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US 2007/0282422 A1 12B US 20070282422A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0282422 A1 Biggs et al. (43) Pub. Date: Dec. 6, 2007 (54) MEDICAL DEVICES AND METHODS FOR Related U.S. Application Data LOCAL DELIVERY OF ELASTN-STABILIZING COMPOUNDS (60) Provisional application No. 60/799,608, filed on May 10, 2006. (75) Inventors: David Paul Biggs, Bloomington, IN (US); Anthony O. Ragheb, West Publication Classification Lafayette, IN (US); Patrick H. Ruane, Redwood City, CA (US) (51) Int. Cl. A6IF 2/82 (2006.01) Correspondence Address: A6F 2/02 (2006.01) BRINKSHOFER GILSON & (52) U.S. Cl. ........................ 623/1.13; 424/423; 623/1.42 LONEACHICAGO/COOK (57) ABSTRACT PO BOX 10395 This invention relates to medical devices and an elastin CHICAGO, IL 60610 (US) stabilizing compound, Such as a phenolic tannin, the medical (73) Assignees: Cook Incorporated; MED Institute, device being adapted to release the elastin-stabilizing com Inc. pound within a body of a patient. This invention also relates to medical devices and methods of treatment of disease. Such (21) Appl. No.: 11/800,217 as aneurysms and aortic dissection. Medical devices may include coated Stents, grafts, stent grafts, balloons and (22) Filed: May 4, 2007 catheters. 20' t 28 26b 12b O O Patent Application Publication Dec. 6, 2007 Sheet 1 of 7 US 2007/0282422 A1 FIGURE 1 Erythrose-PO+PEP HO COH CO2H -- HO COH HO HO Shikimic acid Quinic acid O Gallic acid Tryptophan Hydrolyzable tannins NH ( ) / COH2 areer-es- N -1 CondensedFlavenoids tannins COH2 N. Isoflavones Phenylalanine Cinnamic acid Coumarins Tvrosiney -> HO N COH -es HO-()- N-OH p-Coumaric acid p-Coumaryl alcohol N HO Caffeic acid HO HO CHO N-co. CHO No. Ferulic acid N Coritery alcohol HO HO N COH CHO 5-(OH)-Ferulic acid CHO CHO HO N-coh HO 3. CHO CHO 3 Syringic acid 3 - alcohol polymerization - > grass lignins Legume and dicottignins Patent Application Publication Dec. 6, 2007 Sheet 2 of 7 US 2007/0282422 A1 10 12 Patent Application Publication Dec. 6, 2007 Sheet 3 of 7 US 2007/0282422 A1 24 29 12c ..., . ."...' . i; s:Dejada-PskiD 26c 29 26d / 130 1 11b 11b, is 114 is is iss e 3. ask - 2 as as Patent Application Publication Dec. 6, 2007 Sheet 4 of 7 US 2007/0282422 A1 -- 157 Patent Application Publication Dec. 6, 2007 Sheet 5 of 7 US 2007/0282422 A1 212 200 230 Patent Application Publication Dec. 6, 2007 Sheet 6 of 7 US 2007/0282422 A1 326 310 326 310 Fig. 5B Fig. 5C 326 310 326 310 YIIlyzz // Fig. 5D Fig. 5E 410 440 420 440 430 408 72 ISXSS&KRS2 O is s S7.3S2 S&S w N AN NA NZ passig Ay, Q) Q) \7-N 2 XX. XX XX XXX.X. Q27 NZ Y 63. X SSC Ézis s^XXXX. SSCS/373.6%5 Patent Application Publication Dec. 6, 2007 Sheet 7 of 7 US 2007/0282422 A1 502 510 520 SeezáEigz:SARGIC) aszz SS SASNY S. 522 12 27%22& 530 550 610 602 604 US 2007/0282422 A1 Dec. 6, 2007 MEDICAL DEVICES AND METHODS FOR LOCAL aortic dissections are constantly being sought. Although the DELIVERY OF ELASTN-STABILIZING following discussion focuses on AAA treatment and preven COMPOUNDS tion, it is equally applicable to endovascular disease in other locations, and aortic dissections. RELATED APPLICATIONS 0007 Various implantable medical devices are advanta 0001. The present patent document claims the benefit of geously inserted within various portions of the body. Mini the filing date under 35 U.S.C. S 119(e) of Provisional U.S. mally invasive techniques and instruments for placement of Patent Application Ser. No. 60/799,608, filed May 10, 2006, intralumenal medical devices have been developed to treat which is hereby incorporated by reference. and repair undesirable conditions within body vessels including treatment of conditions that affect blood flow such TECHNICAL FIELD as abdominal aortic aneurysm. Various percutaneous meth ods of implanting medical devices within the body using 0002 This invention relates generally to human and intralumenal transcatheter delivery systems can be used to veterinary medical devices and, more particularly, to treat a variety of Such conditions. One or more intralumenal implantable medical devices incorporating elastin-stabiliz medical devices, such as tubular stent grafts, can be intro ing compounds. The invention also relates to methods of duced to a point of treatment within a body vessel using a treatment and kits and to treating an aorta wall adjacent to delivery catheter device passed through the vasculature an aortic aneurysm as a preventative measure. communicating between a remote introductory location and the implantation site, and released from the delivery catheter BACKGROUND device at the point of treatment within the body vessel. Intralumenal medical devices can be deployed in a body 0003 Diseases of aorta are common in the general popu vessel at a point of treatment and the delivery device lation and may include endovascular disease, including subsequently withdrawn from the vessel, while the medical aneurysms and aortic dissections. device is retained within the vessel to provide sustained 0004 Endovascular