Cerium oxide nanoparticles, dispersion containing cerium oxide nanoparticles, antioxidant, oxidant, and method for producing cerium oxide nanoparticles

Abstract

The present invention addresses the problem of providing cerium oxide nanoparticles having a high anti-oxidant performance. The cerium oxide nanoparticles according to the present invention support at least one metal (M) selected from platinum-group metals, Ag and Au and contains at least one stabiliser selected from heterocyclic amines, aliphatic hydroxycarboxylic acids and aliphatic alkoxycarboxylic acids.

Description

[Technical Field]

[0001] The present invention relates to cerium oxide nanoparticles, a dispersion containing cerium oxide nanoparticles, an antioxidant containing cerium oxide nanoparticles or the dispersion, 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, antibacterial technology that decomposes harmful substances and microorganisms has attracted attention. For example, titanium dioxide has the ability to oxidatively decompose organic substances through its photocatalytic properties, and has been evaluated for its ability to decompose organic dyes. In addition to its use as an antibacterial agent, such oxidative decomposition properties are expected to be used to decompose various harmful substances, including low-molecular-weight compounds such as acetaldehyde and ammonia, allergens, and viruses.

[0003] On the other hand, cerium oxide nanoparticles (nanoceria) have catalytic activity similar to that of redox enzymes such as catalase, oxidase, peroxidase, and superoxide dismutase, and are expected to be used as oxidants and antioxidants. Because this catalytic activity does not require a special light source such as ultraviolet light, they are expected to be used in applications different from those of titanium oxide.

[0004] When metal nanoparticles that tend to aggregate are used as antioxidants, etc., a stabilizer compound is generally used during synthesis to stabilize and disperse the resulting nanoparticles. In the case of cerium oxide nanoparticles, for example, a particle dispersion is obtained by oxidizing cerium (III) ions with hydrogen peroxide using polyacrylic acid as a stabilizer, or by neutralizing cerium (III) ions with an alkali in ammonia water using dextran as a stabilizer.

[0005] Non-Patent Document 1 describes Au-doped cerium oxide nanoparticles in which Au is supported on cerium oxide nanoparticles synthesized in the presence of glycine. However, it also discloses that the radical scavenging activity is almost unchanged whether or not the nanoparticles are doped with Au. Furthermore, Patent Document 1 describes a method for synthesizing cerium oxide nanoparticles using a carboxylic acid such as citric acid or methoxyacetic acid as a stabilizer and doped with a transition metal such as Cu or Fe. It discloses that the transition metal-doped cerium oxide nanoparticles have a higher reduction reaction rate than undoped cerium oxide nanoparticles when used as a catalyst for fuel cells. Furthermore, Patent Document 2 describes cerium oxide composite particles in which the surface of cerium oxide is coated with platinum and a hydroxide or oxide of cerium. Patent Document 2 discloses that cerium oxide composite particles can be synthesized by adding a metal salt of platinum and a cerium salt to a solution containing a sol of cerium oxide under ultrasonic irradiation, mixing the mixture, and heating, and that the resulting particles have low photocatalytic activity of cerium, making them suitable for use as sunscreens. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] M.Anandkumar,J Mater Sci. 2015, 50, 2522-2531. [Patent documents]

[0007] [Patent Document 1] Japanese Patent Application Laid-Open No. 2014-58448 [Patent Document 2] International Publication No. 2014 / 129555 Summary of the Invention [Problem to be solved by the invention]

[0008] The present inventors have investigated the use of cerium oxide nanoparticles as antioxidants and other applications. However, as in Non-Patent Document 1, cerium oxide nanoparticles doped with Au using glycine as a stabilizer were found to have a very low radical scavenging rate in a radical scavenging test using DPPH (2,2-Diphenyl-1-picrylhydrazyl), regardless of whether they were doped with Au. Furthermore, when attempting to synthesize nanoparticles without using a stabilizer, as in Patent Document 2, the reaction did not proceed, and nanoparticles could not be obtained. Based on these results, further investigation was conducted with the goal of obtaining cerium oxide nanoparticles with high antioxidant performance. [Means for solving the problem]

[0009] To solve the above-mentioned problems, the present inventors investigated the structure of stabilizers and cerium oxide. As a result, they found that cerium oxide nanoparticles containing at least one stabilizer selected from heterocyclic amines, aliphatic hydroxycarboxylic acids, and aliphatic alkoxycarboxylic acids and supported with at least one metal selected from platinum group metals, Ag, and Au have high antioxidant properties. In addition, when comparing the radical scavenging activity of a dispersion of cerium oxide nanoparticles containing the above stabilizer but not a metal, with that of a dispersion containing the cerium oxide nanoparticles of the present invention, they found that the dispersion of the present invention exhibited up to three times the radical scavenging activity. On the other hand, when the radical scavenging activity of a solution made by mixing a dispersion of cerium oxide nanoparticles containing the above-mentioned stabilizer and not carrying any metal with a dispersion of Au nanoparticles was measured, it was found to be at the same level as that of the dispersion of cerium oxide nanoparticles alone, and no improvement in antioxidant performance was observed.

[0010] From the above results, it was discovered that cerium oxide nanoparticles containing at least one stabilizer selected from heterocyclic amines, aliphatic hydroxycarboxylic acids, and aliphatic alkoxycarboxylic acids and having a structure in which at least one metal selected from platinum group metals, Ag, and Au is supported have high antioxidant activity and oxidation performance, and the present invention was completed based on this discovery. The present inventors have completed the present invention through the above-mentioned investigations. The present invention is as follows. (1) Cerium oxide nanoparticles carrying at least one metal (M) selected from platinum group metals, Ag, and Au, and containing at least one stabilizer selected from heterocyclic amines, aliphatic hydroxycarboxylic acids, and aliphatic alkoxycarboxylic acids. (2) The cerium oxide nanoparticles according to (1), wherein the metal (M) is contained in an amount of 0.0001 moles or more per mole of elemental cerium. (3) The cerium oxide nanoparticles according to (1) or (2), wherein the heterocyclic amine is an aromatic heterocyclic compound. (4) The cerium oxide nanoparticles according to (3), wherein the aromatic heterocyclic compound is a monocyclic or bicyclic compound having a five-membered ring and / or a six-membered ring structure.

[0011] (5) The cerium oxide nanoparticles according to (1) or (2), wherein the heterocyclic amine is a compound represented by formula (I): [ka] In formula (I), X is NR 2 , O or S, R 1 and R 2 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 a sulfonic acid alkyl group having 1 to 4 carbon atoms. 1 and R 2 may be the same or different. (6) The cerium oxide nanoparticles according to any one of (1) to (5), wherein the metal (M) is Pt or Au.

