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Wo 2007/133479 A2 (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date (10) International Publication Number 22 November 2007 (22.11.2007) PCT WO 2007/133479 A2 (51) International Patent Classification: Not classified (74) Agent: GODLEWSKI, Richard, J.; P.O. Box 2269, Bloomington, IN 47402-2269 (US). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/US2007/0 10828 kind of national protection available): AE, AG, AL, AM, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, (22) International Filing Date: 4 May 2007 (04.05.2007) CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, (25) Filing Language: English IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY,MA, MD, ME, MG, MK, MN, MW, MX, (26) Publication Language: English MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, SY, TJ, TM, (30) Priority Data: TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW 60/799,608 10 May 2006 (10.05.2006) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicants (for all designated States except US): COOK GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, INCORPORATED [US/US]; 750 North Daniel's Way, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), P.O. Box 489, Bloomington, IN 47402-0489 (US). MED European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, INSTITUTE, INC. [US/US]; 1400 Cumberland Avenue, FR, GB, GR, HU, IE, IS, IT, LT,LU, LV,MC, MT, NL, PL, West Lafayette, IN 47906 (US). PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). (72) Inventors; and (75) Inventors/Applicants (for US only): RAGHEB, An¬ Published: thony, O. [US/US]; 2719 Manchester Street, West — without international search report and to be republished Lafayette, IN 47906 (US). RUANE, Patrick, H. [IE/US]; upon receipt of that report 750 Bair Island Road, Bldg. 5, Apt. 104, Redwood For two-letter codes and other abbreviations, refer to the "G uid City, CA 94063 (US). BIGGS, David, P. [US/US]; 3607 ance Notes on Codes and Abbreviations" appearing at the beg in Jordans Way, Bloomington, IN 47401 (US). ning of each regular issue of the PCT Gazette. (54) Title: DELIVERY OF COMPOUNDS 20 (57) Abstract: Medical devices (10) include an elastin- stabilizing compound, such as a phenolic tannin. The medical device (10) is adapted to release the elastin-sta- bilizing compound within a body of a patient. Treatment of disease, such as aneurysms and aortic dissection is de scribed. Medical devices may include coated stents (10), grafts, stent grafts, balloons and catheters (410). DELIVERY OF COMPOUNDS Technical Field This application relates generally to human and veterinary medical devices and, more particularly, t o delivery of compounds. In particular, this application relates to implantable medical devices incorporating elastin-stabilizing compounds. The application also relates t o treatment of an aorta wall adjacent to an aortic aneurysm as a preventative measure and t o kits therefor. Background of the Invention Diseases of the aorta are common in the general population and may include endovascular disease, including aneurysms and aortic dissections. Endovascular disease may be characterized by weakened vessels due t o elastin breakdown, which results in dilation of vessels and aneurysm. An aneurysm is a sac formed by localized dilatation of the wall of an artery, a vein, or the heart. Common areas where aneurysms occur and cause adverse medical conditions include the coronary arteries, the carotid arteries, various cerebral arteries, and the thoracic and abdominal aorta as well as iliac and femoral arteries. When a local dilatation of a vessel occurs, irregular blood flow patterns result in the lumen of the vessel, sometimes leading t o clot formation. Typically, the wall of the vessel also progressively dilates and weakens, often resulting in vessel rupture. Vessel rupture, in turn, often causes dramatic negative consequences such as a stroke, when a cerebral vessel ruptures, or even death, when an abdominal aortic aneurysm (AAA) ruptures. Continued degeneration can result in an increase in aneurysm size due t o thinning of the medial connective tissue of the aorta and loss of elastin. Aortic dissections occur when the inner layer of the aorta's artery wall splits open (dissects). The normal aorta contains collagen, elastin, and smooth muscle cells that contribute t o the intima, media, and adventitia, which are the layers of the aorta. Hypertension with aging is believed t o contribute t o degenerative changes that may lead to breakdown of the collagen, elastin, and smooth muscle cells and ultimately dissection of the aorta. Aortic dissection is more likely t o occur where pressure on the artery wall from blood flow is high, such as the proximal aorta or the ascending aorta (the first segment of the aorta). When the aortic wall splits, the pulses of blood can penetrate the artery wall and its inner layer, causing the