Hair carbonyl protein reducer

Abstract

[Problem] The change in quality of hair with aging is one of problems particularly for women more than 40 years old. If the quality of hair can be improved effectively, the quality of life (QOL) can be further improved. The purpose of the present invention is to provide a novel method and a novel agent both for improving the change in quality of hair with aging. [Solution] The present invention provides a carbonylated protein reducing agent for hair, a water-retaining capacity improving agent for hair, and a hair curvature reducing agent, each of which comprises a reducing agent, an acid catalyst, and a reductive amination agent containing a nitrogen source.

Description

[Technical Field]

[0001] The present invention relates to an agent, composition and method for reducing carbonylated proteins in hair, which increase with age. [Background technology]

[0002] Like skin, hair changes with age, including an increase in gray hair and a decrease in hair volume. Gray hair is a particular concern for women over 40. Until now, the only way to address gray hair was to correct the color by dyeing, and no known method for reversing gray hair has been found. In addition to gray hair, age-related irregularities such as wavy or frizzy hair are also a concern. It has also been reported that aging can cause a decrease in hair luster, density, and lipid content, as well as changes in the morphology of the cuticle layer.

[0003] As a means for preventing or improving gray hair, Patent Document 1 discloses an agent for preventing or improving gray hair or age-related alopecia, an agent for suppressing or improving DNA damage in hair follicle constituent cells, and an agent for suppressing the decrease in melanocyte stem cells, each of which contains as an active ingredient at least one selected from the group consisting of berberrubine, its derivatives, and salts thereof.

[0004] Furthermore, as a novel material capable of improving the appearance of hair and a composition containing the same, Patent Document 2 discloses a composition for improving the appearance of hair, which comprises, as an active ingredient, a peptide having the amino acid sequence of WY or a pharmaceutically acceptable salt or solvate thereof. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent Publication No. 2021-004235 [Patent Document 2] Japanese Patent Publication No. 2020-158413 [Patent Document 3] Patent No. 6802458 [Non-patent literature]

[0006] [Non-Patent Document 1] I. Iwai, T. Hirao, Skin Pharmacol Physiol., 2008, Vol.21, p.269-273 [Non-patent document 2] Y. Kobayashi, I. Iwai, N. Akutsu, T. Hirao, Int. J. Cosmet. Sci., 2008, Vol. 30, pp. 35-40 [Non-patent document 3] T. Toda, Biomed. Gerontol., 2011, Vol.35, p.17-22 [Non-patent document 4] S. Sato, T. Sakamoto, E. Miyazawa, Y. Kikugawa, Tetrahedron60, 2004, pp.7899-7906 [Non-patent document 5] S. Nagase, Y. Kajiura, A. Mamada, H. Abe, S. Shibuichi, N. Satoh, T. Itou, Y. Shinohara, Y. Amemiya, J. Cosmet. Sci., 2009, Vol.60, p.637-648 Summary of the Invention [Problem to be solved by the invention]

[0007] Age-related changes in hair quality are a major concern for women, especially those in their 40s and older, and effectively improving hair quality can further improve their quality of life (QOL).

[0008] Therefore, an object of the present invention is to provide a new method and agent for improving the qualitative changes in hair that occur with aging. [Means for solving the problem]

[0009] In order to solve the above problems, the present inventors analyzed age-related qualitative changes in hair, focusing on black and white hair in people aged 40 or older.

[0010] First, external observations of hair from people in their 40s, 50s, and 60s were performed, and it was found that irregular hair shapes increased with age under both high and low humidity conditions. In particular, wavy and maximally irregular hair shapes were observed more frequently in gray hair than in black hair.

[0011] The irregular shape caused by changes in humidity differed between gray hair and black hair, suggesting that the reactivity to water differs between the two hair types. Therefore, the water penetration measurement method described in Patent Document 3 was then applied to evaluate the water behavior of gray hair and black hair, and the results showed that gray hair has higher water permeability and lower water retention than black hair. Since the contribution of the cortex, which accounts for more than 80% of the cross-sectional area of ​​the hair shaft, is greater than that of the cuticle, the inventors believed that denaturation of keratin protein in the cortex is one of the factors behind the difference in water behavior.

[0012] Therefore, the inventors evaluated the degree of carbonylation, an indicator of aging, using white and black hair from women of various age groups. The results showed that the content of carbonylated proteins in hair increased with age, and significant differences were observed in the carbonylation of white and black hair in women in their 50s and 60s compared to women in their 40s.

[0013] It has been reported that skin carbonylation increases with age and leads to various cosmetic defects (Non-Patent Documents 1 and 2). These documents relate to the correlation between carbonylated proteins in the stratum corneum and physiological parameters of the skin. These documents show that protein carbonylation is inversely proportional to the water content of the stratum corneum, and that carbonylation of keratin proteins in each layer reduces the water-retaining capacity. The present inventors hypothesized that hair keratin proteins may also undergo the same phenomenon by undergoing carbonylation in the same way as skin keratin proteins.

[0014] Previously, it was believed that carbonylated proteins could not be restored to their previous state (Non-Patent Document 3). However, the present inventors have demonstrated that reductive amination treatment using 5-ethyl-2-methylpyridineborane (PEMB) or Hantzsch ester can reduce the carbonylated proteins in hair that increase with age. Furthermore, they have demonstrated that reductive amination treatment improves hair's water-retaining capacity, reduces the mean curvature of hair, and improves irregular hair shape.

