Expression inhibitor of nerve elongation factor

Abstract

To provide an expression inhibitor of a nerve elongation factor. Another object of the present invention is to provide an itching inhibitor and a skin / scalp cosmetic containing an expression inhibitor of a nerve elongation factor.SOLUTION: As a result of intensive studies to solve the above problems, the present inventors have found that the expression of NGF can be suppressed by a combination of a specific seaweed-derived component and a specific mushroom component or a specific natto component, an excellent effect of suppressing itching can be obtained, and an effect of improving skin and scalp conditions by suppressing NGF expression can be obtained, thereby completing the present invention. That is, the present invention provides an agent for suppressing the expression of a neural elongation factor, comprising (i) an ingredient extracted from a marine alga belonging to the family Sargassum or the family Alaria crassifolia, and (ii) at least one ingredient selected from (A) an ingredient cultured or extracted from a mushroom belonging to the family Agaricales and (ii) an ingredient extracted from natto. The present invention also provides an itching inhibitor and a skin / scalp cosmetic containing the expression inhibitor of the nerve elongation factor.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an inhibitor of nerve elongation factor expression that exhibits excellent anti-itching effects. [Background technology]

[0002] Itch, a unique sensation occurring only in the skin, mucous membranes, and cornea, is described as an "unpleasant sensation accompanied by the desire to scratch." Itch is one of the most significant and serious symptoms of inflammatory and allergic skin diseases, including atopic dermatitis, hay fever, food allergies, and urticaria, which have become social problems in recent years. Even among people who have not been diagnosed with these conditions, many suffer from dry skin and acne, which can cause itching. Itch is also a leading scalp concern across many age groups. Scalp itchiness is known to impair skin health, leading to thinning hair, increased hair loss, and loss of hair volume and strength. Because scratching behavior caused by itch can lead to secondary skin lesions, elucidating its mechanism and preventing it is an important challenge. Therefore, there is a need for safe, routinely applicable anti-itch agents. The skin is made up of three layers: the epidermis, dermis, and subcutaneous fat. The epidermis is further divided into four layers: the stratum corneum, stratum granulosum, stratum spinosum, and stratum basale. A normal epidermis acts as a barrier, protecting the body from various external stimuli and maintaining an appropriate amount of moisture within the body.

[0003] It has been reported that in the skin of patients with atopic dermatitis or xerosis, in which the skin barrier function is disrupted, or in their model mice, increased expression of nerve growth factor (NGF) and decreased expression of nerve repulsion factor (Semaphorin (Sema3A)), which causes nerve fiber retraction, are found, resulting in the penetration and proliferation of large numbers of sensory nerve fibers into the epidermis, which normally converge at the epidermal-dermal boundary (Non-Patent Document 1). Therefore, it is thought that if the nerve elongation effect of NGF can be suppressed or the nerve repulsion effect of Sema3A can be promoted, it will be possible to suppress itching in atopic dermatitis, dry skin, sensitive skin, etc. Lemongrass extract (Patent Document 1) and lavender extract (Patent Document 2) have been proposed as ingredients that suppress NGF expression. However, when applied to humans, the effects are limited, and no satisfactory results have been obtained. There is a need for ingredients derived from natural products that have the effect of suppressing NGF expression, are highly safe, and can be used on a daily basis. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2016-190823 [Patent Document 2] Japanese Patent Application Publication No. 2019-081712 [Non-patent literature]

[0005] [Non-Patent Document 1] Mitsutoshi Tominaga & Kenji Takamori, Recent advances in pathophysiological mechanisms of itch, Expert Review of Dermatology, Volume 5, 2010,p.197-212 Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention has been made to solve the above-mentioned problems, and aims to provide an NGF expression inhibitor. Furthermore, it is also possible to provide an anti-itch agent containing an NGF expression inhibitor, an anti-itch agent for skin and scalp application, and The purpose is to provide cosmetics. [Means for solving the problem]

[0007] As a result of extensive research to solve the above problems, the inventors discovered that the expression of NGF can be suppressed by combining specific seaweed-derived components with specific mushroom components and specific natto components, resulting in an excellent anti-itch effect, and furthermore that the suppression of NGF expression has the effect of improving the condition of the skin and scalp, which led to the completion of the present invention.

[0008] That is, the present invention is (i) a seaweed extract component belonging to the Sargassum family or the Sargassum family, and (ii) the following (A) and / or (B): (A) a mushroom culture or extract component belonging to the Agaricales order; (B) Natto extract components, The present invention provides an NGF expression inhibitor comprising: The present invention also provides an anti-itch agent and a cosmetic for the skin and scalp, each of which contains the NGF expression inhibitor. [Effects of the Invention]

[0009] As shown in the examples of the present application, the NGF expression inhibitor of the present invention can exhibit excellent itching suppression effects by suppressing NGF expression, and can also improve skin and scalp conditions by suppressing skin and scalp itching. In the present invention, suppression of NGF expression includes suppression of NGF mRNA expression and the resulting suppression of the expression of NGF (protein) itself. Being able to improve skin and scalp conditions means that the NGF expression inhibitor of the present invention inhibits the expression of NGF, thereby suppressing itching in the skin and scalp, and as a result, improving the condition of the skin and scalp, and thereby improving hair firmness and strength. DETAILED DESCRIPTION OF THE INVENTION

