2) United States Patent Krivoruchko et al. (54) BIORESORBABLE STENT Inventors: Micheal Krivoruchko, Forestville, CA (US); deffrey Allen, Santa Ross, CA (US); Matthew Birdsall, Santa Rosa, caus) (73) Assignoe: Medtronie Vas 1, Santa Rosa, cA US) (*) Notice: Subject to any disclaimer, the term of this pateat is extended or adjusted under 35 USC. 1S4{b) by 206 days. (21) Appl. Nos 1611.53 (22) Filed: Dee. 15,2006 ws) Prior Publication Data US 20080147175 AI Jun, 19, 2008 (1) Inc AGIF 206 (2006.01) (2) US.CL 629/1.38; 623/144; 625/145 (58) Field of Classification Search... 623/1 381.46: ABLE 206 ‘ce application ile for complete search history. 656) References Cited USS. PATENT DOCUMENTS 100 ‘USOO76S1527B2 (10) Patent No. 4s) Date of Patent: US 7,651,527 B2 Jan. 26, 2010 981.987 2/2006 Hunslet a 2002%0004060 AL 1/2002 Heublein eta. donwon3idon AL 22004 Heublen et al. 2004015838 AL* $2000 Matson sas aonen220711 AL 102006, aouwor7it6s AL* 11/2006 Yan Klein exvias FOREIGN PATENT DOCUMENTS DE wo 9ss6983 003068733 111999 2003 * cited by examiner Cotine M MeDerott Jason-Dennis Stewart Primary Examiner Assistant Examiner on ABSTRACT A bioresorbable endoluminal prosthesis for placement in a ‘body kamen bavinga stent substrate ofa first metallic material that has lower electrical potential dhana standard reference electrode, The stent substrate is coated with a biodegrad polymer ving a second metallic material dispersed therein, ‘wherein the second metalic material has hi potential than the standard eferenee electrode, After inyplan- tation ofthe stent within the body lumen, the second metalic ‘material is present in the polymeric coating in a suficient ‘concentration to ease galvani comrosion of the ist metalic ‘material such that over ime the seat substrates bioresorbe le 12 Claims, 1 Drawing SheetU.S. Patent Jan. 26, 2010 US 7,651,527 B2US 7,651,527 B2 1 BIORESORBABLE STENT. FIELD OF THE INVENTION ‘The invention relates generally to temporary endoluminal prostheses for placement in. body lumen, and more pariew- Jarl to stents that ae bioresorbable, BACKGROUND OF THE INVENTION A wide range of medical treatments exist that utilize “endoluminal prostheses” As used herein, endoluminal pros- theses is intended to cover medical devices that are adapted Jor temporary or permanent implantation within a body fumen, including both naturelly occurring and artificially ‘made iumtens, such as without limitation: arteries, whethee located within the coronary, mesentery, peripheral, ar cere- bral vasculature; veins; gastrointestinal tract; biliary tracts ‘aretha: traces hepatic shunts; and fallopian tubes. Accordingly, wide assortment of endoluminal prostheses have been developed, each providing # uniquely beneficial structure to modify the mechanics of the targeted Iumen Wal. For example, stent prosiheses are knowa for implantation ‘within body lumens to provide artificial radial support to the wal tissue, which forms the various lumens within the body. ‘and often more specifically, for implantation within he blood vessel of the boy. Essentially, stents that are presently utilized are made to be permanently or temporarily implanted. A permanent stent is ‘designed to be maintained in a body umen for an indetermi nate amount of time and is typically designed to provide long term support for damaged or traumatized wall tissues of the lumen. There are numerous conventional applications for Permanent stents including cardiovascular, urological, gas- trointestinal, and gynecological applications. temporary stent is designed t0 be maintained in a body lumen for & Timited period of time inorder to maintain the pateney ofthe body lumen, for example afte trauma to 2 lumen eaused by a surgical procedure or an injury. ‘Permanent stents, over time, may become encapsulated ‘and covered with endothelium tissues, for example, in ear- ‘diovascular applications, causing iritation othe surrounding tissue. Further if an additonal interventional procedure is ‘ever warranted, a previously permanently implanted stent ‘may make it more difficult to perform the subsequent proce- dure ‘Temporary stents, on the other hand, preferably do not become incorporated into the walls of the lumen by dssue ingrowth or encapsulation. Temporary stents may advanta- peously be eliminated from body lumens afteran appropriate Period of time, for example, after the