[0015] One-pot reductive amination of aldehydes and ketones is an important transformation in organic synthesis, and it is known that carbonyl compounds can be directly converted to amines by a simple procedure (Non-Patent Document 4). However, it was not known that reductive amination treatment was possible for organic materials. The present inventors have demonstrated for the first time that reductive amination treatment is also useful for organic materials. The present invention was made based on these findings.

[0016] The present invention provides an agent for reducing carbonylated proteins in hair, which comprises a reductive aminating agent containing a reducing agent, an acid catalyst, and a nitrogen source.

[0017] The present invention also provides the agent for reducing carbonylated protein in hair, wherein the reducing agent is an organoborane complex or a compound represented by the following general formula (I): [ka] (In general formula (I), R 1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a carbohydrate having 1 to 16 carbon atoms, adenine dinucleotide, or adenine dinucleotide phosphate, and R 2 and R 3 each independently represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R 4 and R 5 are each independently a hydrogen atom, -COO-R 6 or -CO-NR 6 R 7 represents R 6 and R 7 each independently represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms.

[0018] The present invention also provides the agent for reducing hair carbonylated proteins, wherein the reducing agent is at least one selected from the group consisting of 5-ethyl-2-methylpyridine borane (PEMB), a 5-ethyl-2-methylpyridine borane complex, a picoline borane complex, sodium cyanoborohydride (NaBHCN), and sodium triacetoxyborohydride.

[0019] The present invention also relates to a compound represented by the general formula (I) above, wherein R 1 represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R 4 and R 5 At least one of the following is -COO-R 6 represents R 6 represents an alkyl group having 1 to 3 carbon atoms.

[0020] The present invention also relates to a compound represented by the general formula (I) above, wherein R 1 represents a hydrogen atom, a carbohydrate having 1 to 16 carbon atoms, adenine dinucleotide, or adenine dinucleotide phosphate, and R 4 represents a hydrogen atom, and R 5 Ga-CO-NR 6 R 7 represents R 6 and R 7represents a hydrogen atom.

[0021] The present invention also provides the agent for reducing hair carbonylated proteins, wherein the reducing agent is at least one selected from the group consisting of reduced nicotinamide adenine dinucleotide phosphate (NADPH), reduced nicotinamide adenine dinucleotide (NADH), reduced nicotinamide, and Hantzsch ester.

[0022] The present invention also provides the agent for reducing carbonylated protein in hair, wherein the acid catalyst is at least one selected from the group consisting of acetic acid, citric acid, formic acid, propionic acid, phosphoric acid, and oxalic acid.

[0023] The present invention also provides the agent for reducing carbonylated protein in hair, wherein the nitrogen source is ammonia or an ammonium salt.

[0024] The present invention also provides a hair modifying composition comprising a reductive aminating agent comprising a reducing agent, an acid catalyst, and a nitrogen source, and a solvent.

[0025] The present invention also provides the above hair modifying composition, wherein the above reducing agent is an organoborane complex or a compound represented by the above general formula (I).

[0026] The present invention also provides the hair modifying composition, wherein the reducing agent is at least one selected from the group consisting of 5-ethyl-2-methylpyridine borane (PEMB), a 5-ethyl-2-methylpyridine borane complex, a picoline borane complex, sodium cyanoborohydride (NaBHCN), and sodium triacetoxyborohydride.

[0027] The present invention also relates to a compound represented by the general formula (I) above, wherein R 1 represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R 4 and R 5 At least one of the following is -COO-R 6 represents R6 represents an alkyl group having 1 to 3 carbon atoms.

[0028] The present invention also relates to a compound represented by the general formula (I) above, wherein R 1 represents carbohydrates with 1 to 16 carbon atoms, and R 4 represents a hydrogen atom, and R 5 Ga-CO-NR 6 R 7 represents R 6 and R 7 represents a hydrogen atom.

[0029] The present invention also provides the hair modifying composition, wherein the reducing agent is at least one selected from the group consisting of reduced nicotinamide adenine dinucleotide phosphate (NADPH), reduced nicotinamide adenine dinucleotide (NADH), reduced nicotinamide, and Hantzsch ester.

[0030] The present invention also provides the hair modifying composition, wherein the acid catalyst is at least one selected from the group consisting of acetic acid, citric acid, formic acid, propionic acid, phosphoric acid, and oxalic acid.

[0031] The present invention also provides the hair modifying composition, wherein the nitrogen source is ammonia or an ammonium salt.

[0032] The present invention also provides the hair modifying composition, wherein the solvent is water or ethanol.

[0033] The present invention also provides an agent for improving hair moisture retention, which comprises a reducing agent, an acid catalyst, and a reductive aminating agent containing a nitrogen source.

[0034] The present invention also provides a hair curvature reducing agent containing a reductive aminating agent comprising a reducing agent, an acid catalyst, and a nitrogen source.

[0035] The present invention also provides a method for reducing carbonylated proteins in hair, which comprises treating hair with a reducing agent in a solvent in the presence of an acid catalyst and a nitrogen source by reductive amination.