[0010] The present invention provides (i) a seaweed extract component belonging to the Sargassaceae or Sargassaceae family, and (ii) (A) and / or (B) below: (A) a mushroom culture or extract component belonging to the Agaricales order; (B) Natto extract components, It is an NGF expression inhibitor containing Furthermore, the present invention provides an anti-itch agent and a cosmetic for the skin and scalp, each containing the NGF expression inhibitor. In the present invention, the itch-suppressing effect means, for example, reducing the unpleasant sensation associated with the desire to scratch. In the present invention, the effect of improving the condition of the skin and scalp means improving the moisture content of the stratum corneum of the skin and scalp, normalizing skin turnover, suppressing redness, making pores and wrinkles less noticeable, improving the firmness and strength of hair, etc.

[0011] <Safety> (i) a seaweed extract component belonging to the Sargassaceae family or the Sargassaceae family; (ii) (A) Agaricales mushroom culture or extract, and (ii) (B) Natto extract are both commonly used as ingredients in medicines, folk medicines, foods, and cosmetics, and are highly safe.

[0012] <Explanation of each ingredient> <Seaweed-derived ingredients> Examples of seaweeds belonging to the Sargassum family or the Sargassum family in the present invention include Akamoku, Hijiki, Sargassum frutescens, Sargassum frutescens, and Undaria pinnatifida. Among these, Akamoku extract, Hijiki extract, and Wakame extract are preferred. Furthermore, one or more of these may be used in combination. The Sargassum horneri extract used as one of the components (i) of the present invention is an extract obtained from Sargassum horneri of the genus Sargassum of the Sargassaceae family, and also includes extracts obtained from seaweeds of the same genus. The hijiki extract used as one of the components (i) of the present invention is an extract obtained from hijiki of the genus Sargassum of the family Sargassaceae, and also includes extracts obtained from seaweeds of the same genus. The wakame extract used as component (i) of the present invention is an extract obtained from wakame of the genus Wakame of the family Pyralidae, and also includes extracts obtained from seaweeds of the same genus. The wakame of the genus Undaria of the family Pyralidae can be used in either its thallus or its sporophyll. The wakame extract is preferably an extract obtained from the sporophyll of wakame of the genus Undaria of the family Pyralidae (hereinafter referred to as "Mekabu extract"). For example, various types of Akamoku extract, Hijiki extract, Sargassum extract, and Wakame extract, which are well known in databases for cosmetic engineers, can be used as specific examples.

[0013] The total content of component (i) in the NGF expression inhibitor of the present invention is, in terms of the mass of the dry matter of component (i), Preferably 0.00001 to 10 mass %, More preferably, 0.0001 to 5 mass %. More preferably, it is 0.001 to 3% by mass. If the total content is less than the lower limit, the effects of the present invention may not be obtained, whereas if the total content exceeds the upper limit, the effects commensurate with the content tend not to be obtained, which is disadvantageous in terms of cost.

[0014] <Mushroom-derived ingredients> Examples of mushroom culture or extract components belonging to the Agaricales order in the present invention include extracts and culture solutions obtained from mushrooms such as Coprinus comatus, Pleurotus ostreatus, Lentinula edodes, Pleurotus cornucopius, and Pleurotus ostreatus. Among these, Coprinus comatus and Pleurotus ostreatus are preferred. Among these, Coprinus comatus extract and Pleurotus ostreatus culture broth are preferred. Furthermore, a component obtained by purifying the culture broth or extract may also be used, with Coprinus comatus purified product being preferred. These may be used alone or in combination of two or more. The Coprinus comatus extract used in component (ii)(A) ​​of the present invention is an extract obtained from Coprinus comatus of the genus Coprinus in the family Agaricaceae, and also includes extracts obtained from the same genus. The Coprinus comatus purified product used in component (ii)(A) ​​of the present invention is known to contain ergothioneine, a water-soluble amino acid contained in Coprinus comatus, which belongs to the genus Coprinus and belongs to the family Agaricaceae, and includes ergothioneine purified from the Coprinus comatus extract, and ergothioneine chemically synthesized or extracted and purified from other fungi. The Pleurotus ostreatus culture broth used in component (ii)(A) ​​of the present invention is a culture broth of Pleurotus ostreatus of the family Pleurotus family, and also includes culture broths of fungi of the same genus. For example, various Coprinus comatus extracts, Pleurotus ostreatus culture broth, Lentinula edodes extract, Pleurotus cornucopius extract, and Pleurotus ostreatus extract, which are well known in databases for cosmetic engineers, can be used as specific examples.

[0015] The total content of component (ii)(A) ​​in the NGF expression inhibitor of the present invention is 100% by mass of the dry matter of component (ii)(A). Preferably 0.00001 to 10 mass %, More preferably, 0.0001 to 5 mass %. More preferably, it is 0.001 to 3% by mass. If the total content is less than the lower limit, the effect of the present invention may not be obtained, whereas if it exceeds the upper limit, the effect commensurate with the content tends not to be obtained, which is disadvantageous in terms of cost.

