Nanoparticles of cerium oxide, dispersions, oxidizing agents, antioxidants, and methods for producing nanoparticles of cerium oxide, methods for producing dispersions, methods for producing oxidizing agents, and methods for producing antioxidants

Abstract

The present invention addresses the problem of discovering cerium oxide nanoparticles having high oxidation performance and a dispersion including the same. Provided are cerium oxide nanoparticles and a dispersion including the same, the cerium oxide nanoparticles being manufactured by mixing a solution of an aromatic heterocyclic compound which does not have a substituent or which has at least one substituent selected from the group consisting of a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group, and a cyano group and which includes 2-8 carbon atoms and 1-4 nitrogen atoms in the ring structure thereof, and a cerium (III) salt or a solution including cerium (III) ions, and adding an oxidizing agent.

Description

Technical Field

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

Background Art

[0002] In recent years, with the increasing awareness of safety and hygiene management, antibacterial technologies that decompose harmful substances and microorganisms have attracted attention. For example, titanium oxide has the property of oxidatively decomposing organic substances due to its photocatalytic characteristics and is evaluated in decomposition reactions of organic dyes and the like. Such oxidative decomposition characteristics are expected to be used not only as an antibacterial agent but also in applications for decomposing various harmful substances such as low-molecular-weight substances such as acetaldehyde and ammonia, allergens, and viruses.

[0003] On the other hand, cerium oxide nanoparticles (nanoceria) have catalytic activities similar to redox enzymes such as catalase, oxidase, peroxidase, and superoxide dismutase, and applications as oxidizing agents and antioxidants are expected. Since these catalytic activities do not require a special light source such as ultraviolet rays, utilization in applications different from those of titanium oxide can be expected.

[0004] However, generally, nanoparticles tend to aggregate. Therefore, a method of coexisting a compound serving as a stabilizer during synthesis and stably dispersing the obtained nanoparticles is used. 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 perform alkali neutralization of cerium(III) ions in aqueous ammonia to obtain a particle dispersion.

[0005] Here, Non-Patent Document 1 describes a method for synthesizing cerium oxide nanoparticles whose surfaces are coated with polyacrylic acid or dextran. In Non-Patent Document 1, it is disclosed that, particularly when polyacrylic acid is used as a stabilizer, the oxidase activity, which is a value indicating oxidation performance, increases.

[0006] In addition, Patent Document 1 describes a synthesis method in which pyridine is used as a reaction solvent when producing ceria nanoparticles encapsulated with a surfactant such as oleylamine. The ceria nanoparticles synthesized in this way become water-soluble by further capping and complexing with polyethylene glycol lipid, and it is disclosed that they have catalase activity, which is a characteristic showing antioxidant performance.

[0007] Furthermore, Patent Document 2 describes a synthesis method of a complex in which nicotine, a compound having pyridine in its partial structure, is adsorbed on nanoceria. It is disclosed that this complex can be used for the treatment of neurodegenerative disorders as a biological antioxidant.

[0008] Also, Patent Document 3 describes a synthesis method of cerium oxide nanoparticles whose surfaces are coated with a chelating agent such as citric acid or ethylenediaminedisuccinic acid (EDDS). In particular, it is disclosed that when citric acid / EDDS is used as a stabilizer, the catalase activity, which is a value indicating antioxidant performance, increases.

Prior Art Documents

Non-Patent Documents

[0009]

Non-Patent Document 1

Patent Documents

[0010]

Patent Document 1

Patent Document 2

[0011] The inventors of the present invention examined the use of cerium oxide nanoparticles for their oxidation performance and antioxidant performance. However, when examined as in the comparative examples described later regarding the oxidation performance, even when decomposing organic dyes using cerium oxide nanoparticles whose surfaces were coated with polyacrylic acid as described in Non-Patent Document 1 or commercially available cerium oxide nanoparticles, the decomposition rate was low. Regarding the antioxidant performance, as in the comparative examples described later, there is a problem that the catalase activity of the ceria nanoparticle composite produced by the method described in Patent Document 1 is low. Also, as in the comparative examples described later, even in the dispersion obtained by the production method of post-adding and adsorbing pyridine to cerium oxide nanoparticles with reference to Patent Document 2 or the production method using a stabilizer different from the present invention described in Patent Document 3, the catalase activity was low. From these results, further examination was conducted with the problem of finding cerium oxide nanoparticles having high oxidation performance and antioxidant performance. [Means for Solving the Problems]

[0012] In order to solve the above problems, the inventors of the present invention focused on the production method of cerium oxide nanoparticles and particularly examined stabilizers. As a result, when attempting to decompose an organic dye using a dispersion containing cerium oxide nanoparticles produced by mixing a solution of an aromatic heterocyclic compound and a solution containing cerium(III) ions or a cerium(III) salt and adding an oxidizing agent, it was found that the decomposition rate increased. Also, it was found that the dispersion thus produced has high catalase activity and radical scavenging ability indicating antioxidant performance, and the present invention was completed.

[0013] The present invention is as follows. (1) A solution of an aromatic heterocyclic compound having no substituent or having at least one substituent selected from the group consisting of a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group, and a cyano group, and containing 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in the ring structure, is mixed with a solution containing cerium(III) ions or a cerium(III) salt, and nanoparticles of cerium oxide are produced by adding an oxidizing agent. (2) The nanoparticles of cerium oxide according to (1), wherein the pH is adjusted to 5 or more when adding the oxidizing agent. (3) The nanoparticles of cerium oxide according to (1) or (2), wherein the aromatic heterocyclic compound is a monocyclic or bicyclic compound having a 5-membered ring or / and a 6-membered ring structure.

[0014] (4) The nanoparticles of cerium oxide according to any one of (1) to (3), wherein the compound is pyrazole, imidazole, triazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, tetrazine, indazole, benzimidazole, azaindole, pyrazolopyrimidine, purine, benzotriazole, quinoxaline, cinnoline, quinazoline, phthalazine, naphthyridine, pteridine. (5) Nanoparticles of cerium oxide containing an aromatic heterocyclic compound having no substituent or having at least one substituent selected from the group consisting of a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group, and a cyano group, and containing 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in the ring structure, wherein in the Ce L3-edge XANES spectrum obtained by X-ray absorption fine structure spectrum measurement, the nanoparticles of cerium oxide have maximum absorption at 5726.0 to 5729.0 eV and 5735.0 to 5739.0 eV. (6) A dispersion containing the nanoparticles of cerium oxide according to any one of (1) to (5). (7) An oxidizing agent containing the nanoparticles of cerium oxide according to any one of (1) to (5) or the dispersion according to (6). An antioxidant comprising the cerium oxide nanoparticles according to any one of (1) to (5) or the dispersion according to (6). (9) A solution of an aromatic heterocyclic compound having no substituent or having at least one substituent selected from the group consisting of a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group, and a cyano group, and containing 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in the ring structure is mixed with a solution containing cerium(III) ions or a cerium(III) salt, and an oxidizing agent is added. A method for producing cerium oxide nanoparticles. [[Effect of the Invention]]

