US 2005O129775A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0129775 A1 Lanphere et al. (43) Pub. Date: Jun. 16, 2005 (54) FERROMAGNETIC PARTICLES AND (22) Filed: Aug. 27, 2004 METHODS Related U.S. Application Data (75) Inventors: Janel Lanphere, Pawtucket, RI (US); Erin McKenna, Boston, MA (US); (63) Continuation-in-part of application No. 10/651,475, Thomas V. Casey II, Grafton, MA filed on Aug. 29, 2003. (US) Publication Classification Correspondence Address: FISH & RICHARDSON PC (51) Int. Cl." ........................... A61K 9/127; A61K 9/14; 225 FRANKLIN ST A61K 33/26 BOSTON, MA 02110 (US) (52) U.S. Cl. ............................................ 424/489; 424/646 (73) ASSignee: Siedle Systems, Inc., Maple (57) ABSTRACT (21) Appl. No.: 10/928,452 Ferromagnetic particles and methods are disclosed. Patent Application Publication Jun. 16, 2005 Sheet 1 of 5 US 2005/0129775 A1 Patent Application Publication Jun. 16, 2005 Sheet 2 of 5 US 2005/0129775 A1 s nS) l r N. 1 Yn ESDNIAJ?SdWßd N-EZT| 1 - - - - - - - - - - - - - - - - - - - - - - - - - a - - a - - - - Patent Application Publication Jun. 16, 2005 Sheet 3 of 5 US 2005/0129775 A1 : 3 L D Cl U c). Z Y X C) Patent Application Publication Jun. 16, 2005 Sheet 4 of 5 US 2005/0129775 A1 s s Patent Application Publication Jun. 16, 2005 Sheet 5 of 5 US 2005/0129775 A1 26SS EMBOLIC PARTICLES FIBROID jS. 111 UTERINE ARTERY CATHETER 150 FIG. R., US 2005/0129775 A1 Jun. 16, 2005 FERROMAGNETIC PARTICLES AND METHODS 0011 Heating a particle can include exposing the particle to RF radiation. CROSS-REFERENCE TO RELATED 0012. The particle can be disposed in a body lumen APPLICATIONS before being heated. Heating the particle heats body tissue 0001. This application is a continuation-in-part of, and adjacent the particle. claims priority under 35 U.S.C. S 120 to, U.S. patent appli 0013 The ferromagnetic material can include, for cation Ser. No. 10/651,475, entitled "Embolization,” and example, a transition metal, a metal alloy, and/or a metal filed on Aug. 29, 2003, which is incorporated herein by oxide. reference. 0014. The ferromagnetic material can be, for example, in TECHNICAL FIELD the shape of a particle, a fiber, a flake, and/or a powder. 0002 This invention relates to ferromagnetic particles 0015 The polymeric matrix (e.g., the gel polymeric and methods. matrix) can include, for example, a polyvinyl alcohol, a polyacrylic acid, a polymethacrylic acid, a poly Vinyl Sul BACKGROUND fonate, a carboxymethyl cellulose, a hydroxyethyl cellulose, a Substituted cellulose, a polyacrylamide, a polyethylene 0003) Therapeutic vascular occlusions (embolizations) glycol, a polyamide, a polyurea, a polyurethane, a polyester, are used to prevent or treat pathological conditions in situ. a polyether, a polystyrene, a polysaccharide (e.g. alginate), Compositions including embolic particles are used for a polylactic acid, a polyethylene, a polymethylmethacrylate, occluding vessels in a variety of medical applications. a polycaprolactone, a polyglycolic acid, and/or a poly(lactic Delivery of embolic particles through a catheter is depen co-glycolic) acid. dent on size uniformnity, density and compressibility of the embolic particles. 0016. In some embodiments, the density of the ferromag netic material in the interior region of the particle can be SUMMARY greater than a density of the ferromagnetic material at the Surface region of the particle. 0004. In one aspect, the invention features a method that includes providing a particle having a diameter of from 0017. In certain embodiments, there can be substantially about ten microns to about 3,000 microns. The particle no ferromagnetic material at the Surface region. includes a polymeric matrix, a ferromagnetic material and a 0018. In some embodiments, the particle can further therapeutic agent. The method also includes heating the include a therapeutic agent contained within the polymeric particle to release the therapeutic agent from the particle. matrix. 0005. In another aspect, the invention features a method 0019. In certain embodiments, the particle can further that includes disposing a particle in a body lumen. The include a coating Surrounding the polymeric matrix, the particle has a diameter of from about ten microns to about coating comprising a therapeutic agent. 3,000 microns, and the particle includes a polymeric matrix and a ferromagnetic material. The method also includes 0020. In some embodiments, the particle can further heating the particle to heat body tissue. include a third region between the interior region and the Surface region, the third region having a third density of 0006. In a further aspect, the invention features a particle pores less than the first density and less than the Second that includes a polymeric matrix and a ferromagnetic mate density. rial contained within the polymeric matrix. The particle has a first density of pores in an interior region and a Second 0021. In certain embodiments, a therapeutic agent can be density of pores at a Surface region. The first density being contained in the gel polymeric matrix. different from the second density. 