Method for removing nitrosamine, method for producing composition from which nitrosamine has been removed, composition, removal kit, catalyst composition for removal, removal device, and removal system

Abstract

The present invention provides a method for removing a nitrosamine with high selectivity and high efficiency.　More specifically, the present invention provides a method for removing a nitrosamine, the method including a step in which a substance to be irradiated, which contains the nitrosamine, is irradiated with light in the presence of an aromatic polyamine and a photocatalyst.

Description

Method for removing nitrosamines, method for producing a composition from which nitrosamines have been removed, composition, removal kit, catalyst composition for removal, removal device, and removal system

[0001] The present invention relates to a method for removing nitrosamines, a method for producing a composition from which nitrosamines have been removed, a composition, a removal kit, a catalyst composition for removal, a removal device, and a removal system.

[0002] Nitrosamines are known to be carcinogenic. Therefore, businesses that handle products used by the human body, such as food, must address the risk of nitrosamine contamination (e.g., Non-Patent Document 1). In the pharmaceutical industry, since the detection of nitrosamine contamination, such as N-nitrosodimethylamine (NDMA), in valsartan drug substance in July 2018, numerous cases have been reported both domestically and internationally in which pharmaceutical products using the drug substance were recalled. In Japan as well, there have been recent reports of nitrosamine contamination in pharmaceuticals, such as sartan drugs, ranitidine preparations, and nizatidine preparations (e.g., Non-Patent Document 2).

[0003] As a result, pharmaceutical companies are increasingly required to take measures to reduce the amount of nitrosamines. However, no method for removing nitrosamines has yet been established. For this reason, products whose nitrosamine content must be strictly controlled must be manufactured and stored in a way that prevents the formation of nitrosamines from the beginning, and products that have become contaminated with nitrosamines must be recalled and discarded.

[0004] One of the few methods capable of removing nitrosamines is reported in Patent Document 1, which involves decomposing nitrosamines by heating them with hydrohalic acid at high temperatures. However, the method of Patent Document 1 requires harsh treatment conditions using strong acids and high temperatures, which leads to the problem of decomposing organic compounds other than nitrosamines along with the nitrosamines. On the other hand, even if these methods are carried out for a short period of time to suppress side reactions, nitrosamines cannot be sufficiently removed. In other words, previous nitrosamine removal methods could not be applied to, for example, pharmaceuticals and foods and beverages, which often have complex skeletons and require high safety.

[0005] For these reasons, there is a strong demand for the development of a method that can efficiently remove only nitrosamines.

[0006] Japanese Patent Application Publication No. 2015-016391

[0007] Ministry of Agriculture, Forestry and Fisheries, "Food Safety Risk Profile Sheet: Nitrosamines," November 25, 2021. Pharmaceuticals and Medical Devices Agency, "Safety Measures for the Risk of Nitrosamine Contamination in Pharmaceuticals," Pharmaceutical and Medical Device Safety Information No. 403, August 23, 2023.

[0008] The present invention has been made in view of the above-mentioned current state of the prior art, and has as its main object to provide a method for removing nitrosamines with high selectivity and high efficiency.

[0009] The present inventors have conducted extensive research to achieve the above-mentioned object. As a result, they have found that nitrosamines can be removed with high selectivity and efficiency by irradiating an object containing nitrosamines with light in the presence of an aromatic polyamine and a photocatalyst. Based on this finding, the present inventors have conducted further research and have completed the present invention. That is, the present invention includes the following features.

[0010] Item 1. A method for removing nitrosamines, comprising the step of irradiating an object containing the nitrosamines with light in the presence of an aromatic polyamine and a photocatalyst.

[0011] Item 2. The removal method according to Item 1, wherein in the light irradiation step, the —N(—N═O)— moiety constituting the nitrosamine is converted to an —NH— moiety.

[0012] Item 3. The removal method according to Item 1 or 2, wherein the aromatic polyamine has two or more amino groups on one aromatic ring.

[0013] Item 4. The removal method according to any one of Items 1 to 3, wherein the photocatalyst is a transition metal catalyst, an organic catalyst, or a biocatalyst.

[0014] Item 5. The removal method according to any one of Items 1 to 4, wherein the light is visible light.

[0015] Item 6. The removal method according to any one of Items 1 to 5, wherein the object to be irradiated is a solution containing the nitrosamine.

[0016] Item 7. The removal method according to any one of Items 1 to 6, wherein the content of nitrosamines in the irradiated object after the light irradiation is less than 1 ppm.

[0017] Item 8. The removal method according to any one of Items 1 to 7, wherein the object to be irradiated after the light irradiation is a pharmaceutical composition, a food or drink composition, a cosmetic composition, a tobacco composition, or a feed composition.

[0018] Item 9. A method for producing a composition from which nitrosamines have been removed, comprising the step of irradiating an object containing the nitrosamines with light in the presence of an aromatic polyamine and a photocatalyst.

[0019] Item 10. A composition containing a nitrosamine, an amine obtained by converting the —N(—N═O)— moiety constituting the nitrosamine to an —NH— moiety, and an aromatic polyamine or a derivative thereof.

[0020] Item 11. A nitrosamine removal kit comprising an aromatic polyamine, a photocatalyst, and a solvent.

[0021] Item 12. A catalyst composition for removing nitrosamines, comprising an aromatic polyamine and a photocatalyst.

[0022] Item 13. The catalyst composition for removing nitrosamines according to Item 12, further comprising a solvent, the aromatic polyamine is an aromatic diamine, and the photocatalyst is a photoredox catalyst.

[0023] Item 14. The catalyst composition for removing nitrosamines according to Item 12 or 13, wherein the solvent is 2-methyltetrahydrofuran, the aromatic polyamine is o-phenylenediamine, and the photocatalyst contains iridium.

[0024] Item 15. The catalyst composition for removing nitrosamines according to any one of Items 12 to 14, wherein the aromatic polyamine and the photocatalyst are each supported on a bead-like polymer.

[0025] Item 16. The nitrosamine is N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosoethylisopropylamine (NEIPA), N-nitrosodiisopropylamine (NDIPA), N-nitrosodicyclohexylamine (NDCHA), N-nitrosomethylphenylamine (NMPA), N-nitrosodiphenylamine (NDPhA), N-nitrosopyrrolidine (NPYR), N-nitrosoproline (NPRO), N-nitrosopiperidine (NPIP), N-nitrosomorpholine (NMOR), N-nitroso-N'-methylpiperazine (NMP), N-nitrosodiethanolamine (NDELA), N-nitrosomethylaminobutyric acid (NMBA), N-nitrososarcosine (NSAR), N-nitrosonornico Item 16. The catalyst composition for removing nitrosamines according to any one of Items 12 to 15, wherein the compound is at least one compound selected from the group consisting of N-nitroso-2-hydroxymethyl-thiazolidine-4-carboxylic acid (NHMTCA), N-nitroso-thiazolidine-4-carboxylic acid (NTCA), N-nitroso-2-methyl-thiazolidine-4-carboxylic acid (NMTCA), and N-nitrosopipecolic acid (NPIC).

[0026] Item 17. A nitrosamine removal device comprising a light source and a storage section for storing the catalyst composition for removing nitrosamines according to any one of Items 12 to 16, wherein the light source irradiates the storage section with light.

[0027] Item 18. The nitrosamine removal device according to Item 17, wherein the light is visible light.

[0028] Item 19. The nitrosamine removal device according to Item 17 or 18, wherein the light is blue light.

[0029] Item 20. A nitrosamine removal system comprising the nitrosamine removal device according to any one of Items 17 to 19.

[0030] Item 21. The nitrosamine removal system according to Item 20, further comprising a means for recovering the product after the light irradiation.

[0031] According to the method of the present invention, it is possible to provide a method for removing nitrosamines with high selectivity and high efficiency.

[0032] In this specification, the expressions "contain" and "comprise" include any of "contain," "comprise," "consist only of," "consist essentially only of," and "consist only of."

[0033] In this specification, the expression "A to B" indicating a range of values ​​means "greater than or equal to A and less than or equal to B."

[0034] As used herein, "nitrosamine" refers to a compound having a chemical structure (-N(-N=O)- moiety) formed by bonding a nitroso group (-N=O) to an amine (e.g., primary amine, secondary amine, tertiary amine). For the sake of explanation only, the "-N(-N=O)- moiety" in this specification specifically refers to a compound having the formula: The wavy line in the formula above indicates the bonding site to the adjacent group.