[0036] The present invention also provides a method for improving the water-holding capacity of hair, which comprises treating hair with a reducing agent in a solvent in the presence of an acid catalyst and a nitrogen source by reductive amination.

[0037] The present invention also provides a method for reducing hair curvature, which comprises treating hair with a reducing agent in a solvent in the presence of an acid catalyst and a nitrogen source by reductive amination. [Effects of the Invention]

[0038] The present invention can reduce carbonylated proteins in hair, which increase with age. Therefore, the present invention can improve hair's water-retaining ability, which decreases with age. Furthermore, the present invention can reduce hair curvature, which increases with age, and improve irregular hair shapes. Therefore, the present invention can contribute to further improving quality of life (QOL). [Brief explanation of the drawings]

[0039] [Figure 1] Diagram showing hair bundles in their forties (40s), fifties (50s), and sixties (60s) under relative humidity (RH) conditions of 20% RH (a), 50% RH (b), or 90% RH (c). [Figure 2] A diagram showing the average curvature of hair for each age group. [Figure 3] FIG. 1 shows an example of irregular shapes observed in white hair and dyed white hair. [Figure 4] FIG. 10 shows measurement points for line mapping using an optical microscope image of untreated hair. [Figure 5] A diagram showing the behavior of water in the cortex of black hair (diamond shape) and white hair (triangle) of a Japanese woman in her 50s. [Figure 6]A diagram showing the localization of carbonylated proteins in cross-sections of hair from each age group. [Figure 7] A graph showing the ratio of mean fluorescence intensity in cross sections of white and black hair for each age group. [Figure 8] A diagram showing the localization of carbonylated proteins in a cross-section of hair from a Japanese woman in her 50s. [Figure 9] A diagram showing the behavior of water in the cortex of black hair (diamond shape), white hair (triangle), and white hair treated with reductive amination (square) from a Japanese woman in her 50s. [Figure 10] FIG. 10 shows the mean curvature of hair from the same subjects as in FIGS. 2 and 9. [Figure 11] FIG. 1 is a graph showing the level of amino groups introduced into hair treated with reductive amination. [Figure 12] FIG. 1 shows the effect of reducing carbonylated proteins when Hantzsch ester is used as a reducing agent. [Figure 13] FIG. 1 is a diagram showing a comparison of the effects of different solvents on reducing carbonylated proteins. DETAILED DESCRIPTION OF THE INVENTION

[0040] The present invention provides an agent for reducing carbonylated proteins in hair, which comprises a reductive aminating agent containing a reducing agent, an acid catalyst, and a nitrogen source.

[0041] As used herein, "reducing carbonylated proteins in hair" means reducing the amount of carbonylated proteins contained in hair. As used herein, "hair" includes both the hair shaft extending from the scalp and the hair root within the scalp. "Reducing carbonylated proteins in hair" includes reducing carbonylated proteins in at least one of the hair cuticle, cortex, and medulla. Additionally, as used herein, "reducing carbonylated proteins" includes inhibiting an increase in carbonylated proteins.

[0042] Carbonylated proteins are proteins in which amino acids such as proline, arginine, lysine, or threonine in proteins are oxidized by reactive oxygen species (ROS) to form carbonyl derivatives. Carbonylated proteins are known to be generated in vivo by aging and oxidative stress.

[0043] The hair carbonyl protein reducing agent of the present invention can modify hair through the reduction of hair carbonyl proteins. That is, the hair carbonyl protein reducing agent of the present invention can be used as a hair modifying agent. As used herein, "modifying hair" includes improving hair's water retention ability, reducing the mean curvature of hair, correcting irregular hair shapes, and improving hair appearance.

[0044] As used herein, the term "reductive aminating agent" refers to an agent capable of converting a carbonyl group of a carbonylated protein to an amino group through a reductive amination reaction. A reductive amination reaction is a chemical reaction that converts an aldehyde or ketone into an amine. In the present invention, the reductive aminating agent is a mixture containing a reducing agent, an acid catalyst, and a nitrogen source.

[0045] In the present invention, a reducing agent is used to reduce the reaction intermediate imine to an amine. For example, an organoborane complex can be used as the reducing agent. Examples of organoborane complexes include 5-ethyl-2-methylpyridine borane (PEMB), 5-ethyl-2-methylpyridine borane complex, picoline borane complex, sodium cyanoborohydride (NaBHCN), and sodium triacetoxyborohydride. From the viewpoint of toxicity and safety, 5-ethyl-2-methylpyridine borane complex is preferably used.

[0046] Furthermore, as the reducing agent in the present invention, a compound having a 1,4-dihydropyridine structure represented by the following general formula (I) can be used. [ka]

[0047] In general formula (I), R 1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or a carbohydrate having 1 to 16 carbon atoms. 1 The alkyl group represented by the formula (I) can be, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a cyclopropyl group, or the like.

[0048] In general formula (I), R 2 and R 3 R each independently represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. 2 and R 3 may be the same or different. 2 and R 3 The alkyl group represented by the formula (I) can be, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a cyclopropyl group, or the like.

[0049] In general formula (I), R 4 and R 5 are each independently a hydrogen atom, -COO-R 6 or -CO-NR 6 R 7 Represents R 4 and R 5 may be the same or different.

