Cerium oxide nanoparticles, dispersion, antioxidant, oxidizing agent, and method for producing cerium oxide nanoparticles

Abstract

The present invention addresses the problem of providing: cerium oxide nanoparticles having high antioxidation performance; a liquid dispersion containing cerium oxide nanoparticles; and an antioxidant agent.　The present invention provides cerium oxide nanoparticles produced by mixing a salt of at least one metal element selected from alkaline earth metals, transition metals respectively having atomic numbers of 21 to 29, 39 to 43 and 72 to 74 and lanthanoids, a heterocyclic amine, and a solution containing a cerium (III) ion or a cerium (III) salt together and then adding an oxidizing agent to the resultant product.

Description

[Technical Field]

[0001] The present invention relates to cerium oxide nanoparticles, a dispersion containing the nanoparticles, an antioxidant, an oxidizing agent, and a method for producing cerium oxide nanoparticles. [Background technology]

[0002] In recent years, with increasing awareness of safety and hygiene management, antimicrobial technologies that decompose harmful substances and microorganisms have attracted attention. For example, titanium dioxide has the property of oxidizing and decomposing organic matter through its photocatalytic properties and has been evaluated for its decomposition reactions of organic dyes. In addition to its use as an antimicrobial agent, this oxidative decomposition property is expected to be used in applications to decompose various harmful substances such as low molecular weight substances like acetaldehyde and ammonia, allergens, and viruses.

[0003] On the other hand, cerium oxide nanoparticles (nanoceria) possess catalytic activity similar to oxidoreductases such as catalase, oxidase, peroxidase, and superoxide dismutase, and are expected to have applications as oxidizing agents and antioxidants. Since these catalytic activities do not require special light sources such as ultraviolet light, they are expected to be used in applications different from those of titanium dioxide. However, when using metal nanoparticles that tend to aggregate as antioxidants, etc., a method is used in which a stabilizing compound is present during synthesis to stabilize and disperse the resulting nanoparticles. In the case of cerium oxide nanoparticles, for example, polyacrylic acid is used as a stabilizer to oxidize cerium(III) ions with hydrogen peroxide to obtain a particle dispersion, or dextran is used as a stabilizer to neutralize cerium(III) ions with alkali in ammonia water to obtain a particle dispersion.

[0004] Here, Patent Document 1 discloses a method for synthesizing cerium oxide nanoparticles using carboxylic acids such as citric acid and methoxyacetic acid as stabilizers, and further doped with transition metals such as Cu and Fe. It is disclosed that transition metal-doped cerium oxide nanoparticles exhibit improved reduction reaction rates when used as catalysts for fuel cells compared to undoped cerium oxide nanoparticles. Furthermore, Patent Document 2 discloses a sunscreen composition using metal oxide solid-solution cerium oxide particles, which are obtained by solid-solving metal ions having a larger ionic radius and / or lower valency than tetravalent cerium ions into cerium oxide. It states that cerium oxide particles with solid-solution metal ions have a higher ultraviolet blocking effect compared to cerium oxide. Thus, efforts have been made to improve the performance of cerium oxide by metal doping. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] Japanese Patent Publication No. 2014-58448 [Patent Document 2] Japanese Patent Publication No. 2002-293726 [Overview of the project] [Problems that the invention aims to solve]

[0006] The present inventors investigated the potential uses of cerium oxide nanoparticles, such as antioxidants, using carboxylic acids described in Patent Document 1 as stabilizers and adding specific metal salts. However, in the solution of cerium oxide nanoparticles produced by adding transition metal salts using carboxylic acids described in Patent Document 1 as stabilizers, the radical scavenging rate in the radical scavenging test using DPPH (2,2-Diphenyl-1-picrylhydrazyl) was very low, and no improvement in antioxidant performance was observed with the addition of metal salts. Based on these results, further investigations were conducted with the goal of obtaining cerium oxide nanoparticles with high antioxidant performance. [Means for solving the problem]

[0007] To solve the above problems, the inventors focused on the combination of stabilizers and metal salts used in the production of cerium oxide nanoparticles. As a result, they found that cerium oxide nanoparticles with excellent radical scavenging ability can be obtained by mixing a salt of at least one metal element selected from alkaline earth metals, transition metals with atomic numbers 21-29, 39-43, 72-74, and lanthanides as the metal salt, a heterocyclic amine as the stabilizer, and a solution containing cerium(III) ions or a cerium(III) salt, followed by the addition of an oxidizing agent. In addition, when comparing the radical scavenging activity of a dispersion of cerium oxide nanoparticles obtained without adding a metal salt using a heterocyclic amine as the stabilizer with that of a dispersion containing cerium oxide nanoparticles of the present invention, they found that the dispersion of the present invention exhibits up to 2.4 times greater radical scavenging activity.

[0008] On the other hand, when a carboxylic acid was used as a stabilizer instead of a heterocyclic amine, no radical scavenging activity was observed, regardless of whether a metal salt, such as a copper salt, was added. Furthermore, when a dispersion of cerium oxide nanoparticles produced using a heterocyclic amine as a stabilizer was followed by the addition of a metal salt, such as a copper salt, no improvement in radical scavenging activity was observed with the addition of the metal salt. Based on these results, we found that by using a heterocyclic amine as a stabilizer and adding the aforementioned metal salt before the formation of cerium oxide nanoparticles, the resulting dispersion of cerium oxide nanoparticles exhibits high antioxidant activity and oxidative performance, thus completing the present invention.

[0009] The inventors have completed the present invention after the above-mentioned studies. The present invention is as follows: (1) Cerium oxide nanoparticles produced by mixing a salt of at least one metal element selected from alkaline earth metals, transition metals with atomic numbers 21-29, 39-43, 72-74, and lanthanides with a heterocyclic amine and a solution or cerium(III) salt containing cerium(III) ions, and then adding an oxidizing agent. (2) Cerium oxide nanoparticles comprising at least one metal element selected from alkaline earth metals, transition metals with atomic numbers 21-29, 39-43, 72-74, and lanthanides, and a heterocyclic amine as a stabilizer, characterized in that the radical scavenging rate is 35% or more when 1.5 mmol of DPPH is reacted for 30 minutes per 21 mg of CeO. (3) Cerium oxide nanoparticles according to (1) or (2), wherein the metal element is selected from magnesium (Mg), calcium (Ca), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zirconium (Zr), samarium (Sm), and europium (Eu). (4) Cerium oxide nanoparticles according to (1) or (3), wherein the metal salt is added in a quantity of 0.001 moles or more per mole of cerium element. (5) The heterocyclic amine is an aromatic heterocyclic compound, and one of (1) to (4) is a cerium oxide nanoparticle. (6) The cerium oxide nanoparticle according to (5), wherein the aromatic heterocyclic compound is a monocyclic or bicyclic compound having a five-membered ring and / or a six-membered ring structure.