[0015] When the dispersion containing the cerium oxide nanoparticles of the present invention is used, harmful substances can be oxidized and decomposed at a higher yield than conventional cerium oxide nanoparticles, and active species can be eliminated at a higher yield than conventional cerium oxide nanoparticles. [[Brief Description of the Drawings]]

[0016]

Figure 1

Figure 2

Figure 3

[0017] The dispersion containing the cerium oxide nanoparticles of the present invention may be described as the dispersion of the present invention or the dispersion liquid of the present invention in this specification. In the synthesis of cerium oxide nanoparticles, one of the raw materials is a water-soluble cerium salt, and the synthesis is carried out in water or a solvent compatible with water. From the viewpoint of having appropriate hydrophilicity and being able to form an amine complex with metal ions, a preferred embodiment of the aromatic heterocyclic compound used in the present invention is one containing 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in the ring structure. Further, it is preferable that at least one of the above nitrogen atoms has a lone pair of electrons not included in the π-conjugated system. A more preferred embodiment of the aromatic heterocyclic compound used in the present invention is, in addition to the above characteristics, a monocyclic or bicyclic compound having a 5-membered ring or / and a 6-membered ring structure. As one embodiment, 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, naphthyridine, pteridine. Further, the above aromatic heterocyclic compound may be a derivative having substituents such as a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group, a cyano group, etc. as substituents that do not significantly change the complex formation form and solubility in the reaction solvent.

[0018] In the present invention, the cerium oxide nanoparticles are composed of a mixture of Ce2O3 and CeO2. It is known that cerium oxide can actually include forms such as hydroxides and oxyhydroxides in addition to the above oxide form. The ratio of Ce2O3 to CeO2 can be calculated by X-ray photoelectron spectroscopy (XPS) or the like as the ratio of cerium(III) to cerium(IV).

[0019] The cerium oxide nanoparticles of the present invention or a dispersion containing the same are produced by a production method in which a solution of an aromatic heterocyclic compound having no substituent or having at least one substituent selected from the group consisting of a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group, and a cyano group, containing 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in the ring structure, is mixed with a solution containing cerium(III) ions or a cerium(III) salt, and an oxidizing agent is added. Hereinafter, a method for producing the cerium oxide nanoparticles of the present invention or a dispersion containing the same will be described.

[0020] The first step is a step of mixing a solution of an aromatic heterocyclic compound having no substituent or having at least one substituent selected from the group consisting of a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group, and a cyano group, containing 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in the ring structure (hereinafter sometimes referred to as an "aromatic heterocyclic compound") with a solution containing cerium(III) ions or a cerium(III) salt to obtain a mixed solution. The solution of the aromatic heterocyclic compound used in this step can be prepared by dissolving the aromatic heterocyclic compound in an arbitrary solvent. The solvent is preferably water or a solvent compatible with water. Specific examples of the solvent compatible with water include methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, tetrahydrofuran, acetone, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), glycerol, ethylene glycol, oligoethylene glycol, and the like. Pyrazole, imidazole, triazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, and tetrazine are preferably dissolved in water, and indazole, benzimidazole, azaindole, pyrazolopyrimidine, purine, benzotriazole, quinoxaline, cinnoline, quinazoline, phthalazine, naphthyridine, and pteridine are preferably dissolved in 50% ethylene glycol. When the aromatic heterocyclic compound is difficult to dissolve, it may be dissolved by heating or ultrasonic treatment.

[0021] The amount of the aromatic heterocyclic compound may be in the range of 0.1 to 100 molar equivalents relative to the cerium(III) ions.

[0022] As for the mixing method of the solution of the aromatic heterocyclic compound and the solution containing cerium(III) ions or cerium(III) salt, the solution of the aromatic heterocyclic compound and the solution containing cerium(III) ions may be prepared and mixed respectively, or when the solvent of the solution of the aromatic heterocyclic compound is water or a solvent compatible with water, the cerium(III) salt may be added to the solution of the aromatic heterocyclic compound and mixed. The solution containing cerium(III) ions may be prepared by dissolving the cerium(III) salt in an arbitrary solvent. For the cerium(III) salt, for example, cerium(III) nitrate hexahydrate may be used.

[0023] The amount of the cerium(III) salt can be mixed with the solution of the aromatic heterocyclic compound so that the final concentration of the reaction solution is in the range of 0.01% by mass to 10% by mass. The mixed solution is preferably mixed for 5 minutes or more until the solution becomes uniform.

[0024] In the first step, it is preferable that the solution containing the aromatic heterocyclic compound and cerium(III) ions does not contain a carboxylic acid having 3 or more valences, for example, the compounds shown below. Even if it is contained, the amount is preferably 0.1 equivalent or less, more preferably 0.01 equivalent or less, relative to the cerium(III) ions. Specifically, carboxylic acids having 3 or more valences include nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA), ethylenediaminedisuccinic acid (EDDS), glycol ether diamine tetraacetic acid (EGTA), diethylenetriaminepentaacetic acid (DTPA), citric acid, hydroxyethylethylenediaminetetraacetic acid (HEDTA), polyacrylic acid and / or their salts.

[0025] The second step is a step of adding an oxidizing agent to the mixed solution obtained in the first step. Examples of the oxidizing agent used in the second step include nitric acid, potassium nitrate, hypochlorous acid, chlorous acid, chloric acid, perchloric acid, halogen, hydrogen halide, permanganate, chromic acid, dichromic acid, oxalic acid, hydrogen sulfide, sulfur dioxide, sodium thiosulfate, sulfuric acid, hydrogen peroxide, etc. Among these, hydrogen peroxide is particularly preferred. The addition amount may be 0.1 equivalent or more and 10 equivalents or less, preferably 0.5 equivalent or more and 2 equivalents or less, as a molar equivalent to cerium(III) ions.