[0012] (7) A dispersion containing the cerium oxide nanoparticles according to any one of (1) to (6). (8) An antioxidant comprising the cerium oxide nanoparticles according to any one of (1) to (6) or the dispersion according to (7). (9) An oxidizing agent comprising the cerium oxide nanoparticles according to any one of (1) to (6) or the dispersion according to (7). (10) A method for producing cerium oxide nanoparticles, comprising adding at least one metal salt selected from platinum group metal salts, Ag salts, and Au salts to cerium oxide nanoparticles containing at least one stabilizer selected from heterocyclic amines, aliphatic hydroxycarboxylic acids, and aliphatic alkoxycarboxylic acids, and then adding a reducing agent. (11) The method for producing cerium oxide nanoparticles according to (10), wherein the heterocyclic amine is an aromatic heterocyclic compound.

[0013] (12) The method for producing cerium oxide nanoparticles according to (10), wherein the heterocyclic amine is a compound represented by formula (I): [ka] In formula (I), X is NR 2 , O or S, R 1 and R 2 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 a sulfonic acid alkyl group having 1 to 4 carbon atoms. 1 and R 2 may be the same or different. [Effects of the Invention]

[0014] The cerium oxide nanoparticles and dispersions containing cerium oxide nanoparticles of the present invention exhibit higher radical scavenging activity than conventional cerium oxide nanoparticles and can be suitably used as antioxidants as well as excellent oxidizing agents. [Brief explanation of the drawings]

[0015] [Figure 1] FIG. 1 is an electron microscope photograph of the cerium oxide nanoparticles of the present invention obtained in Example 1, observed by TEM-EDX. DETAILED DESCRIPTION OF THE INVENTION

[0016] The present invention is described in detail below. In this specification, the cerium oxide nanoparticles of the present invention may be simply referred to as the nanoparticles of the present invention, and the dispersion containing the cerium oxide nanoparticles of the present invention may be simply referred to as the dispersion of the present invention.

[0017] The cerium oxide nanoparticles of the present invention contain at least one stabilizer selected from the group consisting of heterocyclic amines, aliphatic hydroxycarboxylic acids, and aliphatic alkoxycarboxylic acids. These stabilizers have moderate hydrophilicity and the ability to form complexes with metal ions, thereby stabilizing the cerium oxide nanoparticles. Preferred embodiments of heterocyclic amines used as stabilizers include alicyclic amines or aromatic heterocyclic compounds represented by chemical formula (I):

[0018] [ka] In formula (I), X is NR 2 , O or S, R 1 and R 2 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 a sulfonic acid alkyl group having 1 to 4 carbon atoms. 1 and R 2 may be the same or different.

[0019] In a more preferred embodiment of the alicyclic amine of formula (I), X is NR 2 or O, R 1 and R 2 R represents 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. 1 and R 2 may be the same or different.

[0020] 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.

[0021] Aromatic heterocyclic compounds, which are preferred embodiments of the heterocyclic amines used in the present invention, contain 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in the ring structure. More preferred embodiments of aromatic heterocyclic compounds include monocyclic or bicyclic compounds having a 5-membered or 6-membered ring structure in addition to the above. Examples of 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-naphthyridine, 1,6-naphthyridine, 1,7-naphthyridine, 1,8-naphthyridine, 2,6-naphthyridine, 2,7-naphthyridine, and pteridine. The aromatic heterocyclic compound may be a derivative having a substituent such as a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group, or a cyano group, which does not significantly change the form of the complex formed or the solubility in the reaction solvent.Moreover, it is more preferable that at least one of the nitrogen atoms has a lone electron pair that is not included in a π-conjugated system.

[0022] Examples of the aliphatic hydroxycarboxylic acid used as a stabilizer include glycolic acid, lactic acid, hydroxybutyric acid, malic acid, tartaric acid, and citric acid. Examples of the aliphatic alkoxycarboxylic acid used as a stabilizer include methoxyacetic acid, ethoxyacetic acid, 2-(methoxy)ethoxyacetic acid, and 2-[2-(2-methoxyethoxy)ethoxy]acetic acid.

[0023] In the cerium oxide nanoparticles of the present invention, it is necessary that at least one metal selected from platinum group metals, Ag, and Au is supported on the cerium oxide nanoparticles containing the stabilizer. These metals can be easily supported on the cerium oxide nanoparticles by reduction reaction, and the supported metals exhibit catalytic activity, thereby further improving the antioxidant performance of the cerium oxide nanoparticles. Platinum group metals include ruthenium (Ru), rhodium (Rh), palladium (Pd), osmium (Os), iridium (Ir), and platinum (Pt). Supporting these metals on cerium oxide nanoparticles results in cerium oxide nanoparticles with improved antioxidant performance. From the viewpoint of ease of support on cerium oxide nanoparticles, platinum group metals and Au are more preferred, and Pt and Au are even more preferred.

[0024] The amount of metal supported on the cerium oxide nanoparticles is preferably 0.0001 moles or more, more preferably 0.0005 moles or more, per mole of Ce element. The amount of Ce element and the amount of metal element can be quantified by inductively coupled plasma (ICP) emission spectrometry and ICP mass spectrometry (ICP-MS), and the amount of metal element relative to Ce element can be calculated from the respective quantitative values.

[0025] In the cerium oxide nanoparticles of the present invention, whether a metal is supported on the cerium oxide nanoparticles can be confirmed by particle observation using TEM-EDX. Taking the example of the Au-supported cerium oxide nanoparticles of the present invention shown in Figure 1, the cerium oxide particle portion and Au portion can be identified by elemental mapping using EDX on the particles observed by TEM. As shown in Figure 1, an image was obtained in which the cerium oxide nanoparticle portion and Au were in contact, confirming that the cerium oxide nanoparticles have a structure in which Au is supported on cerium oxide nanoparticles.

[0026] In the present invention, cerium oxide nanoparticles are composed of a mixture of Ce2O3 and CeO2. In addition to the oxide form, cerium oxide may also be in the form of a hydroxide or oxyhydroxide. The ratio of Ce2O3 to CeO2 can be calculated as the ratio of cerium (III) to cerium (IV) using X-ray photoelectron spectroscopy (XPS) or the like.

[0027] Next, a method for producing cerium oxide nanoparticles of the present invention will be described. The process for producing cerium oxide nanoparticles of the present invention comprises the steps of obtaining cerium oxide nanoparticles containing at least one stabilizer selected from the group consisting of heterocyclic amines, aliphatic hydroxycarboxylic acids, and aliphatic alkoxycarboxylic acids, and supporting a metal on the obtained cerium oxide nanoparticles.