[0010] (7) A cerium oxide nanoparticle according to any one of (1) to (4), wherein the heterocyclic amine is a compound represented by formula (I). [ka] (In equation (I), X is NR) 2 , O, S, R 1 and R 2 R represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyalkyl group having 1 to 4 carbon atoms, an aminoalkyl group having 1 to 4 carbon atoms, or an alkyl sulfonic acid group having 1 to 4 carbon atoms.1 and R 2 may be the same or different.) (8) The cerium oxide nanoparticles according to any one of (1) to (7) above, containing 0.0001 mol or more of the metal element per 1 mol of cerium element. (9) A dispersion containing the cerium oxide nanoparticles according to any one of (1) to (8) above. (10) An antioxidant containing the cerium oxide nanoparticles according to any one of (1) to (8) above or the dispersion according to (9). (11) An oxidizing agent containing the cerium oxide nanoparticles according to any one of (1) to (8) above or the dispersion according to (9). (12) A method for producing cerium oxide nanoparticles, characterized in that a solution containing at least one metal element salt selected from alkaline earth metals, transition metals of atomic numbers 21 to 29, 39 to 43, 72 to 74, and lanthanoids, a heterocyclic amine, and cerium (III) ions or a cerium (III) salt are mixed, and then an oxidizing agent is added.

Advantages of the Invention

[0011] The cerium oxide nanoparticles of the present invention and the dispersion containing the nanoparticles of cerium oxide exhibit higher radical scavenging activity than conventional nanoparticles of cerium oxide, can be suitably used as an antioxidant, and can also be suitably used as an excellent oxidizing agent.

Embodiments for Carrying Out the Invention

[0012] In this specification, the nanoparticles of cerium oxide of the present invention may sometimes be simply described as the nanoparticles of the present invention, and the dispersion containing the nanoparticles of cerium oxide of the present invention may sometimes be simply described as the dispersion of the present invention, respectively.

[0013] The cerium oxide nanoparticles of the present invention are produced by mixing at least one metal element salt selected from alkaline earth metals, transition metals with atomic numbers 21 to 29, 39 to 43, 72 to 74, and lanthanoids, a heterocyclic amine, and a solution containing cerium (III) ions or a cerium (III) salt, and then adding an oxidizing agent. In the synthesis of the cerium oxide nanoparticles, one of the raw materials is a water-soluble cerium (III) salt, and the synthesis is carried out in water or a solvent compatible with water. Therefore, the stabilizer used in the synthesis of the cerium oxide nanoparticles of the present invention needs to be a heterocyclic amine having appropriate hydrophilicity and the property of forming an amine complex with metal ions. Preferred embodiments of the heterocyclic amine used in the present invention include alicyclic amines or aromatic heterocyclic compounds represented by formula (I).

[0014]

Chemical formula

[0015] More preferred embodiments of the alicyclic amine used in the present invention are those in which, in the above formula (I), X represents NR 2 or O, and R 1 and R 2 represent a hydrogen atom, an alkyl group having 1 to 2 carbon atoms, a hydroxyalkyl group having 2 to 3 carbon atoms, an aminoalkyl group having 2 to 3 carbon atoms or a sulfonic acid alkyl group having 2 to 3 carbon atoms. R 1 and R 2 may be the same or different.

[0016] Examples of such alicyclic amines include piperazine, 1-methylpiperazine, N,N'-dimethylpiperazine, 1-ethylpiperazine, N,N'-diethylpiperazine, 1-(2-hydroxyethyl)piperazine, 1,4-bis(2-hydroxyethyl)piperazine, N-(2-aminoethyl)piperazine, 1,4-bis(2-aminoethyl)piperazine, 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid, piperazine-1,4-bis(2-ethanesulfonic acid), morpholine, 4-methylmorpholine, 4-ethylmorpholine, 4-(2-aminoethyl)morpholine, 4-(2-hydroxyethyl)morpholine, 2-morpholinoethanesulfonic acid, and 3-morpholinopropanesulfonic acid.

[0017] A preferred embodiment of the heterocyclic amine used in the present invention is an aromatic heterocyclic compound containing 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in its ring structure. A more preferred embodiment of the aromatic heterocyclic compound is, in addition to the above, a monocyclic or bicyclic compound having a 5-membered ring and / or 6-membered ring structure. Examples of such aromatic heterocyclic compounds include pyrazole, imidazole, triazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, tetrazine, indazole, benzimidazole, azaindole, pyrazolopyrimidine, purine, benzotriazole, quinoxaline, cinnoline, quinazoline, phthalazine, 1,5-naphthiridine, 1,6-naphthiridine, 1,7-naphthiridine, 1,8-naphthiridine, 2,6-naphthiridine, 2,7-naphthiridine, and pteridine. Furthermore, the above aromatic heterocyclic compound may be a derivative having substituents such as a methyl group, ethyl group, amino group, aminomethyl group, monomethylamino group, dimethylamino group, or cyano group as substituents that do not significantly change the form of complex formation or solubility in the reaction solvent. Moreover, it is even more preferable that the aromatic heterocyclic compound has at least one of the nitrogen atoms having a lone pair of electrons that is not included in the π-conjugated system.

[0018] In the dispersion containing cerium oxide nanoparticles of the present invention, it is necessary to use a salt of at least one metal element selected from alkaline earth metals, transition metals with atomic numbers 21-29, 39-43, and 72-74, and lanthanides. The metal ions constituting these metal salts can take on a valence of 2+ or 3+, and when doped into cerium oxide nanoparticles, they create lattice defects, thus improving antioxidant performance. In the present invention, alkaline earth metals refer to beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra). Lanthanides refer to elements with atomic numbers 57-71.

[0019] Specific examples of metal salts include carboxylates, organic acid salts such as sulfonates, phosphorus oxoates such as phosphates and phosphonates, inorganic acid salts such as nitrates, sulfates, and carbonates, as well as halides and hydroxides. Any of these salts that dissolve in the synthesis solvent is acceptable.

[0020] Among these metal salts, magnesium salts, calcium salts, and, if transition metal salts, transition metal salts with atomic numbers 21-29, zirconium (Zr) salts, and, if lanthanides, samarium (Sm) salts and europium (Eu) salts are preferred, as they are easily doped with cerium oxide nanoparticles and further enhance antioxidant activity. More preferably, salts of Mg, Ca, Mn, Fe, Co, Ni, Cu, Zr, Sm, and Eu are used.

