Use of a magnetic material in removal of stones

Abstract

The invention relates to a method of a magnetic material in stone removal, nanoparticles, a preparation method thereof and a stone removing device. Wherein, the magnetic material constitutes a nanoparticle core and a surface modifier monomer is attached to the nanoparticle core by an initiator and/or a crosslinking agent to form a nanoparticle shell. The prepared nanoparticles can surround stones in ureter, thereby, small stones remaining in body can be removed quickly without damage from the body under action of external magnetic field, that is, the stone can be drawn and moved without injuring ureteral wall, and the nanoparticles are placed conveniently without shift.

What is claimed is: 
     
         1 . A method of the use of a magnetic material in removal of a stone, wherein the magnetic material magnetizes the stone by physical adsorption, chemical bonding or the like, and removes the stone by the action of a non-contact magnetic field. 
     
     
         2 . The method according to  claim 1 , wherein the magnetic material comprises the following components; a preparation containing a magnetic metal element or a compound thereof; and materials capable of binding to calcium salt. 
     
     
         3 . The method according to  claim 2 , wherein the preparation containing the magnetic metal element or compound thereof and the materials capable of binding to calcium salt form a structure that may be a clad structure or a core-shell structure, for example, the materials are completely or partially covered on the surface of the preparation; or form a modified structure in which the materials are bonded to the surface of the preparation by absorption; or form a complex structure in which the preparation and the materials form a physical mixture; or form a composite structure of the aforementioned structures. 
     
     
         4 . The method according to  claim 2 , wherein the preparation containing the magnetic metal element or compound thereof is in nano-scale or in micro-scale. 
     
     
         5 . The method according to  claim 2 , wherein the materials capable of binding to calcium salt are surfactants or polymer compounds. 
     
     
         6 . The method according to  claim 2 , wherein the materials capable of binding to calcium salt are macromolecular compounds. 
     
     
         7 . The method according to  claim 1 , wherein the magnetic material includes carboxyl, amido, amino, mercapto, hydroxyl, carbonyl, ether group, amine group, ester group, carbamate group, carbamido or quaternary amine group, sulfonic acid group, sulfhydryl, phosphine group or conjugate acid or base thereof, epoxy group, chlorine group, sulfate group, phosphinic acid, sulfinic acid, carboxylic anhydride group, hydrosilyl group, amine group and moiety of any combination thereof, aldehyde group, unsaturated double bond, phosphoric acid group, halogen group, N-succinimido, maleimido, ethylenediaminetriacetic acid alkyl group, polyethylene glycol, polyamino acid or glycan, preferably carboxyl, amido, mercapto, carbamate group, carbamido, sulfonic acid group, phosphino conjugate acid, phosphino basic group, sulfate group, phosphinic acid, sulfinic acid, N-succinimido, maleimido, polyamino acid. 
     
     
         8 . The method according to  claim 1 , wherein the magnetic material is in the shape of bar, line, band, sheet, tube, pomegranate, cube, three-dimensional flower, petal, chestnut, four-pointed star, shuttle, rice grain, sea urchin, chain ball, rugby ball, string of beads, snowflake, ellipsoid, sphere, regular tetrahedron, regular hexahedron, regular octahedron, quasi-sphere, popcorn, cross, strip, rod, cone, disc, branch, web, simple cubic, body-centered cubic, face-centered cubic, simple tetragon, body-centered tetragon, simple orthogon, body-centered orthogon, single-face-centered orthogon, multi-shell, laminar, preferably the shape of sphere, quasi-sphere, pomegranate, chestnut, sea urchin, chain ball, string of beads. 
     
     
         9 . The method according to  claim 1 , wherein the magnetic material includes a magnetic fluid, a magnetic liposome, a magnetic microcapsule, a magnetic microsphere, a magnetic emulsion, a magnetic nanoparticle, a magnetic nanotube, a magnetic nanowire, a magnetic nanorod, a magnetic nanoribbons, preferably a magnetic fluid, a magnetic liposome, a magnetic microsphere, a magnetic nanotube. 
     
     
         10 . The method according to  claim 9 , wherein the magnetic liposome includes a magnetic liposome which surface is modified to carry a functional group as described in  claim 7 . 
     
     
         11 . The method according to  claim 9 , wherein the type of the magnetic liposome includes a single layer, a multi-layer, a multi-vesicle, and the preparation method of the magnetic liposome includes preferably a film dispersion method and an ultrasonic dispersion method. 
     
     
         12 . The method according to  claim 9 , wherein the magnetic fluid is a stable suspension liquid composed of magnetic particles, a carrier liquid (mineral oil, silicone oil, etc.) and a surfactant, the magnetic particles that can be method for removal of stones comprise magnetic nanoparticles which surface is modified with the functional group according to  claim 7 , and also comprise a surfactant with the functional group as described in  claim 7 . 
     