[0028] A known method can be used to obtain cerium oxide nanoparticles containing a stabilizer. In a preferred embodiment, the method involves adding an oxidizing agent to a solution obtained by mixing a stabilizer with a solution containing cerium (III) ions or a cerium (III) salt, thereby obtaining cerium oxide nanoparticles containing a stabilizer.

[0029] The stabilizer solution used in this step can be prepared by dissolving the stabilizer in any solvent. The solvent is preferably water or a solvent compatible with water. 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 stabilizer is difficult to dissolve, it may be dissolved by heating or ultrasonic treatment. The amount of the stabilizer used may be in the range of 0.1 to 100 molar equivalents per mole of cerium (III) ions.

[0030] The method for mixing the stabilizer with the solution containing cerium (III) ions or the cerium salt may involve preparing a solution containing the stabilizer and a solution containing cerium (III) ions separately and mixing them together, or, when the solvent for the solution containing the stabilizer is water or a solvent compatible with water, adding the cerium (III) salt to the solution containing the stabilizer and mixing them together. A solution containing cerium(III) ions can be prepared by dissolving a cerium(III) salt, such as cerium(III) nitrate hexahydrate, in a suitable solvent. The amount of cerium (III) salt used can be mixed with the stabilizer solution so that the final concentration in the reaction solution is in the range of 0.01% by mass to 10% by mass.

[0031] Examples of oxidizing agents used in this 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 is 0.1 to 10 molar equivalents relative to the cerium(III) ion, preferably 0.5 to 2 molar equivalents.

[0032] When an oxidizing agent is added to a solution containing cerium(III) ions or a cerium(III) salt, the cerium(III) ions are oxidized to cerium(IV), initiating the formation of cerium oxide particles composed of a mixture of Ce2O3 and CeO2. During this reaction, the solution turns yellow, orange, red, brown, or other colors. This coloration is due to the conversion of cerium(III) ions to cerium(IV). 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 completion of the reaction can be determined by the disappearance of the color change. The particle formation reaction is pH-dependent and proceeds in a weakly acidic to basic environment. The pH of the reaction solution can be adjusted using aqueous sodium hydroxide or ammonia. The reaction typically completes within 5 minutes to 1 hour, yielding cerium oxide nanoparticles containing the stabilizer.

[0033] The resulting stabilizer-containing cerium oxide nanoparticles are used in the metal loading process after the post-reaction dispersion is filtered through an ultrafiltration membrane or dialyzed through a semipermeable membrane to remove any unreacted oxidant, cerium (III) ions, and excess stabilizer remaining in the post-reaction dispersion. Alternatively, the cerium oxide nanoparticles can be extracted by drying using an evaporator or freeze-dryer.

[0034] Next, we will explain the process of supporting a metal on cerium oxide nanoparticles. Specifically, this process consists of a first step of adding at least one metal salt selected from platinum group metal salts, Ag salts, and Au salts to cerium oxide nanoparticles containing at least one stabilizer selected from heterocyclic amines, aliphatic hydroxycarboxylic acids, and aliphatic alkoxycarboxylic acids, and a second step of adding a reducing agent.

[0035] In the first step, at least one metal salt selected from platinum group metal salts, Ag salts, and Au salts is added to a dispersion of cerium oxide nanoparticles containing a stabilizer to obtain a mixed solution. At this time, the metal salt may be added as a solid or may be dissolved in any solvent. The solvent used to disperse the stabilizer-containing cerium oxide nanoparticles is preferably water or a water-compatible solvent. 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. These may be mixed in any ratio.

[0036] Examples of platinum group metal salts, Ag salts, and Au salts include organic acid salts such as carboxylates and sulfonates, phosphorus oxoacid salts such as phosphates and phosphonates, inorganic acid salts such as nitrates, sulfates, and carbonates, as well as salts such as halides and hydroxides, and complexes typified by halogen complexes and ammine complexes. For example, hexachloroplatinic (IV) acid and tetrachloroauric (III) acid can be used. These salts may be any salts as long as they are soluble in the synthesis solvent.

[0037] The second step is a step of adding a reducing agent to the dispersion obtained in the first step, which causes the metal to be supported on the cerium oxide nanoparticles containing the stabilizer, thereby obtaining the cerium oxide nanoparticles of the present invention. Examples of the reducing agent used in the second step include aluminum hydride compounds such as lithium aluminum hydride, diisobutylaluminum hydride, and sodium bis(2-methoxyethoxy)aluminum hydride; sodium hydride; boron hydride compounds such as lithium borohydride, sodium borohydride, potassium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride, sodium tris(1,1,1,3,3,3-hexafluoroisopropoxy)borohydride, tetramethylammonium borohydride, and tetrabutylammonium borohydride; borane compounds such as ammonia borane and pyridine borane; silane compounds such as dimethoxy(methyl)silane and trichlorosilane; organic reducing agents such as glucose, acetaldehyde, and oxalic acid, as well as hydrogen and carbon monoxide.

[0038] The amount of reducing agent added should be at least 1 molar equivalent relative to the metal salt. For example, if the supported metal is Au, the addition of the reducing agent causes the solution to change color from red to purple. This occurs because the Au salt is reduced, and Au is supported on the cerium oxide nanoparticles, resulting in the absorption of visible light due to surface plasmon resonance. The end of the reaction can be determined when the color change ceases.

[0039] The nanoparticles of the present invention may be used in the form of a dispersion, and the solvent for the dispersion may be water or a mixed solvent of water and a water-compatible solvent component. 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 added to the dispersion after the reaction is complete, or after filtration through an ultrafiltration membrane. They may also be used as a dialysis solution or added to the dispersion after dialysis. They may also be added to dried cerium oxide nanoparticles to form a dispersion.

[0040] The dispersion of cerium oxide nanoparticles of the present invention may contain an ionic component. Ionic components that impart buffering properties 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 of ionic components include N-Bis(2-hydroxyethyl)glycine (Bicine) and N-Tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid (TAPS), and components that do not impart buffering properties include sodium chloride and potassium chloride. These ionic components can be added so that the final concentration is in the range of 0.1 mM to 1 M. These ionic components may be added to the dispersion after the reaction is completed, or after filtration through an ultrafiltration membrane. An aqueous solution of the ionic components dissolved in water may be used as a dialysis solution, or they may be added to the dispersion after dialysis. They may also be added to dried cerium oxide nanoparticles together with water to form a dispersion.

[0041] The pH of the dispersion of cerium oxide particles of the present invention may be in the range of 2 to 12, preferably 4 to 10, and more preferably 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.