[0026] When an oxidizing agent is added to a mixed solution of an aromatic heterocyclic compound and cerium(III) ions, the cerium(III) ions are oxidized to cerium(IV), and the formation reaction of cerium oxide particles composed of a mixture of Ce2O3 and CeO2 is initiated. Also, during the reaction, the solution is colored yellow, orange, red, brown, etc. This is the coloration 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 nanoparticles of cerium oxide. The end of the reaction can be judged by the disappearance of the color change. At this time, the particle formation reaction depends on pH, and the reaction proceeds in the weakly acidic to basic range. Since the pH tends to shift to the acidic side as the reaction proceeds, it is preferable to adjust the reaction solution to pH 5 or higher, more preferably pH 6 or higher, and even more preferably pH 7 or higher from the time of adding the oxidizing agent until the end of the reaction. An aqueous sodium hydroxide solution or an aqueous ammonia solution can be used to adjust the pH. Usually, the reaction ends in about 5 minutes to 1 hour, and a dispersion containing the nanoparticles of cerium oxide of the present invention is obtained. For example, when 200 μl of a 10 mass% aqueous solution of cerium(III) nitrate hexahydrate is added to a 9.5 mg / 10 ml solution of 1,2,4-triazole, and then 200 μl of a 1.2 mass% aqueous hydrogen peroxide solution is added and stirred at room temperature, the solution changes to orange and the reaction ends in about 10 minutes.

[0027] The dispersion of the present invention may use the dispersion liquid after the reaction as it is, but it can also be filtered through an ultrafiltration membrane or dialyzed through a semipermeable membrane to remove unreacted oxidizing agent, cerium (III) ions, and excess aromatic heterocyclic compounds remaining in the dispersion liquid after the reaction before use. Thereafter, the dispersion of the present invention can be dried using an evaporator, a freeze dryer, etc. to take out the nanoparticles of cerium oxide.

[0028] In addition to the nanoparticles of cerium oxide and water as the solvent, the dispersion of the present invention may contain other solvent components 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, oligoethylene glycol, etc. These solvent components can be contained so as to be 90% by volume or less. These solvent components may be added to the dispersion liquid after the reaction, may be added after filtration through an ultrafiltration membrane, may be used as a dialysis solution, or may be added to the dispersion liquid after dialysis. They may also be added to the dried nanoparticles of cerium oxide to form a dispersion liquid.

[0029] The dispersion of the present invention may contain ionic components. As the ionic components, components that impart buffering performance include acetic acid, phthalic acid, succinic acid, carbonic acid, Tris(hydroxymethyl)aminomethane (Tris), 2-Morpholinoethanesulfonic aci dmonohydrate (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), N-Tris(hydroxymethyl)methyl-2-aminoethanesulfonic 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-propanesulfonicacid) (POPSO), 2-Hydroxy-3-[4-(2-hydroxyethyl)-1-piperazinyl]propanesulfonic acid (HEPSO), 3-[4-(2-Hydroxyethyl)-1-piperazinyl]propanesulfonic acid (HEPPS), (Tricine), N,N-Bis(2-hydroxyethyl)glycine (Bicine), N-Tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid (TAPS) are mentioned, and sodium chloride and potassium chloride are mentioned as components that do not impart buffering performance. These ionic components can be added so that their final concentrations are in the range of 0.1 mM to 1 M.These ionic components may be added to the dispersion after the reaction is completed, may be added after filtration through an ultrafiltration membrane, may be used as a dialysis solution, or may be added to the dispersion after dialysis. They may also be added to the dried cerium oxide nanoparticles to form a dispersion.

[0030] The dispersion of the present invention may be adjusted in pH after purification. The pH of the dispersion of the present invention may be in the range of pH 2 to 12, preferably pH 4 to 10, more preferably pH 5 to 8. The pH may be adjusted by adding a buffer solution, or may be adjusted by adding an acid such as nitric acid, sulfuric acid, hydrochloric acid, or a base such as sodium hydroxide, potassium hydroxide.

[0031] The dispersion of the present invention may be stored as the dispersion after the above reaction is completed as it is, or may be stored as a purified product obtained by filtering the dispersion after the reaction is completed through an ultrafiltration membrane or a purified product dialyzed through a semipermeable membrane. It may also be stored as a dispersion containing the above solvent component and ionic components, or may be stored after adjusting the pH. When storing as a dispersion, refrigerated storage is preferred.

[0032] The cerium oxide nanoparticles of the present invention can be obtained as a dried product by taking them out of the dispersion produced as described above and drying them. For example, the solution after the reaction is filtered through an ultrafiltration membrane or semipermeable membrane dialyzed to remove unreacted oxidizing agent, cerium(III) ions, and excess aromatic heterocyclic compounds remaining in the solution after the reaction is completed, and then dried using an evaporator, freeze dryer, etc., to obtain cerium oxide nanoparticles. Specifically, ultrafiltration membranes such as Amicon Ultra from Merck and Vivaspin from GE Healthcare, and semipermeable membraneIt can be used. As the drying conditions of the extracted dispersion, the temperature and pressure conditions under which the solvent becomes a gas in the state diagram may be used. For example, when the nanoparticles are water-dispersed, the evaporator may be set so that the temperature is 40 °C and the pressure is 50 hPa or less, and water may be removed. As the evaporator, for example, N-1200A of Tokyo Rika Kikai Co., Ltd. can be used. Also, the freeze dryer may be set so that the temperature is -40 °C and the pressure is 20 Pa, and water may be removed. As the freeze dryer, for example, FDU-1200 of Tokyo Rika Kikai Co., Ltd. can be used. Further, it can also be dried by heating with an oil bath so that the temperature is 100 °C or higher, or by heating with a constant temperature dryer so that the temperature is 80 °C or higher.

[0033] The hydrodynamic diameter exhibited by the cerium oxide nanoparticles in the dispersion of the present invention is measured by dynamic light scattering to derive an autocorrelation function, analyzed by the Marquadt method, and calculated as the average particle diameter from the number conversion histogram. For the measurement of dynamic light scattering, ELS-Z of Otsuka Electronics Co., Ltd. is used. The hydrodynamic diameter exhibited by the cerium oxide nanoparticles in the dispersion may be 1 or more and 1000 nm or less, and preferably 1 or more and 200 nm or less.

[0034] The hydrodynamic diameter exhibited by the cerium oxide nanoparticles in the dispersion of the present invention can be adjusted by the molar equivalent of the aromatic heterocyclic compound to the cerium(III) ion. Larger particle size particles can be obtained if the molar equivalent is low, and smaller particle size particles can be obtained if the molar equivalent is high.

