. The wax is permitted to solidify or harden withinlumen103, such as by cooling. Thewire102 is then shaped into the stent pattern with the wax supporting the walls ofwire102. After the wire has been shaped into the stent pattern, the wax is again liquefied and removed from thelumen103. Vacuum or pressure assistance, or a solvent, may be used to assist in draining the liquefied wax fromlumen103. Further, the annealing process, as discussed above, may vaporize any residual wax remaining in thelumen103.
• Openings104 are formed through the wall ofhollow wire102 to accesslumen103 and may assist in draining the fluid, depending on the fluid used. Thus,openings104 may be formed before or after the step of draining the fluid fromhollow wire102.Lumen103 is then filled with a drug, thereby providing a hollow, drug-eluting stent.
• In another embodiment,lumen103 is filled with the biologically or pharmacologically active substance prior to bendinghollow wire102. The biologically or pharmacologically active substance may be pressurized as described above with respect toFIGS. 17-18, but need not be. The biologically or pharmacologically active substance is densely packed intolumen103, thereby providing support tohollow wire102 ashollow wire102 is formed into the stent pattern. In some applications, after forming the stent in the stent pattern, fusing selected crowns of the stent may adversely affect some biologically or pharmacologically active substances due to heat at the fusion site. In some embodiments, the crowns need not be attached to each other at all, thereby avoiding the issue. In other embodiments, the crowns can be attached by mechanical means, spring clips, interconnecting crowns, soldering, adhesives, brazing, sutures, rivets, clamps, micro machined interlocking surfaces or other connecting means known to those skilled in the art, some of which are shown inFIGS. 31-36.
• In another embodiment shown inFIGS. 19-20, aspring element280 is disposed withinlumen103 ofhollow wire102.Spring element280 may be inserted intolumen103 ofhollow wire102 orhollow wire102 may be formed aroundspring element280.Spring element280 may be formed of flattened steel or other suitable materials.Spring element280 supportshollow wire102 whilehollow wire102 is shaped into a stent pattern. Alternatively, the spring element could be placed on the outside of the hollow wire. After shapinghollow wire102 into a stent pattern,spring element280 is pulled, as shown by the arrow inFIG. 20. Pullingspring element280 causesspring element280 to straighten, as indicated at282, thereby simplifying its removal fromlumen103. Afterspring element280 is removed, openings may be cut inhollow wire102 to accesslumen103 andlumen103 may be filled with a biologically or pharmacologically active substance, as explained above, resulting in a hollow wire drug-eluting stent.
• In another embodiment shown inFIGS. 21-22, instead of supportingwire102 with a supporting element in thelumen103, anouter member290 envelopswire102.Outer member290 may be softer thanwire102. For example,outer member290 may be made from tantalum andhollow wire102 may be made from MP35N.Outer member290 may not be attached tohollow wire102.Outer member290 andhollow wire102 are bent together into a stent pattern, such as a sinusoidal pattern.Outer member290 may then be removed, for example, by the methods described in co-pending U.S. application Ser. No. 12/500,359, filed Jul. 9, 2009, which is incorporated herein in its entirety. By havingouter member290 on the outside ofhollow wire102, it may be easier to removeouter member290 compared to a supporting member disposed inlumen103. Afterouter member290 is removed, the stent forming process is finalized as described above andlumen103 is loaded with a biologically or pharmacologically active substance, resulting in a hollow drug-eluting stent.
• In other embodiments, the lumen of the hollow wire may be filled with a filler material such as a gel, hydrogel, alcohol, silica or a polymer, shaped into a stent pattern, and then the filler material may be removed. The filler material may be removed after the wire is shaped into a stent pattern, by exposing the shaped wire to solvent or solution in which the filler material is soluble or reacts but the wire is not soluble or reacts to remove the filler material, which can then be drained from the lumen with the solvent or solution. Examples of solvents may be water or alcohol and examples of a solution would be an acidic or basic solution such as HCL, sulfuric, ammonia, etc. If alcohol is used as a filler material, it can simply evaporate from the lumen.
• In another embodiment shown inFIGS. 23-25, a core wire including anouter member2302 and a core orinner member2304 is swaged, for example, in apress2308 such that a force is directed in the direction ofarrows2306. In this embodiment,inner member2304 is made from a material that is harder than the material of theouter member2302. In a non-limiting example,outer member2302 may be made from MP35N andinner member2304 may be made from a molybdenum-rhenium alloy, which is approximately twice as hard as MP35N. Thus, when the core wire is swaged,outer member2302 deforms into a generally elliptical shape, butinner member2304 remains generally circular, as shown inFIG. 24. This provides a gap orlumen2310 betweenouter member2302 andinner member2304, generally to one side ofinner member2304. The wire is then shaped into a stent pattern andopenings2312 are laser-cut throughouter member2302 to exposeinner member2304. The stent is then exposed to an etchant, for example, xenon difluoride, as described in co-pending U.S. application Ser. No. 12/500,359, filed Jul. 9, 2009, incorporated by reference herein in its entirety. In some instances, some of theopenings2312 may become clogged and therefore impede the etching process. In the present embodiment, withlumen2310 running the length of the wire betweenouter member2302 and2304, if ahole2312 becomes clogged, the etchant from anadjacent hole2312 flows throughlumen2310, as depicted byarrows2314, to etchinner member2302 along the length of the wire.
Sheet Embodiment