[0042] The cerium oxide nanoparticle dispersion of the present invention may be stored as is after the reaction is complete, or may be stored as a purified product obtained by filtering the dispersion after the reaction with an ultrafiltration membrane or dialyzing it with a semipermeable membrane, or may be stored as a dried product obtained by drying the dispersion using an evaporator or freeze dryer, and then extracting the cerium oxide nanoparticles. The dispersion may also be stored as a dispersion containing the solvent components and ionic components, or may be stored after adjusting the pH. Refrigeration is preferred for storage.

[0043] The hydrodynamic diameter of the cerium oxide nanoparticles of the present invention is determined by measuring dynamic light scattering to derive an autocorrelation function, analyzing it using the Marquadt method, and calculating the average particle diameter from a number-transformed histogram. Dynamic light scattering measurements are performed using an ELS-Z manufactured by Otsuka Electronics Co., Ltd. The hydrodynamic diameter of the dispersion may be 1 nm or more and 1000 nm or less, and preferably 1 nm or more and 200 nm or less. The hydrodynamic diameter of the cerium oxide nanoparticles of the present invention can be adjusted by the molar equivalent of the stabilizer relative to the cerium(III) ions: a lower molar equivalent will result in larger particles, and a higher molar equivalent will result in smaller particles.

[0044] The cerium oxide nanoparticles of the present invention may be sterilized before use as an antioxidant, etc. Sterilization may be carried out by passing the nanoparticles through a sterilizing filter.

[0045] 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 inhibits lipid peroxidation or reacts with reactive oxygen species (such as superoxide ions, hydroxyl radicals, and hydrogen peroxide) to inhibit their action ("Standard Chemical Dictionary," 2nd Edition, Maruzen Publishing). For example, these antioxidant properties can be utilized as reducing agents in organic chemical reactions or as radical terminators in polymer polymerization. Furthermore, these nanoparticles can be added to cell culture media or applied to culture vessels such as petri dishes to protect cells from oxidative stress. Furthermore, they can be applied to the skin as a cosmetic to protect the skin from lipid peroxides and reactive oxygen species. Furthermore, these nanoparticles can be used as a substitute for antioxidant enzyme solutions. Specifically, they can be used as a substitute for catalase solutions by coating electrodes with cerium oxide nanoparticles to immobilize them, and then used in hydrogen peroxide detection reactions and electrochemical detection reactions. The dispersion of the present invention can also be used as a neutralizing solution for hydrogen peroxide used in industrial applications such as food, semiconductor, textile, and pulp and paper manufacturing, as well as for sterilizing public baths and removing slime from pipes. Such performance can be evaluated using catalase activity, as described below. Additionally, the dispersion of the present invention can be added as an antioxidant during the molding of rubber or plastics, or to fuels, detergents, foods, and animal feed. Such antioxidant performance can be evaluated using the scavenging reaction of active species, as described below.

[0046] Furthermore, the cerium oxide nanoparticles or dispersions of the present invention can be used as antioxidants in human or animal pharmaceuticals for treating oxidative stress and inflammation. Specifically, the dispersions of the present invention can be administered to a subject locally, enterally, or parenterally, such as by injection, infusion, or transplantation, and used to prevent or treat oxidative stress-related diseases such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and ischemia-reperfusion injury. Furthermore, the dispersions of the present invention can be used as antioxidants to coat the surfaces of medical devices such as cannulas, catheters, and stents, or artificial organs such as dialysis membranes, thereby reducing inflammation locally or systemically.

[0047] The scavenging reaction of active species can be measured, for example, as the decomposition rate of an artificial radical called 2,2-Diphenyl-1-picrylhydrazyl (DPPH). Specifically, a DPPH solution is mixed with a dispersion containing the cerium oxide nanoparticles of the present invention and allowed to stand for a predetermined period of time. The same process is also carried out on a mixed solution of a solution containing the cerium oxide nanoparticles of the present invention and a solvent containing no DPPH, which serves as a background correction solution. As a control, the same process is also carried out on a solution containing no cerium oxide nanoparticles of the present invention. Furthermore, a DPPH solution of the same concentration as the reaction solution is prepared as a reference solution, and the absorption spectrum of the above solution is measured. The absorbance at 517 nm, the maximum absorption wavelength of DPPH, is used for analysis. The absorbance of the reference solution (I ST ) and the absorbance of the control (I CO ) (ΔI0) and the absorbance (I EX ) and the absorbance of the background correction solution (I BG The difference (ΔI) between the former (ΔI0) and the latter (ΔI) is calculated as the DPPH retention rate, and the DPPH scavenging rate can be calculated by subtracting the DPPH retention rate (%) from 100 (%). This value indicates the radical scavenging performance.

[0048] The cerium oxide nanoparticles or dispersions of the present invention can be used as oxidizing agents. For example, by utilizing their oxidizing properties, they can be used as homogeneous catalysts in organic synthesis reactions and polymer polymerization, or as wet etching solutions for semiconductors. Furthermore, by utilizing their oxidizing properties, they can be used as a solution to replace oxidizing enzyme solutions. Specifically, they can be used in detection reactions using antibody-antigen reactions and nucleic acid hybridization, or in tissue staining, as a replacement for oxidase or peroxidase solutions. They can also be used in electrochemical detection reactions by coating electrodes with cerium oxide nanoparticles to immobilize them. Furthermore, they can be used as bleaching agents and disinfectants by utilizing their oxidizing properties to decompose and remove dirt, odors, allergens, bacteria, fungi, and mold. Specifically, they can be used as bleaching agents to clean clothing, tableware, kitchens, toilets, washrooms, bathrooms, medical equipment, and other surfaces. Cleaning methods include soaking, spraying, and spraying using a humidifier or nebulizer. They can also be added to swimming pools, bathtubs, and hot springs as disinfectants, or used in body soap, hand washing detergent, disinfectant, gargle, mouthwash, hand gel, disinfectant spray, germicidal spray, deodorizing spray, wet tissue, and disinfectant sheets. Furthermore, the cerium oxide nanoparticles of the present invention may be left on an object after the cleaning or disinfection process, so that their deodorizing, antiviral, antibacterial, and antifungal effects can be sustained. Their performance as an oxidizing agent can be evaluated by the fading reaction of organic dyes, which will be described later.

[0049] When used as an oxidizing agent, the cerium oxide nanoparticles or dispersions thereof of the present invention can be used in combination with alcohols, surfactants, disinfectants, and natural organic substances. Examples of alcohols include ethanol and isopropyl alcohol. Examples of surfactants include benzalkonium chloride, benzethonium chloride, and alkylpolyaminoethylglycine. Examples of disinfectants include chlorhexidine, acrinol, merbromin, and crystal violet. Examples of natural organic substances include polyphenols, catechin, tannic acid, chitin, chitosan, isothiocyanates, hinokitiol, limonene, polylysine, terpenoids, saponins, flavonoids, and carotenes. When used, these may be combined in combination.