[0016] <Natto-derived ingredients> The natto-derived component of the present invention includes an extract obtained from natto (hereinafter referred to as "natto-derived extract"). The natto-derived extract is an extract obtained from natto obtained by fermenting soybeans of the genus Glycine soja (Leguminosae) with Bacillus subtilis (Bacillaceae) and also includes extracts obtained from substances obtained by fermenting seeds of plants of the same genus with the same bacteria. For example, natto gum and nattokinase can be used as specific examples. The total content of component (ii)(B) in the NGF expression inhibitor of the present invention is 100% by mass of the dry matter of component (ii)(B). Preferably 0.00001 to 10 mass %, More preferably, 0.0001 to 5 mass %. More preferably, it is 0.001 to 3% by mass. If the total content is less than the lower limit, the effect of the present invention may not be obtained, whereas if it exceeds the upper limit, the effect commensurate with the content tends not to be obtained, which is disadvantageous in terms of cost.

[0017] In the present invention, examples of the extraction method for each extract include a method in which each part of seaweed, mushroom, and natto is immersed in an appropriate solvent. During extraction, the subject of extraction may be used as is, but is preferably crushed or dried before use, and more preferably crushed before use. Furthermore, stirring is preferably performed while the subject is immersed in the extraction solvent, but it may also be allowed to stand. Each extract of the present invention can be obtained as a highly concentrated extract by repeating the extraction procedure. There are no particular restrictions on the solvent used for extraction, and examples that can be used include water; lower monohydric alcohols such as methanol, ethanol, propanol, and butanol; polyhydric alcohols such as propylene glycol, dipropylene glycol, butylene glycol, and glycerin; esters such as methyl acetate and ethyl acetate; ketones such as acetone and methyl ethyl ketone; ethers such as diethyl ether and tetrahydrofuran; halogenated hydrocarbons such as chloroform and carbon tetrachloride; and hydrocarbons such as hexane, heptane, and cyclohexane. One of these may be used alone, or a mixed solvent of two or more of them may be used. In particular, polar solvents are preferred, and water and ethanol are more preferred. The extraction procedure is not particularly limited, and an example thereof includes a procedure in which the subject to be extracted is immersed in the solvent at 0 to 120° C. for 1 hour to 7 days, followed by filtration. The obtained extract may be used as it is, or may be diluted, concentrated, freeze-dried, purified, or the like before use as an extract.

[0018] The mushroom culture component of the present invention can be obtained by the following method. A suitable solution is disclosed as follows: a basidiomycete inoculum is inoculated into a liquid medium containing a carbon source, a nitrogen source, inorganic salts, etc., and cultured under aeration and agitation for 5 to 45 days, preferably 10 to 30 days, at a temperature of 15 to 35°C, preferably 20 to 30°C, after which the fungal cells are removed from the culture by centrifugation or filtration, or a solution obtained by concentrating this solution using a vacuum concentrator, etc. Furthermore, to further enhance efficacy and safety, the culture solution may be treated with ultrafiltration or reverse osmosis, or with activated carbon or various resins such as Sepabeads SP-850 (Mitsubishi Chemical Corporation), or concentrates thereof.

[0019] <Combination of ingredients> The combination of each component in the NGF expression inhibitor of the present invention may be Because of the excellent results, For example, Sargassum extract and Pleurotus comatus culture broth, Sargassum extract and Coprinus glabra purified product, Sargassum extract, Hijiki extract and Coprinus comatus purified product, Mekabu extract and Pleurotus comatus culture broth and Coprinus comatus extract, Sargassum extract, Hijiki extract and Natto extract, Mekabu extract and Natto extract, and Mekabu extract, Hijiki extract and Natto extract are preferred. For example, a combination of Sargassum extract and Pleurotus ostreatus culture broth, a combination of Sargassum extract and Coprinus comatus purified product, a combination of Sargassum extract, Hijiki extract and Coprinus comatus purified product, a combination of Mekabu extract and Natto extract, and a combination of Mekabu extract, Hijiki extract and Natto extract are more preferred. When component (i) and component (ii)(A) ​​are combined, the mass ratio of the dry matter of the components is preferably 100:1 to 1:100, more preferably 50:1 to 1:50, from the viewpoint of achieving a more excellent effect in suppressing itching and improving the condition of the skin and scalp. When component (i) and component (ii)(B) are combined, the mass ratio of the dry weights of the components is preferably 100:1 to 1:100, more preferably 50:1 to 1:50, from the viewpoint of achieving a more excellent effect in suppressing itching and improving the condition of the skin and scalp. When component (i), component (ii)(A), and component (ii)(B) are combined, the mass ratio of the dry matter of each component is preferably 100:100:1 to 10:10:100, and more preferably 50:50:5 to 5:5:10, from the viewpoint of achieving a more excellent effect of suppressing itching and improving the condition of the skin and scalp.