[0035] Furthermore, in this specification, the expression "removing nitrosamines" can be interpreted as meaning that it is sufficient to reduce the amount of nitrosamines present in a system, for example, by removing the (-N=O) moiety from nitrosamines (denitrosation), and is not necessarily interpreted as requiring the complete elimination of nitrosamines and compounds derived from nitrosamines from the system. Preferably, in this specification, "removing nitrosamines" means converting nitroso groups present in nitrosamines to hydrogen atoms, thereby eliminating the presence of nitrosamines in a sample.

[0036] 1. Nitrosamine Removal Method The method for removing nitrosamines of the present invention (hereinafter, in this specification, may be simply referred to as the "removal method") comprises a step of irradiating an object containing nitrosamines with light in the presence of an aromatic polyamine and a photocatalyst.

[0037] The removal method of the present invention has the above-mentioned characteristics, and is therefore capable of removing nitrosamines with high selectivity and high efficiency.

[0038] Specifically, the nitrosamine removal efficiency of the removal method of the present invention is not particularly limited, but can be, for example, 99% or more. Thus, the removal method of the present invention can remove nitrosamines with higher efficiency than conventional nitrosamine removal methods. From the perspective of ensuring safety to the human body, the removal efficiency is preferably 99.9% or more, more preferably 99.99% or more, even more preferably 99.999% or more, and particularly preferably 99.9999% or more. The removal efficiency can be determined by LC-MS, LC-MS / MS, GC-MS, GC-MS / MS, and / or NMR. The removal method of the present invention can remove nitrosamines to a level below the detection limit of these analytical methods. In this sense, in the examples described below, a removal efficiency (decomposition rate) of ">99% or more" means that the content of nitrosamines in the irradiated object after light irradiation is below the detection limit (below the detection limit) in the analytical method.

[0039] Furthermore, the removal method of the present invention can remove nitrosamines with high efficiency (more specifically, while removing the (-N=O) moiety from the nitrosamine (denitrosation)), while substantially maintaining the chemical structures of groups other than the -N(-N=O)- moiety present in the nitrosamine and the chemical structures of compounds other than the nitrosamine present in the irradiated object, even after light irradiation. Thus, the removal method of the present invention can remove nitrosamines with higher selectivity than conventional methods for removing nitrosamines.

[0040] Furthermore, the removal method of the present invention can remove nitrosamines with high selectivity and high efficiency, and therefore can be applied to a variety of compounds, compositions, and irradiated objects.

[0041] 1-1. Irradiated Object The irradiated object used in the present invention is not particularly limited as long as it contains nitrosamine.

[0042] The nitrosamine contained in the irradiated object is not particularly limited as long as it has a -N(-N=O)- moiety. The irradiated object is not particularly limited, but for example, the nitrosamine may be a nitrosamine represented by the general formula (1): １１ -N(-N=O)-R １２ (1) [wherein, R １１ and R １２ are the same or different and represent a hydrogen atom or an organic group. １１ and R １２ may form a ring together with the adjacent nitrogen atom.]

[0043] In general formula (1), R １１ and R １２ is not particularly limited, but from the viewpoint of achieving the effects of the present invention, it is preferable that either one of them is an organic group, and it is more preferable that both of them are organic groups.

[0044] The organic group is not particularly limited, but examples thereof include hydrocarbon groups (such as alkyl groups, alkenyl groups, alkynyl groups, aryl groups, and heteroaryl groups).

[0045] The alkyl group is not particularly limited, and examples thereof include chain alkyl groups having 1 to 10 carbon atoms (particularly 1 to 6), such as methyl, ethyl, n-propyl, n-butyl, and n-pentyl groups; branched alkyl groups having 3 to 10 carbon atoms (particularly 3 to 6), such as isopropyl, isobutyl, sec-butyl, and tert-butyl groups; and cyclic alkyl groups having 3 to 10 carbon atoms (particularly 5 to 8), such as cyclopentyl and cyclohexyl groups.

[0046] The alkenyl group is not particularly limited, and examples thereof include linear alkenyl groups having 2 to 10 carbon atoms (particularly 2 to 6), such as ethenyl group (vinyl group), 2-propenyl group (allyl group), and 2-butenyl group, as well as branched alkenyl groups having 3 to 10 carbon atoms (particularly 3 to 6), such as isopropenyl group, 2-methyl-1-propenyl group, and 2-methylallyl group.

[0047] The alkynyl group is not particularly limited, and examples thereof include linear alkenyl groups having 2 to 10 (particularly 2 to 6) carbon atoms, such as ethynyl, n-propynyl, and n-butynyl, as well as branched alkynyl groups having 3 to 20 (particularly 3 to 6) carbon atoms, such as isobutynyl, s-butynyl, and isopentynyl.

[0048] The aryl group is not particularly limited, and any of a monocyclic aryl group, a fused ring aryl group, and a polycyclic aryl group can be used. Examples thereof include aryl groups having 6 to 18 carbon atoms (particularly 6 to 14 carbon atoms), such as a phenyl group, a hydroxyphenyl group, a naphthyl group, an anthracenyl group, a phenanthrenyl group, a biphenyl group, a terphenyl group, a fluorenyl group, an indolyl group, an imidazolyl group, a pyrenyl group, and a triphenylenyl group.

[0049] The heteroaryl group is not particularly limited, and both a monocyclic heteroaryl group and a polycyclic heteroaryl group can be employed. Examples thereof include a pyrrolidyl group, a pyrrolyl group, a tetrahydrothienyl group, a thienyl group, an oxolanyl group, a furanyl group, an imidazolyl group, an N-methylimidazolyl group, a pyrazolyl group, a thiazolyl group, an oxazolyl group, a piperidyl group, a pyridyl group, an N,N-dimethyl-4-aminopyridyl group, a pyrazyl group, an indolyl group, an isoindolyl group, a benzimidazolyl group, a quinolyl group, an isoquinolyl group, and a quinoxalyl group.

[0050] The hydrocarbon group may have a substituent. The substituent is not particularly limited, but examples thereof include a hydroxyl group, a thiol group, a halogen atom (such as a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), a hydrocarbon group, an acyl group, an ester group, a thioester group, an alkoxy group, an amino group, a nitro group, a cyano group, a sulfonyl group, a phosphoryl group, and a boronyl group. When the hydrocarbon group has a substituent, the number of the substituents is not particularly limited, and is preferably 1 to 6, and more preferably 1 to 3.

[0051] The substituent of the hydrocarbon group may have a protecting group. As the protecting group, any protecting group known as a protecting group for the above-mentioned substituent can be used, and examples thereof include alkyl-type protecting groups such as tert-butyl (t-Bu) group, benzyl group, allyl group, methyl group, and triphenylmethyl group (Trt); silyl-type protecting groups such as tert-butyldimethylsilyl group (TBS); aryl-type protecting groups such as p-methoxybenzyl group (PMB) and p-methoxyphenyl group (PMP); amide-type protecting groups such as formyl group and acetyl group (Ac); phthalimide-type protecting groups such as phthaloyl group (Phth); benzyloxy group (Ac); Examples of protecting groups include carbamate-type protecting groups such as a dimethylcarbonyl group (Cbz), a tert-amyloxycarbonyl group (Aoc), a 9-fluorenylmethoxycarbonyl group (Fmoc), a tert-butyloxycarbonyl group (Boc), an allyloxycarbonyl group (Alloc), and a 2,2,2-triethoxycarbonyl group (Troc); and sulfonamide-type protecting groups such as a 3-nitro-2-pyridinesulfenyl group (Npys), a 2-nitrobenzenesulfonyl group (Ns), and a (2-trimethylsilyl)-ethanesulfonyl group (SES). When a protecting group is present, the number of protecting groups is not particularly limited, and is preferably 1 to 6, and more preferably 1 to 3.

[0052] A heteroatom may further be inserted or added to the hydrocarbon group. Examples of the heteroatom include, but are not limited to, a boron atom, a nitrogen atom, an oxygen atom, a silicon atom, a phosphorus atom, a sulfur atom, a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. The heteroatom may be inserted into a carbon-carbon bond in the hydrocarbon.

[0053] R １１and R １２ may form a ring together with the adjacent nitrogen atom. The ring is not particularly limited, and examples thereof include an aziridine ring, an azirine ring, a diaziridine ring, a diazirine ring, an azetidine ring, an azeto ring, a diazeto ring, a pyrrolidine ring, a pyrrole ring, an imidazolidine ring, an imidazole ring, a pyridine ring, a piperidine ring, a piperazine ring, and a morpholine ring.

[0054] R １１ and R １２ The ring optionally formed by may have one or more substituents, and one or more heteroatoms may be inserted or added. The heteroatoms and substituents are not particularly limited, and a wide variety of heteroatoms and substituents that the above-mentioned hydrocarbon groups may have can be used.