[0035] The energy states of cerium(III) and cerium(IV) in Ce2O3 and CeO2 can be observed by X-ray Absorption Fine Structure (XAFS) measurement. In the XAFS spectrum, the structure about 20 eV from the absorption edge is called X-ray Absorption Near Edge Structure (XANES), and the extended X-ray absorption fine structure that appears on the higher energy side more than about 100 eV from the absorption edge is called Extended X-ray Absorption Fine Structure (EXAFS). Information about the valence and structure of the target atom can be obtained from XANES. In EXAFS analysis, information about the local structure of the sample, the atomic species, valence, and distance around the target atom can be obtained by Fourier transform of the actual spectrum (corresponding to the radial distribution function, FT-EXAFS). The energy states of cerium(III) and cerium(IV) related to the redox reaction of cerium oxide are reflected in the peak position and peak intensity ratio of the maximum absorption in the XANES spectrum. The nanoparticles of cerium oxide of the present invention have maximum absorption between 5726.0~5729.0 eV and 5735.0~5739.0 eV in the Ce L3-edge XANES spectrum obtained by X-ray absorption fine structure spectrum measurement. The dispersion of the present invention may be sterilized before use. Examples of the sterilization method include passing through a sterilizing filter.

[0036] The cerium oxide nanoparticles of the present invention or a dispersion containing the nanoparticles can be used as an oxidizing agent. For example, by utilizing the oxidizing action, it can be used in homogeneous catalysts in organic synthesis reactions and polymerizations, or as a wet etching solution for semiconductors. Further, by utilizing the oxidizing action, it can be used as a solution to replace the oxidase solution. Specifically, instead of oxidase or peroxidase solutions, it can be used in detection reactions using antibody-antigen reactions or nucleic acid hybridization, or in tissue staining, or can be used in electrochemical detection reactions by coating electrodes to immobilize the cerium oxide nanoparticles. Additionally, by utilizing the oxidizing action, it can be used as a bleaching agent and disinfectant for decomposing and removing stains, odors, allergens, viruses, bacteria, fungi, and molds. Specifically, as a bleaching agent, it can be used for cleaning clothes, tableware, kitchens, toilets, washrooms, bathrooms, medical instruments, etc. Further, as a disinfectant, it can be added to pools, bathtubs, hot springs, or can be used as body soap, hand wash detergent, disinfectant, gargle, mouthwash, etc. Such performance as an oxidizing agent can be evaluated by the discoloration reaction of organic dyes described later.

[0037] In addition, the cerium oxide nanoparticles of the present invention or the dispersion containing the nanoparticles can be added during the molding of fibers, tubes, beads, rubbers, films, plastics, etc. or applied to the surfaces thereof as additives for imparting oxidation performance, and can be used for deodorization, anti-allergy, anti-virus, antibacterial, and anti-mold treatments. Examples of the products processed with the nanoparticles or dispersion of the present invention include, for example, a drainage port chrysanthemum crack cover for a kitchen sink, a drainage port plug, a packing for fixing a window glass, a packing for fixing a mirror, a waterproof packing for a bathroom, a washbasin, and a kitchen, a packing for lining the door of a refrigerator, a bath mat, an anti-slip rubber for a washbasin and a chair, a hose, a shower head, a packing used in a water purifier, a plastic product of a water purifier, a packing used in a washing machine, a plastic product of a washing machine, a mask, a medical cap, a medical shoe cover, a filter for an air conditioner, a filter for an air cleaner, a filter for a vacuum cleaner, a filter for a ventilation fan, a filter for a vehicle, a filter for air conditioning, a fin of an air conditioner, a louver of an air conditioner outlet, etc., plastic parts such as a blower fan, a fin of a car air conditioner, a louver of a car air conditioner outlet, etc., plastic parts such as a blower fan, clothing, bedding, a net for a screen door, a net for a chicken coop, nets such as a mosquito net, wallpaper, windows, blinds, interior materials for buildings such as in a hospital, interior materials for trains and automobiles, vehicle seats, blinds, chairs, sofas, facilities handling viruses, doors, ceiling boards, floor boards, windows, etc. building materials. Thus, the products processed with the nanoparticles or dispersion of the present invention can be used in various fields as sanitary materials.

[0038] The fading reaction of the organic dye is also used for evaluating the photocatalytic performance of titanium oxide, and the decomposition rate of the obtained dye is used as an index of the property of oxidatively decomposing organic substances. Specifically, the decomposition rate of the dye is calculated as follows. First, the dispersion of the present invention is mixed with an organic dye such as Acid Orange 7 (AO7) and allowed to stand for a predetermined time. As a control, the same treatment is also performed on a solution of AO7 that does not contain cerium oxide nanoparticles. After the reaction, the absorption spectra of all the solutions are measured. For the analysis, the absorbance at 485 nm, which is the maximum absorption wavelength of AO7, is used. The difference between the absorbance of the control and the absorbance of the solution containing the dispersion of the present invention is taken, and the ratio to the absorbance of the control is calculated as the decomposition rate.

[0039] Moreover, a preferred embodiment of the oxidizing agent of the present invention is an aromatic heterocyclic compound that has no substituent or has at least one substituent selected from the group consisting of a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group, and a cyano group, contains 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in the ring structure, and contains cerium oxide nanoparticles, and is a dispersion containing cerium oxide nanoparticles having a decomposition rate of 30% or more in the decomposition reaction of acid orange at 40°C for 1 hour. Since the decomposition rate in the decomposition reaction of acid orange at 40°C for 1 hour is 30% or more, it can be used as an oxidizing agent. The decomposition rate in the decomposition reaction of acid orange at 40°C for 1 hour is preferably 50% or more, and particularly preferably 70% or more.

[0040] The cerium oxide nanoparticles of the present invention or a dispersion containing the nanoparticles can be used as an antioxidant. In the present invention, an antioxidant refers to a substance that has reducing properties and suppresses lipid peroxidation or reacts with reactive oxygen species (such as superoxide ions, hydroxyl radicals, hydrogen peroxide, etc.) to suppress their effects (Standard Chemical Terminology Dictionary, 2nd Edition, Maruzen Publishing). For example, by utilizing such antioxidant effects, it can be used as a reducing agent in organic chemical reactions and a radical terminator in polymer polymerization. Also, by utilizing the antioxidant effect, it can be added to cell culture media or applied to culture containers such as petri dishes to protect cells from oxidative stress. Furthermore, by applying it to the skin as a cosmetic, it can be used to protect the skin from lipid peroxides and reactive oxygen species. Additionally, by utilizing the antioxidant effect, it can be used as a substance to replace antioxidant enzyme solutions. Specifically, instead of a catalase solution, by coating it on an electrode to immobilize cerium oxide nanoparticles, it can be used in the detection reaction of hydrogen peroxide and electrochemical detection reactions. Also, it can be used as a neutralizing solution for hydrogen peroxide used in industrial applications such as food, semiconductor, fiber, paper pulp manufacturing, disinfection of public baths, and removal of slime in pipes. Such performance can be evaluated by catalase activity and the like, which will be described later. Additionally, the dispersion of the present invention can be added as an antioxidant during the molding of rubber and plastics, or added to fuels, detergents, foods, and animal feeds. Such performance as an antioxidant can be evaluated by scavenging reactions of active species and the like, which will be described later.