[0050] When the cerium oxide nanoparticles or dispersion thereof of the present invention are used as an oxidizing agent, they can be used in combination with other known oxidizing agents, such as hypochlorous acid, sodium hypochlorite, povidone-iodine, hydrogen peroxide, ozone water, and peracetic acid, or a combination of two or more of these.

[0051] The oxidizing ability of the cerium oxide nanoparticles or dispersions thereof of the present invention can be confirmed by carrying out a color reaction with TMBZ3,3',5,5'-Tetramethylbenzidine (TMBZ), which is used to determine oxidase activity. Specifically, the cerium oxide nanoparticles or dispersions thereof of the present invention are mixed with an aqueous solution of TMBZ and allowed to stand for a predetermined period of time. As a control, the same treatment is carried out on an aqueous solution of TMBZ without cerium oxide nanoparticles. After the reaction, the absorbance at 655 nm of each solution is measured. If the absorbance is at least twice that of the control, it is determined that the solution has oxidizing ability.

[0052] The cerium oxide nanoparticles or dispersions of the present invention can be used as an additive for imparting oxidation performance when they are added to fibers, tubes, beads, rubber, films, plastics, etc. during molding, or by coating the surfaces of these, for processing to provide deodorizing, antiallergic, antibacterial, antifungal, etc. Products processed with the cerium oxide nanoparticles or dispersions of the present invention include, for example, kitchen sink drain cover covers, drain stoppers, 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, vacuum cleaner filters, etc. Examples of suitable applications include filters, ventilation fan filters, vehicle filters, air conditioning filters, plastic parts such as air conditioner fins and air conditioner outlet louvers, as well as blower fans, car air conditioner fins and car air conditioner outlet louvers, clothing, bedding, nets such as screen door nets, chicken coop nets and mosquito nets, wallpaper, windows, blinds, interior materials for buildings such as hospitals, interior materials for trains and automobiles, vehicle seats, blinds, chairs, sofas, virus-handling equipment, and building materials such as doors, ceiling panels, floor panels and windows. Thus, products processed with the cerium oxide nanoparticles of the present invention or a dispersion thereof can be used as sanitary materials in a variety of fields. [Example]

[0053] The present invention will be further illustrated by the following examples. Materials and Methods Benzimidazole, piperazine dihydrochloride monohydrate, and 2-picolylamine were obtained from Tokyo Chemical Industry Co., Ltd., cerium(III) nitrate hexahydrate, hexachloroplatinic(IV) acid hexahydrate, tetrachloroauric acid tetrahydrate, and 30% by mass hydrogen peroxide were obtained from Fujifilm Wako Pure Chemical Industries, Ltd., and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) was obtained from Sigma-Aldrich Japan, LLC. The ultrafiltration membrane used for purification, Amicon Ultra 15 (molecular weight cutoff 10 kD), was purchased from Merck Millipore. Other reagents were purchased from Fujifilm Wako Pure Chemical Industries, Ltd., Tokyo Chemical Industry Co., Ltd., and Sigma-Aldrich Japan LLC, and were used as is without further purification.

[0054] (Quantitative determination of Ce, Au, and Pt using ICP optical emission spectrometry and ICP-MS) The sample was weighed into a Teflon container and thermally decomposed with sulfuric acid, nitric acid, and hydrochloric acid. The solution was concentrated until white sulfuric acid smoke was generated, and then dissolved in dilute aqua regia to a constant volume. Ce in the resulting constant-volume solution was quantified by ICP atomic emission spectrometry, and Au and Pt by ICP mass spectrometry. The ICP atomic emission spectrometer used was a PS3520VDDII (Hitachi High-Tech Science), and the ICP mass spectrometer used was an Agilent 8800 (Agilent Technologies).

[0055] (Observation of particles using TEM-EDX) The dispersion method was used to prepare the samples. The atomic resolution analytical electron microscope was a JEM-ARM200F Dual-X (manufactured by JEOL), and the EDX detector was a 100mm (manufactured by JEOL). 2 The measurements were carried out using a silicon drift type under the condition of an accelerating voltage of 200 kV.

[0056] Example 1: Preparation of cerium oxide nanoparticles with 0.05 mol of Au supported using benzimidazole as a stabilizer To 10 mL of 50% ethylene glycol solution containing 90 mg / 10 mL of benzimidazole, 100 μL of 1 g / mL cerium nitrate hexahydrate solution was added and stirred at room temperature for 5 minutes. Then, 1 mL of 0.6% hydrogen peroxide solution was slowly added dropwise and allowed to react at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kDa. To the resulting concentrate, 10 mL of 50% ethylene glycol solution was added and purified again using an ultrafiltration membrane. Another 10 mL of 50% ethylene glycol solution was added to the concentrate and purified using an ultrafiltration membrane, yielding a dispersion containing cerium oxide nanoparticles with a 20% yield. The resulting dispersion was adjusted to 10 mL with 50% ethylene glycol solution, and 100 μL of 10 mg / mL tetrachloroauric acid tetrahydrate solution (0.01 mole per mole of cerium nitrate hexahydrate) was added and mixed at room temperature for 5 minutes. Then, 50 μL of 2 mg / mL sodium borohydride solution was added and stirred at room temperature for 1 hour. The resulting reaction solution was purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD. 10 mL of 50% ethylene glycol solution was added to the resulting concentrated solution, and the solution was purified again using an ultrafiltration membrane to obtain a dispersion of Au-loaded cerium oxide nanoparticles. Quantitative analysis by ICP emission spectrometry and ICP-MS revealed that the amount of Au supported on the nanoparticles was 0.05 mol per 1 mol of Ce. The cerium oxide nanoparticles obtained above were also observed by TEM-EDX. Elemental mapping using EDX was performed on the particles observed by TEM, and images of the cerium oxide nanoparticles and Au in contact were obtained, confirming the structure in which Au is supported on the cerium oxide nanoparticles (Figure 1).

[0057] Example 2: Preparation of cerium oxide nanoparticles with 0.01 mol of Au supported using benzimidazole as a stabilizer Cerium oxide nanoparticles were obtained in the same manner as in Example 1, except that the amount of 10 mg / mL tetrachloroauric acid tetrahydrate aqueous solution added was changed to 20 μL (0.002 mol per 1 mol of the raw material cerium nitrate hexahydrate) and the amount of 2 mg / mL sodium borohydride aqueous solution added was changed to 10 μL. Quantitative analysis by ICP emission spectrometry and ICP-MS revealed that the amount of Au supported on the nanoparticles was 0.01 mol per 1 mol of Ce.