[0021] In the present invention, cerium oxide nanoparticles are composed of a mixture of Ce2O3 and CeO2. In addition to the oxide form described above, cerium oxide may also be in the form of hydroxide or oxyhydroxide. The ratio of Ce2O3 to CeO2 can be calculated as the ratio of cerium(III) to cerium(IV) by X-ray photoelectron spectroscopy (XPS) or the like.

[0022] A preferred embodiment of the dispersant of the present invention comprises a salt of at least one metal element selected from alkaline earth metals, transition metals with atomic numbers 21-29, 39-43, 72-74, and lanthanides, a heterocyclic amine, and cerium oxide nanoparticles, and has a radical scavenging rate of 35% or more using DPPH. The dispersant of the present invention, comprising a salt of at least one metal element selected from the above, a heterocyclic amine, and cerium oxide nanoparticles, and having a radical scavenging rate of 35% or more when reacted with 1.5 mmol of DPPH per 21 mg of CeO for 30 minutes, can be suitably used as an antioxidant. The radical scavenging rate of the dispersant of the present invention using DPPH is preferably 40% or more, and particularly preferably 50% or more.

[0023] The cerium oxide nanoparticles according to the present invention preferably contain, for every mole of cerium, a total of 0.0001 moles to 0.3 moles of metallic elements selected from alkaline earth metals, transition metals with atomic numbers 21-29, 39-43, and 72-74, and lanthanides. More preferably, the amount is in the range of 0.001 moles to 0.2 moles.

[0024] The dispersion of the present invention is produced by mixing a salt of at least one metal element selected from alkaline earth metals, transition metals with atomic numbers 21-29, 39-43, 72-74, and lanthanides, a heterocyclic amine, and a solution or cerium(III) salt containing cerium(III) ions, and then adding an oxidizing agent. The method for producing the dispersion of cerium oxide nanoparticles of the present invention will be described below.

[0025] The first step is to mix at least one metal salt selected from alkaline earth metal salts, transition metal salts with atomic numbers 21-29, 39-43, and 72-74, and lanthanide salts with a heterocyclic amine and a solution containing cerium(III) ions or a cerium(III) salt to obtain a mixed solution.

[0026] The heterocyclic amine used in this process can be used as a solution dissolved in any solvent. Water or a water-compatible solvent is preferred. Specific examples of water-compatible solvents include methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, tetrahydrofuran, acetone, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), glycerol, ethylene glycol, and oligoethylene glycol. If the heterocyclic amine is difficult to dissolve, it may be dissolved by heating or sonication. The amount of heterocyclic amine used should be in the range of 0.1 to 100 molar equivalents relative to the cerium(III) ion.

[0027] A method for mixing a metal salt, a heterocyclic amine, and a solution containing cerium(III) ions or a cerium salt is to prepare and mix a solution containing the metal salt, a solution containing the heterocyclic amine, and a solution containing cerium(III) ions separately, or, if the solvent in the heterocyclic amine solution is water or a water-compatible solvent, to add the cerium(III) salt and the metal salt to the heterocyclic amine solution and mix them.

[0028] Regarding the order of mixing, in order to improve the stability of the resulting cerium oxide nanoparticles, it is preferable to first mix the solution containing the heterocyclic amine with the solution containing cerium(III) ions or cerium(III) salt, and then add and mix the metal salt. If the solution containing the heterocyclic amine and the solution containing cerium(III) ions or cerium(III) salt are mixed first, it is preferable to mix for 5 minutes or more to confirm that a homogeneous solution has been achieved, and then add the metal salt and mix for another 5 minutes or more to achieve a homogeneous solution.

[0029] A solution containing cerium(III) ions can be prepared by dissolving a cerium(III) salt in any solvent. For example, cerium(III) nitrate hexahydrate can be used as the cerium(III) salt.

[0030] The metal salt may be added directly to the solution containing the heterocyclic amine and cerium(III) ions or cerium(III) salt in its solid form, or a solution prepared by dissolving the metal salt in any solvent may be added to the solution containing the heterocyclic amine and cerium(III) ions or cerium(III) salt. The amount of cerium(III) salt used is preferably such that the final concentration of the reaction solution is in the range of 0.01% to 10% by mass.

[0031] The amount of metal salt used is preferably in the range of 0.0001 moles to 0.3 moles per mole of cerium(III) ions. More preferably, it is in the range of 0.001 moles to 0.2 moles. Note that the amount of metal elements does not include the amounts of elements other than alkaline earth metal elements, transition metal elements with atomic numbers 21-29, 39-43, 72-74, and lanthanides contained in the metal salt.

[0032] In the first step, the solution containing the metal salt, heterocyclic amine, and cerium(III) ions or cerium(III) salt is preferably free from aliphatic hydroxycarboxylic acids, aliphatic alkoxycarboxylic acids, and trivalent or higher carboxylic acids, for example, the compounds listed below. If they are present, the amount is preferably 0.1 molar equivalent or less, and more preferably 0.01 molar equivalent or less, relative to the cerium(III) ions. Examples of aliphatic hydroxycarboxylic acids include lactic acid, hydroxybutyric acid, and / or salts thereof, and examples of aliphatic alkoxycarboxylic acids include methoxyacetic acid, ethoxyacetic acid, 2-[2-(2-methoxyethoxy)ethoxy]acetic acid (MEEA) and / or salts thereof. Examples of trivalent or higher carboxylic acids include nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA), ethylenediamine disuccinic acid (EDDS), glycol etherdiaminetetraacetic acid (EGTA), diethylenetriaminopentaacetic acid (DTPA), citric acid, hydroxyethylethylenediaminetetraacetic acid (HEDTA), polyacrylic acid, and / or salts thereof.

[0033] The second step is to add an oxidizing agent to the mixed solution obtained in the first step. Examples of oxidizing agents used in the second step include nitric acid, potassium nitrate, hypochlorous acid, chlorous acid, chloric acid, perchloric acid, halogens, hydrogen halides, permanganates, chromic acid, dichromate, oxalic acid, hydrogen sulfide, sulfur dioxide, sodium thiosulfate, sulfuric acid, and hydrogen peroxide. Among these, hydrogen peroxide is particularly preferred. The amount added should be between 0.1 and 10 molar equivalents relative to cerium(III) ions, and preferably between 0.5 and 2 molar equivalents.

[0034] When an oxidizing agent is added to the mixed solution obtained in the first step, cerium(III) ions are oxidized to cerium(IV), initiating the formation reaction of cerium oxide particles composed of a mixture of Ce2O3 and CeO2. During this reaction, the solution turns yellow, orange, red, brown, etc. This coloration is due to the change of cerium(III) ions to cerium(IV), and the degree of coloration is determined by the ratio of cerium(III) to cerium(IV) present on the surface of the cerium oxide nanoparticles. The end of the reaction can be determined when the color change disappears. At this time, the particle formation reaction is pH-dependent and proceeds in weakly acidic to basic conditions. Sodium hydroxide aqueous solution or ammonia aqueous solution can be used to adjust the pH of the reaction solution. The reaction usually finishes in about 5 minutes to 1 hour, and a dispersion containing the cerium oxide nanoparticles of the present invention is obtained.

