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    METHOD OF PREPARATION OF SUPERPARAMAGNETIC NANOPARTICLES BASED ON IRON OXIDES WITH MODIFIED SURFACE AND SUPERPARAMAGNETIC NANOPARTICLES OBTAINED BY SUCH A METHOD
    15.
    发明授权
    METHOD OF PREPARATION OF SUPERPARAMAGNETIC NANOPARTICLES BASED ON IRON OXIDES WITH MODIFIED SURFACE AND SUPERPARAMAGNETIC NANOPARTICLES OBTAINED BY SUCH A METHOD 有权
    工艺基于的表面改性氧化铁PRODUCING磁性纳米粒子SUPER PARA，并通过这种方法生产的顺磁纳米颗粒

    公开(公告)号：EP1991503B1

    公开(公告)日：2010-09-08

    申请号：EP07711106.0

    申请日：2007-02-23

    申请人： Ustav Makromolekularni Chemie Akademie Ved Ceske Republiky, v.v.i ,  Ustav Experimentalni Mediciny Akademie Ved Ceske Republiky, v.v.i.

    发明人： HORAK, Daniel ,  SYKOVA, Eva ,  BABIC, Michal ,  JENDELOVA, Pavla ,  HAJEK, Milan

    IPC分类号： C01G49/08 ,  C01G49/06 ,  A61K49/18 ,  C09C1/24

    CPC分类号： C09C1/24 ,  A61K49/1836 ,  A61K49/1845 ,  A61K49/1854 ,  A61K49/1863 ,  A61K49/1872 ,  A61K49/1896 ,  B82Y5/00 ,  B82Y30/00 ,  C01G49/06 ,  C01G49/08 ,  C01P2004/64 ,  C01P2006/42

    摘要： The subject of the invention is superparamagnetic nanoparticle probes based on iron oxides, to advantage magnetite or maghemite, with modified surface, coated with mono-, di- or polysaccharides from the group including D-arabinose, D-glucose, D-galactose, D-mannose, lactose, maltose, dextrans and dextrins, or with amino acids or poly(amino acid)s from the group including alanine, glycine, glutamine, asparagine, histidine, arginine, L-lysine, aspartic and glutamic acid or with synthetic polymers based on (meth)acrylic acid and their derivatives selected from the group containing poly(N,N-dimethylacrylamide), poly(N,N- dimethylmethacrylamide), poly(N, N- diethylacrylamide), poly (N, iV-diethylmethacrylamide), poly(N-isopropylacrylamide), poly(N-isopropylmethacrylamide), which form a colloid consisting of particles with narrow distribution with polydispersity index smaller than 1.3, the average size of which amounts to 0.5-30 nm, to advantage 1-10 nm, the iron content is 70- 99.9 wt.%, to advantage 90 wt.%, the modification agent content 0.1-30 wt.%, to advantage 10 wt.%. The particles of size smaller than 2 nm with polydispersity index smaller than 1.1 can be obtained by a modified method of preparation. Superparamagnetic nanoparticle probes according to the invention are prepared by pre- precipitation of colloidal Fe(OH)3 by the treatment of aqueous 0.1-0.2M solution of Fe(III) salt, to advantage FeCl3, with less than an equimolar amount Of NH4OH, at 21°C, under sonication, to which a solution of a Fe(II) salt, to advantage FeCl2, is added in the mole ratio Fe(III)/Fe(II) = 2 under sonication and the mixture is poured into five- to tenfold, to advantage eightfold, molar excess of 0.5M NH4OH. The mixture is left aging for 0-30 min, to advantage 15 min, and then the precipitate is repeatedly, to advantage 7-10 times, magnetically separated and washed with deionized water. Then 1-3 fold amount, to advantage 1.5 fold amount, relative to the amount of magnetite, of 0.1 M aqueous solution of sodium citrate is added and then, drop wise, 1-3 fold amount, to advantage 1.5 fold amount, relative to the amount of magnetite, of 0.7 M aqueous solution of sodium hypochlorite. The precipitate is repeatedly, to advantage 7-10 times, washed with deionized water under the formation of colloidal maghemite to which, after dilution, is added drop wise, to advantage under 5 -min sonication, an aqueous solution of a modification agent, in the weight ratio modification agent/iron oxide = 0.1-10, to advantage 0.2 for amino acids and poly(amino acid)s and 5 for saccharides. The particles smaller than 2 nm. with polydispersity index smaller than 1.1 are prepared by mixing at 21°C 1 volume part of 10-60 wt. %, to advantage 50 wt.%, of an aqueous solution of a saccharide, disaccharide or polysaccharide, such as D-arabinose, D-glucose, D-galactose, D-mannose, lactose, maltose, dextran and dextrins, and 1 volume part of aqueous solution of a Fe(II) and Fe(III) salt, to advantage FeCl2 and FeCl3, where the molar ratio Fe(III)/Fe(II) = 2. A 5-15 %, to advantage 7.5 %, solution Of NH4OH is added until pH 12 is attained and the mixture is heated at 60 °C for 15 min. The mixture is then sonicated at 350 W for 5 min and then washed for 24 h by dialysis in water using a membrane with molecular weight cut-off 14,000 until pH 7 is reached. The volume of solution is reduced by evaporation so that the final dry matter content is 50-100 mg/ml, to advantage 80 mg per 1 ml. Superparamagnetic nanoparticle probes according to the invention can be used for labelling cells used in magnetic resonance imaging for monitoring their movement, localization, survival and differentiation especially in detection of pathologies with cell dysfunction and of tissue regeneration and also for labelling and monitoring cells administered for cell therapy purposes, in particular embryo