     
         13 . The method according to  claim 9 , wherein the preparation method for the magnetic fluid includes a chemical co-precipitation method, a sol-gel method, a hydrothermal synthesis method, a microemulsion method, a phase transfer method, preferably a co-precipitation method, a sol-gel method, a hydrothermal synthesis method. 
     
     
         14 . The method according to  claim 9 , wherein the magnetic microsphere is characterized by a surface modified with or covered with the functional group as described in  claim 7 . 
     
     
         15 . The method according to  claim 9 , wherein the preparation method for the magnetic microsphere includes an emulsion volatilization method, a solvent replacement method and a salting-out method. 
     
     
         16 . The method according to  claim 1 , the magnetic nanotube comprises a magnetic nanotube in which a magnetic material is filled in the tube and also a magnetic nanotube in which a magnetic material covers outside the tube, the surface of which has the functional group described in  claim 7 , and the functional group may be derived from the magnetic material covered on surface or from the nanotube itself. 
     
     
         17 . The method according to  claim 1 , wherein the preparation method for the magnetic nanotube includes a chemical vapor deposition method, a co-precipitation method, a dip-pyrolysis method, an electroless plating method and a self-assembly method, and the preferred method is a co-precipitation method. 
     
     
         18 . The method according to  claim 1 , the magnetic nanoparticle is surface-modified or covered with the functional group as described in  claim 7 . 
     
     
         19 . The method according to  claim 1 , wherein the magnetic material constitutes a nanoparticle core; and the nanoparticle core is in-situ modified with a surface modifier monomer by using an initiator and/or a crosslinking agent to form a nanoparticle shell. 
     
     
         20 . The method according to  claim 19 , wherein the nanoparticle core has a diameter of 2-50 nm, and a weight percentage of 30-95% relative to the whole weight of the nanoparticle, and its magnetic material includes a compound of Fe 3+ , Fe 2+ , Mn 2+  or Ni 2+ , or a metal element selected from iron, nickel, copper, cobalt, platinum, gold, europium, gadolinium, dysprosium, terbium, or a composite or oxide of the aforementioned metals, or any one of the above items or a combination of two or more of the above items, preferably a compound of Fe 3+ , Fe 2+ , Mn 2+  or Ni 2+ , more preferably Fe 3+  and Fe 2+  in a ratio of 15% to 85%, preferably 1:2.5 to 1.5:1. 
     
     
         21 . The method according to  claim 19 , wherein the mutual forces for surrounding and crosslinking between the nanoparticle and stone include van der Waals force, hydrophobic interaction, adsorption and surface deposition that form surrounding interaction; a chemical bond formed between carboxyl-stone, including a hydrogen bond, an ester bond, an amide bond and other covalent bonds; physical and chemical inter-chain entanglements between chains and chemical crosslinking between chains. 
     
     
         22 . The method according to any one of  claims 19 - 21 , wherein the surface modifier includes a hydrophilic surface modifier with function, response, a hydrophobic surface modifier with function response, a photosensitive surface modifier with function response, a thermosensitive surface modifier with function response or a pH sensitive surface modifier with function response, wherein the hydrophilic surface modifier includes acrylic acid, methacrylic acid, isobutyl acrylamide or poly N-substituted isopropylacrylamide; the hydrophobic surface modifier includes olefins, preferably polystyrene, polyethylene or oleic acid; the photosensitive surface modifier is selected from the group consisting of azos and quinolines and benzophenones (PVBP), preferably ethylene benzophenone; the thermosensitive surface modifier is selected from amphiphilic polymers with amide bond, preferably polyacrylamide or poly N-substituted isopropylacrylamide; the pH-sensitive surface modifier is selected from the group consisting of polymers with carboxyl group and quaternary ammonium salt, preferably a polyacrylic acid, dimethylaminoethyl ester and dimethylaminopropyl methacrylate; the shell accounts for 2-40% by weight of the nano-particle, preferably the particle is of a shape of sphere, rod or diamond. 
     
     
         23 . The method according to any one of  claims 19  to  21 , wherein the crosslinking agent includes 3-(methacryloyloxy)propyltriethoxysilane, divinylbenzene, diisocyanate or N,N-methylenebisacrylamide, and the initiator includes 3-chloropropionic acid, CuCl, 4,4′-dinonyl-2,2-bipyridine or potassium persulfate. 
     
     
         24 . The method according to any one of  claims 19 - 21 , wherein the preparation method for the nanoparticle includes the steps of:
 a) preparing the nanoparticle core using the magnetic material;   b) forming the nanoparticle by in situ linking the surface modifier monomer to the nanoparticle core by the initiator and/or crosslinking agent to form the nanoparticle shell.   
     
