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An embolic gelling solution based on acrylic copolymers in ethanol for the treatment of arteriovenous malformations
Authors:Aymeric Seron  Laurence Moine  Alexandre Laurent  Michel Wassef  Gérard Guiffant  Patrice Flaud  Denis Labarre
Affiliation:1. Université Paris Sud, UMR CNRS 8612, IFR 141-ITFM, Faculté de Pharmacie, 5 Rue Jean-Baptiste Clement, 92296, Châtenay-Malabry, France;2. CNRS, UMR 8612, IFR 141-ITFM Faculté de Pharmacie, Châtenay-Malabry, France;3. Service de Neuroradiologie et Angiographie Thérapeutique, AP-HP Hôpital Lariboisière, 75010 Paris, France;4. Département d''anatomie, AP-HP Hôpital Lariboisière, 75010 Paris, France;5. Laboratoire M.S.C., Université Paris 7, 75005 Paris, France;1. Department of Biomaterials Science, Institute of Dentistry and Biocity Turku Biomaterials and Medical Device Research Program, University of Turku, Turku, Finland;2. Turku Clinical Biomaterials Centre—TCBC, University of Turku, Turku, Finland;3. College of Materials Science and Engineering, South China University of Technology, Guangzhou, China;4. City of Turku Welfare Division, Oral Health Care, Turku 20101, Finland;1. Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, GA, USA;2. School of Engineering, Virginia Commonwealth University, Richmond, VA, USA;3. Department of Orthopaedics, Otto-von-Guericke University, Magdeburg, Germany;1. College of Engineering and Applied Sciences, Nanjing University, Nanjing 210093, China;2. Nanjing Excellence Technology Center for Interventional Medical Devices, Nanjing 210093, China;3. Department of Chemistry, Stony Brook University, Stony Brook, NY 11790, USA;1. Department of Radiology, University of Minnesota, 420 Delaware Street SE, Mayo B228, Minneapolis, MN 55455;2. Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, Mayo B228, Minneapolis, MN 55455;1. Université de Strasbourg, CNRS, CAMB UMR 7199, F-67000 Strasbourg, France;2. Université de Strasbourg, CNRS, ICS UPR 22, F-67000 Strasbourg, France;3. Université de Strasbourg, CNRS, LBP UMR 7213, F-67000 Strasbourg, France;4. Université de Strasbourg, CNRS, INSERM, Collège de France, IGBMC UMR 7104/UMR_S 964, F-67000 Strasbourg, France
Abstract:We report the preparation of an embolic agent based on specific association of an acrylic copolymer with dedicated particles formulated in ethanol. The copolymers were synthesized by radical polymerization of tertiobutylacrylamide (tBA) and 2-hydroxypropyl methacrylate (HPMA). Influences of the monomers composition, molecular weight and copolymer concentration have been evaluated on an in vitro model. Introduction of tBA units improves significantly the occlusion properties but these properties are similar whatever the molecular weight of the copolymer. As observed by viscosity studies, it seems necessary to work with a relatively high polymer concentration (C > Ce) to form a cohesive embolus. Addition of solid particles composed by a crosslinked polymer of 2-hydroxyethyl methacrylate (HEMA) and N-trishydroxymethyl methacrylamide (TRIS) in the acrylic copolymer solution has allowed to obtain an embole having an enhanced cohesion and giving a more compact structure. An in vivo evaluation has been performed by injection of this embolic agent in intercostal arteries and renal artery of sheep. There was no fragmentation of the plug during and after injection and a complete arterial occlusion by a cohesive embole. The pathological examination confirmed that there was a complete arterial occlusion by the plug and that the dedicated particles were as expected embedded in the precipitate acrylic copolymer.
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