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    • 4. 发明申请
    • SUPERPARAMAGNETIC NANOPARTICLES BASED ON IRON OXIDES WITH MODIFIED SURFACE, METHOD OF THEIR PREPARATION AND APPLICATION
    • WO2007095871A3
    • 2007-08-30
    • PCT/CZ2007/000012
    • 2007-02-23
    • USTAV MAKROMOLEKULARNI CHEMIE AKADEMIE VEDCESKE REPUBLIKY, V.V.IUSTAV EXPERIMENTALNI MEDICINY AKADEMIE VEDCESKE REPUBLIKY.V.V.IHORAK, DanielSYKOVA, EvaBABIC, MichalJENDELOVA, PavlaHAJEK, Milan
    • HORAK, DanielSYKOVA, EvaBABIC, MichalJENDELOVA, PavlaHAJEK, Milan
    • C01G49/08C01G49/06A61K49/18C09C1/24
    • 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 FeCl 3 , with less than an equimolar amount Of NH 4 OH, 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 NH 4 OH. 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 FeCl 2 and FeCl 3 , where the molar ratio Fe(III)/Fe(II) = 2. A 5-15 %, to advantage 7.5 %, solution Of NH 4 OH is added until pH 12 is attained and