[0055] Also, R １１ and R １２ Each of may be a natural or non-natural oligopeptide chain, polypeptide chain, protein motif, protein module, protein domain, oligonucleotide chain, polynucleotide chain, oligomer, polymer, or a complex thereof, or the like, or R １１ and R １２ may be combined with the adjacent —N(—N═O)— moiety to form these. According to the removal method of the present invention, even nitrosamines having complex skeletons can be removed.

[0056] Examples of nitrosamines contained in the irradiated object used in the present invention include N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosoethylisopropylamine (NEIPA), N-nitrosodiisopropylamine (NDIPA), N-nitrosodicyclohexylamine (NDCHA), N-nitrosomethylphenylamine (NMPA), N-nitrosodiphenylamine (NDPhA), N-nitrosopyrrolidine (NPYR), N-nitrosoproline (NPRO), N-nitrosopiperidine (NPIP), N-nitrosomorpholine (NMOR), N-nitroso-N'-methylpiperazine (NMP), N-nitrosodiethanolamine (NDELA), N-nitrosomethylaminobutyric acid (N N-nitrosopropranolol (NNP), N-nitrosomethylethylamine (NMEA), N-nitrosohydroxyproline (NHPRO), N-nitrosodiisobutylamine (NDiBA), N-nitrosodibenzylamine (NDBzA), N-nitroso-2-hydroxymethyl-thiazolidine-4-carboxylic acid (NHMTCA), N-nitroso-thiazolidine-4-carboxylic acid (NTCA), N-nitroso-2-methyl-thiazolidine-4-carboxylic acid (NMTCA), N-nitrosopipecolic acid (NPIC), and the like. Specific examples of nitrosamines include, in addition to the above-mentioned small molecules, proteins such as enzymes, receptors, antibodies, antigens, vaccines, cytokines such as interferons and interleukins, chemokines, and transport proteins; nucleic acids such as DNA, RNA, chimeric nucleic acids of DNA and RNA, and DNA / RNA hybrids; lipids such as fatty acids, neutral fats, phospholipids, glycolipids, and sterols; and sugars such as monosaccharides, disaccharides, oligosaccharides, and polysaccharides, which have an —N(—N═O)— moiety.

[0057] More specifically, examples of the nitrosamines include: etc.

[0058] The irradiated material may contain one type of nitrosamine alone or two or more types of nitrosamines in combination.

[0059] The irradiated object may be in the form of a solid, liquid, or gas. In particular, the irradiated object is preferably a solution or dispersion containing nitrosamines, more preferably a solution containing nitrosamines, from the viewpoint of removing nitrosamines with high selectivity and high efficiency. Even when the irradiated object is a solid or gas, nitrosamines can be removed with high selectivity and high efficiency by irradiating a solution or dispersion in which part or all of the irradiated object is dissolved or dispersed in a solvent with light.

[0060] The solvent constituting the irradiated object or the solvent for dissolving or dispersing the irradiated object is not particularly limited, and any of water, organic solvents, and mixtures thereof can be used. As the organic solvent, any of nonpolar solvents, protic polar solvents, and aprotic polar solvents can be used, and examples thereof include aliphatic solvents such as hexane and cyclohexane; aromatic solvents such as benzene and toluene; halogen solvents such as dichloromethane and chloroform; ester solvents such as methyl formate and ethyl acetate; alcohol solvents such as methanol and ethanol; halogen solvents such as dichloromethane and chloroform; ketone solvents such as acetone and methyl ethyl ketone; ether solvents such as 1,4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, and diethyl ether; amide solvents such as N,N-dimethylformamide and N,N-diethylformamide; sulfoxide solvents such as dimethyl sulfoxide; and nitrile solvents such as acetonitrile.

[0061] Furthermore, an ionic liquid (room temperature molten salt) may be used as the solvent.

[0062] When the object to be irradiated is a liquid containing an aqueous solution, the pH of the aqueous solution is not particularly limited, but can be in the range of 3 to 12.

[0063] The irradiated object may be a product that can be used by humans or non-human mammals, specifically, for example, pharmaceuticals, food and beverages, cosmetics, tobacco, feed, or other industrial products in various forms, or may be their raw materials, modified products, or decomposition products. Compounds contained in these products, modified products, or decomposition products may be converted to carcinogenic nitrosamines, for example, by the reaction of the amino groups (e.g., secondary amino groups) constituting their skeleton with nitrite ions present in the environment during their production and storage. It has been reported that nitrosamines, when converted to diazonium ions by enzymes such as P450 in the liver, irreversibly alkylate DNA. In this regard, since nitrosamines can be contained in a variety of products in a variety of industrial fields, it is clear that the removal method of the present invention can be applied to products in a variety of industrial fields. Non-human mammals include, for example, dogs, cats, monkeys, cows, horses, sheep, goats, pigs, rabbits, mice, rats, camels, and llamas.

[0064] When the irradiated object is a pharmaceutical product or its raw material, denatured product, or decomposition product, specific examples of the irradiated object include, but are not limited to, pharmaceutical products such as valsartan preparations, sartan-based pharmaceutical products, ranitidine hydrochloride, nizatidine hydrochloride, metformin preparations, sitagliptin phosphate hydrate preparations, amoxapine preparations, and nortriptyline hydrochloride preparations, as well as their raw materials, denatured products, and decomposition products.

[0065] When the irradiated object is a food or beverage, or its raw materials, denatured products, or decomposition products, specific examples of the irradiated object include, but are not limited to, processed meat products such as bacon, salami, sausage, and ham; processed fish products such as canned fish, fish ham, fish sausage, fish meal, fish snacks, fish flakes, dried stock, and liquid stock; dairy products such as cheese, yogurt, and milk; processed vegetables such as pickles and grilled vegetables; alcoholic beverages such as beer and whiskey; and seasonings such as soybean oil and soy sauce, as well as their raw materials, denatured products, and decomposition products.

[0066] When the irradiated object is a cosmetic product or its raw materials, modified products, or decomposition products, specific examples of the irradiated object include, but are not limited to, makeup cosmetics such as foundation, lipstick, blush, eye shadow, eyebrows, eyeliner, and mascara; basic cosmetics such as face wash, lotion, emulsion, cream, and serum; fragrances such as natural fragrances and synthetic fragrances; and personal care products such as hand cream, body cream (body lotion), nail products, nail care products, toothbrushes, toothpaste, and other oral care products, as well as their raw materials, modified products, and decomposition products.

[0067] When the irradiated object is tobacco or its raw material, modified product, or decomposition product, specific examples of the irradiated object include, but are not limited to, tobacco such as cigarettes, cigars, kiseru, pipes, smokeless tobacco, and hookah, as well as their raw materials, modified products, and decomposition products.

[0068] When the irradiated object is feed or its raw materials, modified products, or decomposition products, specific examples of the irradiated object include, but are not limited to, grains such as rice, wheat, corn, etc.; feed such as food and beverage manufacturing by-products such as soybean processing by-products, fruit juice processing by-products, alcohol by-products, and sugar refining by-products, as well as their raw materials, modified products, and decomposition products.

[0069] When the irradiated object is a product that can be used by humans or non-human mammals, such as a pharmaceutical, food or beverage, cosmetic, tobacco, or animal feed, the irradiated object may be a recalled product that has been passed from the producer to the trader or consumer and then recalled. The reason for the recall is not particularly limited, but may be, for example, the presence of nitrosamines. The removal method of the present invention can remove nitrosamines contained in such recalled products with high selectivity and efficiency, making it possible to resell the product after removal, thereby minimizing losses and recall costs when nitrosamine contamination is discovered.

[0070] The irradiated materials do not necessarily have to be the above-mentioned products, their raw materials, modified products, or decomposed products, but can also be, for example, organic wastewater such as domestic wastewater, sewage, wastewater from food factories, and wastewater from pulp factories. In this case, various types of wastewater can be purified by the removal method of the present invention.

[0071] The amount of nitrosamine contained in the irradiated object before light irradiation is not particularly limited, and the removal method of the present invention can be applied to irradiated objects containing large amounts of nitrosamine or small amounts of nitrosamine.

[0072] The above is a description of the object to be irradiated before light irradiation. Below, the object to be irradiated after light irradiation will be described.

[0073] In the removal method of the present invention, although not particularly limited, the -N(-N=O)- moiety constituting the nitrosamine can be converted to an -NH- moiety in the light irradiation step described below. In other words, in the light irradiation step, a denitrosation reaction involving the -N(-N=O)- moiety constituting the nitrosamine can proceed. Note that, for the sake of explanation only, the "-NH- moiety" in this specification specifically refers to a group represented by the formula: The wavy line in the formula above indicates the bonding site to the adjacent group.