[0035] The dispersion of the present invention can be filtered through an ultrafiltration membrane or dialyzed through a semipermeable membrane after the reaction is complete to remove any unreacted oxidizing agent, cerium(III) ions, metal salts, and excess heterocyclic amines remaining in the dispersion. Subsequently, the purified dispersion of the present invention can be dried using an evaporator or freeze-dryer to extract cerium oxide nanoparticles.

[0036] The dispersion of the present invention may contain, in addition to cerium oxide nanoparticles and water as the solvent, other solvent components that are compatible with water. Examples of other solvent components include methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, tetrahydrofuran, acetone, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), glycerol, ethylene glycol, and oligoethylene glycol. These solvent components may be included in an amount of 90% by volume or less. These solvent components may be added to the dispersion after the reaction is complete, added after filtration with an ultrafiltration membrane, used as a dialysate, or added to the dispersion after dialysate. They may also be added to dried cerium oxide nanoparticles together with water to form a dispersion.

[0037] The dispersion of the present invention may contain ionic components. Examples of ionic components that provide buffering performance include acetic acid, phthalic acid, succinic acid, carbonic acid, Tris(hydroxymethyl)aminomethane (Tris), 2-Morpholinoethanesulfonic acid monohydrate (MES), Bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane (Bis-Tris), N-(2-Acetamido)iminodiacetic acid (ADA), Piperazine-1,4-bis(2-ethanesulfonic acid) (PIPES), N-(2-Acetamido)-2-aminoethanesulfonic acid (ACES), 2-Hydroxy-3-morpholinopropanesulfonic acid (MOPSO), N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), 3-Morpholinopropanesulfonic acid (MOPS), and N-Tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid. acid(TES), 2-[4-(2-Hydroxyethyl)-1-piperazinyl]ethanesulfonic acid(HEPES), 2-Hydroxy-N-tris(hydroxymethyl)methyl-3-aminopropanesulfonic(TAPSO), Piperazine-1,4-bis(2-hydroxy-3-propanesulfonic acid)(POPSO), 2-Hydroxy-3-[4-(2-hydroxyethyl)-1-piperazinyl]propanesulfonic acid(HEPSO), 3-[4-(2-Hydroxyethyl)-1-piperazinyl]propanesulfonic acid(HEPPS)(Tricine), N,Examples include N-Bis(2-hydroxyethyl)glycine (Bicine) and N-Tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid (TAPS), while sodium chloride and potassium chloride are examples of components that do not impart buffering capacity. These ionic components can be added to a final concentration in the range of 0.1 mM to 1 M. These ionic components may be added to the dispersion after the reaction is complete, added after filtration with an ultrafiltration membrane, used as a dialysate by dissolving them in water, or added to the dispersion after dialysate. They may also be added to dried cerium oxide nanoparticles together with water to form a dispersion.

[0038] The pH of the dispersion of the present invention may be in the range of pH 2 to 12, preferably pH 4 to 10, and more preferably pH 5 to 8. The pH may be adjusted by adding a buffer solution, or by adding an acid such as nitric acid, sulfuric acid, or hydrochloric acid, or a base such as sodium hydroxide or potassium hydroxide.

[0039] The dispersion of the present invention may be stored as is after the reaction is complete, or it may be stored as a purified product obtained by filtering the dispersion through an ultrafiltration membrane or dialyzing it through a semipermeable membrane, or it may be dried using an evaporator or freeze-dryer to extract cerium oxide nanoparticles and store them as a dried product. Alternatively, it may be stored as a dispersion containing the above-mentioned solvent and ionic components, or the pH may be adjusted before storage. Refrigeration is preferred for storage.

[0040] The hydrodynamic diameter of the cerium oxide nanoparticles in this invention is calculated by measuring dynamic light scattering to derive the autocorrelation function, analyzing it using the Marquadt method, and then calculating the average particle diameter from the number-converted histogram. The ELS-Z from Otsuka Electronics Co., Ltd. is used for measuring dynamic light scattering. The hydrodynamic diameter of the dispersion should be between 1 nm and 1000 nm, and preferably between 1 nm and 200 nm.

[0041] The hydrodynamic diameter of the cerium oxide nanoparticles of the present invention can be adjusted by the amount of heterocyclic amine used relative to the amount of cerium(III) ions used. A lower amount of heterocyclic amine results in larger particle sizes, while a higher amount of heterocyclic amine results in smaller particle sizes.

[0042] The cerium oxide nanoparticles or dispersions thereof of the present invention may be sterilized before use as an antioxidant or the like. One method of sterilization is to pass them through a sterilization filter.

[0043] The cerium oxide nanoparticles or dispersions thereof of the present invention can be used as antioxidants. In the present invention, an antioxidant refers to a substance that has reducing properties and suppresses lipid peroxidation or reacts with and inhibits the action of reactive oxygen species (such as superoxide ions, hydroxyl radicals, and hydrogen peroxide) (Standard Chemical Terminology Dictionary, 2nd Edition, Maruzen Publishing). For example, by utilizing such antioxidant activity, it can be used as a reducing agent in organic chemical reactions or as a radical arresting agent in polymer polymerization. Furthermore, by utilizing its antioxidant activity, it can be used to protect cells from oxidative stress by adding it to cell culture media or applying it to culture vessels such as petri dishes. In addition, by applying it to the skin as a cosmetic, it can be used to protect the skin from lipid peroxides and reactive oxygen species. In addition, by utilizing its antioxidant activity, it can be used in antioxidant enzyme solutions. It can be used as a substitute for liquid. Specifically, by coating electrodes with cerium oxide nanoparticles to immobilize them, it can be used in hydrogen peroxide detection reactions and electrochemical detection reactions as a substitute for catalase solution. It can also be used as a neutralizing solution for hydrogen peroxide used industrially in food, semiconductor, textile, and pulp and paper manufacturing, as well as for sterilization of public baths and removal of slime from pipes. Such performance can be evaluated by catalase activity, as described later. In addition, the dispersion of the present invention can be added as an antioxidant during the molding of rubber and plastics, or added to fuels, detergents, food, and animal feed. Such antioxidant performance can be evaluated by scavenging reactions of active species, as described later.