• Another method for forming a stent including hollow struts is described referring toFIGS. 26-30. In this embodiment, rather than forming the stent from a wire bent into a stent pattern, the stent pattern is cut into flat sheets, rolled into a tube, and welded to form a stent with hollow struts. As illustrated schematically inFIG. 26, afirst sheet402 andsecond sheet404 sandwich athird sheet406 therebetween. First andsecond sheets402,404 are made from materials that form a finished stent, such as stainless steel, nitinol, MP35N, etc.Third sheet406 is made from a material that can be removed from between first andsecond sheets402,404 after forming. For example, the materials described in co-pending U.S. application Ser. No. 12/500,359, filed Jul. 9, 2009 and incorporated by reference herein, for the outer member can be used for first andsecond sheets402,404, and the materials described therein for the sacrificial or core member can be used asthird sheet406. In a non-limiting example, first andsecond sheets402,404 are formed from MP35N andthird sheet406 is formed from tantalum.
• Withsheets402,404,406 stacked, a flat stent pattern is stamped out of the sheets, as shown inFIG. 27. The stamping device cuts throughsheets402,404,406, leavingstruts407 of the flat stent pattern. The stamping device has curved edges that pushthird sheet406 inward and first andsecond sheets402,404 together atedges408, as shown in the cross-sectional view ofstruts407 inFIG. 28.Openings104 may be laser cut throughstrut407 to reach the remaining material ofsheet406. The remaining material ofsheet406 can be removed by the methods described herein or in co-pending application Ser. No. 12/500,359, for example, using xenon difluoride gas. After the remaining material ofsheet406 is removed, the flat stent is rolled such thatedges410,412 abut each other, and edges410,412 are bonded to each other, for example by aweld414 as shown inFIG. 29. A cross-sectional view of thestruts407 ofFIG. 29 is shown inFIG. 30, withhole104 accessinglumen103. The stent can then be filled with a biologically or pharmacologically active substance throughopenings104 and/or additional openings drilled for the purpose of filling the stent. Those of ordinary skill in the art would recognize that the step of removing the remaining material ofthird sheet406 may be performed before or after the flat stent is rolled andedges410,412 are welded to each other.
• Examples of biologically or pharmacologically active substance that may be used to fill the lumen of the stents described above are listed in co-pending U.S. application Ser. No. 12/500,359, filed Jul. 9, 2009, which is incorporated by reference herein in its entirety. The term “biologically or pharmacologically active substance” refers to any substance, whether synthetic or natural, that has a pharmacological, chemical, or biological effect on the body or a portion thereof. Suitable biologically or pharmacologically active materials that can be used in embodiments of the present invention include without limitation glucocorticoids (e.g. dexamethasone, betamethasone), antithrombotic agents such as heparin, cell growth inhibitors, hirudin, angiopeptin, aspirin, growth factors such as VEGF, antisense agents, anti-cancer agents, anti-proliferative agents, oligonucleotides, antibiotics, and, more generally, antiplatelet agents, anti-coagulant agents, antimitotic agents, antioxidants, antimetabolite agents, and anti-inflammatory agents may be used. Antiplatelet agents can include drugs such as aspirin and dipyridamole. Aspirin is classified as an analgesic, antipyretic, anti-inflammatory and antiplatelet drug. Dipyridamole is a drug similar to aspirin in that it has anti-platelet characteristics. Dipyridamole is also classified as a coronary vasodilator. Anticoagulant agents may include drugs such as heparin, protamine, hirudin and tick anticoagulant protein. Anti-cancer agents may include drugs such as taxol and its analogs or derivatives. Taxol is also classified as a cell-growth inhibitor. Antioxidant agents may include probucol. Anti-proliferative agents may include drugs such as amlodipine, doxazosin, and sirolimus (rapamycin) or other—limus family compounds. Antimitotic agents and antimetabolite agents may include drugs such as methotrexate, azathioprine, vincristine, vinblastine, 5-fluorouracil, adriamycin and mutamycin. Antibiotic agents can include penicillin, cefoxitin, oxacillin, tobramycin, and gentamicin. Suitable antioxidants include probucol. Also, genes or nucleic acids, or portions thereof may be used. Such genes or nucleic acids can first be packaged in liposomes or nanoparticles. Furthermore, collagen-synthesis inhibitors, such as tranilast, may be used.
• Further, due to the relatively large volume of the biologically or pharmacologically active substance that can be carried by a hollow stent, such stent may be particularly useful for delivering chemotherapy or radiation therapy directly to a target location.
• The step of fillinglumen103 with biologically or pharmacologicallyactive substances112, and other steps in processing the stent, such as cleaning, may be accomplished by the methods described in co-pending U.S. application Ser. Nos. (Attorney Docket Nos. P36494, P37957, P38015, P38005, P37967, and P36172), each of which is incorporated by reference herein in its entirety, or any other suitable methods known to those skilled in the art.
• While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of illustration and example only, and not limitation. It will be apparent to persons skilled in the relevant art that various changes in form and detail can be made therein without departing from the spirit and scope of the invention. Thus, the breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the appended claims and their equivalents. It will also be understood that each feature of each embodiment discussed herein, and of each reference cited herein, can be used in combination with the features of any other embodiment. Furthermore, there is no intention to be bound by any expressed or implied theory presented in the preceding technical field, background, brief summary or the detailed description. All patents and publications discussed herein are incorporated by reference herein in their entirety.