[0020] <When adding other ingredients> The NGF expression inhibitor of the present invention is a mixture of at least one selected from component (i) and at least one selected from component (ii)(A) ​​and / or at least one selected from component (ii)(B), but may also contain other components as shown below. Other components that can be used in the NGF expression inhibitor of the present invention include, for example, water, excipients, thickeners, solvents, buffers, preservatives, antioxidants, moisturizers, blood circulation promoters, cell activators, anti-inflammatory agents, antibacterial agents, peroxide inhibitors, surfactants, conditioning agents, UV absorbers, chelating agents, fragrances, colorants, components with hair growth and nourishing effects, components with itching suppressing effects, and various extracts derived from plants, animals, and microorganisms other than those mentioned above. Specifically, these include water; excipients such as lactose and sucrose; thickeners such as natural gums, cellulose derivatives, and acrylic acid polymers; solvents such as alcohols, glycols, and animal and vegetable oils; buffers such as phosphates, acetates, and carbonates; preservatives such as parahydroxybenzoates, chlorobutanol, benzyl alcohol, phenoxyethanol, and benzoic acid; sulfites, ascorbic acid, dibutylhydroxytoluene (BHT), dibutylhydroxyanisole (BHA), and acetic acid. Antioxidants such as tocopherol and arbutin; moisturizers such as glycerin, urea, amino acids, hyaluronic acid, squalane, macadamia nut oil, olive oil, jojoba oil, and silicone oil; blood circulation promoters such as vitamin E and capsicum tincture; cell activators such as nucleic acids; anti-inflammatory agents such as glycyrrhizin, allantoin, and piroctone olamine; antibacterial agents such as hinokitiol, benzalkonium chloride, and chlorhexidine salts; and peroxidants such as superoxide dismutase (SOD). Antioxidants; surfactants such as polyoxyethylene sorbitan monooleate, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycol, polyethylene glycol, sodium lauryl sulfate, sodium laureth sulfate, cocamidopropyl betaine, cocamide monoethanolamide, sodium cocoyl methyl taurate, behentrimonium chloride, and stearyltrimonium chloride; conditioning agents such as polyquaternium-10; UV absorbers such as ethylhexyl methoxycinnamate; chelating agents such as EDTA-2Na; fragrances; colorants such as caramel; ingredients with hair growth and nourishing effects such as herbal medicines such as aloe and ginger, and their extracts, and compounds such as pantothenyl ethyl ether, tocopherol acetate, and forskolin; ingredients with anti-itching effects such as plants such as St. John's wort and peony, and their extracts, and compounds such as glycyrrhizinate dipotassium; ginkgo extract, placenta extract, milk Examples of the extract include various extracts derived from plants, animals, and microorganisms other than those mentioned above, such as acid bacteria culture extracts. The NGF expression inhibitor of the present invention can be incorporated into various topical preparations including pharmaceuticals, quasi-drugs, and medicinal or cosmetic preparations, but because its excellent NGF expression inhibitory effect provides excellent effects in improving skin condition, including the scalp, and suppressing itching, it is suitable for incorporation into cosmetics to be applied to the skin and scalp. The formulation of the cosmetic is not particularly limited, and examples thereof include pastes, creams, gels, ointments, lotions, emulsions, packs, powders, poultices, hair styling products, hair tonics, shampoos, conditioners, treatments, hair rinses, hair care products, and hair growth products. The cosmetic composition for skin and scalp of the present invention contains the NGF expression inhibitor.

[0021] <Concentration (total content)> Cosmetics containing the NGF expression inhibitor of the present invention can also contain ingredients that are conventionally used in cosmetics for the skin and scalp, as long as the effects of the present invention are not impaired. Examples of such ingredients include the other ingredients listed above that can be used in NGF expression inhibitors. The total content of component (i), component (ii)(A), and component (ii)(B) in a cosmetic composition containing the NGF expression inhibitor of the present invention is not particularly limited, but when formulated, can be appropriately selected depending on the dosage form, frequency of use, types of excipients and additives to be blended, etc. For example, when at least one selected from component (i), at least one selected from component (ii)(A), and / or at least one selected from component (ii)(B) are used as a hair tonic, the total content of the dry matter of the components can be, for example, 0.00001 to 10% by mass. In cosmetics containing the NGF expression inhibitor of the present invention, the amounts of component (i), component (ii)(A), and component (ii)(B) may be adjusted appropriately so that the total content of the active ingredients falls within the above-mentioned range. If the total content is less than the lower limit, the effect of the present invention may not be obtained, whereas if it exceeds the upper limit, the effect commensurate with the content tends not to be obtained, which is disadvantageous in terms of cost.

[0022] <How to use> To obtain the effects of the cosmetic composition containing the NGF expression inhibitor of the present invention, the total amount of components (i), (ii)(A), and (ii)(B) is, for example, 0.00001 to 0.1 g per day for an adult, calculated as the dry weight of the components. This amount (preferably 0.000001 to 0.05 g / application) of the cosmetic composition is applied to the target area, such as the scalp or entire face, several times a day (preferably 1 to 2 times), and massaged in. The cosmetic composition is preferably used according to its formulation, frequency of application, and, when applied to the scalp, the amount of hair. [Example]

[0023] EXAMPLES The present invention will be described below in more detail with reference to examples, but the present invention is not limited to these examples in any way.

[0024] <Test Method> (1) NGF expression inhibition test (1-1) Cell culture Normal human epidermal keratinocytes (Kurabo Industries, Ltd.) were used as cells. Subconfluent epidermal keratinocytes were detached by trypsinization, seeded into each well of a 24-well plate, and cultured in Humedia-KG2 (Kurabo Industries, Ltd.), a serum-free medium for epidermal cell proliferation, at 37°C and 5% CO2 until subconfluent. The raw materials used were added to the medium so that the dry matter amounts of each component were as shown in Tables 1 and 2, and the medium was cultured for 24 hours. After culture, the cells were treated as unstimulated. When environmental stimuli were applied after culture, the following environmental stimuli were applied. In the present invention, environmental stimuli refer to ultraviolet rays, dryness, and air pollutants such as pollen, yellow sand, PM2.5, and house dust.