traumatized tssaes of the lumen hive healed and a stent is ao longer newded 0 ‘maintain the pateney ofthe lumen. As such, temporary stents may be removed surgically orb made bioubsorbable?biode- ‘aradabe, "Temporary stents may be made from bioabsorbable and biodegradable materials that are selected to absorb or degrade invivo overtime. However, there are disadvantages nd lime tations associated with these of ioahsorbable or biodegrad- able stens. Many bioabsorbable or biodegradable materials have insuficient mechanical strength or other properties, such asa lack of plastic deformability to perform adequately ‘under the loading conditions withina treatment Ioeaion upon ‘implantation, Othe imitations arise in controlling the break ‘dow af the bioabsorbable materials from which such stents fare made, asi, preventing the material fom breaking down two quickly of too slowly. Ifthe material is absorbed too 0 o 2 ‘quickly, the stent will not provide sufficient time forthe vessel tohcal, orif absorbed to slowly, the attendant disadvantages of permanently implanted stents may aise Tn order to obtain the ideal properties fora bioresorbable vascularimplant, the implant must have sufficient mechanical properties to withstand the loading conditions within the {reatment location upon implantation. This requires high degree of mechanical strength initially upon actte implant ‘ion to resis forees exerted on the implant by the surounding tissue. However, due tothe dynamic healing response ofthe body these forces decrease over time asthe surrounding issve remodels, This remodeling process begins immediately aller implantation and may continue for several months, even years. From a stent design viewpoint, there isa point in time At which the remodeling. process has achieve suficent nechanical scaffolding to prevent undesirable clinical eel ‘reollapse without the need ofa metallic implant. tis there- {ore desirable to havea vascular implant with ahigh degree of ‘mechanical srenath initially, but diminishing strength as time proceeds, Accordingly, there is « ged fora temporary sent {hat provides sufficient suppor ina body fumen forthe dura- tion of a therapeutically appropriate period of time, whieh thon degrades to be elinsinated fom the patient's body with- cut surgical intervention, BRIEF SUMMARY OF THE INVENTION Anembodiment of the present invention isa bioresorbable ‘endoluminal prosthesis for placement in a body lumen. The endoluminal prosthesis includes a stent substrate ofa first ‘talc material that has a lower electrical potential than @ standard reference electrode. The stent substrate is coated ‘witha Biodegradable polymer having asosond metalliemate- sia dispersed therein, wherein the second metallic material ‘has a higher electrical potential than the standard reference electrode. After implantation of the stent within the body lumen, the second metallic material is present ia the poly meric coating in a sullicient particulate density or count t0 ‘cause galvanic eorosion ofthe frst metallic material, sue ‘that overtime the stent substrate is bioresorbed, BRIEF DESCRIPTION OF DRAWINGS ‘The foregoing and other features and advantages of the invention wll be apparent ftom the following description of the invention as illustrated in the socompanying drawings. ‘The acoompanying 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 ‘nthe perinent arto make and use the invention. The draw ngs are not to sale FIG. 1a perspective view of an exemplary stent in avcor- dance with an embodiment of the presen invention FIG. 2 isa schematic cross-sectional view of a stnt strat taken slong line A-A of FIG. 1 showing a coating in accor. {dance with an embodiment of the presen invention, DETAILED DESCRIPTION OF THE INVENTION An embodiment ofthe present invention includes a biore- sorbable stent that utilizes a metal impregnated polymeric coating to control degradation and bioresorption of «metalic substrate ofthe sea. A stent that is ioresorbable” is one that will gradual breakdown and disperse in the circulation and thereby be removed from supporting, or otherwise rsid- ing in, abody lumen. Inanembodiment, the stent substrate oF ‘rameworks formed ito its desired shape fromm tube, sheetUS 7,651,527 B2 3 ‘or wire ofa frst metallic material, wherein the first metallic material possesses the requisite meclinieal properties