[0041] Furthermore, the cerium oxide nanoparticles of the present invention or a dispersion containing the nanoparticles can be used as a pharmaceutical for humans or animals related to oxidative stress and inflammation as an antioxidant. Specifically, by administering the dispersion of the present invention to a subject by a local, enteral, or parenteral method such as injection, infusion, or transplantation, oxidative stress-related diseases such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and ischemia-reperfusion injury can be used for prevention and treatment. In addition, by coating the dispersion of the present invention on the surface of medical devices such as cannulas, catheters, or stents or artificial organs represented by dialysis membranes as an antioxidant, inflammation can be reduced locally or systemically.

[0042] Catalase activity can be determined according to the protocol using AmplexRed Catalase Assay Kit (A22180) from Thermo Fisher Scientific as shown in Table 2018-508568 of the Japanese Patent Application Laid-Open. The Reaction Buffer included in the kit, the dispersion of the present invention, and an aqueous hydrogen peroxide solution are mixed and allowed to stand for 30 minutes to carry out the decomposition reaction of hydrogen peroxide. The reaction solution is passed through a 30 kD ultrafiltration membrane, and the flow-through solution is mixed with the Working Solution included in the kit and reacted at 37°C for 30 minutes. Resorufin generated by the reaction is excited at 544 nm, and the fluorescence intensity at 590 nm is measured. The catalase activity of the dispersion of the present invention is calculated by comparing it with a calibration curve prepared with a catalase standard with a known activity value included in the kit. For the measurement of catalase activity, EnzyChrom Catalase Assay Kit from BioAssay System s and the like can also be used.

[0043] A preferred embodiment of the antioxidant of the present invention has no substituent or has at least one substituent selected from the group consisting of a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group, and a cyano group, and contains an aromatic heterocyclic compound having 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in the ring structure, and nanoparticles of cerium oxide. The concentration of the nanoparticles of cerium oxide is such that the catalase activity in the decomposition reaction of hydrogen peroxide water using the AmplexRed Catalase Assay Kit (A22180) of Thermo Fisher Scientific at 4 μg / ml is 0.5 U / ml or more. ze It is a dispersion containing nanoparticles of cerium oxide. The catalase activity in the decomposition reaction of hydrogen peroxide water using the AmplexRed Catalase Assay Kit (A22180) is 0.5 U / ml or more. ze Due to the catalase activity being 0.5 U / ml or more, it can be used as an antioxidant. ze The catalase activity is preferably 0.7 U / ml or more, and particularly preferably 0.8 U / ml or more.

[0044] The scavenging reaction of active species can be measured as the dye retention rate by the method as shown in Y. Xue, J. Phys. Chem. C 2011, 115, 4433 - 4438. Specifically, an aqueous solution of iron(II) chloride and an aqueous solution of hydrogen peroxide are mixed to generate hydroxyl radicals by the Fenton reaction. Then, the dispersion of the present invention is added thereto to perform a radical scavenging reaction. This mixed solution is mixed with an organic dye such as methylene blue and allowed to stand for a predetermined time. As a control, the same treatment is performed on a solution not containing the dispersion of the present invention. Further, a methylene blue solution having the same concentration as the reaction solution is prepared as a reference solution, and the absorption spectrum of the above solution is measured. For the analysis, the absorbance at 664 nm, which is the maximum absorption wavelength of methylene blue, is used. The difference (ΔI0) between the absorbance (I0) of the reference solution and the absorbance of the control (I c ) and the absorbance (I) of the solution containing the dispersion of the present invention and the control (I cCalculate the difference in absorbance (ΔI). Calculate the ratio of the latter (ΔI) to the former (ΔI0) as the decomposition rate, which is taken as the dye retention rate. This value indicates the radical scavenging performance. The dye retention rate can also be determined using methyl violet instead of methylene blue.

Example

[0045] The present invention will be further specifically described by the following examples. <Materials and Methods> Pyrazole, imidazole, 1-methylimidazole, 1,2,3-triazole, 1,2,4-triazole, 2-aminomethylpyridine, 2-cyanopyridine, 4-dimethylaminopyridine, pyridazine, pyrimidine, benzimidazole, adenine, Acid Orange 7 were obtained from Tokyo Chemical Industry Co., Ltd., and pyridine, cerium(III) nitrate hexahydrate, and 30% by mass hydrogen peroxide solution were obtained from Fujifilm Wako Pure Chemical Corporation. The commercially available cerium oxide dispersion (796077) used in the comparative example was obtained from Merck. AmplexRed Catalase Assay Kit (A22180) was obtained from Thermo Fisher Scientific.

[0046] For other reagents, they were purchased from Fujifilm Wako Pure Chemical Corporation, Tokyo Chemical Industry Co., Ltd., and Sigma-Aldrich Japan K.K. and used as they were without any special purification. For the measurement of the hydrodynamic diameter of the dispersion containing the cerium oxide nanoparticles of the present invention, the zeta potential and particle measurement system ELS-Z of Otsuka Electronics Co., Ltd. was used. The heat block used was ND-SO1 of Nichinichi Rika Co., Ltd. For absorbance measurement, the plate reader used was SpectraMax iD3 of MOLECULAR DEVICE.

[0047] (Comparative Example 1) Dispersion containing cerium oxide nanoparticles with polyacrylic acid as a stabilizer With reference to Non-Patent Document 1, cerium oxide nanoparticles were prepared for comparison of oxidation activity. To 10 ml of a 1 mass% aqueous sodium polyacrylate solution, 200 μl of a 10 mass% aqueous cerium(III) nitrate hexahydrate solution was added, and the mixture was stirred at room temperature for 5 minutes. Then, 200 μl of a 1.2 mass% aqueous hydrogen peroxide solution was added, and the mixture was heated to 40 °C and reacted for 1 hour. The reaction solution was purified with a 30 kD ultrafiltration membrane to obtain a yellow dispersion containing cerium oxide nanoparticles.

[0048] (Example 1) Preparation of a dispersion of cerium oxide nanoparticles using pyridine as a stabilizer To 10 ml of a 12 mg / 10 ml aqueous pyridine solution, 200 μl of a 10 mass% aqueous cerium(III) nitrate hexahydrate solution was added, the pH was adjusted to 7, and the mixture was stirred at room temperature for 5 minutes. Then, 200 μl of a 1.2 mass% aqueous hydrogen peroxide solution was added, and the mixture was reacted at room temperature for 1 hour. The reaction solution was purified with a 30 kD ultrafiltration membrane to obtain an orange dispersion containing cerium oxide nanoparticles.