[0025] [Table 1]

[0026] [Table 2]

[0027] (A) UV stimulation: UV-B ultraviolet lamp (manufactured by Sankyo Electric Co., Ltd.) with an integrated light dose of 100 mJ / cm 2 After irradiation, the medium was replaced with a new one, and the test substance was added to the concentration shown in Table 2, followed by further culturing for 24 hours. (a) Dryness stimulation: The medium was removed, and the plate was left standing in a clean bench with the lid open for 5 minutes. After standing, new medium and the test substance were added, and the plate was further cultured for 24 hours. (c) Pollen stimulation: Ragweed pollen (manufactured by Info and Care) was added to the medium at a concentration of 250 μg / mL, and the medium was cultured for 24 hours. (D) Yellow sand stimulus: Gobi Kosa Dust (GKD, NIES CRM) No. 30) was added to the medium at 20 μg / mL and cultured for 24 hours.

[0028] After culturing without stimulation and with each of the environmental stimuli (a) to (d), the medium was removed, ISOGENII (Nippon Gene Co., Ltd.) was added to the epidermal keratinocytes, and the cells were cultured according to the attached protocol. Thus, total RNA was obtained.

[0029] <Raw materials used> Akamoku extract: Akamoku extract-P (Sansho Pharmaceutical) Mekabu extract: Mekabu Extract-P (Sansho Pharmaceutical) Hijiki extract: Hijiki extract BG (Maruzen Pharmaceuticals) Giant Pleurotus oyster mushroom culture medium: Farbio PC (Sansho Pharmaceutical) Coprinus comatus extract: Coprino extract-LC (Oryza oil & fat chemicals), Coprinus comatus purified product: THIOTAINE (Nikko Chemicals) Natto extract: Phytocollage PFE(N) (Ichimaru Falcos)

[0030] (1-2) Quantification of NGF mRNA expression by real-time reverse transcription-polymerase chain reaction (RT-PCR) Using the purified total RNA, a total of 10 μL of reaction solution (0.4 μM each of forward and reverse primers) was prepared in each well of a 96-well PCR plate using the One Step TB Green® PrimeScript® RT-PCR Kit II (Perfect Real Time) (manufactured by Takara Bio Inc.) according to the attached protocol, and real-time RT-PCR measurements were performed using Thermal Cycler Dice Real Time System Software (manufactured by Takara Bio Inc.). The real-time RT-PCR reaction consisted of 40 cycles of initial denaturation at 95°C for 30 seconds, denaturation at 95°C for 5 seconds, and annealing and extension at 60°C for 30 seconds. Table 3 shows the sequences of the primers used for amplifying NGF and the primers (Invitrogen) used for amplifying glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a housekeeping gene. The threshold cycle value (the number of cycles required to reach a certain level of fluorescence intensity) was analyzed from the fluorescence intensity during the amplification process, and the mRNA expression levels of NGF and GAPDH were calculated using the ΔΔCt method. The expression level of NGF mRNA was calculated by correcting the expression level of NGF by that of GAPDH. The mRNA expression levels of NGF in the Examples and Comparative Examples were defined as (a) and the mRNA expression level of NGF in the blank (Comparative Example 1) without any additives as (b), and the ratio of mRNA expression levels was calculated using the following formula. mRNA expression ratio = (a) / (b)

[0031] The ratio of mRNA expression levels when no stimulation was applied and when each of the environmental stimulations (a) to (d) was applied was scored according to the following evaluation criteria.

[0032] [Table 3]

[0033] (Evaluation criteria) 5 points: mRNA expression ratio is 0.8 or less 4 points: mRNA expression ratio >0.8, ≤0.9 3 points: mRNA expression ratio >0.9, ≤1.0 2 points: mRNA expression ratio > 1.0, ≤ 1.2 1 point: mRNA expression ratio > 1.2 (judgement) The average evaluation score of the mRNA expression level ratio when no stimulation was applied and when each of the environmental stimulations (a) to (d) was applied was calculated using the following formula. Average score (points) = (total score of mRNA expression ratio when no stimulation and when each of the environmental stimulations (a) to (d) was given) / 5 Samples with an average calculated evaluation score of 3 or more were deemed to have passed. The evaluation results are shown in Tables 1 and 2.

[0034] (2) Scalp and hair condition improvement test The NGF expression inhibitor of the present invention was incorporated into a scalp and hair cosmetic (hair tonic) and evaluated for its itching suppressing effect and scalp condition improving effect.

[0035] (2-1) Preparation of scalp and hair cosmetics As a test cosmetic for scalp and hair, a hair tonic was prepared with the composition shown in Table 4 below. The unit of blending amount is parts by mass, and the remaining amount of purified water is the amount required to make the total amount 100 parts by mass.