for orming 2 stent that is deliverable and implantable within a body lumen. The fist metallic material is also selected to be ‘an “active” muerial, which is a material that asa lower oF negative electrical potential relative toa standard reference ‘electrode, suchas saturated calomel electrode (SCE), ‘The “active” stent substrate is then coated with a biode= tgnidable polymer that has a second metallic material dis- persed therein. In an embodiment, the second metalic mate- Fal ay be dispersed within the biadegredable polymsrin the form ofa powder. The second metallic material is selected 10 bea passive or aoble material, which is material that has & higher clecrical potential relative to a standard reference ‘eleviznde, for example an electrical potential higher than the (0241 V of a SCE. The second metalic matecal is present in the biodegradable polymer insufficient particulate density! ‘numberof concentration by weight soa to promote galvanic ‘corrosion ofthe fist metallic material ofthe stent substrate "upon, or some specified time after, implantation of the stent within a body lamen. Due tothe galvanic corosion the stent substrate will then degrade or corode over a therapeutically appropriate period of time to eventually be eliminated fom the body umen. In an embodiment, the stent structure is bioresorbed fist with the biodegradable coating fully degrad- ing thereafter, such that no portion of thestent remains within the body lumen, FIGS. 1 and ilhsiratean endoluminal prosbesis in accor. danceswith an embodiment of the presen invention Stent 100 js patterned tubular device that includes a plurality of rade ally expandable cylindrical rings 12. Cylindrical rings 12 are ormed from struts 14 formed in 4 generally sinusoidal pat- teen including peaks 16, valleys 18, and generally straight seuments 20 connecting peaks 16 and valleys 18. Connecting Finks 22 connect adjacent eylindrial rings 12 together In FIG. 1, connecting links 22 are shown as generally straight links connecting peak 16 of ane ring 12 to valley 18 of aa adjacent ring 12 However, connecting links 22 may connect ‘peak 16 of one ring 12 to peak 16 of an adjacent ring, oF & ‘alley 18 0a valley 18, ora sight segment 20 astrsight segment 20, Further, connecting links 22 may be curve. ‘Connecting Tinks 22 may also be excluded, with a peak 16 of ‘one ring 12 being direcily attached to a valley. 18 of aa ‘adjacent ring 12, sich asby welding, soldering, or the manner Jn which stent 100 is formed, such 2s by etching the pattern from a flat sheet o a tube. Iwill be appreciated by those of ondinary skill in the art that stent 100 of FIG. 1s merely an exemplary stent and that stents of various forms and methods of fabrication ean be tsed in accordance with various embodiments ofthe present invention, For example, ina typical method of making stent, ‘thin-walled, small diameter metallic tube i eu to produce the desired stent patter, using methods such as laser cutting ‘or chemical etching. The cut stent may then be de-scaled, polished, cleaned and rinsed. Some examples of methods of orming tens and structures fr stents are shown in U.S. Pat. No. 4,743,665 to Palmaz, US. Pat, No.4 800.882 fo Gianl- urco, US, Pat No, 4,886,062 to Wiktor, US, Pat, No, 5133, 732 o Wiktor, US. Pat. No. 5,292,331 to Boneau, U.S. Pat. No, 5,421,955 to Lau, US, Pat No. 5,935,162 t Dang, US. Pat. No. 6,090,127 to Globerman, and US. Pat. No. 6.730, 116 to Wolinsky et al, each of which is incomorated by reference herein in its entire. Further, balloon-expandable stents may also be utilized in various embodiments of the present invention, such as those disclosed in US. Pat No. 5,776,161 to Globerman, U.S. Pat, No. 6,113,627 to Jang, and 4 US. Pat, No, 6,663,661 to Roneau, each of which is incor porated by reference herein in its entirety. Tn accordance with various embodiments ofthe present invention, an “activo” of anodic metallic material 10, o” an ally thereof is to be used in making the metalic substrate of the framework ofstent 100, Ananodicmetalie material sone that possesses an electrical potential that is lower than a standard reference electrode, such as a saturated calomel clectrode ar SCE, The lower oF more negative the electric potential relativeta the standard reference elect the more aetve" the metallic material is considered. In embodiments ccording to the