[0050] In general formula (I), R 6 and R 7 R each independently represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. 6 and R 7 may be the same or different. 6 and R 7 The alkyl group represented by the formula (I) can be, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a cyclopropyl group, or the like.

[0051] As used herein, the term "alkyl group" includes straight-chain and branched alkyl groups, such as methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, neopentyl, and hexyl groups.

[0052] As used herein, "carbohydrate" includes monosaccharides, disaccharides, oligosaccharides, amino sugars, and alditols. Monosaccharides can be pyranosides or furanosides. Carbohydrates can be, for example, D-glucose, D-mannose, D-galactose, D-allose, D-altrose, D-idose, D-talose, D-xylose, D-ribose, and D-arabinose. Carbohydrates can also have a structure in which two or more monosaccharides are linked by one to three phosphate groups. The monosaccharides constituting carbohydrates can be, for example, nucleosides or nucleotides in which ribose is linked to a nucleic acid base. Carbohydrates can be, for example, adenine dinucleotide or adenine dinucleotide phosphate.

[0053] In the present invention, the alkyl group and the carbohydrate may have a substituent. The substituent includes, for example, a halogen atom, a nitrogen atom, a sulfur atom, a hydroxyl group, a nitro group, a cyano group, a methoxy group, an ethoxy group, a carboxyl group, a carboxymethyl group, a carboxyethyl group, and methylenedioxy. The halogen atom includes, for example, fluorine, chlorine, bromine, and iodine.

[0054] In the general formula (I), preferably R 1 represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R 4 and R 5 At least one of the following is -COO-R 6 represents R 6 represents an alkyl group having 1 to 3 carbon atoms. More preferably, R 1 represents a hydrogen atom, and R 2 and R 3 represent a methyl group, and R 4 and R 5are -COO-R respectively 6 represents R 6 represents an ethyl group. The reducing agent in the present invention is preferably a Hantzsch ester represented by the following formula (II): [ka]

[0055] In the general formula (I), preferably R 1 represents a hydrogen atom or a carbohydrate having 1 to 16 carbon atoms, and R 4 represents a hydrogen atom, and R 5 Ga-CO-NR 6 R 7 represents R 6 and R 7 represents a hydrogen atom. More preferably, R 1 represents a hydrogen atom, adenine dinucleotide, or adenine dinucleotide phosphate, and R 2 , R 3 and R 4 represents a hydrogen atom, and R 5 Ga-CO-NR 6 R 7 represents R 6 and R 7 Each represents a hydrogen atom. The reducing agent in the present invention is, for example, reduced nicotinamide adenine dinucleotide phosphate (NADPH), reduced nicotinamide adenine dinucleotide (NADH), or reduced nicotinamide. NADPH / NADH is a compound having the following structure. Reduced niacinamide is a compound obtained by isolating only the active site of NADH / NADPH, and both are biological molecules. [ka]

[0056] In the present invention, it is preferable to use Hantsch ester as the reducing agent from the viewpoints of economy and stability, since Hantsch ester can be purchased in large quantities at low cost and can be easily stored.

[0057] The compound represented by general formula (I) is used as a reducing agent in a reduced form, and functions as a reducing agent by releasing two electrons to become an oxidized form.

[0058] The use of the compound represented by the general formula (I) as the reducing agent of the present invention reduces the burden on the environment and enhances safety for the human body. Furthermore, since water, ethanol, or the like can be used as a solvent, safety for the human body can be further enhanced.

[0059] The compound of general formula (I) can be synthesized by any synthetic procedure known to those skilled in the art. Commercially available compounds can be used, including 5-ethyl-2-methylpyridine borane (PEMB), 5-ethyl-2-methylpyridine borane complex, picoline borane complex, sodium cyanoborohydride (NaBHCN), and sodium triacetoxyborohydride, as well as reduced nicotinamide adenine dinucleotide phosphate (NADPH), reduced nicotinamide adenine dinucleotide (NADH), reduced nicotinamide, and Hantzsch ester. The reduced compounds can also be obtained by reducing the oxidized compounds according to standard procedures.

[0060] In the present invention, the acid catalyst is an acid used for the purpose of adding a proton to the carbonyl group to activate it. The acid catalyst may be any Bronsted acid, and is not particularly limited, but examples thereof include acetic acid, citric acid, formic acid, propionic acid, phosphoric acid, and oxalic acid. From the viewpoints of safety and simplicity, the acid catalyst is not particularly limited, but is preferably acetic acid or phosphoric acid.

[0061] In the present invention, a nitrogen source is used to convert a carbonyl group to an imine. The nitrogen source is not particularly limited, but for example, ammonia or an ammonium salt can be used. Ammonia and ammonium salts can restore the carbonylated amino acid to its original amino acid structure. Specific examples of the nitrogen source that can be used include aqueous ammonia, ammonium formate, ammonium acetate, ammonium carbonate, and ammonium bicarbonate. From the viewpoint of ease of operation, the nitrogen source is not particularly limited, but preferably, aqueous ammonia or ammonium acetate can be used.

[0062] The present invention also provides a hair modifying composition comprising a reductive aminating agent comprising a reducing agent, an acid catalyst, and a nitrogen source, and a solvent.