[0044] Furthermore, the cerium oxide nanoparticles or dispersions thereof of the present invention can be used as pharmaceuticals for humans or animals for oxidative stress and inflammation as antioxidants. Specifically, the dispersion of the present invention can be administered to subjects by local, enteral, or parenteral methods such as injection, intravenous infusion, or transplantation, and can be used to prevent or treat oxidative stress-related diseases such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and ischemia-reperfusion injury. In addition, the dispersion of the present invention can be used as an antioxidant to reduce inflammation locally or systemically by coating the surface of medical devices such as cannulas, catheters, or stents, or artificial organs such as dialysis membranes.

[0045] The scavenging reaction of the active species can be measured, for example, as the decomposition rate of an artificial radical called 2,2-Diphenyl-1-picrylhydrazyl (DPPH). Specifically, a solution of DPPH is mixed with a dispersion containing the cerium oxide nanoparticles of the present invention and allowed to stand for a predetermined time. The same treatment is performed on a mixture of the solution containing the cerium oxide nanoparticles of the present invention and a solvent without DPPH as a background correction solution. The same treatment is performed on a solution without the cerium oxide nanoparticles of the present invention as a control. Furthermore, a solution of DPPH at the same concentration as the reaction solution is prepared as a reference solution, and the absorption spectrum of the above solution is measured. For analysis, the absorbance at 517 nm, the maximum absorption wavelength of DPPH, is used. Absorbance of the reference solution (I ST ) and absorbance of control (I CO The difference between (△I0) and the absorbance (I) of the solution containing the cerium oxide nanoparticles of the present invention. EX ) and absorbance of background correction solution (I BG The difference (△I) between the two is calculated. The ratio of the latter (△I) to the former (△I0) is calculated as the DPPH retention rate, and by subtracting the DPPH retention rate (%) from 100 (%), the DPPH scavenging rate can be calculated. This value represents the radical scavenging performance.

[0046] The cerium oxide nanoparticles or dispersions thereof of the present invention can be used as an oxidizing agent. For example, by utilizing its oxidizing properties, it can be used as a homogeneous catalyst in organic synthesis reactions and polymer polymerization, or as a wet etching solution for semiconductors. It can also be used as a substitute for oxidase solutions by utilizing its oxidizing properties. Specifically, it can be used as a substitute for oxidase or peroxidase solutions in detection reactions using antibody-antigen reactions and nucleic acid hybridization, as well as in tissue staining. It can also be used in electrochemical detection reactions by coating electrodes with cerium oxide nanoparticles to immobilize them. Furthermore, by utilizing its oxidizing properties, it can be used as a bleaching and disinfecting agent to decompose and remove dirt, odors, allergens, bacteria, fungi, and mold. Specifically, it can be used as a bleaching agent for cleaning clothing, dishes, kitchens, toilets, washrooms, bathrooms, medical equipment, etc. Cleaning methods include soaking, spraying, and spraying using a humidifier or nebulizer. Furthermore, it can be added to swimming pools, bathtubs, and hot springs as a disinfectant, or used in body soaps, hand soaps, disinfectants, mouthwashes, rinses, hand gels, antibacterial sprays, germicidal sprays, deodorizing sprays, wet wipes, and antibacterial sheets. In addition, the cerium oxide nanoparticles of the present invention may be left on the object after the above-mentioned cleaning or disinfection to provide sustained deodorizing, antiviral, antibacterial, and antifungal effects. Such performance as an oxidizing agent can be evaluated by the discoloration reaction of organic dyes described later.

[0047] The cerium oxide nanoparticles or dispersions thereof of the present invention can be used in combination with alcohols, surfactants, disinfectants, and natural organic substances when used as an oxidizing agent. Examples of alcohols include ethanol and isopronol; examples of surfactants include benzalkonium chloride, benzethonium chloride, and alkylpolyaminoethylglycine; examples of disinfectants include chlorhexidine, acrinol, merbromin, and crystal violet; and examples of natural organic substances include polyphenols, catechins, tannic acid, chitin, chitosan, isothiocyanates, hinokitiol, limonene, polylysine, terpenoids, saponins, flavonoids, and carotenes. Multiple combinations of these may be used.

[0048] The cerium oxide nanoparticles or dispersions of the present invention can be used in combination with other known oxidizing agents when used as an oxidizing agent. Examples include hypochlorous acid, sodium hypochlorite, povidone-iodine, hydrogen peroxide, ozonated water, and peracetic acid, and several of these may be used in combination.

[0049] The oxidizing performance of the cerium oxide nanoparticles or dispersion of the present invention can be confirmed by performing a color reaction with TMBZ3,3',5,5'-Tetramethylbenzidine (TMBZ), which is used to determine oxidase activity. Specifically, the cerium oxide nanoparticles or dispersion of the present invention are mixed with an aqueous solution of TMBZ and allowed to stand for a predetermined time. As a control, the same treatment is performed on an aqueous solution of TMBZ that does not contain cerium oxide nanoparticles. After the reaction, the absorbance at 655 nm of each solution is measured. If the absorbance is more than twice that of the control, it can be determined that the solution has oxidizing performance.

[0050] The cerium oxide nanoparticles or dispersions of the present invention can be used as an additive to impart oxidation properties to fibers, tubes, beads, rubber, films, plastics, etc., by adding them during molding or applying them to their surfaces for deodorizing, anti-allergic, antibacterial, and antifungal processing. Examples of products processed with the cerium oxide nanoparticles or dispersions of the present invention include drain covers for kitchen sinks, drain plugs, window glass fixing gaskets, mirror fixing gaskets, waterproof gaskets for bathrooms, washbasins and kitchens, refrigerator door lining gaskets, bath mats, non-slip rubber for washbasins and chairs, hoses, shower heads, gaskets used in water purifiers, plastic products for water purifiers, gaskets used in washing machines, plastic products for washing machines, masks, medical caps, medical shoe covers, air conditioner filters, air purifier filters, and vacuum cleaners. Examples of applications include filters for ventilation fans, vehicle filters, air conditioning filters, plastic parts such as air conditioner fins and air conditioner outlet louvers, and blower fans, plastic parts such as car air conditioner fins and car air conditioner outlet louvers, and blower fans, clothing, bedding, nets for screen doors, nets for chicken coops, nets for mosquito nets, wallpaper, windows, blinds, interior materials for buildings such as hospitals, interior materials for trains and automobiles, vehicle seats, blinds, chairs, sofas, equipment for handling viruses, doors, ceiling panels, floor panels, windows, and other building materials. Thus, products processed with cerium oxide nanoparticles or dispersions thereof according to the present invention can be used as sanitary materials in a variety of fields. [Examples]

[0051] The present invention will be further described in detail by the following examples. <Materials and Methods> Benzimidazole and 1-(2-hydroxyethyl)piperazine were obtained from Tokyo Chemical Industry Co., Ltd., cerium(III) nitrate hexahydrate, copper(II) sulfate pentahydrate, calcium chloride, samarium(III) nitrate hexahydrate, and 30% by mass hydrogen peroxide were obtained from Fujifilm Wako Pure Chemical Corporation, and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) was obtained from Sigma-Aldrich Japan LLC. Other reagents were purchased from Fujifilm Wako Pure Chemical Corporation, Tokyo Chemical Industry Co., Ltd., and Sigma-Aldrich Japan LLC, and were used without any special purification.