[0058] Example 3: Preparation of cerium oxide nanoparticles with 0.005 mol of Au supported using benzimidazole as a stabilizer Cerium oxide nanoparticles were obtained in the same manner as in Example 1, except that the amount of 10 mg / mL tetrachloroauric acid tetrahydrate aqueous solution added was changed to 10 μL (0.001 mol per 1 mol of the raw material cerium nitrate hexahydrate) and the amount of 2 mg / mL sodium borohydride aqueous solution added was changed to 5 μL. Quantitative analysis by ICP emission spectrometry and ICP-MS revealed that the amount of Au supported on the nanoparticles was 0.005 mol per 1 mol of Ce.

[0059] Example 4: Preparation of cerium oxide nanoparticles with 0.001 mol of Au supported using benzimidazole as a stabilizer Cerium oxide nanoparticles were obtained in the same manner as in Example 1, except that 20 μL (0.0002 mol per 1 mol of the raw material cerium nitrate hexahydrate) of a 1 mg / mL aqueous solution of tetrachloroauric acid tetrahydrate and 10 μL of a 0.2 mg / mL aqueous solution of sodium borohydride were added. Quantitative analysis by ICP emission spectrometry and ICP-MS revealed that the amount of Au supported on the nanoparticles was 0.001 mol per 1 mol of Ce.

[0060] Example 5: Preparation of cerium oxide nanoparticles with 0.0005 mol of Au supported using benzimidazole as a stabilizer Cerium oxide nanoparticles were obtained in the same manner as in Example 1, except that 10 μL (0.0001 mol per 1 mol of the raw material cerium nitrate hexahydrate) of a 1 mg / mL aqueous solution of tetrachloroauric acid tetrahydrate and 5 μL of a 0.2 mg / mL aqueous solution of sodium borohydride were added. Quantitative analysis by ICP emission spectrometry and ICP-MS revealed that the amount of Au supported on the nanoparticles was 0.0005 mol per 1 mol of Ce.

[0061] Example 6 Preparation of cerium oxide nanoparticles with 0.005 mol of Pt supported using benzimidazole as a stabilizer Cerium oxide nanoparticles were obtained in the same manner as in Example 1, except that 10 μL (0.001 mol per 1 mol of the raw material cerium nitrate hexahydrate) of 12.6 mg / mL hexachloroplatinic (IV) acid hexahydrate and 5 μL of 2 mg / mL aqueous sodium borohydride solution were added. Quantitative analysis by ICP emission spectrometry and ICP-MS revealed that the amount of Pt supported on the nanoparticles was 0.005 mol per 1 mol of Ce.

[0062] Reference Example 1: Preparation of cerium oxide nanoparticles using benzimidazole as a stabilizer To 10 mL of 50% ethylene glycol solution of 90 mg / 10 mL of benzimidazole, 100 μL of 1 g / mL cerium nitrate hexahydrate solution was added and stirred at room temperature for 5 minutes. Then, 1 mL of 0.6% hydrogen peroxide solution was slowly added dropwise and allowed to react at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD to obtain cerium oxide nanoparticles as a dispersion.

[0063] Comparative Example 1: Preparation of a mixed solution of a solution containing cerium oxide nanoparticles stabilized with benzimidazole and an Au nanoparticle solution The cerium oxide nanoparticles produced in Reference Example 1 were diluted with 50% ethylene glycol to a concentration of 0.4 mg / mL. To this was added 1 mL of a 5-fold diluted solution of commercially available Au nanoparticle solution, yielding a mixed dispersion of cerium oxide nanoparticles and Au nanoparticles stabilized with benzimidazole. The absorbance at 525 nm of the resulting dispersion was measured, and it was confirmed to have the same Au concentration as in Example 1. The prepared mixed dispersion was used without dilution in the radical scavenging test of Comparative Example 3, described below.

[0064] Example 7 Preparation of cerium oxide nanoparticles with 0.05 mol of Au supported using 2-picolylamine as a stabilizer To 10 mL of a 50% ethylene glycol solution containing 83 mg / 10 mL of 2-picolylamine (pH adjusted to 8 with nitric acid), 100 μL of a 1 g / mL cerium nitrate hexahydrate solution was added and stirred at room temperature for 5 minutes. Then, 1 mL of a 0.6% hydrogen peroxide solution was slowly added dropwise, and the mixture was allowed to react at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kDa. To the resulting concentrate, 10 mL of a 50% ethylene glycol solution was added, and the mixture was purified again using an ultrafiltration membrane. Another 10 mL of a 50% ethylene glycol solution was added to the concentrate, and the mixture was purified using an ultrafiltration membrane, yielding a dispersion containing cerium oxide nanoparticles in a 20% yield. The resulting dispersion was adjusted to a constant volume of 10 mL by adding 50% ethylene glycol aqueous solution. 100 μL of 10 mg / mL tetrachloroauric acid tetrahydrate aqueous solution (0.01 mole per mole of raw cerium nitrate hexahydrate) was added and mixed at room temperature for 5 minutes. 50 μL of 2 mg / mL sodium borohydride aqueous solution was then added and stirred at room temperature for 1 hour. The resulting reaction solution was purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD. 10 mL of 50% ethylene glycol aqueous solution was added to the resulting concentrated solution, and the solution was purified again using an ultrafiltration membrane to obtain Au-loaded cerium oxide nanoparticles. Quantitative analysis by ICP emission spectrometry and ICP-MS revealed that the amount of Au supported on the nanoparticles was 0.05 mol per 1 mol of Ce.

[0065] (Reference Example 2) Preparation of cerium oxide nanoparticles using 2-picolylamine as a stabilizer To 10 mL of a 50% ethylene glycol solution of 83 mg / 10 mL of 2-picolylamine (pH adjusted to 8 with nitric acid), 100 μL of a 1 g / mL aqueous solution of cerium nitrate hexahydrate was added and stirred at room temperature for 5 minutes. Then, 1 mL of a 0.6% aqueous solution of hydrogen peroxide was slowly added dropwise, and the mixture was allowed to react at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD, yielding cerium oxide nanoparticles as a dispersion.