    PROCESS FOR PRODUCTION OF SURFACE-COATED INORGANIC PARTICLES
    16.
    发明公开
    PROCESS FOR PRODUCTION OF SURFACE-COATED INORGANIC PARTICLES 有权
    VERFAHREN ZUR HERSTELLUNG VONOBERFLÄCHENBESCHICHTETENANORGANISCHEN TEILCHEN

    公开(公告)号：EP2184262A1

    公开(公告)日：2010-05-12

    申请号：EP08791605.2

    申请日：2008-07-25

    申请人： Tokyo Institute of Technology

    发明人： HANDA, Hiroshi ,  HATAKEYAMA, Mamoru ,  ABE, Masanori ,  SAKAMOTO, Satoshi ,  MASAIKE, Yuka ,  NISHIO, Kosuke ,  KITA, Yoshinori ,  KISHI, Hiroshi

    IPC分类号： C01G49/00 ,  A61K49/00 ,  B22F1/02 ,  H01F1/20 ,  H01F1/34 ,  H01F1/36

    CPC分类号： H01F1/0045 ,  A61K41/0052 ,  A61K49/183 ,  A61K49/1833 ,  A61K49/1836 ,  A61K49/1851 ,  A61K49/1854 ,  B22F1/0022 ,  B22F1/0062 ,  B82Y25/00 ,  B82Y30/00 ,  C01G49/00 ,  C01P2006/42 ,  C09C1/24 ,  C09C3/08 ,  C09C3/10 ,  C09C3/12 ,  G01N33/53 ,  G01N33/54393 ,  H01F1/0054

    摘要： Nano-sized inorganic particles having uniform particle sizes and precisely controlled particle diameters have already been produced by synthesis in an organic solvent, but these nano-sized inorganic particles are hindered from dispersing in a polar solvent because of the adsorption of a long-chain fatty acid on the surfaces of the particles. Further, it was difficult to form nano-sized inorganic particles dispersible in a polar solvent by replacing the long-chain fatty acid coats. According to the invention, various surface-coated inorganic particles dispersible in polar solvents can be produced from fatty acid-coated inorganic particles by adding a temporary coating substance such as thiomalic acid to a nonpolar solvent containing fatty acid-coated inorganic particles dispersed therein to replace the fatty acid coats by the temporary coating substance, dispersing the inorganic particles coated with the temporary coating substance in a polar solvent, and then adding a coating substance dispersible in a polar solvent, e.g., citric acid to the obtained dispersion to replace the temporary coating substance coats covering the inorganic particles by the coating substance dispersible in a polar solvent.

    摘要翻译： 已经通过在有机溶剂中合成来制备具有均匀粒径和精确控制的粒径的纳米尺寸的无机颗粒，但这些纳米尺寸的无机颗粒由于吸附长链脂肪而被阻碍分散在极性溶剂中 酸在颗粒的表面上。 此外，通过代替长链脂肪酸涂层，难以形成分散在极性溶剂中的纳米级无机颗粒。 根据本发明，分散在极性溶剂中的各种表面涂覆的无机颗粒可以通过向包含分散在其中的含脂肪酸涂覆的无机颗粒的非极性溶剂添加例如硫代酸的临时涂层物质，由脂肪酸包覆的无机颗粒制备，以代替 通过临时涂布物质的脂肪酸涂层，将涂覆有临时涂层物质的无机颗粒分散在极性溶剂中，然后将分散在极性溶剂（例如柠檬酸）中的涂覆物质加入到所得分散体中以代替临时涂层 通过可分散在极性溶剂中的涂层物质覆盖无机颗粒的物质外套。

    AMINE FUNCTIONALIZED SUPERPARAMAGNETIC NANOPARTICLES FOR THE SYNTHESIS OF BIOCONJUGATES AND USES THEREFOR
    18.
    发明公开
    AMINE FUNCTIONALIZED SUPERPARAMAGNETIC NANOPARTICLES FOR THE SYNTHESIS OF BIOCONJUGATES AND USES THEREFOR 有权
    胺功能SUPERPARAMAGNETISIERTE纳米粒子生物共轭物的合成

    公开(公告)号：EP1469989A2

    公开(公告)日：2004-10-27

    申请号：EP03705645.4

    申请日：2003-01-02

    申请人： Visen Medical, Inc.

    发明人： GAW, Debra, A. ,  JOSEPHSON, Lee

    IPC分类号： B32B5/16 ,  G01N33/15 ,  G01N33/543

    CPC分类号： A61K49/1854 ,  A61K9/5026 ,  A61K9/5094 ,  B82Y5/00

    摘要： Amine functionalized magnetic nanoparticle compositions and processes for synthesizing the same are described. The process consists of obtaining a carboxylated polymer in substantially pure form, which is used to prepare a substantially size homogeneous, polymer coated carboxyl, functionalized magnetic nanoparticle. The carboxyl groups are converted to reactive primary amino groups by the use of a water-soluble carbodiimide followed by reaction of a large excess of a diamine. The amine-terminated nanoparticles are then reacted with bifunctional crosslinking agents and with various biomolecules to make nanoparticles for in vitro assays, cell sorting applications and target specific MR contrast agents.