[0074] The irradiated object after light irradiation is not particularly limited, but for example, a compound represented by the general formula (2): R ２１ -NH-R ２２ (2) [wherein, R ２１ and R ２２ are the same or different and represent a hydrogen atom or an organic group. ２１ and R ２２ may form a ring together with the adjacent nitrogen atom.

[0075] R in general formula (2) ２１ represents R in the above general formula (1). １１ Similarly, R in general formula (2) can be the same as ２２ represents R in the above general formula (1). １２Thus, the removal method of the present invention is advantageous over conventional methods for removing nitrosamines in that it can remove the (—N═O) moiety from the —N(—N═O)— moiety while maintaining the chemical structures of groups other than the —N(—N═O)— moiety present in the nitrosamine.

[0076] In addition, R in general formula (2) ２１ represents R in the above general formula (1). １１ It is not necessary to be identical to R １１ Similarly, R in general formula (2) can be different from ２２ represents R in the above general formula (1). １２ It is not necessary to be identical to R １２ That is, the removal method of the present invention does not itself substantially affect the chemical structure of groups other than the —N(—N═O)— moiety present in the nitrosamine, but does not prevent the chemical structure from changing after removal due to an intramolecular reaction or an intermolecular reaction after removal of the (—N═O) moiety from the —N(—N═O)— moiety.

[0077] In general formula (2), R ２１ and R ２２ Each of the １１ and R １２ R may be a hydrogen atom or an organic group, regardless of whether it is the same as R or R. ２１ and R ２２ is not particularly limited, but from the viewpoint of achieving the effects of the present invention, it is preferable that either one of them is an organic group, and it is more preferable that both of them are organic groups. ２１ and R ２２ The organic group represented by the above R １１ and R １２ Any organic group defined as R ２１ and R ２２ For example, R １１ and R １２ The substituents and protecting groups of the above may be eliminated.

[0078] When the irradiated object before light irradiation contains a nitrosamine represented by general formula (1), the irradiated object after light irradiation contains a nitrosamine represented by general formula (2'): １１ -NH-R １２ (2') [wherein, R １１ and R １２ is the same as above].

[0079] After the light irradiation, the irradiated object preferably contains an amine obtained by converting the —N(—N═O)— moiety constituting the nitrosamine to an —NH— moiety.

[0080] The nitrosamine content in the irradiated object after light irradiation is not particularly limited, but can be, for example, less than 1 ppm, where the total amount of the irradiated object is 100% by mass. Thus, the removal method of the present invention can remove nitrosamines more efficiently than conventional nitrosamine removal methods. From the viewpoint of ensuring safety to the human body, the nitrosamine content after light irradiation is preferably less than 0.1 ppm, more preferably less than 0.01 ppm, even more preferably less than 0.001 ppm, and particularly preferably less than the detection limit. The nitrosamine content can be determined by LC-MS, LC-MS / MS, GC-MS, GC-MS / MS, and / or NMR, etc. In this case, the removal method of the present invention can provide a composition that meets the nitrosamine management standards required for pharmaceuticals, foods, beverages, etc.

[0081] In the removal method of the present invention, an example of a by-product is water. The removal method of the present invention not only can remove nitrosamines, but also is unlikely to produce dangerous by-products. Therefore, the irradiated object after light irradiation is highly safe for the human body.

[0082] The irradiated material after light irradiation is useful as a product or raw material for various industrial fields. In addition, the irradiated material after light irradiation can be used as, for example, a pharmaceutical composition, a food or drink composition, a cosmetic composition, a tobacco composition, a feed composition, or other oral compositions.

[0083] 1-2. Aromatic Polyamine The aromatic polyamine used in the present invention is not particularly limited as long as it is an aromatic compound having two or more amino groups.

[0084] The aromatic polyamine is not particularly limited, but may be, for example, a polyamine represented by the general formula (3): In the formula, Ar represents an aromatic ring, and n represents an integer of 2 or more.

[0085] In general formula (3), the aromatic ring represented by Ar is not particularly limited, and examples thereof include a benzene ring, biphenyl, naphthalene ring, anthracene ring, tetracene ring, pentacene ring, triphenylene ring, terphenyl, pyrene ring, fluorene ring, indene ring, thiophene ring, furan ring, pyrrole ring, benzothiophene ring, benzofuran ring, indole ring, dibenzothiophene ring, dibenzofuran ring, carbazole ring, thiazole ring, benzothiazole ring, oxazole ring, benzoxazole ring, imidazole ring, benzimidazole ring, pyridine ring, pyrimidine ring, pyrazine ring, pyridazine ring, quinoline ring, isoquinoline ring, quinoxaline ring, benzothiadiazole ring, etc. Among these, the aromatic ring represented by Ar is preferably a hydrocarbon ring such as a benzene ring or a naphthalene ring, and more preferably a benzene ring, from the viewpoints of removing nitrosamines with high selectivity and high efficiency and of easy availability.

[0086] In general formula (3), the number of amino groups represented by n is not particularly limited and can be within the range of 2 to the maximum number that can be substituted (for example, 2, 3, 4, 5, or 6 or more). Among these, from the viewpoint of removing nitrosamines with high selectivity and high efficiency, n is preferably 2 to 4, more preferably 2 or 3, and even more preferably 2. That is, the aromatic polyamine is preferably an aromatic diamine.

[0087] The aromatic polyamine is not particularly limited, but from the viewpoint of removing nitrosamines with high selectivity and high efficiency, it preferably has two or more amino groups on one aromatic ring, more preferably has two amino groups on two to five adjacent carbon atoms on one aromatic ring (for example, ortho (o-) positions, meta (m-) positions, para (p-) positions), and even more preferably has two amino groups on two adjacent carbon atoms on one aromatic ring (for example, ortho (o-) positions). The two or more amino groups can be directly or indirectly bonded to the aromatic ring.

[0088] The two or more amino groups contained in the aromatic polyamine may be the same or different and may be primary amino groups or secondary amino groups. The two or more amino groups are preferably primary amino groups from the viewpoint of removing nitrosamines with high selectivity and high efficiency, but are not particularly limited thereto. When the amino group is a secondary amino group, the amino group may have, on its nitrogen atom, a group such as a hydroxyl group, a thiol group, a halogen atom, a hydrocarbon group, an acyl group, an ester group, a thioester group, an amide group, an alkoxy group, an amino group, a nitro group, a cyano group, a sulfonyl group, a phosphoryl group, or a boronyl group.

[0089] In general formula (3), the aromatic ring represented by Ar may have a substituent other than an amino group. The substituent that the aromatic ring may have is not particularly limited, but examples thereof include a hydroxyl group, a thiol group, a halogen atom, a hydrocarbon group, an acyl group, an ester group, a thioester group, an amide group, an alkoxy group, a nitro group, a cyano group, a sulfonyl group, a phosphoryl group, and a boronyl group. When the aromatic ring has a substituent, the number of the substituents is not particularly limited, and is preferably 1 to 6, and more preferably 1 to 3.

[0090] Specific examples of the aromatic polyamine represented by the general formula (3) include, but are not limited to, o-phenylenediamine, m-phenylenediamine, p-phenylenediamine, 1,2,3-benzenetriamine, 1,2,4-benzenetriamine, 1,3,5-benzenetriamine, 2,3-toluenediamine, 3,4-toluenediamine, 2,3-diaminochlorobenzene, 3,4-diaminochlorobenzene, 3,4-diaminonitrobenzene, 2,3-diaminomethylsulfonylbenzene, and the like. benzene, 3,4-diaminoacetophenone, methyl 2,3-diaminobenzoate, 3,4-diaminobenzoic acid, 2,3-diaminoanisole, 3,4-diaminothioanisole, 2,2'-biphenyldiamine, 2,3'-biphenyldiamine, 1,2-naphthalenediamine, 1,3-naphthalenediamine, 1,4-naphthalenediamine, 1,5-naphthalenediamine, 1,8-naphthalenediamine, 2,3-naphthalenediamine, 2,3-anthracenediamine, 2,3-tetracenediamine Amines, 2,3-pentacenediamine, 1,2-triphenylenediamine, 2,3'-terphenyldiamine, 4,5-pyrenediamine, 2,3-fluorenediamine, 1,2-indenediamine, 5,6-indenediamine, 3,4-thiophenediamine, 3,4-furandiamine, 3,4-pyrrolediamine, 5,6-benzothiophenediamine, 5,6-benzofurandiamine, 5,6-indolediamine, 3,4-dibenzothiophenediamine, 3,4-dibenzofurandiamine amine, 3,4-carbazolediamine, 2,3-thiazolediamine, 2,3-benzothiazolediamine, 4,5-oxazole, 5,6-benzoxazole, 4,5-imidazole, 5,6-benzimidazole, 2,3-diaminopyridine, 4,5-diaminopyrimidine, 2,3-diaminopyrazine, 4,5-diaminopyridazine, 6,7-diaminoquinoline, 6,7-diaminoisoquinoline, 2,3-diaminoquinoxaline, and 5,6-benzothiadiazole.