[0066] Example 8 Preparation of cerium oxide nanoparticles supporting 0.05 mol of Au using piperazine as a stabilizer To 10 mL of 50% ethylene glycol solution containing 150 mg / 10 mL of piperazine dihydrochloride monohydrate, 100 μL of 1 g / mL cerium nitrate hexahydrate solution was added and stirred at room temperature for 5 minutes. Then, 1 mL of 0.6% hydrogen peroxide solution was slowly added dropwise and allowed to react at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kDa. To the resulting concentrate, 10 mL of 50% ethylene glycol solution was added and purified again using an ultrafiltration membrane. Another 10 mL of 50% ethylene glycol solution was added to the concentrate and purified using an ultrafiltration membrane, yielding a dispersion containing cerium oxide nanoparticles with a 20% yield. The resulting dispersion was adjusted to a constant volume of 10 mL by adding 50% ethylene glycol aqueous solution. 100 μL of 10 mg / mL tetrachloroauric acid tetrahydrate aqueous solution (0.01 mole per mole of raw cerium nitrate hexahydrate) was added and mixed at room temperature for 5 minutes. 50 μL of 2 mg / mL sodium borohydride aqueous solution was then added and stirred at room temperature for 1 hour. The resulting reaction solution was purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD. 10 mL of 50% ethylene glycol aqueous solution was added to the resulting concentrated solution, and the solution was purified again using an ultrafiltration membrane to obtain Au-loaded cerium oxide nanoparticles. Quantitative analysis by ICP emission spectrometry and ICP-MS revealed that the amount of Au supported on the nanoparticles was 0.05 mol per 1 mol of Ce.

[0067] (Reference Example 3) Preparation of cerium oxide nanoparticles using piperazine as a stabilizer To 10 mL of 50% ethylene glycol solution containing 150 mg / 10 mL of piperazine dihydrochloride monohydrate, 100 μL of 1 g / mL cerium nitrate hexahydrate solution was added and stirred at room temperature for 5 minutes. Then, 1 mL of 0.6% hydrogen peroxide solution was slowly added dropwise and allowed to react at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD to obtain cerium oxide nanoparticles as a dispersion.

[0068] Example 9: Preparation of cerium oxide nanoparticles supporting 0.05 mol of Au using methoxyacetic acid as a stabilizer To 10 mL of a 14 mg / 10 mL methoxyacetic acid solution (pH adjusted to 7 with sodium hydroxide), 200 μL of a 0.1 g / mL cerium nitrate hexahydrate solution was added and stirred at room temperature for 5 minutes. 200 μL of a 1.2% hydrogen peroxide solution was then added dropwise and allowed to react at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD, yielding a dispersion containing cerium oxide nanoparticles in 20% yield. The resulting dispersion was adjusted to 10 mL with Milli-Q water, and 20 μL of a 10 mg / mL aqueous solution of tetrachloroauric acid tetrahydrate (0.01 mole per mole of cerium nitrate hexahydrate) was added and mixed at room temperature for 5 minutes. Then, 10 μL of a 2 mg / mL aqueous solution of sodium borohydride was added, and the mixture was stirred at room temperature for 1 hour. The resulting reaction solution was purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD, yielding a solution of Au-loaded cerium oxide nanoparticles. Quantitative analysis by ICP emission spectrometry and ICP-MS revealed that the amount of Au supported on the nanoparticles was 0.05 mol per 1 mol of Ce.

[0069] (Reference Example 4) Dispersion containing cerium oxide nanoparticles stabilized with methoxyacetic acid To 10 mL of a 14 mg / 10 mL methoxyacetic acid solution (pH adjusted to 7 with sodium hydroxide), 200 μL of a 0.1 g / mL cerium nitrate hexahydrate solution was added and stirred at room temperature for 5 minutes. 200 μL of a 1.2% hydrogen peroxide solution was then added dropwise and allowed to react at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD to obtain a dispersion containing cerium oxide nanoparticles.

[0070] Comparative Example 2: Preparation of cerium oxide nanoparticles supporting 0.05 mol of Au using glycine as a stabilizer Cerium oxide nanoparticles were synthesized using glycine as a stabilizer with reference to Non-Patent Document 1. 200 μL of 0.1 g / mL cerium nitrate hexahydrate aqueous solution was added to 10 mL of 4.2 mg / mL glycine aqueous solution and stirred at room temperature for 5 minutes. 200 μL of 1.2% hydrogen peroxide aqueous solution was then slowly added dropwise, and the mixture was allowed to react at room temperature for 1 hour. The resulting reaction solution was heated at 70°C for 2 hours, cooled to room temperature, and purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD, yielding a dispersion containing cerium oxide nanoparticles in a 20% yield. The resulting dispersion was adjusted to 10 mL with Milli-Q water, and 20 μL of a 10 mg / mL aqueous solution of tetrachloroauric acid tetrahydrate (0.01 mole per mole of cerium nitrate hexahydrate) was added and mixed at room temperature for 5 minutes. Then, 10 μL of a 2 mg / mL aqueous solution of sodium borohydride was added, and the mixture was stirred at room temperature for 1 hour. The resulting reaction solution was purified using an ultrafiltration membrane with a molecular weight cutoff of 10 kD, yielding a solution of Au-loaded cerium oxide nanoparticles. Quantitative analysis by ICP emission spectrometry and ICP-MS revealed that the amount of Au supported on the nanoparticles was 0.05 mol per 1 mol of Ce.

[0071] Reference Example 5: Preparation of cerium oxide nanoparticles using glycine as a stabilizer Cerium oxide nanoparticles were synthesized using glycine as a stabilizer with reference to Non-Patent Document 1. 200 μL of 0.1 g / mL cerium nitrate hexahydrate aqueous solution was added to 10 mL of 4.2 mg / mL glycine aqueous solution and stirred at room temperature for 5 minutes. 200 μL of 1.2% hydrogen peroxide aqueous solution was then slowly added dropwise, and the mixture was allowed to react 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, yielding a dispersion containing cerium oxide nanoparticles.

[0072] (Example 10) Measurement of antioxidant performance by radical scavenging test using DPPH 100 μL of a 0.3 mM DPPH ethanol solution was mixed with 100 μL of the cerium oxide nanoparticle dispersions obtained in Examples 1 to 9, Comparative Examples 1 and 2, and Reference Examples 1 to 5, which had been diluted with 50% ethylene glycol aqueous solution to a concentration of 0.2 mg / mL. The mixture was then allowed to stand at room temperature for 30 minutes in the dark. A solution prepared by mixing 100 μL of the 0.2 mg / mL cerium oxide nanoparticle dispersion with 100 μL of ethanol was also subjected to the same treatment as a background correction solution. A control solution prepared by mixing 100 μL of 50% ethylene glycol aqueous solution with 100 μL of ethanol was also subjected to the same treatment. A reference solution was also prepared by mixing 100 μL of a 0.3 mM DPPH ethanol solution with 100 μL of 50% ethylene glycol aqueous solution. The absorption spectra of the above solutions were measured. For the analysis, absorbance at 517 nm, the maximum absorption wavelength of DPPH, was used. The DPPH scavenging rate was calculated using the following formula using the absorbance of each solution. For the cerium oxide nanoparticles obtained in Examples 1 to 6, 7, 8, and 9, the activity improvement rate was calculated by multiplying the DPPH scavenging rates of Reference Examples 1, 2, 3, and 4, respectively, by 1 (reference). For the cerium oxide nanoparticles obtained in Comparative Examples 1 and 2, the activity improvement rate was calculated by multiplying the DPPH scavenging rates of Reference Examples 1 and 5, respectively, by 1 (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 containing a dispersion of cerium oxide nanoparticles mixed with DPPH I BG : A solution (background) of a mixture of a dispersion containing cerium oxide nanoparticles and ethanol Absorbance of ground correction solution I ST : Absorbance of a solution (reference solution) made by mixing DPPH and 50% ethylene glycol aqueous solution I CO : Absorbance of a solution (control) made by mixing 50% ethylene glycol aqueous solution and ethanol