disease may be characterized by improvement in valve function or to increase vessel patency. weakened vessels due to elastin breakdown, which results in For example, an implanted stent graft can improve vessel dilation of vessels and aneurysm. An aneurysm is a sac function by permitting relatively less turbulent fluid flow formed by localized dilatation of the wall of an artery, a vein, through the stent graft conduit bridging the site of an or the heart. Common areas where aneurysms occur and aneurysm. cause adverse medical conditions include the coronary arter ies, the carotid arteries, various cerebral arteries, and the SUMMARY thoracic and abdominal aorta as well as iliac and femoral 0008. In one embodiment, the invention provides a medi arteries. When a local dilatation of a vessel occurs, irregular cal device and an elastin-stabilizing compound, the medical blood flow patterns result in the lumen of the vessel, device being adapted to release an elastin-stabilizing com Sometimes leading to clot formation. Typically, the wall of pound within a body of a patient. The medical device may the vessel also progressively dilates and weakens, often be implantable. The elastin-stabilizing compound may be a resulting in vessel rupture. Vessel rupture, in turn, often phenolic tannin. The phenolic tannin may be a hydrolyzable causes dramatic negative consequences such as a stroke, tannin or a condensed tannin. The phenolic tannin may be when a cerebral vessel ruptures, or even death, when an selected from gallotannins, ellagitannins, epicatechins, cat abdominal aortic aneurysm (“AAA”) ruptures. Continued echins, proanthocyanidins, derivatives, and mixtures degeneration can result in an increase in aneurysm size due thereof. The phenolic tannin may be selected from the group to thinning of the medial connective tissue of the aorta and of compounds: tannic acid; B-1.2.3.4.6-Pentagalloyl-O-D- loss of elastin. Glucopyranose; B-1.2.2.3,6-Pentagalloyl-O-D-glucose; 1.2, 3.6-tetragalloyl glucose, 1.3.4.6-tetragalloyl glucose: Acer 0005 Aortic dissections occur when the inner layer of the itannin=2,6-di-O-galloyl-1,5-anhydro-D-glucitol; aorta’s artery wall splits open (dissects). The normal aorta Hamamelitannin; Ellagitannin; Eugeniin, Casuarictin; contains collagen, elastin, and Smooth muscle cells that Corilagin; Geraniin, Davidiin, Castalagin; Vescalagin; contribute to the intima, media, and adventitia, which are the Euphorbin: Oenethein B: Epicatechenin: Catechin: Epigal layers of the aorta. Hypertension with aging is believed to locatechin; Gallocatechin: Epiafzelechin: Afzelechin: Epi contribute to degenerative changes that may lead to break catechin (4B->8)-catechin: Epicatechin (4B->8)-epicatechin; down of the collagen, elastin, and Smooth muscle cells and Catechin (4C.->8)-catechin: Catechin (4C.->8)-epicatechin; ultimately dissection of the aorta. Aortic dissection is more Sorghum procyanidin; epicatechin-(4b->8)-epicatechin 15 likely to occur where pressure on the artery wall from blood (4b->8)-catechin: Aurantinidin; Cyanidin; Delphinidin; flow is high, such as the proximal aorta or the ascending Europinidin; Luteolinidin; Pelargonidin; Malvidin; Peoni aorta (the first segment of the aorta). When the aortic wall din; Petunidin; Apigeninidin; Robinetinidin; Fisetinidin; splits, the pulses of blood can penetrate the artery wall and Guibourtinidin; Robinetinidol-(4C->8)-catechin-(6C.->4a)- its inner layer, causing the aorta to tear or split further. This robinetinidol; Profisetinidin; Epicatechin (2B-->7.4?-->8)- tear usually continues distally (away from the heart) down epicatechin; Leucofisetinidin; Leucopelargonidin; Leuco the descending aorta and into its major branches. Less often, cyanidin; Leucodelphinidin; Leucoapigeninidin; the tear may run proximally (back toward the heart). Aortic Leucoluteolinidin, derivatives, and mixtures thereof. The dissection can also start in the descending (distal) segment phenolic tannin may be pentagalloyl glucose (PGG). The of the aorta. medical device may be an implantable medical device. The 0006. In light of these consequences, improved devices implantable medical device may be an endolumenal medical and methods of treating and/or preventing aneurysms and device Such as a stent, the elastin-stabilizing compound US 2007/0282422 A1 Dec. 6, 2007 releasably associated with the stent. The stent may comprise 0015 FIG. 2B is a cross section of a strut of an implant a plurality of interconnected Struts and bends, the elastin able medical device comprising a single-layer coating con stabilizing compound releasably associated with the struts, figuration. bends, or a combination thereof. Alternatively, the stent may comprise a plurality of Z-STENTSR). The implantable medi 0016 FIG. 2C is a cross section of a strut of an implant cal device may be a stent graft comprising a Support frame able medical device comprising a two-layer coating con attached to a flexible tubular covering, the elastin-stabilizing figuration.
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