[0052] (Example 1) A dispersion containing cerium oxide nanoparticles doped with a Cu compound at a concentration of 0.01 mol, with benzimidazole as a stabilizer. To 10 mL of a 50% ethylene glycol aqueous solution containing 90 mg / 10 mL of benzimidazole, 100 μL of an aqueous solution of 1 g / mL cerium nitrate hexahydrate was added and the mixture was stirred at room temperature for 5 minutes. Next, 23 μL of an aqueous solution of 0.1 M copper sulfate pentahydrate (0.01 moles per mole of cerium nitrate hexahydrate) was added and the mixture was stirred at room temperature for 5 minutes. Then, 1 mL of an aqueous solution of 0.6% hydrogen peroxide was gradually added dropwise and the mixture was reacted at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and then purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD to obtain a dispersion containing cerium oxide nanoparticles.

[0053] (Example 2) A dispersion containing cerium oxide nanoparticles doped with a Cu compound at a concentration of 0.001 mol, with benzimidazole as a stabilizer. A dispersion containing cerium oxide nanoparticles was obtained in the same manner as in Example 1, except that the amount of 0.1 M copper sulfate pentahydrate aqueous solution added was changed to 2.3 μL (0.001 moles per mole of cerium nitrate hexahydrate).

[0054] (Example 3) A dispersion containing cerium oxide nanoparticles doped with a Cu compound at a concentration of 0.0025 molars, with benzimidazole as a stabilizer. A dispersion containing cerium oxide nanoparticles was obtained in the same manner as in Example 1, except that the amount of 0.1 M copper sulfate pentahydrate aqueous solution added was changed to 5.8 μL (0.0025 moles per mole of cerium nitrate hexahydrate).

[0055] (Example 4) A dispersion containing cerium oxide nanoparticles doped with a Ca compound at a concentration of 0.01 mol, with benzimidazole as a stabilizer. To 10 mL of a 50% ethylene glycol aqueous solution containing 90 mg / 10 mL of benzimidazole, 100 μL of an aqueous solution of 1 g / mL cerium nitrate hexahydrate was added and the mixture was stirred at room temperature for 5 minutes. Next, 23 μL of a 0.1 M aqueous calcium chloride solution (0.01 moles per mole of cerium nitrate hexahydrate) was added and the mixture was stirred at room temperature for 5 minutes. Then, 1 mL of a 0.6% aqueous hydrogen peroxide solution was gradually added dropwise and the mixture was reacted at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and then purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD to obtain a dispersion containing cerium oxide nanoparticles.

[0056] (Example 5) A dispersion containing cerium oxide nanoparticles doped with a Ca compound at a concentration of 0.001 molars, with benzimidazole as a stabilizer. A dispersion containing cerium oxide nanoparticles was obtained in the same manner as in Example 4, except that the amount of 0.1 M calcium chloride aqueous solution added was changed to 2.3 μL (0.001 moles per mole of cerium nitrate hexahydrate).

[0057] (Example 6) A dispersion containing cerium oxide nanoparticles doped with 0.0025 mol of Ca compound, with benzimidazole as a stabilizer. A dispersion containing cerium oxide nanoparticles was obtained in the same manner as in Example 4, except that the amount of 0.1 M calcium chloride aqueous solution added was changed to 5.8 μL (0.0025 moles per mole of cerium nitrate hexahydrate).

[0058] (Example 7) A dispersion containing cerium oxide nanoparticles doped with 0.05 mol of Ca compound, with benzimidazole as a stabilizer. A dispersion containing cerium oxide nanoparticles was obtained in the same manner as in Example 4, except that the added metal salt aqueous solution was changed to 11.5 μL of 1 M calcium chloride aqueous solution (0.05 moles per mole of cerium nitrate hexahydrate).

[0059] (Example 8) A dispersion containing cerium oxide nanoparticles doped with 0.1 mol of a Ca compound, with benzimidazole as a stabilizer. A dispersion containing cerium oxide nanoparticles was obtained in the same manner as in Example 4, except that the added metal salt aqueous solution was changed to 23 μL of 1 M calcium chloride aqueous solution (0.1 moles per mole of cerium nitrate hexahydrate).

[0060] (Example 9) A dispersion containing cerium oxide nanoparticles doped with 0.2 mol of a Ca compound, with benzimidazole as a stabilizer. A dispersion containing cerium oxide nanoparticles was obtained in the same manner as in Example 4, except that the added metal salt aqueous solution was changed to 46 μL of 1 M calcium chloride aqueous solution (0.2 moles per mole of cerium nitrate hexahydrate).

[0061] (Reference Example 1) Dispersion containing cerium oxide nanoparticles with benzimidazole as a stabilizer To 10 mL of a 50% ethylene glycol aqueous solution containing 90 mg / 10 mL of benzimidazole, 100 μL of an aqueous solution of 1 g / mL cerium nitrate hexahydrate was added and the mixture was stirred at room temperature for 5 minutes. Then, 1 mL of a 0.6% aqueous hydrogen peroxide solution was gradually added dropwise, and the mixture was reacted at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and then purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD to obtain a dispersion containing cerium oxide nanoparticles.

[0062] (Comparative Example 1) A dispersion containing cerium oxide nanoparticles stabilized with benzimidazole, to which 0.01 moles of a Cu compound were added later. A dispersion containing cerium oxide nanoparticles with added Cu compound was obtained by adding 5.8 μL of 0.01 M copper sulfate aqueous solution (0.01 moles per mole of cerium oxide) to 100 μL of a solution prepared by separating the cerium oxide nanoparticles prepared in Reference Example 1 to a concentration of 10 mg / mL, and then mixing the mixture.

[0063] (Example 10) A dispersion containing cerium oxide nanoparticles doped with a Cu compound at a concentration of 0.0025 mol, with 1-(2-hydroxyethyl)piperazine as a stabilizer. To 10 mL of a 50% ethylene glycol aqueous solution of 1-(2-hydroxyethyl)piperazine at a concentration of 50 mg / 10 mL, nitric acid was added to adjust the pH to 7. 200 μL of 0.1 g / mL cerium nitrate hexahydrate aqueous solution was added to this solution, and the mixture was stirred at room temperature for 5 minutes. Next, 11.5 μL of 0.01 M copper sulfate pentahydrate aqueous solution (0.0025 moles per mole of cerium nitrate hexahydrate) was added, and the mixture was stirred at room temperature for 5 minutes. Then, 200 μL of 1.2% hydrogen peroxide aqueous solution was gradually added dropwise, and the mixture was reacted at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and then purified using a 10 kD ultrafiltration membrane to obtain a dispersion containing cerium oxide nanoparticles.