[0036] (2-2) Evaluation method Regarding scalp and hair cosmetics (hair tonic), 63 men and women in their 30s to 50s were used as subjects and divided into 9 groups of 7 people each. The specific hair tonic shown in Table 4 was filled in a spray bottle and applied 8 pumps (approximately 2.4 g) to the entire scalp every day before going to bed and after waking up, and the scalp was massaged in. This monitoring test was continued for three months, and before and after the test, the scalp stratum corneum moisture content, the stratum corneum delamination rate were evaluated by keratin staining, and the itching score was evaluated by questionnaire. After another three months, the hair firmness was evaluated by a single-bending test. Each was evaluated according to the following criteria. During this period, if any scalp and hair cosmetics other than those mentioned above were used, they were used as they normally would. No one complained of any skin or physical abnormalities during the period.

[0037] [Table 4]

[0038] (2-2-1) Evaluation of scalp stratum corneum moisture content The moisture content of the scalp stratum corneum of the test subjects was measured using a high-sensitivity stratum corneum thickness and moisture meter (ASA-MX3, manufactured by Nippon Ash Co., Ltd.). The test subjects' scalps were measured five times on the top of their heads, and the average moisture content of each scalp layer was calculated. The improvement rate of moisture content in each scalp layer was calculated using the following formula. Improvement rate of scalp stratum corneum moisture content (%) = (average moisture content of each scalp layer after the test / average moisture content of each scalp layer before the test) x 100 The improvement rate of moisture content in each layer of the scalp was scored according to the following evaluation criteria.

[0039] (Evaluation criteria) 5 points: Scalp stratum corneum moisture content improved by 150% or more 4 points: Improvement rate of scalp moisture content in each layer is 120% or more but less than 150% 3 points: Improvement rate of scalp moisture content in each layer is 100% or more but less than 120% 2 points: Improvement rate of moisture content in each layer of the scalp is 90% or more but less than 100% 1 point: Improvement rate of moisture content in each layer of the scalp is less than 90% (judgement) The average score for each group was calculated, and samples with an average score of 3 or more were deemed to have passed.

[0040] (2-2-2) Evaluation of layer peeling rate The stratum corneum of the scalp was collected from the test subjects' scalps using tape stripping. The collected keratinocytes were transferred to a Crestcoat slide glass (manufactured by Matsunami Glass Industry Co., Ltd.) and stained with gentian violet. The cells were observed under an all-in-one fluorescence microscope (BZ-X800, manufactured by Keyence Corporation), and the ratio of the area of ​​delaminated keratinocytes to the total area of ​​keratinocytes (hereinafter referred to as the "delaminated rate") was calculated using image analysis software Image J. Layer peeling rate (%) = (layer peeling area / total keratinocyte area) x 100

[0041] The difference between the layer peeling rate before the start of the test and after the test was taken as the improvement in the layer peeling rate, and the improvement in the layer peeling rate was calculated using the following formula. Improvement in layer peeling rate (%) = layer peeling rate after test - layer peeling rate before test The degree of improvement in the layer peeling rate was scored according to the following evaluation criteria.

[0042] (Evaluation criteria) 5 points: Improvement in layer peeling rate is 20% or more 4 points: Improvement in layer peeling rate is 10% or more but less than 20% 3 points: Improvement in layer peeling rate is 0% or more but less than 10% 2 points: Improvement in layer peeling rate is between -10% and 0% 1 point: Improvement in layer peeling rate is less than -10% (judgement) The average score for each group was calculated, and samples with an average score of 3 or more were deemed to have passed.

[0043] (2-2-3) Itching score evaluation A questionnaire was administered to test subjects, and they were asked to rate the itchiness they felt on their scalp before and after the test on an 11-point scale from 0 to 10, with 0 being no itchiness at all and 10 being the most itchy they had ever experienced, to create an itch score. The difference in the itchiness scores before and after the test was taken as the degree of improvement in itchiness, and the degree of improvement in itchiness was calculated using the following formula. Itching improvement level = (itching score before the start of the test) - (itching score after the end of the test) The degree of improvement in itching was scored according to the following evaluation criteria.

[0044] (Evaluation criteria) 5 points: Itching improvement level of 4 or more 4 points: Itching improvement level is 2 or more but less than 4 3 points: Itching improvement level is 0 to less than 2 2 points: Itching improvement level is between -1 and 0 1 point: Itching improvement level less than -1 (judgement) The average score for each group was calculated, and samples with an average score of 3 or more were deemed to have passed.

[0045] (2-2-4) Evaluation of hair firmness Thirty hairs were collected from the back of the head of each subject before and after the test, and the bending stiffness of each hair was measured using a single-hair bending tester (KES-FB2-SH, manufactured by Kato Tech Co., Ltd.). The average bending stiffness of the 30 hairs (hereinafter referred to as the "average bending stiffness of all hairs") was then calculated. Furthermore, the improvement rate of hair firmness was calculated using the following formula. Hair firmness improvement rate (%) = (average bending stiffness value of all hairs after the test / average bending stiffness value of all hairs before the test) x 100 The improvement rate of hair firmness and strength was scored according to the following evaluation criteria to obtain the evaluation score.

[0046] (Evaluation criteria) 5 points: Hair firmness and strength improved by 120% or more 4 points: Hair firmness and elasticity improvement rate is 110% or more but less than 120% 3 points: Hair firmness and elasticity improvement rate is 100% or more but less than 110% 2 points: Hair firmness and elasticity improvement rate is 90% or more but less than 100% 1 point: Hair firmness improvement rate is less than 90% (judgement) The average score for each group was calculated, and samples with an average score of 3 or more were deemed to have passed.