[0063] The solvents used in the present invention are not particularly limited, but include, for example, protic solvents, aprotic polar solvents, and aprotic solvents. Protic solvents include, for example, water, methanol, ethanol, 1-propanol, 2-propanol, propylene glycol, glycerin, butylene glycol, and 1,3-BG. Aprotic polar solvents include, for example, dimethyl sulfoxide, dimethylformamide, acetonitrile, and hexamethylphosphoramide. Aprotic solvents include, for example, diethyl ether, chloroform, toluene, 1,4-dioxane, and liquid hydrocarbons. Of these, water, methanol, or ethanol are preferred due to their reactivity and ease of handling. Furthermore, water or ethanol is preferred due to its safety to the human body.

[0064] The present invention also provides a method for reducing carbonylated proteins in hair, which comprises treating hair with a reducing agent in a solvent in the presence of an acid catalyst and a nitrogen source by reductive amination.

[0065] In the method of the present invention, the reducing agent, acid catalyst, nitrogen source, and solvent described above can be used. That is, in the method of the present invention, hair can be treated with the agent or composition of the present invention described above.

[0066] In the method of the present invention, the method of subjecting hair to reductive amination treatment with a reducing agent may, for example, involve preparing a composition containing a nitrogen source such as an aqueous ammonia solution and a reducing agent in a solvent containing an acid catalyst, and treating the hair with this composition.

[0067] The present invention also provides an agent for improving hair water retention capacity, which contains a reductive aminating agent including a reducing agent, an acid catalyst, and a nitrogen source. The present invention also provides a method for improving hair water retention capacity, which comprises treating hair with a reducing agent in a solvent in the presence of an acid catalyst and a nitrogen source by reductive amination.

[0068] As used herein, "improving hair's water retention ability" means improving hair's water retention ability that has decreased with age, and includes improving hair's water retention ability that has decreased with age and inhibiting the decrease in water retention ability that occurs with age.

[0069] The present invention also provides an agent for reducing hair curvature, which contains a reductive amination agent including a reducing agent, an acid catalyst, and a nitrogen source. The present invention also provides a method for reducing hair curvature, which comprises treating hair with a reducing agent in a solvent in the presence of an acid catalyst and a nitrogen source by reductive amination.

[0070] As used herein, "reducing hair curvature" includes reducing the hair curvature that has increased with age and inhibiting the increase in hair curvature due to age. "Hair curvature" refers to the degree of hair disorder, and the higher the curvature, the greater the degree of hair disorder.

[0071] In addition to the above-mentioned components, the agent and composition of the present invention can contain any other components depending on the purpose of use, as long as the effects of the present invention are not impaired.For example, the agent and composition of the present invention can contain anionic surfactants such as lauryl sulfate, polyoxyethylene lauryl ether sulfate, lauryl benzene sulfonate, and sodium lauroylmethyl-β-alanine; amphoteric surfactants such as 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazonium betaine, coconut oil fatty acid amidopropyl betaine, and coconut oil alkyl N-carboxyethyl-N-hydroxyethyl imidazolinium betaine sodium; polymers such as cationized cellulose, polyacrylic acid, and poly(diallyldimethylammonium chloride); sorbitol, inositol, glycerin, propylene glycol, butylene ... It may also contain humectants such as ethylene glycol, dipropylene glycol, and isoprene glycol; anti-dandruff ingredients such as zinc pyrithione and benzalkonium chloride; lower alcohols such as ethanol, methanol, propyl alcohol, and isopropyl alcohol; higher alcohols such as cetyl alcohol, stearyl alcohol, and behenyl alcohol; quaternary cations such as behentrimonium chloride and stearyltrimonium chloride; amino acids such as DL-alanine, L-arginine, glycine, L-cysteine, and L-threonine; and other ultraviolet absorbers, preservatives, sugars, fragrances, colorants, sequestering agents, antioxidants, and various other drugs.

[0072] The agent and composition of the present invention may be in any form, such as a liquid, emulsion, cream, gel, paste, or foam, depending on the purpose of use.

[0073] The agent and composition of the present invention can be in the form of, for example, a hair cosmetic. Hair cosmetics include, for example, hair rinses, hair conditioners, hair treatments, leave-in treatments, hair packs, hair foams, hair waxes, pomades, hair gels, hair creams, hair sprays, hair mists, hair waters, hair liquids, hair oils, hair tonics, hair lotions, hair colors, perm agents, and hair care products. These hair cosmetics can be produced by conventionally known methods. [Example]

[0074] (Samples and Materials) The subjects were healthy Japanese women aged 40-60 who had not dyed or permed their hair for one week prior to the test. They only used shampoo the day before the test, and did not use any hair styling products or hair treatments on the day of the test. The hair samples were immersed in ion-exchange water for 10 minutes to remove temporary hair shapes, and the intrinsic shape of the hair was evaluated.

[0075] Deuterium oxide (99.8% D) was obtained from Kanto Chemical Co., Ltd. (Tokyo, Japan). 2-(N-morpholino)ethanesulfonic acid (MES) and phosphate-buffered saline (PBS) were obtained from Fujifilm Wako Pure Chemical Industries, Ltd. (Osaka, Japan). Fluorescein-5-thiosemicarbazide (5-FTSC) and 5-ethyl-2-methylpyridine borane complex (PEMB) were obtained from Sigma (St. Louis, MO, USA). The chemical structure of PEMB is shown below.