present invention, a metallic material 10 for ‘se asthe stent substrate asa voye potenilin the range ot “0.1 -2.0 volts versus SCE. Such an “active” metal is one that is sosceptible to corrosion or degradation throwgh gal- vanic coupling, ie, when coupled or contacted with cathodic or noble material, as discussed in more detail below. Examples of such metas for use in embodiments of the present invention include, but are no imited to, magnesium, nickel. and manganese, andalloys thereof, as well a active stainless soo alloys. Intheembodiment of FIG. 2,a biocompatible coating 261s illustrated as disposed on an outer surface 24 of metalic ‘material 10 of stent 100, Coating 26 s comprised of a bide- _gradabe polymer 4 dispersed with particles 28 ofa cathodic for noble metallic material. In an embodiment, the noble ‘italic material may be dispersed within the biodegradable polymer as a powder by any method known i the art. A fathodic metallic materi is one that possesses eleetecal potential that is higher than a standard relerence electrode, Such as the SCE mentioned above, The greater, oF more positive, the electric potential relative to the standard refer- fence electrode, the more noble of “inactive” the metalic ‘material is considered. In embodiments according to the present invention, a oblemetallic particulate 2S foruse inthe polymeric coating 26 has a voltage potential in the range of 11010 3.5 volts versus SCE. Fxamples of noble metals, which are also radiopaque, for use in embodiments of the preseat vention include, but are not Fimited to, platiaum, gold, Git sium, silver, tantalum, and iridium, and alloys thereof ‘After stent 100 is implanted within a body lumen, noble metallic particulate 25 within the coating 26 allow eleetecal conductivity wih the anodic material 10 of te stent sub- strate, sch that galvanic coerosion ofthe stent framework ‘occurs. Therefore, a particulate count or density of noble ‘metalic particulate 25 with the biodegradable polymer 34 ‘must be great enough to facilitate this interaction, nd may be ‘increased or decreased inorder to conto he dissolution rate ‘ofthe"active” metallicmaterial 10of the stent substrate, Ina embodiment, after placement ofthe stent within the ody Jumen, biodegradable coating 26 must fist at least panally egradelerode before noble metallic particulate 28 are exposed, such that galvanic corrosion of the stent stuctare begins afer a therapeutically appropriate period of time, ‘whieh isthe time period during which the fll-strength ofthe sent structure is needed to restore patency tothe vessel In another embodiment, after placement ofthe stent within the body lumen, noble metalic particulate 28 are distributed within coating 26, such that galvanie corrosion ofthe stent structure ous priorto erosion or degradation of coating 26. ‘Overtime, the stent framework: willbe fully bioresorbed ‘and the polymer costing completely degraded leaving no remnant ofthe stent stricture ots material within the body lumen. In an embodiment, the “active” metallic material of the stent substrate is filly bioresorbed prior tothe polymer completely Jearading. In another embodiment, theUS 7,651,527 B2 5 polymer coating completely degrades before the “active” ‘elallic material ofthe stent substrate is fully bioresorbed. Tan embodiment, the rte of degradation or bioresorbtion| of the stent structre may be controlled hy selecting the fnodic andl eathodie materials, ic the fst and second mctal- Tiematerils, to inerease or decrease thie relative potential. nother embodiment, the rate of degradation or bioresorbtion ‘of the stent stricture may be controlled by varying the ‘exposed surface area of the stent substrate, wherein some surface areas are coated with the polymer and partieulate ‘material and other areas remain uncoated ‘Examples of biodegrdable polymers for use in embod ‘ments ofthe present invention, includ, but re not limited to: poly(a-hydrexy acids), such as, polycapro lactone (PCL). poly(lactide-co-glycolide) (PLGA), polylatide (PLA), and polyglyeolide (PGA), and combinations and blends thereof, PLGA-PEG (polyetivlene glycol), PLA-PEG, PLA-PEG- PLA, polyanhydrides,rimethylene carbonates, polyorhoe- ser polyasirinpolypopngene, and trie polyear In the embodiment of FIG. 2, only outer surfice 24 of metallic material 10 ofthe stent substrate i shovsn coated. By ‘example, coating 26 may be ofa thickness “Cin the rangeof (05-10 un with the metal material 10 ofthe stent substrate being ofa thickness “Tin the range of 50-100 pm. Flowever ‘tshouldbe understood that a vriousother embodiment, ll ‘or portions of outer surface 24, imner surface 28, andor side surfaces 30 may be coated with coating 26s maybe desired to achieve an appropriate rate of degradation ofthe underly~ Jing metallic material 10 that makes-up the substrate of stent 100. While various embodiments according to the present ‘invention have been deserted above, itshould be understood that they have been presented by way of illustration and ‘example only, and not limitation. Itwill be apparent to per- ons skilled inthe relevant art that varius changes i. on ‘and detail can be made therein without departing from the spiritand scope ofthe invention. Thus the breadth and seope ‘of the present invention shoudl not be limited by aay’ ofthe above-described exemplary embodiments, but should be dfined only in accordance with the appended clsims and thir equivalents, Ie wll alsa be understood that cach feature ‘of each embadiment discussed herein, and ofeach reference ‘ited herein, can be used in combination with the features of any other embodiment. ll patents and publications discussed herein are incorporated by reference herein in thei entirety ‘he invention claimed is: 1. An endoluminal prosthesis for placement in a body lumen comprising: 4 stent substrate comprised of a first metallic material that Tha lower electrical potential than standard elerence electrode, and biocompatible costing disposedon the stent substrate the coating being comprised of a biodegradable polymer having a second metallic material dispersed therein, ‘wherein the second metallic material has higher elec- trical potential than the standard reference electrode and is presentinthecoatingina sufficient particulatedensity to cause galvanic comsion of the first metallic materi after placement ofthe endoluminal prosthesis within the body lumen 2. Tho endoluminal prosthesis of claim 4, wherein the standard reference elocttade is one of a standard hydrogen electrode and a saturated calomel electrode '3. The endoluminal prosthesis of claim 2, wherein the first ‘metalic material is selected from a group consisting of mage esium, zine, aluminum, stainless steel nickel, and manga- nese, and alloys thereof 4. The endoluminal prosthesis of claim 3, wherein the second metallic material is selected from a group consisting ofplatinum, god, titanium, silver, tantalum, and idiom, and alloys threo! The endoluminal prosthesis of claim 4, wherein the second metallic material is dispersed within the coating as a powder. 6. The endoluminal prosthesis of elaim 2, wherein the clecizical potential of the frst metallic material isin the range fof -0.1 t9 -20 volts with respect to the saturated calomel clectode, "7. The endoluminal prosthesis of claim 6, wherein the electrical potetil ofthe second metallic material is in the fringe of 0 to 40 volts with respect tothe saturated alomel eleciode, '8. The endoluminal prosthesis of claim 7, wherein the second metallic material is dispersed within the coating as 4 powder. 9. The endoluminal prosthesis of claim 1, wherein the stent stibstmte is bioresorbe! de to the galvanic corosion. 10, The endoluminal prosthesis of claim 9, wherein the stent substrate i filly bieresorbed prior to complete degre {dation of the biodegradable polymer costing 11, The endoluminal prosthesis of claim 9, whercin the biodegradable polymer coating is completely degraded prior to the tent subsirate being filly boresorbed 12, The endoluminal prosthesis of elaim 1, wherein gal- vani corosion of the stent sbsratehegins therapeutically appropriate period of time after placement ofthe prosthesis ‘within the body lien,UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION PATENT NO. 7,651,527 B2 Page 1 of 1 APPLICATION NO. : 11/611533 DATED. January 26, 2010 INVENTOR(S) Krivoruchko et al Itis certified that error appears in the above-identfied patent and that said Letters Patent is hereby corrected as shown below Title Page, Item (75) Inventors: “Micheal Krivoruchko™ should be changed to --Michael Krivoruchko— Signed and Sealed this Twenty-first Day of December, 2010 (uc Oe Capps David. Kappos Director af the Unite States Patent and Trademark Ofce