[0091] The aromatic polyamine is not particularly limited, but may be, for example, a compound represented by the general formula (3'): [Wherein, Ar and n are the same as above. The wavy line indicates a bonding site.] The aromatic polyamine-containing polymer may be an aromatic polyamine-containing polymer having one or more aromatic polyamine moieties (hereinafter, in this specification, may be simply referred to as "aromatic polyamine moieties") represented by the formula: [Wherein, Ar and n are the same as above. The wavy line indicates a bonding site.] By using such an aromatic polyamine-containing polymer, it becomes easier to remove and recover the aromatic polyamine from the irradiated object after removing the nitrosamine.

[0092] The aromatic polyamine-containing polymer can have, but is not limited to, one or more aromatic polyamine moieties in the backbone, in side chains, or in pendant chains.

[0093] The aromatic polyamine-containing polymer can be, but is not limited to, for example, a polystyrene, polyester, polyamide, polyether, polycarbonate, or polythioether having one or more aromatic polyamine moieties.

[0094] The mass average molecular weight of the aromatic polyamine-containing polymer is not particularly limited, but can be within the range of 500 to 1,000,000 (preferably 500 to 100,000, more preferably 500 to 10,000).

[0095] The aromatic polyamine-containing polymer is not particularly limited, but may contain, for example, 10% by mass or more of the aromatic polyamine moiety.

[0096] In the removal method of the present invention, although not particularly limited, when a compound represented by general formula (3) is used as the aromatic polyamine, in the light irradiation step described below, the compound represented by general formula (3) may be a compound represented by general formula (4): [wherein Ar is the same as above.] Alternatively, in the removal method of the present invention, although not particularly limited, when an aromatic polyamine-containing polymer is used as the aromatic polyamine, in the light irradiation step described later, the aromatic polyamine moiety represented by general formula (3') can be converted into a heterocyclic compound represented by general formula (4'): wherein Ar is the same as defined above.

[0097] That is, in the removal method of the present invention, in the light irradiation step, two amino groups of an aromatic polyamine can be converted into a ring containing three or more consecutive nitrogen atoms in the skeleton by reacting with a nitrogen atom derived from a nitrosamine. The aromatic polyamine derivative obtained after this conversion can contain, for example, a 1,2,3-triazole ring, a 1,2,3-triazine ring, a 1,2,3,4-tetrazine ring, or a 1,2,3-benzotriazine ring. In this case, the removal method of the present invention can remove nitrosamine with high selectivity and efficiency while suppressing the production of dangerous by-products.

[0098] The aromatic polyamine may be supported on a carrier. The carrier for the aromatic polyamine is not particularly limited, and a wide variety of known carriers can be used. More specifically, examples of the carrier for the aromatic polyamine include organic polymers, silica gel, alumina, activated carbon, titania, and alumina. By using such a carrier, the aromatic polyamine and aromatic polyamine derivative can be easily removed and recovered from the irradiated object after removing the nitrosamine. The shape of the aromatic polyamine carrier can be bead-like, powder-like, particulate-like, spherical, block-like, flake-like, pellet-like, or honeycomb-like. From the viewpoint of recovery efficiency, it is preferable that the aromatic polyamine be supported on a bead-like polymer.

[0099] The aromatic polyamines may be used alone or in combination of two or more.

[0100] The amount of aromatic polyamine used is not particularly limited, but from the viewpoint of removing nitrosamine with high selectivity and high efficiency, it is preferably 0.1 mol to 10 mol, more preferably 0.2 mol to 5 mol, and even more preferably 0.5 mol to 2 mol, per 1 mol of nitrosamine contained in the irradiated material.

[0101] 1-3. Photocatalyst The photocatalyst used in the present invention is not particularly limited as long as it has the effect of removing nitrosamines.

[0102] As the photocatalyst used in the present invention, for example, a transition metal complex, an organic catalyst, or a biocatalyst can be adopted.

[0103] The transition metal complex can be a complex containing a central metal species that is a transition metal and its ligands.

[0104] The central metal species of the transition metal complex is not particularly limited, and a wide range of known transition metals used as photocatalysts can be used. Specific examples of the central metal species include cobalt, ruthenium, rhodium, rhenium, iridium, nickel, palladium, osmium, and platinum. Among these, from the viewpoint of removing nitrosamines with high selectivity and high efficiency, iridium, ruthenium, and palladium are preferred, and iridium is more preferred.

[0105] The ligand that transition metal complex has is not particularly limited, and can widely adopt the known ligand that is used as a photocatalyst.Specifically, as the ligand, for example, can be listed as nitrogen-containing compounds such as diamine compounds such as ethylenediamine, pyridine, bipyridine, phenanthroline, pyrrole, indole, carbazole, imidazole, pyrazole, quinoline, isoquinoline, acridine, pyridazine, pyrimidine, pyrazine, phthalazine, quinazoline, quinoxaline, etc. nitrogen-containing heterocyclic compounds; diketones such as dipivaloylmethane, furan, benzofuran, oxazole, pyran, pyrone, coumarin, benzopyrone, etc. oxygen-containing heterocyclic compounds; sulfur-containing compounds such as sulfur-containing heterocyclic compounds such as thiophene, thionaphthene, thiazole, etc.

[0106] The number of ligands contained in the transition metal complex is not particularly limited, and can be, for example, one or more.

[0107] Specific examples of the transition metal complex include, but are not limited to, Ir(ppy) ３ , [Ir{dF(CF ３ ) ppy} ２ (dtbpy)]PF ６ , [Ir(dtbbpy)(ppy) ２ ][PF ６ ], Ir(ppy) ３ Iridium catalysts such as Ru(bpy) ３ Cl２ ・6H ２ O, [Ru(bpz) ３ ][PF ６ ] ２ , [Ru (bpm) ３ ][Cl] ２ , [Ru(bpy) ２ (phen-5-NH ２ ) ] [PF ６ ] ２ , [Ru(bpy) ３ ][PF ６ ] ２ , Ru(phen) ３ Cl ２ Ruthenium catalysts such as Pd(PPh ３ ) ４ Palladium catalysts such as Cu(dap) ２ Examples of suitable catalysts include copper catalysts such as Cl, and 9-mesityl-10-methylacridinium perchlorate.

[0108] The organic catalyst can be a low molecular weight compound that does not contain a metal element.

[0109] Specific examples of the organic catalyst include, but are not limited to, rose bengal, erythrosine, eosin (e.g., eosin B, eosin Y, etc.), acriflavine, lipoflavin, thionine, and the like.

[0110] The biocatalyst can be a biologically derived protein such as an enzyme, or the microorganism itself.

[0111] Specific examples of biocatalysts include, but are not limited to, chlorophyll, rhodopsin, phytochrome, cryptochrome, phototropin, and the like.

[0112] As the photocatalyst, from the viewpoint of removing nitrosamines with high selectivity and high efficiency, a visible light responsive photocatalyst, a near-infrared light responsive photocatalyst, or an infrared light responsive photocatalyst is preferred. More specifically, as the photocatalyst, a photocatalyst that can exhibit catalytic activity by being excited by light with a wavelength of 400 nm to 25,000 nm (more preferably 410 nm to 2,500 nm, and even more preferably 450 nm to 800 nm) is preferred, and among them, a photoredox catalyst is more preferred.

[0113] Furthermore, as the photocatalyst, from the viewpoint of removing nitrosamines with high selectivity and high efficiency, an electron donor is preferred, and a one-electron oxidation-reduction catalyst is more preferred, as this facilitates the removal of nitrosamines.

[0114] The photocatalyst may be supported on a carrier. The photocatalyst carrier is not particularly limited, and a wide variety of known carriers can be used. More specifically, examples of the photocatalyst carrier include organic polymers, silica gel, alumina, activated carbon, titania, and alumina. By using such a carrier, the catalyst can be easily removed and recovered from the irradiated object after removing the nitrosamine. The shape of the photocatalyst carrier can be bead-shaped, powder-shaped, granular, spherical, block-shaped, flake-shaped, pellet-shaped, or honeycomb-shaped. From the viewpoint of recovery efficiency, it is preferable that the photocatalyst be supported on a bead-shaped polymer.

[0115] The photocatalysts may be used alone or in combination of two or more.

[0116] The amount of photocatalyst used is not particularly limited, but from the viewpoint of removing nitrosamines with high selectivity and high efficiency, the amount is preferably 0.0001 mol to 0.1 mol, more preferably 0.001 mol to 0.05 mol, and even more preferably 0.005 mol to 0.02 mol, relative to 1 mol of nitrosamine contained in the irradiated object.