[0076] [ka]

[0077] (statistical analysis) Statistical analysis was performed using Dunnett's multiple comparison test or Student's t-test, with significance defined as p<0.05.

[0078] [Test 1: External observation of hair] Hair samples were prepared from 20 strands each from individuals in their 40s, 50s, and 60s. The hair was kept at 25°C and the relative humidity (RH) was changed from 50% to 90% or from 50% to 20%. The appearance of the hair was observed. Figure 1 shows hair tresses from individuals in their 40s (40s), 50s (50s), and 60s (60s) under 20% (a), 50% (b), or 90% (c) RH conditions. External observations showed that irregular hair shape increased with age under both high and low humidity conditions.

[0079] To quantify this irregular shape, the mean curvature of the hair was measured using the method described in Non-Patent Document 5. Specifically, the hair fiber was immersed in water at 25°C for 10 minutes to remove temporary water set formed during drying of the hair fiber and resulting from the exchange of hydrogen bonds. Next, the hair fiber was placed in an image scanner (GT-X830, manufactured by Seiko Epson Corporation) to obtain two-dimensional images of the hair shape, and the curvature of each curve from the root to the tip was analyzed. Because hair color has little effect on hair shape, shape measurements were performed without distinguishing between color-treated and uncolored hair.

[0080] Figure 2 shows the average curvature of hair in each age group (mean ± SD (n = 20)). As shown in Figure 2, the average curvature increased with age.

[0081] Furthermore, careful observation of these hair strands revealed that the most irregular shapes were observed in white hair or dyed white hair. Figure 3 shows an example of the irregular shapes observed in white hair and dyed white hair.

[0082] [Test 2: Water behavior evaluation] The irregular shape caused by changes in humidity was different between white and black hair, suggesting that the reactivity to water differs between the two hair types. Therefore, the behavior of water inside the hair was measured.

[0083] The water behavior evaluation was performed using a method that applied the water penetration measurement method described in Patent Document 3. Specifically, a smooth hair slice was sandwiched between diamond cells developed in-house using a rotary microtome, and heavy water was injected into the cell gap. The hair slice was continuously evaluated using a Fourier transform infrared microscope (Thermo Fisher Scientific, Nicolet iN10). The water behavior was monitored in real time by line mapping measurement every 10 μm from the medulla to the cuticle, showing a concentration of heavy water at approximately 2500 cm. -1 The OD stretching peak intensity was evaluated at 1000 kJ / s, and the OD stretching peak intensity was evaluated at 1000 kJ / s. Figure 4 shows the measurement points of line mapping using an optical microscope image of untreated hair. The measurements were performed at a resolution of 8 cm. -1 , 256 accumulations, 4000~650 cm -1 The spectra were acquired in the wavenumber range of

[0084] Figure 5 shows the behavior of water in the cortex of black hair (diamond shape) and white hair (triangle shape) from the same Japanese woman in her 50s (approximately 2500 cm -1 OD stretching peak intensity at 100°C (first 30 minutes under heavy water penetration conditions, followed by a 4-hour drying process at 25°C and 50% RH). This result indicates that the rate at which water penetrates from the outside is faster in gray hair than in black hair. During the drying process, gray hair lost moisture one hour faster than black hair. These results indicate that gray hair has a lower water retention capacity than black hair.

[0085] Test 3: Evaluation of local carbonylation of hair Changes in hair proteins were thought to be responsible for the different water behavior observed between white and black hair, so carbonylation was assessed in white and black hair at different age groups.

[0086] After adjusting the thickness to a uniform thickness using a rotary microtome (Leica RM2265), the hair samples were immersed in 20 μM 5-FTSC / 0.1 M MES-Na (pH 5.5) and incubated in the dark for 1 hour. The hairs were then washed four times with PBS and observed under a fluorescence microscope. The resulting images were analyzed using ImageJ, and the fluorescence intensity per unit area of ​​the hair sample was defined as the degree of carbonylation.

[0087] Figure 6 shows the localization of carbonylated proteins in hair cross-sections from each age group ((a) black hair in people in their 40s; (b) black hair in people in their 50s; (c) black hair in people in their 60s; (d) white hair in people in their 40s; (e) white hair in people in their 50s; (f) white hair in people in their 60s). As shown in Figure 6, an increase in carbonylated proteins was observed with age. It was also shown that white hair contained more carbonylated proteins than black hair.

[0088] These measurements were quantified using fluorescence intensity. Figure 7 shows the ratio of mean fluorescence intensity in cross-sections of white and black hair for each age group (n = 10; ** p < 0.01 vs. hair in women in their 40s (Dunnett's multiple comparison test)). Compared with women in their 40s, women in their 50s and 60s showed significantly higher carbonylation in white hair than in black hair.

[0089] [Test 4: Effect of reductive amination reaction] Aged hair was subjected to the following reductive amination reaction treatment. A dispersion solution containing 28% aqueous ammonia and 201 mg of PEMB was prepared in methanol:acetic acid (10:1; 5.5 mL). Next, thinly cut hair samples (100 mg) were placed in the solution at room temperature for 4 days. After the reaction, the hair samples were washed four times with methanol.