aorta to tear or split further. This tear usually continues distally (away from the heart) down the descending aorta and into its major branches. Less often, the tear may run proximatly (back toward the heart). Aortic dissection can also start in the descending (distal) segment of the aorta. In light of these consequences, improved devices and methods of treating and/or preventing aneurysms and aortic dissections are constantly being sought. Although the following discussion focuses on AAA treatment and prevention, it is equally applicable t o endovascular disease in other locations, and aortic dissections. Various implantable medical devices are advantageously inserted within various portions of the body. Minimally invasive techniques and instruments for placement of intralumenal medical devices have been developed t o treat and repair undesirable conditions within body vessels including treatment of conditions that affect blood flow such as abdominal aortic aneurysm. Various percutaneous methods of implanting medical devices within the body using intralumenal transcatheter delivery systems can be used t o treat a variety of such conditions. One or more intralumenal medical devices, such as tubular stent grafts, can be introduced to a point of treatment within a body vessel using a delivery catheter device passed through the vasculature communicating between a remote introductory location and the implantation site, and released from the delivery catheter device at the point of treatment within the body vessel. Intralumenal medical devices can be deployed in a body vessel at a point of treatment and the delivery device subsequently withdrawn from the vessel, while the medical device is retained within the vessel to provide sustained improvement in valve function or to increase vessel patency. For example, an implanted stent graft can improve vessel function by permitting relatively less turbulent fluid flow through the stent graft conduit bridging the site of an aneurysm. Summary of the Invention According t o an aspect of the present invention, there is provided a medical device and an elastin-stabilizing compound, the medical device being operable t o release the elastin-stabilizing compound within a body lumen of a patient. In one embodiment, the invention provides an implantable medical device. The elastin-stabilizing compound may be a phenolic tannin. The phenolic tannin may be a hydrolysable tannin or a condensed tannin. The phenolic tannin may be or may include a gallotannin, an ellagitannin, an epicatechin, a catechin, a proanthocyanidin, a derivative thereof, and/or mixtures thereof. The phenolic tannin may be or may include tannic acid; - 1,2,3,4,6-Pentagalloyl-O-D- Glucopyranose; - 1,2,2,3,6-Pentagalloyl-O-D-glucose; 1,2,3,6-tetragalloyl glucose; 1,3,4, 6-tetragalloyl glucose; Aceritannin = 2,6-di-O-galloyl-1 ,5-anhydro- D-glucitol; Hamamelitannin; Ellagitannin; Eugeniin; Casuarictin; Corilagin; Geraniin; Davidiin; Castalagin; Vescalagin; Euphorbin; Oenethein B; Epicatechenin; Catechin; Epigallocatechin; Gallocatechin; Epiafzelechin; Afzelechin; Epicatechin (4 - > 8)-catechin; Epicatechin (4 - > 8)-epicatechin; Catechin {4 - > 8)-catechin; Catechin (4 - > 8)-epicatechin; Sorghum procyanidin; epicatechin-[(4b-> 8)- epicatechin]1 5-(4b-> 8)-catechin; Aurantinidin; Cyanidin; Delphinidin; Europinidin; Luteolinidin; Pelargonidin; Malvidin; Peonidin; Petunidin; Apigeninidin; Robinetinidin; Fisetinidin; Guibourtinidin; Robinetinidol-(4 - > 8)-catechin-(6 ->4a)- robinetinidol; Profisetinidin; Epicatechin {2 - > 7,4 - > 8)-epicatechin; Leucofisetinidin; Leucopelargonidin; Leucocyanidin; Leucodelphrnidin; Leucoapigeninidin; or Leucoluteol ϊnidin, or derivatives thereof, and/or mixtures thereof. The phenolic tannin may be or may include pentagalloyl glucose (PGG). The medical device may be an implantable medical device. The implantable medical device may be an endolurnenal medical device such as a stent, the elastin-stabilizing compound releasably associated with the stent. The stent may include a plurality of interconnected struts and bends, the elastin-stabilizing compound releasably associated with the struts, bends, or a combination thereof. The stent may include a plurality of Z-STENTS®. The implantable medical device may be a stent graft comprising a support frame attached t o a flexible tubular covering, the elastin-stabilizing compound releasably associated with at least a - A - portion of the stent graft. The medical device may also include at least one surface adapted for contact with a body vessel wall and including the elastin- stabilizing compound coated on at least a portion of the at least one surface. The medical device may include an elongated member having a lumen extending longitudinally along the length of the elongated member, the elongated member having an ablumenal surface and a lumenal surface.
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