[0117] The ratio of the amount of photocatalyst used to the amount of aromatic polyamine used (amount of photocatalyst used / amount of aromatic polyamine used; molar ratio) is not particularly limited, but from the viewpoint of removing nitrosamines with high selectivity and high efficiency, it is preferably 0.001 to 1, more preferably 0.005 to 0.5, and even more preferably 0.01 to 0.1.

[0118] 1-4. Light The light (irradiation light) used in the present invention is not particularly limited as long as it has the effect of removing nitrosamines.

[0119] As the light (irradiation light), from the viewpoint of removing nitrosamines with high selectivity and high efficiency, at least one type of light selected from the group consisting of visible light, near-infrared light, and infrared light is preferred, at least one type of light selected from the group consisting of visible light and near-infrared light is more preferred, visible light is even more preferred, and blue light is particularly preferred.

[0120] When the light (irradiation light) is visible light, near-infrared light, or infrared light, the wavelength of the light (irradiation light) can be appropriately selected, for example, from the range of 400 nm to 25,000 nm (preferably 410 nm to 2,500 nm, more preferably 450 nm to 800 nm) depending on the combination with the photocatalyst.

[0121] The light source for the light (irradiation light) is not particularly limited, and examples thereof include light sources derived from natural light such as sunlight, and light irradiation devices such as low-, medium-, or high-pressure mercury lamps, tungsten lamps, and light-emitting diodes (LEDs). As the light source, a light irradiation device that irradiates visible light is preferred, and a light irradiation device equipped with a blue light-emitting diode is more preferred.

[0122] The light may be used alone or in combination of two or more kinds.

[0123] The irradiation time is not particularly limited and can be, for example, 5 minutes or more. From the viewpoint of removing nitrosamines with high selectivity and high efficiency, the irradiation time is preferably 30 minutes to 24 hours, and more preferably 1 hour to 12 hours.

[0124] Light irradiation may be started, interrupted, resumed, or terminated at any time.

[0125] The intensity of light irradiation is not particularly limited as long as it is sufficient to supply the minimum amount of energy necessary for removing nitrosamines, and can be appropriately adjusted, for example, by selecting the output of the light source, the position of the light source, the irradiation time, etc., based on common technical knowledge.

[0126] 1-5. Others The light irradiation step can be carried out in a batch system or a continuous system (flow system).

[0127] The light irradiation step can be carried out in the presence of additives such as surfactants, emulsifiers, dispersants, pH adjusters, stabilizers, light stabilizers, UV absorbers, radical generators, acids, bases, oxidizing agents, reducing agents, and salts.

[0128] The light irradiation step can be carried out in air, but is not particularly limited thereto. Alternatively, the light irradiation step can be carried out in a non-oxidizing atmosphere, such as Ar or N ２ In an inert gas atmosphere such as H ２ Alternatively, the reaction may be carried out under a reduced pressure state with a sufficiently low oxygen concentration, for example, a reduced pressure of about 20 Pa or less (particularly 1 Pa to 20 Pa).

[0129] The reaction temperature in the light irradiation step is not particularly limited, but can be, for example, within the range of 0°C to 100°C (preferably 10°C to 60°C, more preferably 20°C to 40°C).

[0130] In the removal method of the present invention, the irradiated material can be separated (purified) after the light irradiation step, if necessary. As the separation (purification) method, a wide variety of known purification methods can be used, such as separation, adsorption, crystallization, filtration, centrifugation, solvent extraction, drying, filtration, distillation, concentration, and combinations thereof. In the removal method of the present invention, from the viewpoint of improving safety to the human body, it is preferable to separate the irradiated material from the aromatic polyamine, the photocatalyst, and compounds derived therefrom after the light irradiation step.

[0131] 2. Method for Producing a Composition from Which Nitrosamines Have Been Removed The present invention also provides a method for producing a composition from which nitrosamines have been removed (hereinafter, sometimes simply referred to as the "production method" in this specification). The production method of the present invention comprises a step of irradiating an object containing nitrosamines with light in the presence of an aromatic polyamine and a photocatalyst.

[0132] The irradiated object, aromatic polyamine and its derivative, photocatalyst and light used in the removing composition of the present invention, as well as the effects thereof, can be understood from the explanation of "1. Nitrosamine Removal Method" above.

[0133] The production method of the present invention may optionally include a step of separating (purifying) the irradiated material after the light irradiation step. As the separation (purification) method, a wide variety of known purification methods can be used, such as separation, adsorption, crystallization, filtration, centrifugation, solvent extraction, drying, filtration, distillation, concentration, and combinations thereof.

[0134] The composition obtained by the production method of the present invention preferably does not substantially contain the above-mentioned nitrosamines. The content of nitrosamines contained in the composition obtained by the production method of the present invention can be, for example, less than 1 ppm, where the total amount of the composition is 100% by mass. From the viewpoint of ensuring safety to the human body, it is preferably less than 0.1 ppm, more preferably less than 0.01 ppm, even more preferably less than 0.001 ppm, and particularly preferably less than the detection limit.

[0135] The composition obtained by the production method of the present invention preferably contains the above-mentioned amine. The content of the amine contained in the composition obtained by the production method of the present invention can be, for example, 90% by mass or more, where the total amount of the composition is 100% by mass. From the viewpoint of providing a high-purity active substance (active ingredient), the content is preferably 95% by mass or more, more preferably 99% by mass or more, even more preferably 99.9% by mass or more, and particularly preferably 99.99% by mass or more.

[0136] The composition obtained by the production method of the present invention is preferably substantially free of the aromatic polyamine and the aromatic polyamine derivative. The content of the aromatic polyamine and the aromatic polyamine derivative contained in the composition obtained by the production method of the present invention can be, for example, less than 5% by mass, where the total amount of the composition is 100% by mass. From the viewpoint of providing a high-purity active substance, it is preferably less than 1% by mass, more preferably less than 0.1% by mass, even more preferably less than 0.01% by mass, and particularly preferably less than 0.001% by mass.

[0137] The composition obtained by the production method of the present invention preferably does not substantially contain the photocatalyst. The content of the photocatalyst contained in the composition obtained by the production method of the present invention can be, for example, less than 5% by mass, where the total amount of the composition is 100% by mass. From the viewpoint of providing a high-purity active substance, it is preferably less than 1% by mass, more preferably less than 0.1% by mass, even more preferably less than 0.01% by mass, and particularly preferably less than 0.001% by mass.

[0138] With respect to the composition obtained by the production method of the present invention, the contents of each component, such as the amine, the aromatic polyamine and its derivative, and the photocatalyst, can be measured by appropriately selecting a measurement method used for known components.

[0139] The composition obtained by the production method of the present invention may or may not contain the solvent that can be contained in the irradiated material, depending on the desired formulation.

[0140] In the production method of the present invention, when the aromatic polyamine and / or the photocatalyst are supported on a carrier, they are easily removed after removing the nitrosamine, and therefore the purity of the desired active substance can be increased.

[0141] The composition obtained by the production method of the present invention may contain the above-mentioned components and may further contain other components within the range that does not impair the effects of the present invention. Examples of other components include pharmaceutically or food hygienically acceptable bases, excipients, flavorings, colorings, emulsifiers, stabilizers, thickeners, enzymes, preservatives, lubricants, surfactants, disintegrants, disintegration inhibitors, binders, absorption enhancers, adsorbents, humectants, solubilizers, preservatives, flavors, sweeteners, etc.

[0142] In the composition obtained by the production method of the present invention, the active ingredient is preferably the above-mentioned amine. Specifically, in the composition obtained by the production method of the present invention, the active ingredient is preferably an amine obtained by converting the —N(—N═O)— moiety constituting the above-mentioned nitrosamine to an —NH— moiety.

[0143] The composition obtained by the production method of the present invention is useful as a product or raw material for a variety of industrial fields. The composition obtained by the production method of the present invention can also be used as, for example, a pharmaceutical composition, a food or drink composition, a cosmetic composition, a tobacco composition, a feed composition, or other compositions.

[0144] The dosage form of the composition obtained by the production method of the present invention is not particularly limited, and examples thereof include tablets, pills, capsules, powders, fine granules, granules, liquids, troches, jellies, injections, plasters, extracts, suppositories, suspensions, tinctures, ointments, poultices, nasal drops, inhalants, liniments, lotions, and aerosols.

[0145] The subjects to which the composition obtained by the production method of the present invention is administered are not particularly limited, and examples include humans and non-human mammals.

[0146] The dosage (intake) of the composition obtained by the production method of the present invention is not particularly limited, and is determined depending on the age, weight, sex, severity of symptoms, administration method, etc. of the subject to be administered.