[0049] (Example 2) Preparation of a dispersion of cerium oxide nanoparticles using pyrazole as a stabilizer In Example 1, the reaction was carried out under the same conditions as in Example 1 except that the stabilizer was a 10 mg / 10 ml aqueous pyrazole solution, and an orange aqueous solution containing cerium oxide nanoparticles was obtained.

[0050] (Example 3) Preparation of a dispersion of cerium oxide nanoparticles using imidazole as a stabilizer In Example 1, the reaction was carried out under the same conditions as in Example 1 except that the stabilizer was a 10 mg / 10 ml aqueous imidazole solution, and an orange aqueous solution containing cerium oxide nanoparticles was obtained.

[0051] (Example 4) Dispersion of cerium oxide nanoparticles using 1-methylimidazole as a stabilizer In Example 1, the reaction was carried out under the same conditions as in Example 1 except that the stabilizer was a 12 mg / 10 ml aqueous 1-methylimidazole solution, and an orange aqueous solution containing cerium oxide nanoparticles was obtained.

[0052] (Example 5) Dispersion of cerium oxide nanoparticles with 1,2,3-triazole as a stabilizer In Example 1, the reaction was carried out under the same conditions as in Example 1 except that the stabilizer was a 10 mg / 10 ml aqueous solution of 1,2,3-triazole, and an orange aqueous solution containing cerium oxide nanoparticles was obtained.

[0053] (Example 6) Dispersion of cerium oxide nanoparticles with 1,2,4-triazole as a stabilizer In Example 1, the reaction was carried out under the same conditions as in Example 1 except that the stabilizer was a 10 mg / 10 ml aqueous solution of 1,2,4-triazole, and an orange aqueous solution containing cerium oxide nanoparticles was obtained.

[0054] (Example 7) Dispersion of cerium oxide nanoparticles with 2-(aminomethyl)pyridine as a stabilizer In Example 1, the reaction was carried out under the same conditions as in Example 1 except that the stabilizer was a 16 mg / 10 ml aqueous solution of 2-(aminomethyl)pyridine, and an orange aqueous solution containing cerium oxide nanoparticles was obtained.

[0055] (Example 8) Dispersion of cerium oxide nanoparticles with 2-cyanopyridine as a stabilizer In Example 1, the reaction was carried out under the same conditions as in Example 1 except that the stabilizer was a 16 mg / 10 ml aqueous solution of 2-cyanopyridine, and an orange aqueous solution containing cerium oxide nanoparticles was obtained.

[0056] (Example 9) Dispersion of cerium oxide nanoparticles with 4-dimethylaminopyridine as a stabilizer In Example 1, the reaction was carried out under the same conditions as in Example 1 except that the stabilizer was a 19 mg / 10 ml aqueous solution of 4-dimethylaminopyridine, and an orange aqueous solution containing cerium oxide nanoparticles was obtained.

[0057] (Example 10) Dispersion of cerium oxide nanoparticles with pyridazine as a stabilizer In Example 1, the reaction was carried out under the same conditions as in Example 1 except that the stabilizer was an aqueous solution of pyridazine at 12 mg / 10 ml, and an orange aqueous solution containing cerium oxide nanoparticles was obtained.

[0058] (Example 11) Dispersion of cerium oxide nanoparticles using pyrimidine as a stabilizer In Example 1, the reaction was carried out under the same conditions as in Example 1 except that the stabilizer was an aqueous solution of pyrimidine at 12 mg / 10 ml, and an orange aqueous solution containing cerium oxide nanoparticles was obtained.

[0059] (Example 12) Dispersion of cerium oxide nanoparticles using benzimidazole as a stabilizer In Example 1, the reaction was carried out under the same conditions as in Example 1 except that the stabilizer was a 50% aqueous ethylene glycol solution of benzimidazole at 18 mg / 10 ml, and an orange aqueous solution containing cerium oxide nanoparticles was obtained.

[0060] (Example 13) Dispersion of cerium oxide nanoparticles using adenine as a stabilizer In Example 1, the reaction was carried out under the same conditions as in Example 1 except that the stabilizer was an aqueous solution of adenine at 26 mg / 10 ml, and an orange aqueous solution containing cerium oxide nanoparticles was obtained.

[0061] (Example 14) Measurement of the hydrodynamic diameter of the dispersion containing cerium oxide nanoparticles The hydrodynamic diameter of the dispersions containing cerium oxide nanoparticles prepared in Examples 1 to 13 was measured by dynamic light scattering (DLS). The solvent during the measurement was water, and the average particle diameter of the hydrodynamic diameter was obtained by number conversion. The obtained values are shown in Table 1.

[0062]

Table 1

[0063] (Example 15) Measurement of oxidation performance by dye decomposition test To 30 μl of the dispersion of the present invention prepared in Examples 1 to 13 prepared to be 2 mg / ml, 60 μl of 0.5 mg / ml Acid Orange 7 (AO7) as a sample containing an organic substance and 1.41 ml of distilled water were added respectively. Using a heat block, the mixture was allowed to stand at 40 °C for 1 hour to carry out the decomposition reaction of the dye. As a control, the same treatment was also carried out on a solution of AO7 that does not contain cerium oxide nanoparticles. After the reaction, 100 μl of each solution was taken and diluted with 1.9 ml of distilled water, and the absorption spectrum was measured. No change in the absorption spectrum was observed for the control sample before and after heating. For the analysis, the absorbance at 485 nm, which is the maximum absorption wavelength of AO7, was used. The difference in absorbance between the absorbance of each dispersion and the absorbance of the control was taken, and the ratio of each absorbance difference to the absorbance of the control was calculated as the decomposition rate. The results are shown in Table 2. From these results, it was confirmed that the dispersions containing cerium oxide nanoparticles of Examples 1 to 13 have oxidation performance capable of decomposing the dye at a high decomposition rate. On the other hand, for the commercially available dispersion of cerium oxide nanoparticles and the dispersion of cerium oxide nanoparticles prepared in Comparative Example 1, the oxidation performance was measured in the same manner, but almost no decomposition of the dye was confirmed.