0022. In some embodiments, the particle can further 0007. In an additional aspect, the invention features a include a coating Surrounding the gel polymeric matrix, the particle that includes a gel polymeric matrix and a ferro coating containing a therapeutic agent. magnetic material homogeneously distributed in the gel 0023 Embodiments of the invention may have one or polymer. more of the following advantages. 0008 Embodiments can include one or more of the 0024. In some embodiments, the positioning of the par following. ticle within a body lumen can be relatively easily and/or 0009. The particle can be heated, for example, to a non-invasively controlled using a magnetic field (e.g., a temperature of at least about 40 C. and/or a temperature of magnetic field outside a Subject, a magnetic field inside a at most about 200 C. Subject, or both). As an example, the particle can be steered through a body lumen (e.g., to a relatively distal location of 0010. In some embodiments, the method can include a lumen that might otherwise be difficult for the particle to providing a plurality of particles. Each of the particles can reach) by applying a magnetic field to the particle. AS have a diameter of from about ten microns to about 3,000 another example, the ability of the particle to migrate from microns, and each of the particles can include a polymeric a desired location can be reduced by applying a magnetic matrix, a ferromagnetic material and a therapeutic agent. field. The method can also include heating at least Some of the plurality of particles to release the therapeutic agent from the 0025. In certain embodiments, the particle can enhance particle. tissue heating and/or ablation procedures. For example, US 2005/0129775 A1 Jun. 16, 2005 when exposed to RF radiation, the particle can become 0037 AS used herein, a ferromagnetic material refers to heated and, in turn, heat the tissue. a material that has a magnetic Susceptibility of at least about 0.075 or more (e.g., at least about 0.1 or more; at least about 0.026 Features and advantages are in the description, 0.2 or more; at least about 0.3 or more; at least about 0.4 or drawings, and claims. more; at least about 0.5 or more; at least about one or more; at least about ten or more, at least about 100 or more, at least DESCRIPTION OF DRAWINGS about 1,000 or more; at least about 10,000 or more) when 0.027 FIG. 1 is a cross-sectional view of a particle. measured at 25 C. A ferromagnetic material can be, for example, a metal (e.g., a transition metal Such as nickel, 0028 FIG. 2 is a cross-sectional view of a particle. cobalt, or iron), a metal alloy (e.g., a nickel-iron alloy Such 0029 FIG. 3 is a cross-sectional view of a particle. as Mu-metal), a metal oxide (e.g., an iron oxide Such as magnetite), a ceramic nanomaterial, a Soft ferrite (e.g., 0030 FIG. 4 is a cross-sectional view of a particle. nickel–zinc-iron), a magnet alloy (e.g., a rare earth magnet 0.031 FIG. 5 is a cross-sectional view of a particle. alloy Such as a neodymium-iron-boron alloy or a Samarium cobalt alloy), an amorphous alloy (e.g., iron-Silicon-boron), 0.032 FIG. 6A is a schematic of an embodiment of a a non-earth alloy, or a silicon alloy (e.g., an iron-Zirconium system for manufacturing particles, and FIG. 6B is an copper-boron-Silicon alloy, an iron-Zirconium-copper-bo enlarged schematic of region 6B in FIG. 6A. ron-Silicon alloy). Magnetite is commercially available from 0.033 FIG. 7A is a schematic illustrating an embodiment FerroTec Corporation (Nashua, N.H.), under the tradename of injection of an embolic composition including embolic EMG 1111 Ferrofluid. Iron-copper-niobium-boron-silicon particles into a vessel, and FIG. 7B is an enlarged view of alloys are commercially available from Hitachi Metals of the region 7B in FIG. 7A. America under the tradename FinemetTM. Iron-zirconium copper-boron-Silicon alloys are commercially available DETAILED DESCRIPTION from MAGNETEC GmbH under the tradename Nanop ermE). In certain embodiments, the ferromagnetic material is 0034. The particle typically includes a polymeric matrix a biocompatible material (e.g., magnetite). In Some embodi (e.g., a gel polymeric matrix) and a ferromagnetic material. ments, the ferromagnetic material is a bioerodible material, 0035. The polymeric matrix can include one or more such that the material can eventually break down in the body polymer materials. Typically, the polymer material(s) is and either be dispersed throughout the body or excreted biocompatible.