[0147] The composition obtained by the production method of the present invention may be administered once a day, or may be administered in divided doses (for example, about 2 to 5 times) per day.

[0148] The method of administration of the composition obtained by the production method of the present invention is not particularly limited, and examples thereof include oral administration and parenteral administration (e.g., intravenous, arterial, intramuscular, subcutaneous, peritoneal, rectal, transdermal, topical, etc.).

[0149] 3. Composition The present invention also provides a composition from which nitrosamines have been removed (hereinafter, sometimes simply referred to as the "composition" in this specification). The nitrosamine-removed composition of the present invention contains a nitrosamine, an amine obtained by converting the —N(—N═O)— moiety that constitutes the nitrosamine to an —NH— moiety, and an aromatic polyamine or a derivative thereof, and the nitrosamine content is less than 1 ppm, based on 100% by mass of the total amount of the composition.

[0150] The aspects and effects of the nitrosamines, amines, aromatic polyamines, and derivatives thereof used in the composition of the present invention can be understood from the above explanation of "1. Method for removing nitrosamines." In particular, the constitution and effects of the composition of the present invention can be understood from the above explanation of the composition (nitrosamine-removed composition) obtained in "2. Method for producing a composition from which nitrosamines have been removed."

[0151] From the viewpoint of ensuring safety to the human body, the content of nitrosamines contained in the composition of the present invention is preferably less than 0.1 ppm, more preferably less than 0.01 ppm, even more preferably less than 0.001 ppm, and particularly preferably less than the detection limit, based on 100% by mass of the total amount of the composition. Thus, the present invention can provide a composition that satisfies the nitrosamine control standards required for pharmaceuticals, foods, beverages, etc.

[0152] In addition to the above components, the composition of the present invention may further contain other components such as the photocatalyst, the additives, etc. The aspects and effects of the photocatalyst when it is contained can also be understood from the explanation of "1. Nitrosamine Removal Method" above.

[0153] The composition of the present invention is not particularly limited, but can be obtained, for example, by the above-mentioned removal method of the present invention or the above-mentioned production method of the present invention.

[0154] 4. Nitrosamine Removal Kit The present invention also provides a nitrosamine removal kit (hereinafter sometimes simply referred to as a "removal kit" in this specification). The removal kit of the present invention includes an aromatic polyamine, a photocatalyst, and a solvent.

[0155] The aspects of the aromatic polyamine, photocatalyst, and solvent used in the removal kit of the present invention, as well as the effects thereof, can be understood from the explanation of "1. Nitrosamine Removal Method" above.

[0156] The removal kit of the present invention can remove nitrosamines from an object (e.g., the above-mentioned irradiated object) containing nitrosamines by irradiating the solution or dispersion obtained by dissolving or dispersing the object in a solvent with the above-mentioned light.

[0157] The removal kit of the present invention can be used for purification. That is, the removal kit of the present invention can be used not only to remove nitrosamines from various types of products in the industrial field, such as pharmaceuticals, foods and beverages, cosmetics, tobacco, feed, and other industrial products, as well as their raw materials, modified products, or decomposed products, but also to purify organic wastewater such as domestic wastewater, sewage, food factory wastewater, and pulp factory wastewater.

[0158] The nitrosamine removal efficiency (purification efficiency) when using the removal kit of the present invention is not particularly limited, but can be, for example, 99% or more. From the viewpoint of ensuring safety to the human body, 99.9% or more is preferable, 99.99% or more is more preferable, 99.999% or more is even more preferable, and 99.9999% or more is particularly preferable.

[0159] 5. Catalyst Composition for Removing Nitrosamines The present invention also provides a catalyst composition for removing nitrosamines (hereinafter, sometimes simply referred to as the "catalyst composition" in this specification). The catalyst composition of the present invention contains an aromatic polyamine and a photocatalyst.

[0160] The aspects of the aromatic polyamine and photocatalyst used in the catalyst composition of the present invention, as well as their effects, can be understood from the explanation of "1. Nitrosamine Removal Method" above.

[0161] The catalyst composition of the present invention preferably further contains a solvent. The mode and effect of containing a solvent can also be understood from the above explanation of "1. Method for removing nitrosamines."

[0162] In the catalyst composition of the present invention, the aromatic polyamine is preferably an aromatic diamine, and the photocatalyst is preferably a photoredox catalyst. In the catalyst composition of the present invention, the solvent is preferably 2-methyltetrahydrofuran, the aromatic polyamine is preferably o-phenylenediamine, and the photocatalyst preferably contains iridium. In this case, nitrosamines can be removed with higher selectivity and higher efficiency.

[0163] In the catalyst composition of the present invention, the aromatic polyamine and the photocatalyst are preferably supported on a bead-like polymer, respectively, which can increase the recovery efficiency of the aromatic polyamine and the photocatalyst, thereby increasing the purity of the target product.

[0164] In the catalyst composition of the present invention, the nitrosamines to be removed are N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosoethylisopropylamine (NEIPA), N-nitrosodiisopropylamine (NDIPA), N-nitrosodicyclohexylamine (NDCHA), N-nitrosomethylphenylamine (NMPA), N-nitrosodiphenylamine (NDPhA), N-nitrosopyrrolidine (NPYR), N-nitrosoproline (NPRO), N-nitrosopiperidine (NPIP), N-nitrosomorpholine (NMOR), N-nitroso-N'-methylpiperazine (NMP), N-nitrosodiethanolamine (NDELA), N-nitrosomethylaminobutyric acid (NMBA), N-nitro Preferably, the compound is at least one compound selected from the group consisting of sosarcosine (NSAR), N-nitrosonornicotine (NNN), N-nitrosoanabasine (NAB), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosonortriptyline (NNORT), and N-nitrosopropranolol (NNP), N-nitrosomethylethylamine (NMEA), N-nitrosohydroxyproline (NHPRO), N-nitrosodiisobutylamine (NDiBA), N-nitrosodibenzylamine (NDBzA), N-nitroso-2-hydroxymethyl-thiazolidine-4-carboxylic acid (NHMTCA), N-nitroso-thiazolidine-4-carboxylic acid (NTCA), N-nitroso-2-methyl-thiazolidine-4-carboxylic acid (NMTCA), and N-nitrosopipecolic acid (NPIC).

[0165] The content of the aromatic polyamine is not particularly limited, but from the viewpoint of removing nitrosamine with high selectivity and high efficiency, it is preferably 1 mol to 10 mol, more preferably 1 mol to 5 mol, and even more preferably 1 mol to 2 mol per mol of the nitrosamine to be removed.

[0166] The content of the photocatalyst is not particularly limited, but from the viewpoint of removing nitrosamines with high selectivity and high efficiency, it is preferably 0.0001 mol to 0.1 mol, more preferably 0.001 mol to 0.05 mol, and even more preferably 0.005 mol to 0.02 mol per 1 mol of the nitrosamine to be removed.

[0167] The ratio of the photocatalyst content to the aromatic polyamine content (photocatalyst content / aromatic polyamine content; molar ratio) is not particularly limited, but from the viewpoint of removing nitrosamines with high selectivity and high efficiency, it is preferably 0.001 to 1, more preferably 0.005 to 0.5, and even more preferably 0.01 to 0.1.

[0168] When the catalyst composition of the present invention contains a solvent, the content of the solvent can be, for example, 1% by mass to 99% by mass (preferably 5% by mass to 95% by mass, more preferably 50% by mass to 90% by mass), where the total amount of the catalyst composition is 100% by mass.

[0169] The catalyst composition of the present invention may further contain components such as the additives described above in addition to the components described above.

[0170] The catalyst composition of the present invention is not particularly limited, but can be obtained, for example, by mixing the above components using a known mixing method.

[0171] 6. Nitrosamine Removal Apparatus The present invention also provides a nitrosamine removal apparatus (hereinafter sometimes simply referred to as a "removal apparatus" in this specification). The removal apparatus of the present invention includes a light source and a storage section in which the catalyst composition is stored, and the light source irradiates the storage section with light.

[0172] The configuration of the removal device is not particularly limited, and the configuration of a known device used in photoreaction (for example, a photoreactor) can be adopted.

[0173] The aspects of the light source and catalyst composition used in the removal device of the present invention, as well as the effects thereof, can be understood from the explanations of "1. Nitrosamine removal method" and "5. Catalyst composition for removing nitrosamines" above.

[0174] The storage section preferably contains the irradiated object in addition to the catalyst composition. In this case, the nitrosamines contained in the irradiated object can be removed. The aspects of the irradiated object used in the removal device of the present invention and their effects can be understood from the explanation of "1. Nitrosamine Removal Method" above.