[0090] [ka]

[0091] Local carbonylation was then assessed. Figure 8 shows the localization of carbonylated proteins in hair sections from a Japanese woman in her 50s (Reagent: reductive amination treatment). Reductive amination treatment was shown to reduce the amount of carbonylated proteins, regardless of whether the hair was black or white.

[0092] In addition, the behavior of water in hair that had undergone reductive amination treatment was evaluated. Figure 9 shows the behavior of water in the cortex of black hair (diamond shape), white hair (triangle), and white hair that had undergone reductive amination treatment (square) from the same Japanese woman in her 50s (approximately 2500 cm). -1 (OD stretching peak intensity at 1000 kJ / min; first 30 minutes under heavy water penetration conditions, followed by a 4-hour drying process at 25°C and 50% RH). Gray hair treated with reductive amination showed improved water retention and exhibited water behavior equivalent to that of black hair.

[0093] Figure 10 shows the mean curvature of hair from the same subjects as in Figures 2 and 9 (mean ± SD (n = 20); * p < 0.05 vs. hair from people in their 50s at 90% RH (Student's t-test)). At 90% RH, the mean curvature of hair from people in their 50s that had undergone reductive amination treatment was significantly reduced compared to hair that had not undergone reductive amination treatment. This result indicates that reductive amination treatment also improves hair shape.

[0094] [Test 5: Level of amino group introduction in hair treated with reductive amination] We confirmed whether externally applied amino groups were introduced into hair through reductive amination. Ammonia was replaced with a fluorescent reagent containing amino groups (DBD-ED), and reductive amination was performed. Specifically, a dispersion solution containing 21 mg of DBD-ED (solid) and 10.26 mg of PEMB was prepared in methanol:acetic acid (10:1; 1 mL). Hair (mixed black and white) from a person in their 60s was cut into 1 cm pieces and used. Ten hair samples were placed in the solution at room temperature for four days. After the reaction, the hair samples were washed four times with methanol. As a control, a sample without PEMB was also tested in the same manner.

[0095] The fluorescence intensity in the cross section of the treated hair was measured, and the level of amino group introduction was quantified. Figure 11 shows the level of amino group introduction in hair treated with reductive amination. As shown in Figure 11, the level of amino group introduction was higher in hair treated with PEMB than in the absence of PEMB (control), indicating that a large amount of DBD-ED was introduced into the hair. This result indicates that PEMB treatment introduces amino groups into hair.

[0096] Test 6: Reductive amination with Hantzsch ester The carbonylated protein reduction effect was investigated using Hantsch ester as a reducing agent. Aged hair was subjected to the following reductive amination reaction treatment. A dispersion solution containing 28% aqueous ammonia and 201 mg of Hantsch ester (obtained from Tokyo Chemical Industry Co., Ltd.) (30 mg) was prepared in methanol:acetic acid (10:1; 5.5 mL). Next, a 1 cm section from the root of the hair was used as a sample and stirred in the solution at room temperature for 4 days. After the reaction, the hair sample was washed four times with methanol. A control test was also performed using a sample without Hantsch ester.

[0097] Then, sections of the sample hair were prepared and the carbonyl level was evaluated by fluorescent staining. Figure 12 shows the effect of reducing carbonylated proteins when Hantsch ester was used as a reducing agent. It was shown that the amount of carbonylated proteins was reduced in hair treated with Hantsch ester.

[0098] [Test 7: Confirmation of solvent effect] The effect of using water or ethanol instead of methanol as the solvent on reducing carbonylated proteins was investigated. Aged hair was subjected to the following reductive amination reaction treatment. A dispersion solution containing 28% aqueous ammonia and 30 mg of Hantsch ester (201 mg) was prepared in various solvents: acetic acid (10:1; 5.5 mL). Next, a 1 cm section from the root of the hair was used as a sample and stirred in the solution at room temperature for 4 days. After the reaction, the hair sample was washed four times with methanol. Water, methanol, and ethanol were used as the solvent. A control test was also performed using a sample without Hantsch ester but using methanol as the solvent.

[0099] The hair samples were then sectioned and the carbonyl levels assessed by fluorescent staining. Figure 13 shows a comparison of the carbonyl protein reduction effect of different solvents. The results showed that the amount of carbonyl protein was reduced even in hair treated with water or ethanol as the solvent.

[0100] (Conclusion) These results indicate that gray hair, which increases with age, has a higher concentration of carbonylated proteins than black hair from the same individual, leading to reduced water-retaining capacity and an irregular water-related shape. Furthermore, while it was previously thought that carbonylated proteins could not return to their original shape, these test results demonstrated that carbonylated proteins were reduced by reductive amination using PEMB and Hantzsch ester. Furthermore, reductive amination also improved hair water-retaining capacity and curvature. These results suggest that modifying hair shape through reductive amination may be useful for improving quality of life. [Industrial Applicability]

[0101] The present invention can be suitably used in cosmetics and pharmaceuticals for improving hair quality.

Claims

1. A hair carbonyl protein reducer comprising a reductive aminating agent including a reducing agent, an acid catalyst, and a nitrogen source.