[0064]

Table 2

[0065] (Comparative Example 2) Preparation of a dispersion containing cerium oxide nanoparticles with pyridine added later To compare the antioxidant performance due to the difference in the production method with the dispersion containing cerium oxide nanoparticles of Example 1 prepared by adding an oxidizing agent in the coexistence of pyridine as a stabilizer and cerium(III) salt, referring to Patent Document 2 (Japanese Patent Application Laid-Open No. 2017-525658), a dispersion containing cerium oxide nanoparticles was prepared by a production method in which pyridine was added later to cerium oxide nanoparticles and adsorbed. A commercially available dispersion of cerium(IV) oxide nanoparticles (Merck, 796077) was diluted to 0.2 mg / ml, 12.2 mg of pyridine was added to 10 ml of the diluted solution, and the mixture was stirred at room temperature for 1 hour. Then, the solution was purified through a 30 kD ultrafiltration membrane to obtain a brown aqueous solution containing cerium oxide nanoparticles.

[0066] (Comparative Example 3) Preparation of a dispersion containing cerium oxide nanoparticles with citric acid and EDDS as stabilizers With reference to Patent Document 3 (Japanese Patent Application Laid-Open No. 2018-508568), in order to compare the antioxidant performance with a dispersion containing cerium oxide nanoparticles prepared using a stabilizer different from that of the present invention, a dispersion containing cerium oxide nanoparticles was prepared using citric acid / EDDS as the stabilizer. 0.8 g of cerium nitrate, 0.24 g of citric acid monohydrate, and 0.41 g of EDDS were dissolved in water, and the pH was adjusted to 9.5 with 30% aqueous ammonia. Then, 640 μl of 30% hydrogen peroxide was added dropwise while stirring for 1 hour to obtain a brown aqueous solution. Then, the solution was purified through a 3 kD ultrafiltration membrane to obtain a brown dispersion containing cerium oxide nanoparticles.

[0067] (Comparative Example 4) Preparation of a dispersion of cerium oxide nanoparticles with benzimidazole added later To compare the oxidation performance due to the difference in the production method with the dispersion containing cerium oxide nanoparticles prepared in Example 12, a dispersion of nanoparticles was prepared by a production method in which benzimidazole was added later to cerium oxide nanoparticles (IV) for adsorption. Using 18 mg of benzimidazole instead of pyridine and using a 50% aqueous ethylene glycol solution as the solvent, a brown aqueous solution containing cerium oxide nanoparticles was obtained under the same operations and conditions as in Comparative Example 2.

[0068] (Example 16) Measurement of antioxidant performance by catalase activity measurement Catalase activity was measured according to the protocol using the AmplexRed Catalase Assay Kit (A22180) from Thermo Fisher Scientific. Briefly, 50 μl of Reaction Buffer, 25 μl of the dispersion of the present invention prepared in Examples 1 to 13 at 16 μg / ml, and 25 μl of a 40 μM aqueous hydrogen peroxide solution were mixed and allowed to stand for 30 minutes to conduct the decomposition reaction of hydrogen peroxide. The reaction solution was passed through a 30 kD ultrafiltration membrane, 100 μl of the flow-through solution was mixed with 50 μl of the Working Solution, and the mixture was reacted at 37°C for 30 minutes. Resorufin generated by the reaction was excited at 544 nm, and the fluorescence intensity at 590 nm was measured. The catalase activity of the dispersion was calculated using a calibration curve prepared with a catalase standard of known activity value. The results are shown in Table 3. From these results, it was confirmed that the dispersions containing the cerium oxide nanoparticles of the present invention prepared in Examples 1 to 13 had high catalase activity. On the other hand, for the dispersion prepared by post-adding pyridine in Comparative Example 2, the dispersion prepared using a stabilizer different from the present invention in Comparative Example 3, and the dispersion adjusted by post-adding benzimidazole in Comparative Example 4, the antioxidant performance was measured in the same manner, but the catalase activity was lower than that of the dispersion of the present invention.

[0069] [Table 3]

[0070] (Reference Example 1) Estimation of Catalase Activity The catalase activity of the ceria nanoparticle complex described in Patent Document 1 (Japanese Patent Application Laid-Open No. 2015-518480) was estimated from FIGS. 2 and 3(a) in the document. Assuming from FIG. 2 that the volume of the solution is about 2 ml and from FIG. 3(a) that up to 1 M of hydrogen peroxide was completely decomposed in 3 weeks. Thus, 2 mmol of hydrogen peroxide was decomposed in 3 weeks, and the reaction rate was calculated to be about 0.066 μmol / min. Since the activity of catalase of 1 U is 1 μmol / min, it becomes about 0.066 U, and since the reaction volume is about 2 ml, the catalase activity of the ceria nanoparticle complex described in Patent Document 1 is estimated to be about 0.033 U / ml. This estimated value is shown in Table 3. Compared with the dispersions of the present invention prepared in Examples 1 to 13, the catalase activity of the ceria nanoparticle complex of Reference Example 1 was a significantly lower value.

[0071] (Example 17) Measurement of antioxidant performance by radical scavenging test using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) 100 μl of a 0.3 mM DPPH ethanol solution was mixed with 100 μl of the dispersion of the present invention prepared in Example 12 prepared to be 0.5 mg / ml, and allowed to stand at room temperature for 30 minutes. The same treatment was performed on a solution not containing cerium oxide nanoparticles as a control. Also, a reference solution was prepared by mixing 100 μl of a 0.3 mM DPPH ethanol solution and 100 μl of distilled water. The absorption spectra of the above solutions were measured. For the analysis, the absorbance at the maximum absorption wavelength of DPPH, 517 nm, was used. The difference between the absorbance of the reference solution and the absorbance of the control, and the difference between the absorbance of this dispersion and the absorbance of the control were calculated. The ratio of the latter absorbance difference to the former absorbance difference was calculated as the DPPH retention rate (%), and the value obtained by subtracting the DPPH retention rate from 100 was defined as the DPPH scavenging rate (%). The results are shown in Table 4. From these results, it was confirmed that the dispersion containing cerium oxide nanoparticles of the present invention has high radical scavenging performance. On the other hand, for the dispersions of the nanoparticles prepared in Comparative Examples 2 and 3, the radical scavenging performance was measured in the same manner, but the DPPH scavenging rate was lower compared to the dispersion of the present invention.