[0175] It is preferable that a part or all of the surfaces of the container be made of a light-transmitting material.

[0176] The housing may cover the light source or may be covered by the light source.

[0177] The light source can be appropriately selected depending on the wavelength of the light to be irradiated onto the storage unit, or the wavelength of the light to be irradiated onto the storage unit can be appropriately selected by using a filter that transmits only light of a specific wavelength.

[0178] The light irradiation is preferably carried out after the catalyst composition is contained in the container, and if necessary, the light irradiation is more preferably carried out after the object to be irradiated is contained in the container.

[0179] The efficiency of nitrosamine removal when using the removal device of the present invention is not particularly limited, but can be, for example, 99% or more. From the viewpoint of ensuring safety for the human body, 99.9% or more is preferable, 99.99% or more is more preferable, 99.999% or more is even more preferable, and 99.9999% or more is particularly preferable.

[0180] 7. Nitrosamine Removal System The present invention also provides a nitrosamine removal system (hereinafter sometimes simply referred to as the "removal system" in this specification). The removal system of the present invention has the above-described nitrosamine removal device as a means for removing nitrosamines.

[0181] The aspects of the removal device used in the removal system of the present invention and the effects thereof can be understood from the above description and the explanation in "6. Nitrosamine Removal Device."

[0182] The removal system of the present invention preferably further comprises a means for recovering the product after light irradiation. As the recovery means, a wide range of conventionally known recovery methods can be used, such as extraction, separation, distillation, adsorption, crystallization, drying, filtration, and centrifugation.

[0183] In the removal system of the present invention, examples of the product include amines obtained by converting the —N(—N═O)— moiety constituting nitrosamines to —NH— moieties, aromatic polyamines, photocatalyst derivatives, and water.

[0184] When a bead-like polymer is used as the recovery means, the recovery efficiency of the aromatic polyamine, the photocatalyst, and their derivatives can be increased, and as a result, the purity of the target product can be increased.

[0185] The recovery means may be used alone or in combination of two or more.

[0186] The efficiency of nitrosamine removal when using the removal system of the present invention is not particularly limited, but can be, for example, 99% or more. From the viewpoint of ensuring safety to the human body, 99.9% or more is preferred, 99.99% or more is more preferred, 99.999% or more is even more preferred, and 99.9999% or more is particularly preferred.

[0187] EXAMPLES Hereinafter, examples and comparative examples will be shown to further clarify the features of the present invention, but the present invention is not limited to the following examples.

[0188] Example 1 In a glass screw-cap bottle (volume 4 mL), N-nitrosodimethylamine (NDMA; 0.2 mmol), tris(2-phenylpyridinato)iridium(III) (Ir(ppy) ３(0.01 molar equivalent; Tokyo Chemical Industry Co., Ltd.), o-phenylenediamine (Fujifilm Wako Pure Chemical Industries, Ltd.; 1.1 molar equivalent), and 2-methyltetrahydrofuran (2 mL; Tokyo Chemical Industry Co., Ltd.) were added together with a stir bar, and the mixture was stirred at room temperature for 3 hours while irradiating with blue LED light (CS Inc., PD3-5024-4-PI, LDL2-146X30BL2, 470 nm). After the reaction, the mixture was filtered using Celite® No. 535 (Kanto Chemical Co., Ltd.) and analyzed by gas chromatography (Shimadzu Corporation, GC-17A) using mesitylene (Tokyo Chemical Industry Co., Ltd.) as an internal standard. The removal efficiency (decomposition rate) was >99%. The selectivity was >99%. In other words, reactions other than the denitrosation reaction did not substantially occur.

[0189] Example 2: Irradiation and filtration were carried out in the same manner as in Example 1, except that N-nitrosodimethylamine (NDMA; 0.2 mmol) was replaced with N-nitrosodibutylamine. After filtration, the mixture was vacuum-dried under reduced pressure and analyzed with a nuclear magnetic resonance (NMR) spectrometer (JEOL Ltd., JEOL ESC 400 MHz) using mesitylene (Tokyo Chemical Industry Co., Ltd.) as an internal standard. The removal efficiency (decomposition rate) was >99%. The selectivity was >99%. In other words, reactions other than the denitrosation reaction did not substantially occur.

[0190] In Examples 3 to 20, removal and analysis were carried out in the same manner as in Example 1 or Example 2, except that the nitrosamines were changed. The nitrosamines to be removed, their removal efficiency, and analytical methods are shown in Table 1. The analytical methods used were gas chromatography for compounds with low boiling points and HPLC for compounds with high boiling points. １ H-NMR was selected.

[0191]

Claims

1. A method for removing nitrosamines, comprising the step of irradiating an object containing the nitrosamines with light in the presence of an aromatic polyamine and a photocatalyst.

2. The removal method according to claim 1, wherein in the light irradiation step, the -N(-N=O)- moiety constituting the nitrosamine is converted to an -NH- moiety.

3. The removal method according to claim 1 or 2, wherein the aromatic polyamine has two or more amino groups on one aromatic ring.

4. The removal method according to claim 1 or 2, wherein the photocatalyst is a transition metal catalyst, an organic catalyst, or a biocatalyst.

5. The removal method according to claim 1 or 2, wherein the light is visible light.

6. The removal method according to claim 1 or 2, wherein the object to be irradiated is a solution containing the nitrosamine.

7. A removal method according to claim 1 or 2, wherein the content of nitrosamines in the irradiated object after the light irradiation is less than 1 ppm.

8. The removal method according to claim 1 or 2, wherein the irradiated object after the light irradiation is a pharmaceutical composition, a food or beverage composition, a cosmetic composition, a tobacco composition, or an animal feed composition.

9. A method for producing a composition from which nitrosamines have been removed, comprising the step of irradiating an object containing the nitrosamines with light in the presence of an aromatic polyamine and a photocatalyst.

10. A composition containing a nitrosamine, an amine obtained by converting the —N(—N═O)— moiety constituting the nitrosamine to an —NH— moiety, and an aromatic polyamine or a derivative thereof.

11. A nitrosamine removal kit comprising an aromatic polyamine, a photocatalyst, and a solvent.

12. A catalytic composition for removing nitrosamines, comprising an aromatic polyamine and a photocatalyst.

13. The catalyst composition for removing nitrosamines according to claim 12, further comprising a solvent, wherein the aromatic polyamine is an aromatic diamine, and the photocatalyst is a photoredox catalyst.

14. The catalyst composition for removing nitrosamines according to claim 13, wherein the solvent is 2-methyltetrahydrofuran, the aromatic polyamine is o-phenylenediamine, and the photocatalyst contains iridium.

15. The catalyst composition for removing nitrosamines according to claim 13, wherein the aromatic polyamine and the photocatalyst are each supported on a bead-shaped polymer.

16. The nitrosamines include N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosoethylisopropylamine (NEIPA), N-nitrosodiisopropylamine (NDIPA), N-nitrosodicyclohexylamine (NDCHA), N-nitrosomethylphenylamine (NMPA), N-nitrosodiphenylamine (NDPhA), N-nitrosopyrrolidine (NPYR), N-nitrosoproline (NPRO), N-nitrosopiperidine (NPIP), N-nitrosomorpholine (NMOR), N-nitroso-N'-methylpiperazine (NMP), N-nitrosodiethanolamine (NDELA), N-nitrosomethylaminobutyric acid (NMBA), N-nitrososarcosine (NSAR), N-nitro 14. The catalyst composition for removing nitrosamines according to claim 13, which is at least one compound selected from the group consisting of sonornicotine (NNN), N-nitrosoanabasine (NAB), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosonortriptyline (NNORT), N-nitrosopropranolol (NNP), N-nitrosomethylethylamine (NMEA), N-nitrosohydroxyproline (NHPRO), N-nitrosodiisobutylamine (NDiBA), N-nitrosodibenzylamine (NDBzA), N-nitroso-2-hydroxymethyl-thiazolidine-4-carboxylic acid (NHMTCA), N-nitroso-thiazolidine-4-carboxylic acid (NTCA), N-nitroso-2-methyl-thiazolidine-4-carboxylic acid (NMTCA), and N-nitrosopipecolic acid (NPIC).

17. A nitrosamine removal device comprising a light source and a storage section in which the catalyst composition for removing nitrosamines according to claim 15 is stored, said light source irradiating said storage section with light.

18. The nitrosamine removal device of claim 17, wherein the light is visible light.

19. The nitrosamine removal device of claim 18, wherein the light is blue light.

20. A nitrosamine removal system comprising the nitrosamine removal device according to any one of claims 17 to 19.

21. The nitrosamine removal system of claim 20, further comprising a means for recovering the product after said light irradiation.