[0073] [Table 1]

[0074] All of the dispersions containing cerium oxide nanoparticles in Examples 1 to 9 exhibited high radical scavenging activity. Furthermore, the activity improvement rate was 1.9 to 11.1 times higher than that of the dispersions containing cerium oxide nanoparticles without metal support in Reference Examples 1 to 3. On the other hand, the mixed solution of cerium oxide nanoparticles and Au nanoparticles in Comparative Example 1 showed no improvement in radical scavenging activity compared to Reference Example 1, which did not contain gold nanoparticles. Furthermore, the cerium oxide nanoparticles in Comparative Example 2, which used glycine as a stabilizer, showed very low radical scavenging activity, and showed no improvement in radical scavenging activity, even compared to Reference Example 4, which did not support a metal. From the above results, it was found that the cerium oxide nanoparticles of the present invention, which contain at least one stabilizer selected from heterocyclic amines, aliphatic hydroxycarboxylic acids, and aliphatic alkoxycarboxylic acids and which are supported with at least one metal selected from platinum group metals, Ag, and Au, and dispersions containing the same, exhibit excellent radical scavenging activity and can be used as antioxidants.

[0075] (Example 11) Measurement of oxidation performance using TMBZ 100 μL of a 10 mg / mL aqueous solution of TMBZ·HCl (3,3',5,5'-Tetramethylbenzidine, dihydrochloride, dihydrate) was mixed with 100 μL of the dispersion containing cerium oxide nanoparticles prepared in Example 1 and Reference Example 1, which had been diluted with 50% ethylene glycol aqueous solution to 0.2 mg / mL, and the mixture was left to stand at room temperature for 10 minutes. As a control, a solution prepared by mixing 100 μL of 50% ethylene glycol aqueous solution with 100 μL of 10 mg / mL TMBZ·HCl aqueous solution was also treated in the same way. For the analysis, absorbance at 655 nm, the maximum absorption wavelength of the oxidation product of TMBZ, was used. A dispersion showing absorbance at least twice that of the control was judged to have oxidizing properties. The results are shown in Table 2. The dispersion containing the cerium oxide nanoparticles of the present invention showed absorbance at least 10 times higher than the control, demonstrating its usability as an oxidizing agent.

[0076] [Table 2]

Claims

1. Cerium oxide nanoparticles containing at least one stabilizer selected from the group consisting of heterocyclic amines, aliphatic hydroxycarboxylic acids, and aliphatic alkoxycarboxylic acids, The cerium oxide nanoparticles containing a stabilizer have a structure in which at least one metal (M) selected from platinum group metals, Ag, and Au is supported. Cerium oxide nanoparticles characterized by:

2. 2. The cerium oxide nanoparticles according to claim 1, wherein the metal (M) is contained in an amount of 0.0001 mole or more per mole of cerium element.

3. 3. The cerium oxide nanoparticles according to claim 1, wherein the heterocyclic amine is an aromatic heterocyclic compound.

4. 4. The cerium oxide nanoparticles according to claim 3, wherein the aromatic heterocyclic compound is a monocyclic or bicyclic compound having a five-membered ring and / or a six-membered ring structure.

5. 3. The cerium oxide nanoparticles according to claim 1, wherein the heterocyclic amine is a compound represented by formula (I): 【Chemistry 1】 (In formula (I), X is NR 2 , O or S, R 1 and R 2 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 a sulfonic acid alkyl group having 1 to 4 carbon atoms. 1 and R 2 may be the same or different.)

6. 6. The cerium oxide nanoparticles according to claim 1, wherein the metal (M) is Pt or Au.

7. A dispersion comprising the cerium oxide nanoparticles according to any one of claims 1 to 6.

8. An antioxidant comprising cerium oxide nanoparticles according to any one of claims 1 to 6 or a dispersion according to claim 7.

9. An oxidizing agent comprising the cerium oxide nanoparticles according to any one of claims 1 to 6 or the dispersion according to claim 7.

10. a step of adding an oxidizing agent to a solution obtained by mixing at least one stabilizer selected from heterocyclic amines, aliphatic hydroxycarboxylic acids, and aliphatic alkoxycarboxylic acids with a solution containing cerium (III) ions or a cerium (III) salt, thereby obtaining cerium oxide nanoparticles containing the stabilizer; adding at least one metal salt selected from platinum group metal salts, Ag salts, and Au salts to a dispersion of the cerium oxide nanoparticles containing the stabilizer to obtain a mixed solution of the cerium oxide nanoparticles containing the stabilizer and the metal salt; a step of adding a reducing agent to the obtained mixed solution to support the metal (M) of the metal salt on the cerium oxide nanoparticles containing the stabilizer; Including, the amount of the stabilizer used is in the range of 0.1 to 100 molar equivalents relative to 1 mole of the cerium (III) ion or the cerium (III) ion of the cerium (III) salt; the amount of the oxidizing agent added is 0.1 equivalents or more and 10 equivalents or less in terms of molar equivalents relative to the cerium (III) ions or the cerium (III) ions of the cerium (III) salt; The amount of the reducing agent added is 1 molar equivalent or more relative to the metal salt.

3. A method for producing cerium oxide nanoparticles having a structure in which the metal (M) is supported and the stabilizer is contained.

11. The method for producing cerium oxide nanoparticles according to claim 10, wherein the heterocyclic amine is an aromatic heterocyclic compound.

12. The method for producing cerium oxide nanoparticles according to claim 10, wherein the heterocyclic amine is a compound represented by formula (I): 【Chemistry 2】 (In formula (I), X is NR 2 , O or S, R 1 and R 2 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 a sulfonic acid alkyl group having 1 to 4 carbon atoms. 1 and R 2 may be the same or different.)

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