Claims (16)

1. A method of forming a medical device comprising the steps of:

utilizing a hollow wire having an outer member and a lumen of the outer member;

filling the lumen with a liquid to form a supported hollow wire;

shaping the supported hollow wire into a pattern;

forming openings through the outer member; and

after the step of shaping the supported hollow wire into the pattern, processing the supported hollow wire such that the liquid is removed from the lumen of the outer member without adversely affecting the outer member.

2. The method ofclaim 1, further comprising the step of filling the lumen of the outer member with a biologically or pharmacologically active substance after the liquid has been removed.

3. The method ofclaim 2, wherein the biologically or pharmacologically active is selected from the group consisting of antineoplastic, antimitotic, antiinflammatory, antiplatelet, anticoagulant, anti fibrin, antithrombin, antiproliferative, antibiotic, antioxidant, and antiallergic substances as well as combinations thereof.

4. The method ofclaim 2, wherein the medical device is a stent.

5. The method ofclaim 1, wherein the liquid is oil.

6. The method ofclaim 1, wherein the liquid is pressurized during the step of shaping the supported hollow wire.

7. The method ofclaim 1, wherein the liquid is a noncompressible fluid.

8. The method ofclaim 1, further comprising the step of solidifying the liquid in the lumen prior to the step of shaping the support hollow wire.

9. A method of forming a medical device comprising the steps of:

utilizing a hollow wire having an outer member and a lumen of the outer member;

filling the lumen with a fluid;

pressurizing the fluid within the lumen to form a supported hollow wire;

shaping the supported hollow wire into a pattern;

forming openings through the outer member; and

after the step of shaping the supported hollow wire into the pattern, processing the supported hollow wire such that the fluid is removed from the lumen of the outer member without adversely affecting the outer member.

10. The method ofclaim 9, further comprising the step of filling the lumen of the outer member with a biologically or pharmacologically active substance after the liquid has been removed.

11. The method ofclaim 9, wherein the fluid is selected from the group consisting of air, water, alcohol, oils (hydrocarbon or silicone based), waxes, meltable polymers, and slurries of water and particles where the particles can be metal, silica or polymeric.

12. A method of forming a medical device comprising the steps of:

utilizing a hollow wire having an outer member and a lumen of the outer member;

filling the lumen with a liquefied wax;

solidifying the liquefied wax within the lumen to form a supported hollow wire;

shaping the supported hollow wire into a pattern;

forming openings through the outer member; and

after the step of shaping the supported hollow wire into the pattern, processing the supported hollow wire such that the wax is removed from the lumen of the outer member without adversely affecting the outer member.

13. The method ofclaim 12, wherein the step of processing the supported hollow wire comprises re-liquefying the wax and draining it from the lumen.

14. The method ofclaim 13, wherein the step of processing the supported hollow wire further comprises adding pressure or a vacuum to remove the re-liquefied wax from the lumen.

15. The method ofclaim 13, wherein the step of re-liquefying the wax comprises heating the supported hollow wire to a temperature higher than the melt temperature of the wax and lower than the melt temperature of the outer member.

16. The method ofclaim 12, wherein the wax is paraffin.

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