[0064] (Example 11) A dispersion containing cerium oxide nanoparticles doped with 0.001 mol of Sm compound, with 1-(2-hydroxyethyl)piperazine as a stabilizer. A dispersion containing cerium oxide nanoparticles was obtained in the same manner as in Example 10, except that the added metal salt aqueous solution was changed to 4.6 μL of 0.01 M samarium nitrate hexahydrate (0.001 moles per mole of cerium nitrate hexahydrate).

[0065] (Reference Example 2) Dispersion containing cerium oxide nanoparticles with methoxyacetic acid as a stabilizer To 10 mL of a 14 mg / 10 mL aqueous solution of methoxyacetic acid, whose pH was adjusted to 7 with sodium hydroxide, 200 μL of an aqueous solution of 0.1 g / mL cerium nitrate hexahydrate was added and the mixture was stirred at room temperature for 5 minutes. Then, 200 μL of a 1.2% aqueous solution of hydrogen peroxide was gradually added dropwise and the mixture was reacted at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and then purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD to obtain a dispersion containing cerium oxide nanoparticles.

[0066] (Comparative Example 2) A dispersion containing cerium oxide nanoparticles doped with a Cu compound at a concentration of 0.01 mol, with methoxyacetic acid as a stabilizer. To 10 mL of a 14 mg / 10 mL aqueous solution of methoxyacetic acid, whose pH was adjusted to 7 with sodium hydroxide, 200 μL of an aqueous solution of 0.1 g / mL cerium nitrate hexahydrate was added and the mixture was stirred at room temperature for 5 minutes. Next, 4.6 μL of an aqueous solution of 0.1 M copper sulfate pentahydrate (0.01 moles per mole of cerium nitrate hexahydrate) was added and the mixture was stirred at room temperature for 5 minutes. Then, 200 μL of an aqueous solution of 1.2% hydrogen peroxide was gradually added dropwise and the mixture was reacted at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and then purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD to obtain a dispersion containing cerium oxide nanoparticles.

[0067] (Reference Example 3) Dispersion containing cerium oxide nanoparticles stabilized with 1-(2-hydroxyethyl)piperazine To 10 mL of a 50% ethylene glycol aqueous solution of 1-(2-hydroxyethyl)piperazine at a concentration of 50 mg / 10 mL, nitric acid was added to adjust the pH to 7. 200 μL of 0.1 g / mL cerium nitrate hexahydrate aqueous solution was added to this solution, and the mixture was stirred at room temperature for 5 minutes. Then, 200 μL of 1.2% hydrogen peroxide aqueous solution was gradually added dropwise, and the mixture was reacted at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and then purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD to obtain a dispersion containing cerium oxide nanoparticles.

[0068] (Example 12) A dispersion containing cerium oxide nanoparticles doped with 0.01 mol of Fe compound, with benzimidazole as a stabilizer. To 10 mL of a 50% ethylene glycol aqueous solution containing 90 mg / 10 mL of benzimidazole, 100 μL of a 1 g / mL aqueous solution of cerium nitrate hexahydrate was added and the mixture was stirred at room temperature for 5 minutes. Next, 23 μL of a 0.1 M aqueous solution of iron(II) chloride tetrahydrate (0.01 moles per mole of cerium nitrate hexahydrate) was added and the mixture was stirred at room temperature for 5 minutes. Then, 1 mL of a 0.6% aqueous solution of hydrogen peroxide was gradually added dropwise and the mixture was reacted at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and then purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD to obtain a dispersion containing cerium oxide nanoparticles.

[0069] (Example 13) A dispersion containing cerium oxide nanoparticles doped with 0.05 mol of Fe compound, with benzimidazole as a stabilizer. To 10 mL of a 50% ethylene glycol aqueous solution containing 90 mg / 10 mL of benzimidazole, 100 μL of a 1 g / mL aqueous solution of cerium nitrate hexahydrate was added and the mixture was stirred at room temperature for 5 minutes. Next, 11.5 μL of a 1 M aqueous solution of iron(II) chloride tetrahydrate (0.01 moles per mole of cerium nitrate hexahydrate) was added and the mixture was stirred at room temperature for 5 minutes. Then, 1 mL of a 0.6% aqueous solution of hydrogen peroxide was gradually added dropwise and the mixture was reacted at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and then purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD to obtain a dispersion containing cerium oxide nanoparticles.

[0070] (Example 14) Measurement of antioxidant performance by radical scavenging test using DPPH 100 μL of 0.3 mM DPPH ethanol solution and 100 μL of dispersions containing cerium oxide nanoparticles prepared in Examples 1-13, Reference Examples 1-3, and Comparative Examples 1 and 2 (diluted to 0.2 mg / ml in 50% ethylene glycol aqueous solution) were mixed and allowed to stand at room temperature for 30 minutes in the dark. The same treatment was performed on a solution prepared by mixing 100 μL of the dispersion containing cerium oxide nanoparticles (prepared to 0.2 mg / mL) with 100 μL of ethanol as a background correction solution. As a control, a solution prepared by mixing 100 μL of 50% ethylene glycol aqueous solution with 100 μL of ethanol was also performed. A reference solution was prepared by mixing 100 μL of 0.3 mM DPPH ethanol solution with 100 μL of 50% ethylene glycol aqueous solution. The absorption spectra of the above solutions were measured. The absorbance at 517 nm, the maximum absorption wavelength of DPPH, was used for the analysis. The DPPH scavenging rate was calculated using the following formula based on the absorbance of each solution. Furthermore, for Examples 1-9, 12, and 13, the DPPH scavenging rate of Reference Example 1 was set to 1 (reference), and for Examples 10 and 11, the radical scavenging rate of Reference Example 3 was set to 1. The activity improvement rate was calculated as the multiple increase in the radical scavenging rate of each example. For Comparative Example 1, the activity improvement rate was calculated using the DPPH scavenging rate of Reference Example 1 as the reference, and for Comparative Example 2, the activity improvement rate was calculated using the DPPH scavenging rate of Reference Example 2 as the reference. The results are shown in Table 1. DPPH erasure rate (%)=100-(I EX -I BG ) / (I ST -I CO ) I EX Absorbance of a solution obtained by mixing a dispersion containing cerium oxide nanoparticles with DPPH. I BG :A solution of a dispersion containing cerium oxide nanoparticles mixed with ethanol (back Absorbance of ground correction solution I ST Absorbance of a solution (reference solution) prepared by mixing DPPH and a 50% ethylene glycol aqueous solution. I CO Absorbance of a solution (control) prepared by mixing 50% ethylene glycol aqueous solution and ethanol.