[0072]

Table 4

[0073] (Example 18) XAFS Observation X-rays were respectively irradiated onto the dispersions (8 mg / ml) of the cerium oxide nanoparticles of the present invention prepared in Examples 1 and 12, and the X-ray absorption fine structure spectra were measured by measuring the absorption amounts. The measurement conditions were as follows: the experimental facility was the Photon Factory BL12C of the High Energy Accelerator Research Organization, the spectrometer was a Si(111) 2-crystal spectrometer, the absorption edge was the Ce L3 absorption edge, the detection method was the transmission method, and the detector was an ion chamber. The CeL3-edge XANES spectra are shown in FIGS. 1 and 2, respectively. The vertical axis was set by taking the ratio with the average value of the absorption in the range of -150 to -30 eV from E0 as 0 and the average value of the absorption in the range of +150 to +400 eV from E0 as 1, with 5724.4 eV of the spectrum as the absorption edge (E0). The nanoparticles of cerium oxide prepared in Example 1 had maximum absorptions at 5728.306 eV and 5736.407 eV, and the nanoparticles of cerium oxide prepared in Example 12 had maximum absorptions at 5728.145 eV and 5736.246 eV, respectively. From this result, it became clear that the nanoparticles of cerium oxide of the present invention have maximum absorptions at 5726.0 to 5729.0 eV and 5735.0 to 5739.0 eV. On the other hand, for the solutions of the nanoparticles of cerium oxide prepared by post-adding a stabilizer in Comparative Examples 2 and 4, XAFS observations were also carried out under the same operations and conditions, and the obtained CeL3-edge XANES spectra are shown in FIGS. 1 and 2, respectively. The nanoparticles of cerium oxide in Comparative Example 2 had maximum absorptions at 5729.426 eV and 5736.246 eV, and the nanoparticles of cerium oxide in Comparative Example 4 had maximum absorptions at 5729.426 eV and 5736.407 eV, respectively. Although these nanoparticles of cerium oxide had maximum absorptions between 5735.0 and 5739.0 eV, they did not have maximum absorptions between 5726.0 and 5729.0 eV, and it was found that they showed spectra different from those of the nanoparticles of cerium oxide of the present invention.

[0074] (Reference Example 2) XAFS Observation As cerium compounds that were not nanoparticles, XAFS observation was carried out under the same operations and conditions as in Example 18 above, except that cerium oxide crystal, cerium(III) carbonate, cerium(III) nitrate, and ammonium cerium(IV) nitrate were used. The obtained CeL3-edge XANES spectra are shown in Figure 3. The cerium oxide crystal had maximum absorptions at 5729.751 eV and 5736.582 eV, cerium(III) carbonate had a maximum absorption at 5725.161 eV, cerium(III) nitrate had a maximum absorption at 5725.316 eV, and ammonium cerium(IV) nitrate had maximum absorptions at 5725.796 eV and 5736.105 eV, respectively. It was found that none of these cerium compounds had maximum absorptions between 5726.0 and 5729.0 eV and between 5735.0 and 5739.0 eV, which was different from the nanoparticles of cerium oxide of the present invention.

Claims

1. nanoparticles of cerium oxide produced by mixing a solution of an aromatic heterocyclic compound having no substituent or having at least one substituent selected from the group consisting of a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group and a cyano group and containing 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in a ring structure with a solution containing cerium(III) ions or a cerium(III) salt and adding an oxidizing agent, wherein the oxidizing agent is nitric acid, potassium nitrate, hypochlorous acid, chlorous acid, chloric acid, perchloric acid, a halogen, a permanganate, chromic acid, dichromic acid, sulfuric acid or hydrogen peroxide.

2. The nanoparticles of cerium oxide according to Claim 1, wherein the pH is adjusted to 5 or more when adding the oxidizing agent.

3. The nanoparticles of cerium oxide according to Claim 1 or 2, wherein the aromatic heterocyclic compound is a monocyclic or bicyclic compound having a 5-membered ring or / and a 6-membered ring structure.

4. The nanoparticles of cerium oxide according to any one of Claims 1 to 3, wherein the aromatic heterocyclic compound is pyrazole, imidazole, triazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, tetrazine, indazole, benzimidazole, azaindole, pyrazolopyrimidine, purine, benzotriazole, quinoxaline, cinnoline, quinazoline, phthalazine, naphthyridine, pteridine.

5. Nanoparticles of cerium oxide comprising an aromatic heterocyclic compound having no substituent or having at least one substituent selected from the group consisting of a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group and a cyano group, and containing 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in the ring structure, wherein in the Ce L3-edge XANES spectrum obtained by X-ray absorption fine structure spectrum measurement, the nanoparticles of cerium oxide have maximum absorption at 5726.0 to 5729.0 eV and 5735.0 to 5739.0 eV.

6. A dispersion containing the nanoparticles of cerium oxide according to any one of claims 1 to 5.

7. An oxidizing agent containing the nanoparticles of cerium oxide according to any one of claims 1 to 5 or the dispersion according to claim 6.

8. An antioxidant containing the nanoparticles of cerium oxide according to any one of claims 1 to 5 or the dispersion according to claim 6.

9. A method for producing nanoparticles of cerium oxide, comprising mixing a solution of an aromatic heterocyclic compound having no substituent or having at least one substituent selected from the group consisting of a methyl group, an ethyl group, an amino group, an aminomethyl group, a monomethylamino group, a dimethylamino group and a cyano group, and containing 2 to 8 carbon atoms and 1 to 4 nitrogen atoms in the ring structure with a solution containing cerium(III) ions or a cerium(III) salt, and adding an oxidizing agent, The method for producing nanoparticles of cerium oxide, characterized in that the oxidizing agent is nitric acid, potassium nitrate, hypochlorous acid, chlorous acid, chloric acid, perchloric acid, a halogen, a permanganate, chromic acid, dichromic acid, sulfuric acid or hydrogen peroxide.

10. The method for producing nanoparticles of cerium oxide according to claim 9, wherein the pH is adjusted to 5 or more when adding the oxidizing agent.

11. The method for producing the cerium oxide nanoparticles according to claim 9 or 10, wherein the aromatic heterocyclic compound is a monocyclic or bicyclic compound having a 5-membered ring or / and 6-membered ring structure.

12. The method for producing the cerium oxide nanoparticles according to any one of claims 9 to 11, wherein the aromatic heterocyclic compound is pyrazole, imidazole, triazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, tetrazine, indazole, benzimidazole, azaindole, pyrazolopyrimidine, purine, benzotriazole, quinoxaline, cinnoline, quinazoline, phthalazine, naphthyridine, pteridine.

13. A method for producing a dispersion, including the cerium oxide nanoparticles produced by the method for producing the cerium oxide nanoparticles according to any one of claims 9 to 12.

14. A method for producing an oxidizing agent, including the cerium oxide nanoparticles produced by the method for producing the cerium oxide nanoparticles according to any one of claims 9 to 12 or the dispersion produced by the method for producing the dispersion according to claim 13.

15. A method for producing an antioxidant, including the cerium oxide nanoparticles produced by the method for producing the cerium oxide nanoparticles according to any one of claims 9 to 12 or the dispersion produced by the method for producing the dispersion according to claim 13.

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