2. 2. The hair carbonyl protein reducer according to claim 1, wherein the reducing agent is an organoborane complex or a compound represented by the following general formula (I): 【Chemical 1】 (In general formula (I), R 1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a carbohydrate having 1 to 16 carbon atoms, adenine dinucleotide, or adenine dinucleotide phosphate, and R 2 and R 3 each independently represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R 4 and R 5 are each independently a hydrogen atom, -COO-R 6 or -CO-NR 6 R 7 represents R 6 and R 7 each independently represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms.

3. 3. The hair carbonyl protein reducer according to claim 2, wherein the reducing agent is at least one selected from the group consisting of 5-ethyl-2-methylpyridine borane (PEMB), 5-ethyl-2-methylpyridine borane complex, picoline borane complex, sodium cyanoborohydride (NaBHCN), and sodium triacetoxyborohydride.

4. The reducing agent is a compound represented by the general formula (I), and R 1 represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R 4 and R 5 At least one of the following is -COO-R 6 represents R 6 The agent for reducing carbonyl protein in hair according to claim 2, wherein represents an alkyl group having 1 to 3 carbon atoms.

5. The reducing agent is a compound represented by the general formula (I), and R 1 represents a hydrogen atom, a carbohydrate having 1 to 16 carbon atoms, adenine dinucleotide, or adenine dinucleotide phosphate, and R 4 represents a hydrogen atom, and R 5 Ga-CO-NR 6 R 7 represents R 6 and R 7 The hair carbonyl protein reducer according to claim 2, wherein represents a hydrogen atom.

6. 3. The hair carbonyl protein reducer according to claim 2, wherein the reducing agent is at least one selected from the group consisting of reduced nicotinamide adenine dinucleotide phosphate (NADPH), reduced nicotinamide adenine dinucleotide (NADH), reduced nicotinamide, and Hantzsch ester.

7. The hair carbonyl protein reducer according to any one of claims 1 to 6, wherein the acid catalyst is at least one selected from the group consisting of acetic acid, citric acid, formic acid, propionic acid, phosphoric acid, and oxalic acid.

8. The agent for reducing carbonylated protein in hair according to any one of claims 1 to 7, wherein the nitrogen source is ammonia or an ammonium salt.

9. A hair modifying composition comprising a reductive aminating agent including a reducing agent, an acid catalyst, and a nitrogen source, and a solvent.

10. 10. The hair modifying composition according to claim 9, wherein the reducing agent is an organoborane complex or a compound represented by the following general formula (I): 【Chemistry 2】 (In general formula (I), R 1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a carbohydrate having 1 to 16 carbon atoms, adenine dinucleotide, or adenine dinucleotide phosphate, and R 2 and R 3 each independently represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R 4 and R 5 are each independently a hydrogen atom, -COO-R 6 or -CO-NR 6 R 7 represents R 6 and R 7 each independently represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms.

11. 11. The hair modifying composition according to claim 10, wherein the reducing agent is at least one selected from the group consisting of 5-ethyl-2-methylpyridine borane (PEMB), 5-ethyl-2-methylpyridine borane complex, picoline borane complex, sodium cyanoborohydride (NaBHCN), and sodium triacetoxyborohydride.

12. The reducing agent is a compound represented by the general formula (I), and R 1 represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R 4 and R 5 At least one of the following is -COO-R 6 represents R 6 The hair modifying composition according to claim 10, wherein represents an alkyl group having 1 to 3 carbon atoms.

13. The reducing agent is a compound represented by the general formula (I), and R 1 represents a hydrogen atom, a carbohydrate having 1 to 16 carbon atoms, adenine dinucleotide, or adenine dinucleotide phosphate, and R 4 represents a hydrogen atom, and R 5 Ga-CO-NR 6 R 7 represents R 6 and R 7 The hair modifying composition according to claim 10, wherein represents a hydrogen atom.

14. 11. The hair modifying composition according to claim 10, wherein the reducing agent is at least one selected from the group consisting of reduced nicotinamide adenine dinucleotide phosphate (NADPH), reduced nicotinamide adenine dinucleotide (NADH), reduced nicotinamide, and Hantzsch ester.

15. The hair modifying composition according to any one of claims 9 to 14, wherein the acid catalyst is at least one selected from the group consisting of acetic acid, citric acid, formic acid, propionic acid, phosphoric acid, and oxalic acid.

16. The hair modifying composition according to any one of claims 9 to 15, wherein the nitrogen source is ammonia or an ammonium salt.

17. The hair modifying composition according to any one of claims 9 to 16, wherein the solvent is water or ethanol.

18. A hair moisture retention improving agent comprising a reducing agent, an acid catalyst and a reductive aminating agent containing a nitrogen source.

19. A hair curvature reducing agent comprising a reductive aminating agent including a reducing agent, an acid catalyst, and a nitrogen source.

20. A method for reducing carbonylated proteins in hair, comprising treating hair with a reducing agent in a solvent in the presence of an acid catalyst and a nitrogen source by reductive amination.

21. A method for improving the water-retaining capacity of hair, comprising treating hair with a reducing agent in a solvent in the presence of an acid catalyst and a nitrogen source by reductive amination.

22. A method for reducing hair curvature, comprising treating hair with a reducing agent in a solvent in the presence of an acid catalyst and a nitrogen source by reductive amination.

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