[0071] [Table 1-1]

[0072] [Table 1-2]

[0073] The dispersions containing cerium oxide nanoparticles in Examples 1 to 13 all showed high radical scavenging activity. Furthermore, the activity improvement rate was 1.2 to 2.4 times higher compared to the dispersions containing cerium oxide nanoparticles produced without the addition of metal salts in Reference Examples 1 and 3. On the other hand, the dispersion containing cerium oxide nanoparticles in Comparative Example 2 showed almost no radical scavenging activity, and no improvement in activity due to the metal salt was observed compared to the dispersion containing cerium oxide nanoparticles in Reference Example 2, which was produced without the addition of metal salts. In addition, the dispersion in Comparative Example 1 to which a Cu compound was later added did not show an improvement in radical scavenging activity compared to Reference Example 1, which did not contain metal salts. From these results, it was found that the cerium oxide nanoparticles of the present invention, produced by adding a heterocyclic amine and a metal salt, and the dispersion containing them, exhibit excellent radical scavenging activity and can be used as antioxidants.

[0074] (Example 15) Determination of Ce, Ca, Cu, Fe, and Sm using ICP emission spectrometry and ICP-MS Samples of cerium oxide nanoparticles from Examples 1-13 were weighed into Teflon® containers, heated and decomposed with sulfuric acid, nitric acid, and hydrochloric acid or hydrofluoric acid, and then concentrated until sulfuric acid fumes were produced. The solution was then dissolved in dilute nitric acid and brought to a fixed volume. Ce in the resulting fixed-volume solution was quantified by ICP emission spectrometry, and Ca, Cu, Fe, and Sm were quantified by ICP mass spectrometry. An ICP emission spectrometer PS3520VDDII (Hitachi High-Tech Science) was used, and an ICP mass spectrometer Agilent 8800 (Agilent Technologies) was used. The results obtained are shown in Table 2. In the cerium oxide nanoparticles of Examples 1 to 13, the amount of metal elements was 0.00035 to 0.30 moles per mole of Ce element.

[0075] [Table 2]

[0076] (Measurement of oxidation performance using TMBZ) 100 μL of a 10 mg / mL aqueous solution of TMBZ·HCl (3,3',5,5'-Tetramethylbenzidine dihydroxide dihydrate) and 100 μL of a dispersion containing cerium oxide nanoparticles prepared in Examples 1, 13, and Reference Example 1 (diluted to 0.2 mg / mL in a 50% aqueous ethylene glycol solution) were mixed and allowed to stand at room temperature for 10 minutes. As a control, a solution prepared by mixing 100 μL of a 50% aqueous ethylene glycol solution with 100 μL of a 10 mg / mL aqueous solution of TMBZ·HCl was subjected to the same treatment. The absorbance at 655 nm, the maximum absorption wavelength of the TMBZ oxidation product, was used for the analysis. Oxidizing properties were determined to be present if the absorbance was more than twice that of the control. The results are shown in Table 3. The dispersion containing cerium oxide nanoparticles of the present invention showed an absorbance more than 10 times higher than the control, and it was confirmed that it had higher oxidizing properties than the dispersion containing cerium oxide nanoparticles produced without the addition of the metal salt in Reference Example 1.

[0077] [Table 3]

Claims

1. It comprises at least one metallic element selected from alkaline earth metals, transition metals with atomic numbers 21, 24, 26, 27, 28, 29, and 39, and lanthanides excluding cerium, and a heterocyclic amine as a stabilizer, and CeO ２ Cerium oxide nanoparticles having a radical scavenging rate of 35% or more when reacted with 1.5 mmol of DPPH per 1 mg for 30 minutes, The aforementioned heterocyclic amine, Aromatic heterocyclic compounds of any of the following: pyrazole, imidazole, triazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, tetrazine, indazole, benzimidazole, azaindole, pyrazolopyrimidine, purine, or benzotriazole, or It is an alicyclic amine, one of the following: piperazine, 1-methylpiperazine, N,N'-dimethylpiperazine, 1-ethylpiperazine, N,N'-diethylpiperazine, 1-(2-hydroxyethyl)piperazine, N-(2-aminoethyl)piperazine, 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid, piperazine-1,4-bis(2-ethanesulfonic acid), morpholine, 4-methylmorpholine, 4-ethylmorpholine, 4-(2-hydroxyethyl)morpholine, 2-morpholinoethanesulfonic acid, or 3-morpholinopropanesulfonic acid. Cerium oxide nanoparticles characterized by the following features.

2. The cerium oxide nanoparticle according to claim 1, comprising 0.0001 moles or more of the metal element per mole of cerium element.

3. A dispersion containing cerium oxide nanoparticles according to claim 1 or 2.

4. An antioxidant comprising cerium oxide nanoparticles according to claim 1 or 2, or the dispersion according to claim 3.

5. An oxidizing agent comprising cerium oxide nanoparticles according to claim 1 or 2 or a dispersion according to claim 3.

6. A first step is to obtain a mixed solution by mixing a salt of at least one metal element selected from alkaline earth metals, transition metals with atomic numbers 21, 24, 26, 27, 28, 29, and 39, and lanthanides excluding cerium, a heterocyclic amine, and a solution containing cerium(III) ions or a cerium(III) salt. A second step involves adding an oxidizing agent to the mixed solution, A method for producing cerium oxide nanoparticles containing, The aforementioned heterocyclic amine, Aromatic heterocyclic compounds of any of the following: pyrazole, imidazole, triazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, tetrazine, indazole, benzimidazole, azaindole, pyrazolopyrimidine, purine, or benzotriazole, or It is an alicyclic amine, one of the following: piperazine, 1-methylpiperazine, N,N'-dimethylpiperazine, 1-ethylpiperazine, N,N'-diethylpiperazine, 1-(2-hydroxyethyl)piperazine, N-(2-aminoethyl)piperazine, 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid, piperazine-1,4-bis(2-ethanesulfonic acid), morpholine, 4-methylmorpholine, 4-ethylmorpholine, 4-(2-hydroxyethyl)morpholine, 2-morpholinoethanesulfonic acid, or 3-morpholinopropanesulfonic acid. A method for producing cerium oxide nanoparticles, characterized by the above.

7. The method for producing cerium oxide nanoparticles according to claim 6, wherein 0.001 moles or more of the salt of the metal element are added per mole of cerium element.

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