     
         25 . The method according to  claim 24 , wherein the magnetic material includes a compound of Fe 3+ , Fe 2+ , Mn 2+  or Ni 2+ , or a metal element selected from iron, nickel, copper, cobalt, platinum, gold, europium, gadolinium, dysprosium, terbium, or a composite or oxide of the aforementioned metals, or any one of the above items or a combination of two or more of the above items, preferably Fe 3 O 4 , MnFe 2 O 4 , γ-Fe 2 O 3  or other nanoscale-sized ferrite particles, more preferably FeCl 3 .6H 2 O and FeCl 2 .4H 2 O in a molar ratio of 15% to 85%, preferably 1:2.5 to 1.5:1, and is prepared by the following steps:
 dissolving a proportion of the metal salt-containing material in water; 
 feeding nitrogen to expel oxygen in the solution; 
 adding a catalyst at a room temperature of 10-40° C. preferably 30° C. to adjust the pH to 7-12, preferably 10; 
 keeping agitation for 10-60 minutes; and 
 reacting under condition of 40-100° C. preferably 70° C. water bath, for 20-40 minutes, then separating with a magnet and drying to obtain the magnetic nanoparticle core. 
 
     
     
         26 . The method according to  claim 25 , wherein when aqueous ammonia is used as the catalyst for preparing the nanoparticle, the method for adding aqueous ammonia is a continuous dropping method with assistance of an electronic pump at a speed of 20-100 drops/minute, preferably 40-60 drops/minute; and when the magnetic material is a liquid monomer material, the liquid monomer is added drop wise in continuous manner with assistance of an electronic pump, and the reaction agitation is at a speed of 100-1000 revolutions/minute, preferably 500-700 revolutions/minute. 
     
     
         27 . The method according to any one of  claims 25 - 26 , wherein said method further includes performing hydrophobic surface modification on the obtained nanoparticle core, comprising the steps of:
 dispersing the prepared nanoparticle core in an aqueous solution and added with a xylene solution of 3-chloropropionic acid, polystyrene, CuCl and 4,4′-dinonyl-2,2-dipyridine, and the molar ration between the above-mentioned nanoparticle core and the reaction solution is 1:1;   reacting the above mixture at 130° C. with continuous agitation for 15-30 h, preferably for 24 hours; and   collecting the nanoparticle with a magnet and washing repeatedly with toluene to obtain a hydrophobic polystyrene-coated magnetic nanoparticle.   
     
     
         28 . The method according to any one of  claims 25 - 26 , wherein said method further includes performing hydrophilic surface modification on the obtained nanoparticle core comprising the steps of:
 dispersing the nanoparticle core in xylene, and adding a silane coupling agent, wherein the ratio of the added nanoparticles, xylene and silane coupling agent is 95:5;   reacting under protection of nitrogen atmosphere at a temperature of 20 to 100° C., preferably 80° C. for 2 to 5 hours, preferably 3 hours;   washing with an alcohol solvent and drying for 12 h, dispersing in an aqueous solution under ultrasonic condition, adding with potassium persulfate;   reacting under protection of nitrogen atmosphere at 40-80° C. for 10 minutes, then adding with acrylic acid and continuously reacting at 40-80° C. for 1 hour, preferably reacting at 70° C.; and   separating by a magnet, washing and drying to prepare and obtain a polyacrylic acid-modified hydrophilic nanoparticle.   
     
     
         29 . The method according to any one of  claims 25 - 26 , wherein said method further includes performing a photosensitive, thermosensitive or pH-sensitive surface modification based on the resulting nanoparticle core or hydrophilic surface, or a hydrophilic, hydrophobic, photosensitive, thermosensitive and pH-sensitive co-modification based on the resulting nanoparticle core, wherein the re-modification on the hydrophilic surface includes the steps of:
 dissolving and dispersing the polyacrylic acid-modified magnetic nanoparticles in an alcoholic solvent, adding with a photosensitive monomer such as ethylene benzophenone, a thermosensitive monomer such as N-isopropylacrylamide, or a pH-sensitive monomer such as dimethylaminopropyl methacrylate or a blend monomer of acrylic acid and styrene, keeping reaction at 40-80° C. for 1 h, preferably at a reaction temperature of 70° C.; and separating with a magnet, washing and drying to obtain a photosensitive, thermosensitive or pH sensitive functional monomer-modified magnetic nanoparticles, respectively.   
     
     
         30 . The method according to  claim 1 , wherein the stone includes urinary system, stones, such as kidney stones, ureteral stones and bladder stones, human biliary system stones, and stone-like particles in other organs. 
     
     
         31 . The method according to  claim 1 , wherein the interactions between the magnetic material and stone include ionic bonds, van der Waals forces that form surrounding interactions, hydrophobic interactions, adsorption and surface deposition; chemical bonds between the carboxyl-stone, including hydrogen bonds, ester bonds, amide bonds and other covalent bonds; physical and chemical inter-chain entanglement between chains and chemical crosslinking between chains.