[0047] (2-3) Overall Judgment In (2-2-1) to (2-2-4), samples that received a score of 3 or higher were considered to have passed the test.

[0048] (3) Skin condition improvement test The NGF expression inhibitor of the present invention was blended into a skin cosmetic (skin lotion) and the effect of improving skin conditions was evaluated.

[0049] (3-1) Preparation of skin cosmetics As a test skin cosmetic, a skin lotion was prepared with the composition shown in Table 5. The blend amounts are in parts by mass, and the remaining amount of purified water is the amount required to make the total amount 100 parts by mass.

[0050] (3-2) Evaluation method Regarding skin cosmetics (skin lotion), 63 men and women in their 30s to 50s were used as subjects and divided into 9 groups of 7 people each. The specific skin lotion shown in Table 5 was filled into a spray bottle and applied four pumps (approximately 1.2 g) to the entire face and two pumps (approximately 0.6 g) to the inside of the left forearm every day before going to bed and after waking up, and then massaged into the skin with the hands. This monitoring test was continued for one month, and before and after the test, the moisture content of the stratum corneum on the inside of the forearm, the redness of the cheeks, the number of pores on the cheeks, and the wrinkles at the corners of the eyes were evaluated. Each was evaluated according to the following evaluation criteria. During this period, if any skin cosmetics other than those mentioned above were used, they were used as they normally would. No one complained of any skin or physical abnormalities during the period.

[0051] [Table 5]

[0052] (3-2-1) Evaluation of stratum corneum moisture content The stratum corneum moisture content of the test subject's arm was measured using a skin surface stratum corneum moisture meter (SKICON-200EX-USB, manufactured by Yayoi Co., Ltd.). The stratum corneum moisture content of the inner left forearm of the test subject was measured five times, and the average value of the stratum corneum moisture content was calculated. The improvement rate of stratum corneum moisture content was then calculated using the following formula. Improvement rate of stratum corneum moisture content (%) = (average value of stratum corneum moisture content after the test / average value of stratum corneum moisture content before the test) x 100 The improvement rate of the moisture content of the stratum corneum of the skin was scored according to the following evaluation criteria.

[0053] (Evaluation criteria) 5 points: Improvement rate of stratum corneum moisture content is 150% or more 4 points: Improvement rate of stratum corneum moisture content is 130% or more but less than 150% 3 points: Improvement rate of stratum corneum moisture content is 100% or more but less than 130% 2 points: Improvement rate of stratum corneum moisture content is 90% or more but less than 100% 1 point: Improvement rate of stratum corneum moisture content is less than 90% (judgement) The average score for each group was calculated, and the effect of each sample on improving the moisture content of each layer of the skin was evaluated. Samples with an average score of 3 or more were considered to have passed.

[0054] (3-2-2) Evaluation of cheek redness The left cheek of the test subject was photographed using a skin analyzer (Antera 3D, manufactured by Nippon Ash Co., Ltd.), and the hemoglobin level was measured using the attached image analysis software. Next, the redness suppression rate was calculated using the following formula. Redness suppression rate (%) = (1 - (hemoglobin level after test / hemoglobin level before test)) x 100 The calculated redness suppression rate was scored according to the following evaluation criteria: The average score for each group was calculated, and the redness suppression effect of each sample was evaluated.

[0055] (Evaluation criteria) 5 points: Redness reduction rate of 10% or more 4 points: Redness reduction rate is 5% or more but less than 10% 3 points: Redness suppression rate is 0% or more but less than 5% 2 points: Redness reduction rate is between -10% and 0% 1 point: Redness reduction rate is less than -10% (judgement) The average score for each group was calculated to evaluate the effect of each sample on reducing redness. Samples with an average score of 3 or more were considered to have passed the test.

[0056] (3-2-3) Evaluation of cheek pore count The left cheek of the test subject was photographed using a skin analyzer (Antera 3D, manufactured by Nippon Ash Co., Ltd.), and the number of pores on the cheek was counted using the attached image analysis software. Next, the reduction rate of the number of pores was calculated using the following formula. Pore ​​count reduction rate (%) = (1 - (number of pores after test completion / number of pores before test completion)) x 100 The calculated reduction rate of the number of pores was scored according to the following evaluation criteria.

[0057] (Evaluation criteria) 5 points: Pore count reduction rate of 20% or more 4 points: Pore count reduction rate is 10% or more but less than 20% 3 points: Pore count reduction rate is between 0% and 10% 2 points: Pore count reduction rate -10% or more to 0% 1 point: Pore count reduction rate -10% (judgement) The average score for each group was calculated to evaluate the effect of each sample in improving the number of pores. Samples with an average score of 3 or more were considered to have passed.

[0058] (3-2-4) Evaluation of wrinkles around the eyes The test subjects' left corner of the eye was photographed using a skin analyzer (Antera 3D, manufactured by Nippon Ash Co., Ltd.), and the maximum depth of wrinkles was measured using the attached image analysis software. The wrinkle improvement rate was then calculated using the following formula. Wrinkle improvement rate (%) = (1 - (maximum wrinkle depth after test completion / maximum wrinkle depth before test start)) x 100 The calculated wrinkle improvement rate was scored according to the following evaluation criteria.

[0059] (Evaluation criteria) 5 points: Wrinkle improvement rate of 20% or more 4 points: Wrinkle improvement rate is 10% or more but less than 20% 3 points: Wrinkle improvement rate is 0% or more but less than 10% 2 points: Wrinkle improvement rate is -10% or more, but less than 0% 1 point: Wrinkle improvement rate less than -10% (judgement) The average score for each group was calculated, and the effect of each sample on improving wrinkles around the eyes was evaluated. Samples with an average score of 3 or more were deemed to have passed.

[0060] (3-3) Overall Judgment In (3-2-1) to (3-2-4), samples that received a score of 3 or higher were considered to have passed the test.

[0061] (4) Overall evaluation When component (i) was combined with component (ii)(A) ​​and / or component (ii)(B), an effect of suppressing NGF expression was observed (Examples 1 to 21). On the other hand, when the various components used in the present invention were tested individually, none of them exhibited the effect of suppressing NGF expression and were judged to be unsatisfactory (Comparative Examples 31 to 36).Furthermore, the components described in the prior art, the combination of component (i) alone, and the combination of component (ii)(A) ​​and component (ii)(B) also did not exhibit the effect of suppressing NGF expression and were judged to be unsatisfactory (Comparative Examples 37 to 44). In a scalp and hair cosmetic containing the NGF expression inhibitor of the present invention, the scalp and hair condition was evaluated for its effect of improving scalp and hair condition in a scalp stratum corneum moisture content measurement test. The average score for Comparative Example 61 (placebo) was 2.1 points, while Comparative Examples 62-64, which contained individual components, and Comparative Example 65, which contained a combination of component (ii)(A) ​​and component (ii)(B), were 2.6-2.7 points. In comparison, Examples 51-54 all achieved an average score of 3.0 points or higher, demonstrating a significant improvement. In a keratin staining test, Comparative Examples 61-65 all achieved an average score of 2.7 points or lower, while Examples 51-54 all achieved an average score of 3.1 points or higher. In an itching score evaluation test, Comparative Examples 61-65 all achieved an average score of 2.6 points or lower, while Examples 51-54 all achieved an average score of 3.0 points or higher. In the bending test, the average evaluation score for Comparative Examples 61 to 65 was 2.1 points or less, whereas the average evaluation score for Examples 51 to 54 was 3.1 points or more. Therefore, the scalp and hair cosmetic composition containing the NGF expression inhibitor of the present application was found to have a high scalp and hair condition improving effect in all evaluation items, including scalp stratum corneum moisture content, stratum corneum delamination rate, itching score, and hair firmness and strength. The skin cosmetics containing the NGF expression inhibitor of the present invention showed an effect of improving skin conditions, with respect to stratum corneum moisture content, with the placebo group, Comparative Example 66, scoring an average of 2.6 points, while Comparative Examples 67 to 69, which contained each ingredient alone, and Comparative Example 70, which contained a combination of ingredient (ii)(A) ​​and ingredient (ii)(B), scored 2.7 points or less, whereas Examples 55 to 58 all scored 3.4 points or more. With respect to cheek redness, Comparative Examples 66 to 70 all scored 2.7 points or less, whereas Examples 55 to 58 all scored 3.0 points or more. The average score for the number of pores on the cheeks was 2.6 points or less for all Comparative Examples 66 to 70, while the average score for all Examples 55 to 58 was 3.0 points or more. The average score for wrinkles at the corners of the eyes was 2.3 points or less for all Comparative Examples 66 to 70, while the average score for all Examples 55 to 58 was 3.1 points or more. Therefore, the skin cosmetic containing the NGF expression inhibitor of the present application was found to have a high skin condition improvement effect in all evaluation items, namely, moisture content of the stratum corneum, redness of the cheeks, number of pores on the cheeks, and wrinkles at the corners of the eyes. As is clear from the above results, the scalp and hair cosmetics and skin cosmetics containing the NGF expression inhibitor of the present invention exhibited excellent effects of improving scalp, hair and skin conditions and suppressing itching. [Industrial Applicability]

[0062] The NGF expression inhibitor of the present invention exhibits excellent NGF expression inhibitory activity, resulting in excellent itching suppression. Furthermore, it also exhibits an effect of improving scalp, hair, and skin conditions. Furthermore, cosmetics containing the NGF expression inhibitor of the present invention also exhibit excellent NGF expression inhibitory activity, similar to the NGF expression inhibitor of the present invention, resulting in an itching suppression effect, as well as an effect of improving scalp and skin conditions and improving hair firmness and elasticity by suppressing scratching behavior. This enables the inhibitor to be used in various topical scalp, hair, and skin preparations, including cosmetics, aimed at reducing discomfort caused by itching and improving rough skin and loss of hair firmness associated with scratching behavior.

Claims

1. (i) a seaweed extract component belonging to the Sargassaceae family or the Sargassaceae family, and (ii) (A) and / or (B) below: (A) a mushroom culture or extract component belonging to the Agaricales order; (B) natto extract component, An inhibitor of nerve elongation factor expression, comprising:

2. An anti-itch agent comprising the nerve elongation factor expression inhibitor according to claim 1.

3. A cosmetic for the skin and scalp, comprising the nerve elongation factor expression inhibitor according to claim 1.

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